SAJCC Vol 32, No 1 (2016) by HMPG

SAJCC SOUTHERN AFRICAN JOURNAL OF CRITICAL CARE

July 2016 Vol. 32 No. 1

• Physiotherapy in ICU • Reducing paediatric VAP • Vitamin C in septic shock • Thrombocytopenia • Abstracts – 2016 Critical Care Congress

THE OFFICIAL JOURNAL OF THE CRITICAL CARE SOCIETY OF SOUTHERN AFRICA

In ICU patients, appropriate antifungal choices are critical in the management of invasive fungal infections. ¹

Help them in the fight of their lives Cancidas®: •

ESCMID 2012 Guidelines for the Diagnosis and Management of Candida Diseases Strongly Recommend CANCIDAS® 2

•

Broad Spectrum Coverage Against Many Species of Candida and Aspergillus. 3

•

Registered in children from 3 months and above. 3

Indications 3: •

Empirical therapy for presumed fungal infections in febrile, neutropaenic patients.

•

Treatment of Invasive Candidiasis, including candidaemia.

•

Treatment of Oesophageal and Oropharyngeal Candidiasis where IV antifungal therapy is appropriate.

•

Treatment of invasive Aspergillosis in patients who are refractory or intolerant of other therapies including amphotericin B, lipid formulations of amphotericin B and itraconazole.

References: 1. Schelenz, S. Management of Candidiasis in the intensive care unit. J Antimicrob Chemoth 2008; 61 ( Suppl 1) i31-i34. 2. Cornely OA, Bassetti M, Calandra T, et al for ESCMID Fungal Infection Study Group(EFISG). ESCMID 2012 Guidelines for the Diagnosis and Management of Candida Diseases: non-neutropaenic adult patients. Clin Microbiol Infect 2012;18(suppl7)19-37. 3. Cancidas Approved Package Insert-12 May 2015. For full prescribing information refer to the package insert approved by the Medicines Regulatory Authority. S4 CANCIDAS® 50 mg Lyophilised Powder for Solution for Infusion. Reg. No. 37/20.2.2/0544. Each vial contains 50 mg caspofungin anhydrous free base, equivalent to 55,5 mg caspofungin acetate. S4 CANCIDAS® 70 mg Lyophilised Powder for Solution for Infusion. Reg. No. 37/20.2.2/0545. Each vial contains 70 mg caspofungin anhydrous free base, equivalent to 77,7 mg caspofungin acetate. MSD (Pty) Ltd (Reg. No. 1996/003791/07), Private Bag 3, Halfway House, 1685. Tel: (011) 655-3000. www.msd.co.za. Copyright © 2016 Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Whitehouse Station, NJ, USA. All rights reserved.MSD. AINF-1099838-0001 01/2018

19859

SAJCC THE SOUTHERN AFRICAN JOURNAL OF CRITICAL CARE

The Official Journal of the Critical Care Society of Southern Africa July 2016 Vol. 32 No. 1

CONTENTS 3

EDITORIAL

Physiotherapy in the intensive care unit S Hanekom

ARTICLES

6 Physiotherapy contributions to weaning and extubation of patients from mechanical ventilation D Morar, H van Aswegen

11 Physiotherapy practice in South African intensive care units M Lottering, H van Aswegen

17 Reducing paediatric ventilator-associated pneumonia – a South African challenge! H Kunzmann, K Dimitriades, B Morrow, A Argent

21 An observational study on the relationship between plasma vitamin C, blood glucose, oxidative stress, endothelial dysfunction and outcome in patients with septic shock K G H Katundu, L T Hill, L M Davids, I A Joubert, M G A Miller, J L Piercy, W L Michell

28 Incidence and risk factors for thrombocytopenia in the intensive care units of a tertiary hospital in northern India C Mehta, J V George, Y Mehta, M T Ali, M K Singh

CASE REPORT

EDITOR Lance Michell DEPUTY EDITOR Brenda Morrow ASSOCIATE EDITORS Andrew Argent (UCT) Dean Gopalin (UKZN) Lauren Hill (Private Practice) Ivan Joubert (UCT) David Linton (Hadassa University, Jerusalem) Rudo Mathiva (Wits) Mervyn Mer (Wits) Sam Mokgokong (UP) Fathima Paruk (Wits) Helen Perrie (Wits) Guy Richards (Wits) Juan Scribante (Wits) PUBLISHED BY Health and Medical Publishing Group (HMPG), a subsidiary of the South African Medical Association HEAD OFFICE Health and Medical Publishing Group (Pty) Ltd Block F, Castle Walk Corporate Park, Nossob Street, Erasmuskloof Ext. 3, Pretoria, 0181 Tel. 012 481 2069 Email: dianes@hmpg.co.za EDITORIAL OFFICE Suites 9 & 10, Lonsdale Building, Gardener Way, Pinelands, 7405 Tel. 021 532 1281 | Cell. 072 635 9825 Email: publishing@hmpg.co.za HMPG CEO AND PUBLISHER Hannah Kikaya CONSULTING EDITOR J P de V van Niekerk EXECUTIVE EDITOR Bridget Farham MANAGING EDITORS Ingrid Nye Claudia Naidu

C Deepa, S Kamat, V Ravindran

TECHNICAL EDITORS Emma Buchanan Paula van der Bijl

ABSTRACTS

PRODUCTION MANAGER Emma Jane Couzens

Post-tracheostomy tracheo-oesophageal fistula – an unusual presentation

35 Abstracts of scientific presentations at the 2016 Annual National Conference of the Critical Care Society of Southern Africa

DTP AND DESIGN Carl Sampson CHIEF OPERATING OFFICER Diane Smith Tel. (012) 481-2069

Articles listed in EXCERPTA MEDICA (EM BASE), BIOLOGICAL ABSTRACTS (BIOSIS), SCIENCE CITATION INDEX (SCISEARCH), CURRENT CONTENTS/CLINICAL MEDICINE, SCIENTIFIC ELECTRONIC LIBRARY ONLINE (SCIELO)

ISSN 1562-8264

This Journal is accredited by the Department of Higher Education and Training. This Journal is also published online at www.sajcc.org.za Critical Care Society of Southern Africa Contact details: Alison Shaw, CCSSA Secretariat, 5 Hayman Park, Sunbury Park, Douglas Saunders Drive, La Lucia Ridge, KwaZulu-Natal, 4051, South Africa Tel: (031) 831 6416, Email: secretariat@criticalcare.org.za, Website: www.criticalcare.org.za The views and opinions expressed in the SA Journal of Critical Care are those of the authors and do not necessarily reflect the views of the Editors of the Journal or the Critical Care Society of Southern Africa. The appearance of advertising in the Journal does not denote a guarantee or an endorsement by the Society of the products or the claims made for the products by the manufacturers. Copyright 2000 by the SA Medical Association. This work is copyright under the Berne Convention. It is also copyright in terms of the Copyright Act 98 of 1978. No part of this publication may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, recording, or otherwise, without permission of the copyright holder.

Plagiarism is defined as the use of another’s work, words or ideas without attribution or permission, and representation of them as one’s own original work. Manuscripts containing plagiarism will not be considered for publication in the SAMJ. For more information on our plagiarism policy, please visit http:// www.samj.org.za/index.php/samj/about/editorialPolicies Use of editorial material is subject to the Creative Commons Attribution – Noncommercial Works License. http://creativecommons. org/licenses/by-nc/3.0 PRINTED BY TANDYM PRINT

ROAD ACCIDENT BENEFIT SCHEME A NEW DAWN BECKONS The present: The relationship between the Road Accident Fund (RAF), injured road crash victims and the private health care industry has for decades been dissatisfactory, largely as a result of the common-law, fault-based, compensation scheme administered by the RAF, and the consequent impact it has on the payment of claims. Under the RAF dispensation, a service provider who provides treatment to a road crash victim is faced with a number of risks, foremost of which are: complex claim procedures; the risk of the claim payment being rejected because the patient was solely at fault; the risk of the claim being reduced because of the patient’s contributory negligence; the risk of the claim becoming litigated because the patient’s negligence is in dispute; and, the lengthy time it takes for the RAF to assess the claim, before payment is made. Except for instances where the injured road crash victim is a member of a medical scheme, it is rare for the private health care industry to provide services to road crash victims.

A new dawn: A step towards the future: In order to improve road crash victims’ access to timely and appropriate health care services, the Road Accident Fund Act, 1996, is being amended. The amended Act will provide - among other things - for an initial no-fault claim period and for a single, clear, market-related, medical tariff. In terms of the amendments, claims for medical treatment provided to injured road crash victims, during the period of 30 days immediately following the road crash, will not be rejected or reduced because of fault. This amendment significantly reduces the risks currently faced by service providers. When coupled with faster claims payments by the RAF, due to expedited claim assessment as a result of the removal of the fault requirement, and taking into account the new clear, market-related, single medical tariff, it is anticipated that the role played by the private health care industry in servicing road crash victims will increase substantially.

The Road Accident Benefit Scheme (RABS) is the new social security scheme that will replace the RAF, thereby bringing to an end the artificial adversarial relationship created in statute, which has over decades stood in the way of closer collaboration with the health care industry. Under RABS the fault requirement is removed entirely; medical treatment and rehabilitation of the injured road crash victim is prioritized; and, claim procedures are simplified. Even more significant is RABS’ ability to establish a national network of contracted public- and private health care service providers, to provide health care and associated services to road crash victims, in terms of a contracted rate. Meanwhile, services provided by non-contracted health care service providers will be compensated in terms of a prescribed, clear, marketrelated, single medical tariff and treatment protocols. RABS is the future of road accident assistance provided to the victims of road crashes and creates exciting new opportunities for collaboration.

EDITORIAL

Physiotherapy in the intensive care unit Begin with the end in mind. (Sean Covey) While physiotherapy has been recommended by scientific societies as integral to the management of critically ill patients, great variation has been reported in the role of the physiotherapist in the intensive care unit (ICU), the service provided and the techniques used.[1] Clearly, this may impact on patient outcome. In a bid to address these variations, ICU physiotherapists have taken the initiative to drive a research agenda and to standardise clinical pathways to facilitate optimal patient outcome. The long-term sequelae associated with surviving an episode of critical illness are becoming increasingly apparent as the population of ICU survivors grows. The body of literature reporting on the 6- to 12-month outcome of survivors has increased from three publications in 1970 to ~300 published since 2000.[2] The majority of studies highlight the poor outcome of survivors. This includes reports of a 59% 1-year mortality, physical and cognitive impairments and poor health-related quality of life (HRQoL) in survivors of critical illness. Decreased muscle strength, joint stiffness, and decreased exercise capacity are lingering symptoms that persist up to 1 year after ICU discharge, and highlight the reality that decisions made and management options used in ICU affect the morbidity and HRQoL of ICU survivors. It is recognised that immobility in ICU and time spent on a ventilator are detrimental to long-term patient outcome. Much work has been done to ensure that early mobilisation of ICU patients is feasible and safe, and that patients are liberated from mechanical ventilation in a timely manner. Practices regarding optimal nutrition, sedation, weaning and early mobility have been reported.[1] While a recent review postulates that strategies aimed at improving respiratory muscle function will improve the long-term outcome of survivors, the association between respiratory muscle dysfunction and functional outcomes is unclear.[3] Similarly, despite a focus on facilitating the early mobility of critically ill patients, the effect of these early activities on the outcome of survivors is unclear. A recent trial reported no difference in hospital length of stay or muscle strength at 6 months when comparing in-unit standardised rehabilitation with usual care.[4] A better understanding of the underlying pathophysiology of post-intensive-care syndrome (PICS), and respiratory muscle dysfunction, is needed for clinicians to develop effective strategies to attenuate the consequences of this syndrome. As rehabilitation experts within the multidisciplinary team caring for ICU patients, physiotherapists are uniquely positioned to drive this research agenda. Standardising clinical pathways has been advocated to address the observed variations in clinical practice.[5] It has been postulated that these variations could be related to the training of therapists. While all universities in South Africa (SA) provide compulsory training to undergraduate physiotherapy students in the management of critically ill patients, the Health Professions Council of SA does not regulate the content of physiotherapy curricula. The results of a task team that has been working on the establishment of minimum standards for training since 2012 are awaited. As no standards exist for the training of therapists working in critical care environments â&#x20AC;&#x201C; nationally or internationally â&#x20AC;&#x201C; work is being done to inform the development of a competency framework for physiotherapists working in ICU. Ultimately, the framework will be endorsed and used throughout SA ICUs.[5] Through a consensus-building process, SA physiotherapists working in ICU were invited to identify core concepts to include in such a framework. Therapists agreed on six concepts that should be included when formulating minimum standards for physiotherapy clinical practice in SA ICUs. Physiotherapists working

in ICU should have the necessary knowledge and skills to understand normal integrated physiology and anatomy and to use clinical reasoning to execute holistic assessments and effective physiotherapy techniques. As we move towards the implementation of minimum standards of physiotherapy practice in SA, the two surveys included in this edition of SAJCC[6,7] provide valuable data on current physiotherapy practice in SA ICUs. The information is valuable as an international benchmark and to determine the training needs of physiotherapists practising in SA units. Lottering and Van Aswegen[6] aimed to describe the current practice of physiotherapists in SA ICUs. A strength of their study is that they attempted to survey both state and private units. Unfortunately, the response rate was only 33.9%, the majority of respondents were from the private sector (60%), and practitioners providing service in one province, Gauteng, were over-represented (48%). Despite the shortcomings, their article provides a clear picture of current physiotherapy practice within SA units. Although the physiotherapy service is aligned with current available evidence, it is clear from the data that work is needed to ensure that therapists incorporate the use of objective outcome measures into daily practice. Using the Medical Research Council scale to identify patients presenting with PICS before ICU discharge could facilitate targeted rehabilitation of these patients. In addition, the collection and reporting of objective measures may inform the development of process measurements as quality indicators for physiotherapy services in ICU.[8] In the other survey, Morar and Van Aswegen[7] aimed to establish the extent of involvement of SA physiotherapists in the weaning of patients from mechanical ventilation (MV) and describe current physiotherapy practice related to weaning and extubation. The response rate for this survey was 44% and the majority of respondents were from the public sector (66%). It is evident from the data that the SA therapists surveyed have limited involvement in the adjustment of MV settings, decision-making regarding initiation of patient weaning, make limited contributions towards the development of weaning protocols for their units and do not participate in the extubation of patients. These results could be explained by the large number of therapists with <5 yearsâ&#x20AC;&#x2122; experience (62%) participating in this survey. It also confirms the need for standardisation of curricula. It is encouraging that the majority of respondents contribute towards weaning of patients from MV through prescription of exercise therapy, early out-of-bed mobilisation and deep breathing exercises. However, the survey highlights the need for further training of physiotherapists on the criteria for patient weaning and additional targeted methods that could be employed to facilitate respiratory muscle training. Both the articles highlight the importance of developing and implementing minimum standards for physiotherapists working in SA ICUs. Outcomes are the end result of the care that a patient receives.[8] In addition to mortality, morbidity and health-related quality of life have been identified as outcomes that should be used to evaluate the quality of care provided to critically ill patients. As we move beyond mortality as the primary outcome, physiotherapists are positioned as integral members of the multidisciplinary team that will ensure optimal outcome for ICU survivors. Prof. S Hanekom (PhD)

Head of Physiotherapy Division, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa sdh@sun.ac.za SAJCC July 2016, Vol. 32, No. 1

1. Stiller K. Physiotherapy in intensive care: An updated systematic review. Chest 2013;144(3):825847. DOI:10.1378/chest.12-2930 2. Turnbull A, Rabiee A, Davis W, et al. Outcome measurement research from 1970 to 2013: A scoping review of 425 publications. Crit Care Med 2016;44(7):1267-1277. DOI:10.1097/ CCM.0000000000001651 3. Shellekens WJ, Van Hees HW, Doorduin J, et al. Strategies to optimize respiratory muscle function in ICU patients. Crit Care 2016;20(1):103. DOI:10.1186/s13054-016-1280-y 4. Morris PE, Berry MJ, Files DC, et al. Standardised rehabilitation and hospital length of stay among patients with acute respiratory failure: A randomized controlled trial. JAMA 2016;315(24):26942702. DOI:10.1001/jama.2016.7201 5. Hanekom S, Van Aswegen H, Plani N, Patman S. Developing minimum clinical standards for physiotherapy in South African intensive care units: The nominal group technique in action. J Eval Clin Pract 2015;2(1):118-127. DOI:10.1111/jep.12257

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6. Lottering M, Van Aswegen H. Physiotherapy practice in South African intensive care units. S Afr J Crit Care 2016;32(1):11-16. DOI: 10.7196/SAJCC.2016.v32i1.248 7. Morar D, Van Aswegen H. Physiotherapy contributions to weaning and extubation of patients from mechanical ventilation. S Afr J Crit Care 2016;32(1):6-10. DOI:10.7196/SAJCC.2016. v32i1.254 8. Murphy DJ, Ogbonna CO, Coopersmith C. ICU director data: Using data to assess value, inform local change, and relate to the external world. Chest 2015;147(4):1168-1178. DOI:10.1378/ chest.14-1567

S Afr J Crit Care 2016;32(1):3-4. DOI:10.7196/SAJCC.2016.v32i1.293

ARTICLE

Physiotherapy contributions to weaning and extubation of patients from mechanical ventilation D Morar, MSc Physiotherapy; H van Aswegen, PhD Department of Physiotherapy, School of Therapeutic Sciences, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa Corresponding author: H van Aswegen (helena.vanaswegen@wits.ac.za)

Background. Liberation of patients from mechanical ventilation (MV) is an important goal of patient care, to avoid the complications and risks associated with prolonged MV. Objective. To determine the extent of South African physiotherapists’ involvement in weaning and extubation of patients from MV and whether current practice is evidence based. Method. A survey questionnaire was developed, and content validated and made available electronically and in hard copy. Physiotherapists working in adult intensive care units in public and private sector hospitals in South Africa (SA) were identified and invited to participate. Results. Response rate was 43% (n=184). The majority of respondents (n=135, 73%) ‘never’ or ‘seldom’ got involved in decision-making to wean patients from MV; a minority (n=8, 4%) were ‘routinely’ involved in decision-making. Some respondents (n=54, 29%) performed extubation ‘often’ or ‘routinely’. The majority used exercises (n=149, 81%), early mobilisation out of bed (n=142, 77%) and deep breathing exercises (DBEs) (n=142, 77%) ‘routinely’ to aid in respiratory muscle training. The majority of respondents ‘never’ adjusted ventilator settings other than fraction of inspired oxygen. No association was found between type of physiotherapy degree respondents held and their involvement in weaning (p=0.24). Conclusion. SA physiotherapists’ contributions towards weaning of patients from MV through prescription of exercise therapy, early outof-bed mobilisation and DBEs is evidence based. Involvement in adjustment of MV settings, decision-making regarding patient weaning, development of weaning protocols for their units and extubation is limited. S Afr J Crit Care 2016;32(1):6-10. DOI:10.7196/SAJCC.2016.v32i1.254

Management of patients with critical illness often includes intubation and mechanical ventilation (MV) to assist patients through periods of exhaustion and poor gas exchange resulting from respiratory failure. Liberation of patients from MV is an important goal of patient care to avoid the complications and risks associated with prolonged MV, such as diaphragm dysfunction, dyspnoea and hypercapnia, physical deconditioning and muscle weakness, exercise intolerance, increased risk for morbidity and mortality, prolonged intensive care unit (ICU) length of stay and reduced health-related quality of life.[1-3] Weaning involves either abrupt or gradual withdrawal of MV support.[4] Reducing MV support too quickly, however, may result in fatigue or cardiovascular instability, either of which may delay the weaning process. Physiotherapists’ involvement in weaning of patients from MV includes provision of muscle-strengthening exercises, early mobilisation, administration of checklists to assess patient readiness for weaning, and identification of and treatment for patients receiving non-invasive ventilation (NIV).[3,5-9] In the South African (SA) critical care setting, physiotherapists not only provide care to patients in the form of pulmonary therapy, exercise and mobilisation interventions but are also actively involved in extubation of patients.[10] A pilot study by Van Aswegen and Potterton[10] on the scope of physiotherapy practice in ICU showed, however, that SA physiotherapists had little involvement in weaning of patients from MV. More recently, Plani et al.,[11] in a single-centred, non-randomised experimental trial, investigated the effect of a nurse- and physiotherapist-driven weaning and extubation protocol on MV duration and ICU length of stay of patients with traumatic injuries in an ‘open’-type ICU in SA. They reported a clinically significant reduction in MV duration and proposed that the role of SA physiotherapists and ICU nurses in weaning and extubation of patients in ‘open’-type ICUs should be expanded.[11] In an attempt to begin

SAJCC July 2016, Vol. 32, No. 1

addressing this issue, the authors set out to: (i) establish the extent of involvement of physiotherapists nationwide in weaning patients from MV and (ii) describe current physiotherapy practice related to weaning and extubation.

Methods

A descriptive, quantitative, survey-based study was performed. Ethics clearance was received from the University of the Witwatersrand Human Research (Medical) Ethics Committee prior to commencement (clearance no.: M110901). A survey questionnaire was developed based on the available literature regarding the involvement of physiotherapists in weaning and extubation of patients on MV. Content validation of the questionnaire was performed in January 2012, whereby a panel consisting of two experienced cardiopulmonary physiotherapy lecturers and two senior physiotherapists with vast ICU working experience critically analysed each question in the questionnaire. Each panellist was emailed the questionnaire and study aims and objectives 2 weeks prior to the meeting with the researchers, to familiarise themselves with the documents. At the meeting, suggestions and points of improvement were noted. Once these changes were made, the questionnaire was emailed back to the panel members for review. After consensus was reached on the final version of the questionnaire, it was loaded electronically onto SurveyMonkey for data collection. The final version of the questionnaire consisted of the following sections: demographics and ICU categorisation; weaning protocol; adjustment of mechanical ventilator settings; weaning and extubation; weaning interventions and physiotherapy modalities; physiotherapy autonomy; and education (qualification of respondent, existing opportunities for ongoing professional development and interest in further training). Physiotherapists who worked in adult ICUs in the public or private healthcare sectors were invited to participate in the survey.

Physiotherapists who did not work in ICU, physiotherapy assistants, undergraduate physio therapy students and community service physio therapists were excluded. The process of obtaining contact details for public and private sector hospitals lasted from March to July 2012. Firstly, the Department of Health was contacted to determine the name and location of all public sector hospitals in SA that had ICU facilities. The head of each public hospital physiotherapy department was contacted telephonically and, with permission via email, given information about the survey. This included a description of the purpose of the survey as well as inclusion and exclusion criteria. Heads of departments were asked to discuss the survey with their staff and whether email or postal surveys were preferred as the method of questionnaire delivery. Secondly, the Hospital Association of SA was contacted to source the main private hospitals under the Netcare, Mediclinic and Life hospital brands. Each private hospital ICU was contacted to acquire the names and contact details of private physiotherapy practices that served the ICU. After permission was obtained from private practice owners to share their information with the researchers, each practice was contacted telephonically, with permission via email, to share information about the survey. Practice owners were asked to share the information with their staff. Lastly, the national chairperson of the SA Society of Physiotherapy Cardiopulmonary Physiotherapy Rehabilitation Special Interest Group (CPRG) was contacted regarding the purpose of and criteria for the survey, and asked to share this information with CPRG members. Once heads of departments and private practice owners had identified staff members who were interested in participating and who fit the criteria for the survey, a list of email and postal addresses of participants was compiled by the researchers. The electronic link to the survey was emailed to participants. Hardcopy questionnaires with self-addressed return envelopes were posted to those who requested such. All hardcopy questionnaires were coded. Once the CPRG chairperson gave consent to approach CPRG members about the survey, the researchers sent the relevant documents and electronic link to the survey to the CPRG secretary, who disseminated the information to their membership. Participants were given 2 months to complete the survey. A courtesy email was sent 2 - 4 weeks after the initial email to thank participants who had completed the online survey and remind those who had

not to do so by the due date. A courtesy call was made, at similar time intervals, to departments and participants who requested hardcopy questionnaires to determine whether they received the questionnaires and to remind participants to complete and return the questionnaires by the due date. All completed questionnaires received via post or electronically were included and analysed.

Table 1. Demographics of respondents and their work environment at the time of the survey Variable Position held (N=183)

Statistical analysis

Descriptive statistics were used for analysis using Stata statistics and data analysis software version 11 (StataCorp, USA). Continuous data were summarised as means and standard deviations (SDs). Categorical data were summarised as frequencies and percentages. Fischer’s exact test was used to determine the involvement of physiotherapists in weaning in relation to number of years qualified and type of physiotherapy degree held. Logistic regression was used to determine if the number of years qualified had an influence on respondents’ involvement in weaning. A p-value <0.05 was deemed statistically significant.

Results

A total of 425 questionnaires were distributed among physiotherapists in SA who met the inclusion criteria. The response rate for postal questionnaires was 55% (n=109) and for the online survey was 33% (n=75), resulting in a combined response rate of 43% (n=184). Table 1 summarises demographic infor mation about the respondents and their work environments. The majority of respondents were senior physiotherapists or managers (n=119, 65%) and most respondents worked in the public healthcare sector (n=120, 66%). Most respondents had worked in an ICU for between 1 and 5 years (n=113, 62%), with only 11% (n=20) reporting ≥16 years’ ICU work experience. Most (n=155, 91%) held a Bachelor of Science degree in physiotherapy. Most respondents reported that they worked in an ‘open’ ICU setting, and the majority worked in mixed medical, surgical and trauma ICUs. An open-type ICU was defined as an ICU that was nonspecific physician led. Thirty-eight per cent of respondents (n=69) reported that their ICU had a guideline or protocol for weaning in place; however, only 16% (n=11) of respondents were involved in the development of these guidelines or protocols. The majority of respondents ‘never’ adjusted ventilator settings related to ventilation mode, respiratory rate, tidal volume, inspiratory

n (%)

Junior physiotherapist (<3 years’ work experience)

64 (35)

Senior physiotherapist (≥3 years’ work experience)

10 (5)

Head of department

79 (43)

Practice owner

30 (16)

Years qualified (N=184) 1-5

95 (52)

6 - 10

39 (21)

11 - 15

24 (13)

≥16

26 (14)

Years of ICU work experience (N=183) 1-5

113 (62)

6 - 10

40 (22)

11 - 15

9 (5)

≥16 or more

21 (11)

Type of qualification held by respondents (N=171) Diploma in Physiotherapy

7 (4)

Bachelor of Science in Physiotherapy

155 (91)

Master of Science in Physiotherapy

9 (5)

Doctor of Philosophy

0 (0)

Healthcare sector (N=183) Public

120 (66)

Private

63 (34)

Classification of ICU* Open

165

Closed

Type of ICU† Surgical

Cardiac/cardiothoracic

Trauma

Medical

Neurology

Burns

Mixed medical and surgical

Mixed medical, surgical and trauma

123

*More than one ICU per hospital †

Respondents worked in more than one ICU.

pressure and positive end-expiratory pressure (PEEP) (Fig. 1). It appears that respondents were more involved in adjusting the fraction of inspired oxygen (FiO2) setting on the

SAJCC July 2016, Vol. 32, No. 1

% of physiotherapists

100 90 80 70 60 50 40 30 20 10 0

Ventilator Respiratory Tidal Inspiratory Pressure mode rate volume pressure support

PEEP

FiO2

Ventilator setting Never

Seldom

Frequently

Often

Routinely

Uncertain

Fig. 1. Frequency with which respondents adjust MV settings.

% of physiotherapists

ventilator. This is reflected by 12% (n=22) reporting that they ‘routinely’ adjusted FiO2; 11% (n=20) reported they ‘often’ made this adjustment and 14% (n=26) reported that they ‘frequently’ adjusted FiO2. Seventy-three per cent (n=135) of respondents indicated that they ‘never’ or ‘seldom’ got involved in decision-making to start weaning a patient from MV, in contrast to a minority (n=8; 4%) who were ‘routinely’ involved in such decision-making. The majority of respondents (n=113, 61%) were ‘seldom’ or ‘never’ involved in providing advice to the interprofessional team in ICU on extubation of patients. Some respondents (n=54, 29%) performed extubation ‘often’ or ‘routinely’. The majority of respondents (n=119, 65%) indicated that they ‘never’ implemented a spontaneous breathing trial to facilitate weaning of a patient from MV. Similarly, many respondents (n=101, 55%) ‘never’ implemented NIV in patient care after extubation. Fig. 2 shows which physiotherapy modalities were used by respondents to facilitate resp iratory muscle strengthening in patients who are mechanically ventilated. The majority of respondents (n=149, 81%) used exercises ‘routinely’ in the form of active-assisted and active exercises to aid in respiratory muscle training. Many respondents used early mobilisation out of bed (n=142, 77%) and DBE (n=142, 77%) ‘routinely’. Interventions not used ‘often’ were DBE with biofeedback from the ventilator, DBE with adjustment of pressure support (PS) levels and DBE with manual hyperinflation (MHI). The most common modality ‘never’ used by respondents to strengthen respiratory muscles was DBE with adjustment of PS (n=125, 68%). This is in keeping with a majority of respondents (n=158, 86%) who reported to ‘never’ adjust the PS setting on the ventilator (Fig. 1). Physiotherapy autonomy was defined as the ability of respondents to make decisions on the weaning of a patient from MV in the unit where they worked and implementation of the decision without direct supervision from a medical colleague. Respondents were asked to rate their autonomy using a Likerttype scale. A mean (SD) rate of 1.9 (1.6) was calculated, where ‘1’ correlated to no autonomy and ‘10’ to complete autonomy. When asked how often respondents’ contributions influenced decisions regarding MV in their unit, a mean rate of 2.9 (2.2) was recorded. On this scale, ‘1’ correlated to never and ‘10’ to always. There was no association between the number of years respondents were qualified

90 80 70 60 50 40 30 20 10 0

Exercises

Early DBE only mobilisation out of bed

DBE with MV biofeedback

DBE with PS

DBE with MHI

DBE with manual resistance

Physiotherapy modalities Never

Seldom

Frequently

Often

Routinely

Uncertain

Fig. 2. Physiotherapy interventions used to facilitate respiratory muscle strengthening for patients on MV. and their involvement in weaning (p=0.43). Respondents qualified for >11 years were more routinely involved in the weaning of mechanically ventilated patients. There was no association between the type of physiotherapy degree respondents held and their involvement in weaning (p=0.24). Ninety-one per cent (n=168) of respondents reported to be keen to receive further training in the role of physiotherapy in the management of mechanically ventilated patients to prepare them for weaning and extubation.

Discussion

The main findings of this survey were that some respondents were involved in the devel opment of weaning protocols for the units that they work in, in decision-making about the initiation of weaning and in extubation, but the majority were not. Most respondents did not adjust MV settings, other than FiO2, during the process of weaning patients from MV, but mostly used DBE, exercise therapy

and early out-of-bed mobilisation to assist with weaning. The majority of respondents held a Bachelor of Science degree in physiotherapy, worked in mixed ICU settings and in public sector hospitals, and had between 1 and 5 years of work experience in ICUs. All eight univer sities that offer physiotherapy quali fications in SA provide compulsory training to undergraduate physiotherapy students in the management of critically ill patients. The content of physiotherapy curricula pertaining to theoretical and clinical aspects of care of critically ill patients is, however, not standardised across universities owing to poorly defined minimum criteria for training set out by the Health Professions Council of SA (HPCSA); therefore, the content taught is often influenced by the amount of experience that academic staff have in the critical care setting. In 2012, the HPCSA put together a task team to develop criteria related to minimum standards of training for undergraduate

physiotherapy students, the results of which are awaited. In addition, SA physiotherapy researchers with a special interest in critical care are in the process of developing minimum standards for physiotherapy practice in ICUs in an attempt to address this inequality in training.[12] The low level of involvement of respondents in the development of weaning guidelines for their units and in decision-making about initiation of patient weaning from MV may, therefore, be ascribed to the differing levels of training received at undergraduate level about this aspect of patient care. Historically, SA physiotherapists have had a low level of involvement in the process of weaning patients from MV, as reported by Van Aswegen and Potterton,[10] who showed that only 12 - 15% of their respondents were involved in weaning of patients from MV in ICUs. This is in contrast to a European physiotherapy survey, which reported that 22% of respondents supervised weaning of patients from MV and 25% performed extubation.[13] Therefore, other members of the interprofessional team in an ICU might not deem it necessary for physiotherapists to be involved in the development of guidelines or in decision-making related to patient weaning. It is known that within the public healthcare sector in SA, new graduates fill most available posts and they do not work exclusively in the ICU.[12] Even though a large number of respondents held senior positions, their relative inexperience in the ICU setting may account for their limited involvement in weaning of patients from MV. Research published on the effects of non-physician-driven weaning and extubation protocols in the liberation of patients from MV stems mostly from the USA, involving respiratory therapists and nurses.[14] Fewer studies have been published on the effects of physiotherapist involvement in the use of weaning and extubation protocols in ICU[7,11] despite the fact that physiotherapists, and not respiratory therapists, work in critical care settings in various other countries.[8] The prevalence of reporting on respiratory therapist involvement in weaning and extubation might, therefore, influence physicians’ perceptions regarding the role that physiotherapists potentially play in this aspect of patient care. This perception is reflected by the low level of autonomy and decision-making in weaning patients from MV reported by respondents in this survey. In a large single-centred, randomised controlled trial from Italy, patients who received a nurse- and physiotherapist-lead weaning and extubation protocol had a significantly lower reintubation rate after extubation than those managed solely according to the physician’s judgement.[7] The authors stated that despite ICU staff reports that the protocol increased their work load, the nurses and physiotherapists reported their involvement in this protocol had a positive effect on their professional roles in the ICU.[7] Plani et al.,[11] as mentioned previously, showed that physiotherapist and nurse involvement in a weaning and extubation protocol for patients with traumatic injury led to a clinically significant reduction in MV duration. The results of both of these studies suggest that physiotherapists who work in the ICU may have a valuable contribution to make towards weaning and extubation of patients from MV, especially in open-type ICU settings. Respondents who had >11 years of ICU work experience were more likely to be involved in weaning patients from MV, according to the current survey. This suggests that with clinical experience, physiotherapists enhance their confidence and clinical reasoning skills and are therefore more likely to contribute meaningfully towards weaning practices in their units. Although few respondents in this survey adjusted MV settings for the purpose of respiratory muscle training during their daily practice, the majority indicated that they

would be interested in receiving further education and training in the process of weaning of patients from MV. Such training might assist in raising the profile of physiotherapists in the provision of patient care in SA ICUs, especially in the public healthcare sector. Exercise therapy, early out-of-bed mobilisation and DBE were routinely performed by the majority of respondents. It is known that muscle activity has an anti-inflammatory function[15] and plays a beneficial role in the recovery of patients from critical illness by positively altering inflammatory cytokine activity.[16] Early mobilisation in intensive care and maintenance of muscle strength have been shown to reduce the number of ventilator-dependent days, shorten ICU and hospital length of stay and increase functional outcomes at hospital discharge.[8,9] Certain muscles of the upper limb insert onto and stabilise the rib cage. As these muscles are trained as part of whole-body exercise therapy, recruitment of accessory inspiratory muscles occurs, resulting in increased inspiratory muscle strength and more efficient ventilation patterns.[5] The routine use of exercise therapy and early mobilisation by respondents in this survey, which affects global weakness associated with critical illness, to facilitate patient weaning from MV is therefore in keeping with evidence-based practice.[5,8,9] Only some respondents in this survey performed extubation of patients. This finding is in contrast to that reported by Van Aswegen and Potterton,[10] where 65% of physiotherapists in public and private sector hospitals indicated that they performed extubation. Possible explanations for this decreased involvement of physiotherapists in patient extubation could be the differing levels of training received at undergraduate level, relatively low levels of work experience in the ICU or because extubation is not the sole scope of practice of physiotherapists in SA, as nurses and doctors are also trained to perform this procedure. As physiotherapists in the public sector do not work exclusively in ICUs,[12] other professionals may step in to perform extubation if the physiotherapist had left the unit prior to the orders for extubation being relayed. A meta-analysis on the use of NIV for weaning showed that NIV use in recently extubated patients was associated with reduced ICU and hospital length of stay, incidence of pneumonia and reintubation rates.[17] NIV was implemented after extubation by few respondents in this survey. Moran et al.[6] investigated physiotherapy involvement in NIV hospital services in the British Isles using a survey study design. The authors reported that physiotherapists’ involvement was mainly in the treatment of patients on NIV and not assessing a patient’s need for or setting them up on NIV. They felt that these aspects of care were the responsibility of any appropriately trained member of the interprofessional team in the ICU and not solely that of the physiotherapist.[6] This suggests that SA physiotherapists’ limited involvement in implementation of NIV is in keeping with international practice.

Study limitations

The quality of research findings from survey-based studies is influenced by response rate.[18] The study has a 57% non-response bias and therefore the results should be interpreted with caution. Findings were limited by the low response rate from physiotherapists working in private sector ICUs, the reasons for which are unknown. The survey did not include physiotherapists’ use of inspiratory muscle trainer devices to facilitate respiratory muscle training for weaning purposes. Research evidence suggests that inspiratory muscle training increases maximal inspiratory pressure and reduces MV and weaning time;[2] therefore, future surveys should include this aspect of respiratory muscle training in the ICU.

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Conclusion

SA physiotherapists contribute towards weaning of patients from MV through prescription of exercise therapy, early out-of-bed mobilisation and DBE. Their involvement in adjustment of MV settings, decisionmaking regarding initiation of patient weaning and contributions towards development of weaning protocols for their units and extubation is limited. There is a need for further training of physiotherapists in the criteria for patient weaning and the additional methods employed to facilitate respiratory muscle training to ensure successful extubation. References 1. El-Khatib MF, Bou-Khalil P. Clinical review: Liberation from mechanical ventilation. Crit Care 2008;12(4):221. DOI:10.1186/cc6959 2. Gosselink R, Clerckx B, Robbeets C, et al. Physiotherapy in the intensive care unit. Neth J Crit Care 2011;15(2):66-75 3. Dantas CM, Dos Santos Silva PF, De Siqueira FHT, et al. Influence of early mobilisation on respiratory and peripheral muscle strength in critically ill patients. Rev Bras Ter Intensiva 2012;24(2):173-178. DOI:10.1590/S0103-507X2012000200013 4. Blackwood B, Alderdice F, Burns K, et al. Use of weaning protocols for reducing duration of mechanical ventilation in critically ill adult patients: Systematic review and meta-analysis. Br Med J 2011;10:342-356. DOI:10.1136/bmj.c7237 5. Martin UJ, Hincapie L, Nimchuk M, et al. Impact of whole-body rehabilitation in patients receiving chronic mechanical ventilation. Crit Care Med 2005;33(10):2259-2265. DOI:10.1097/01. ccm.0000181730.02238.9b 6. Moran FM, Bradley JM, Elborn JS, et al. Physiotherapy involvement in non-invasive ventilation hospital services: A British Isles survey. Int J Clin Pract 2005;59(4):453-456. DOI:10.1111/j.13685031.2005.00400.x

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7. Navalesi P, Frigerio P, Moretti MP, et al. Rate of reintubation in mechanically ventilated neurosurgical and neurological patients: Evaluation of a systematic approach to weaning and extubation. Crit Care Med 2008;36(11):2986-2992. DOI:10.1097/CCM.0b013e31818b35f2 8. Ambrosino N, Makhabah DN. Comprehensive physiotherapy management in ARDS. Minerva Anestesiol 2013;79(5):554-563 9. Cameron S, Ball I, Cepinskas G, et al. Early mobilisation in the critical care unit: A review of adult and pediatric literature. J Crit Care 2015;30(4):664-672. DOI:10.1016/j. jcrc.2015.03.032 10. Van Aswegen H, Potterton J. A pilot survey of the current scope of practice of South African physiotherapists in intensive care units. S Afr J Physiother 2005;61:17-21 11. Plani N, Becker P, Van Aswegen H. The use of a weaning and extubation protocol to facilitate effective weaning and extubation from mechanical ventilation in patients suffering from traumatic injuries: A non-randomized experimental trial comparing a prospective to retrospective cohort. Physiother Theory Pract 2013;29(3):211-221. DOI:10.3109/09593985.20 12.718410 12. Hanekom S, Van Aswegen H, Plani N, et al. Developing minimum clinical standards for physiotherapy in South African intensive care units: The nominal group technique in action. J Eval Clin Pract 2015;21(1):118-127. DOI:10.1111/jep.12257 13. Norrenberg M, Vincent JL. Brief report: A profile of European intensive care unit physiotherapists. Intensive Care Med 2000;26(7):988-994. DOI:10.1007/s001340051292 14. Haas CF, Loik PS. Ventilator discontinuation protocols. Respir Care 2012;57(10):1649-1662. DOI:10.4187/respcare.01895 15. Gleeson M, Bishop NC, Stensel DJ, et al. The anti-inflammatory effects of exercise: mechanisms and implications for the prevention and treatment of disease. Nat Rev Immunol 2011;11(9):607615. DOI:10.1038/nri3041 16. Winkelman C, Johnson KD, Hejal R, et al. Examining the positive effects of exercise in intubated adults in ICU: A prospective repeated measures clinical study. Intensive Crit Care Nurs 2012;28(6):307-320. DOI:10.1016/j.iccn.2012.02.007 17. Glossop AJ, Shepherd N, Bryden DC, et al. Non-invasive ventilation for weaning, avoiding reintubation after extubation and in the postoperative period: A meta-analysis. Br J Anaesth 2012;109(3):305-314. DOI:10.1093/bja/aes270 18. Fincham JE. Response rates and responsiveness for surveys, standards and the journal. Am J Pharm Educ 2008;72(2):43. DOI:10.5688/aj720243

ARTICLE

Physiotherapy practice in South African intensive care units M Lottering, MSc (Physiotherapy); H van Aswegen, PhD

Department of Physiotherapy, School of Therapeutic Sciences, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa Corresponding author: H van Aswegen (helena.vanaswegen@wits.ac.za)

Background. Physiotherapists are integral members of the interprofessional team that provides care and rehabilitation for patients in intensive care units (ICUs). Objectives. To describe the current practice of physiotherapists in ICUs, determine if physiotherapists’ practice has changed since a previous report and determine if practice is evidence based. Methodology. A questionnaire was content validated and made available electronically and in hard copy. Physiotherapists who work in ICUs in public or private sector hospitals or who are members of the South African Society of Physiotherapy were identified and invited to participate. Results. Survey response rate was 33.9%. Patient assessment techniques performed ‘very often’ included ICU chart assessment (n=90, 83.3%), chest auscultation (n=94, 81.8%) and cough effort (n=81, 75%). Treatment techniques performed ‘very often’ included manual chest clearance (n=101, 93.5%), in-bed mobilisation and positioning (n=91, 84.3%; n=91, 84.3%, respectively), airway suctioning (n=89, 82.4%), out-of-bed mobilisation (n=84, 77.8%), deep breathing exercises (n=83, 76.9%) and peripheral muscle-strengthening exercises (n=72, 73.1%). More respondents used intermittent positive pressure breathing (57 v. 28%, p=0.00), used adjustment of mechanical ventilation (MV) settings (30 v. 15%, p=0.01), were involved with weaning patients from MV (42 v. 19%, p=0.00) and used incentive spirometry (76 v. 46%, p=0.00) than reported previously. More respondents performed suctioning (99 v. 70%, p=0.00), extubation (60 v. 25%, p=0.00) and adjustment of MV settings (30 v. 12%, p=0.02) than reported internationally. Conclusion. Physiotherapy practice in ICUs is evidence based. Care focuses largely on mobilisation, exercise therapy and multimodality respiratory therapy. S Afr J Crit Care 2016;32(1):11-16. DOI:10.7196/SAJCC.2016.v32i1.248

Research activity in critical care literature is currently focused on early rehabilitation of patients with critical illness and its effects on length of stay, number of ventilator-free days and functional outcomes.[1,2] Physiotherapists are integral members of the interprofessional team that provides care and rehabilitation to patients with critical illness, on an international and national level.[1,3,4] Recently, there has been a drive to establish minimum standards of clinical practice for physiotherapists in South African (SA) intensive care units (ICUs) to ensure that safe and effective patient care is provided.[4] Few reports on physiotherapy practice in ICU could be sourced. In 2000, Norrenberg and Vincent[5] conducted a study to establish the profile of physiotherapists working in ICUs in Europe. Van Aswegen and Potterton[6] subsequently amended the survey questionnaire compiled by the aforementioned authors for use in an SA setting and conducted a pilot survey to determine the scope of practice of physiotherapists in ICUs. Content validation of the modified questionnaire was not carried out at the time and, therefore, the reported results were preliminary. Defining the current practice of physiotherapists working in ICUs is important to assist with the development of clinical practice guidelines and minimum standards of physiotherapy practice. It was therefore decided to conduct a nation wide survey to: (i) determine the current practice of physiotherapists in SA ICUs; (ii) determine if physiotherapists’ practice in ICUs had changed since the previous report; and (iii) validate the survey questionnaire. In addition, SA physiotherapists’ practice in ICU was compared with that reported in critical care and rehabilitation literature, to determine if current practice is evidence based.

Method

A cross-sectional, quantitative, descriptive, survey-based study was performed. Ethical clearance was sought and obtained from the University of the Witwatersrand Human Research Ethics (Medical) Committee (clearance no.: M130131) prior to commencement. The first

phase of the study consisted of content validation of the questionnaire used by van Aswegen and Potterton.[6] The questionnaire and survey objectives were sent electronically to a group of five physiotherapists experienced in working in ICUs. They were asked to review the documents prior to a meeting scheduled with the authors. At the meeting, questions that were deemed unsuitable were either adjusted or removed from the questionnaire and additional questions were added where indicated. The amended questionnaire was emailed back to the group members for further scrutiny. A few minor adjustments were then suggested and made by the authors. After consensus was reached on the content of the final version of the questionnaire, it was loaded onto SurveyMonkey for the second phase of the study. The final version of the questionnaire consisted of the following sections: participant demographics, ICU type in which physiotherapists work, patient referral method, after-hours service provision, assessment and treatment techniques used in patient management, participation in interprofessional team meetings and professional development activities. Physiotherapists with work experience of 3 years or more in adult ICUs in public or private sector hospitals or who were members of the Cardiopulmonary Physiotherapy Rehabilitation Group (CPRG) of the SA Society of Physiotherapy (SASP) were contacted in 2013 and invited to participate in the survey. Potential participants were identified using the following methods: (i) The Department of Health was contacted to obtain a list of all public sector hospitals in SA. Using this list, all physiotherapy heads of departments (HODs) in public sector hospitals that had ICUs were contacted and informed of the aims of and inclusion criteria for the survey. (ii) A list of hospitals belonging to the Life, Mediclinic and Netcare groups was obtained from their respective websites and hospitals with ICUs were contacted. The unit manager of the ICU was contacted for

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Gauteng

Free State

North-West

Northern Cape

Eastern Cape

KwaZulu-Natal

Mpumalanga

Limpopo

Western Cape

16%

10%

47%

11% 4%

Fig. 1. Geographical representation of respondents (n=108). 60 Percentage of respondents (%)

details of the physiotherapy private practices working in their unit. After agreement was received from practice owners for their details to be shared, unit managers passed the information to the authors who contacted them regarding the aims of and inclusion criteria for the survey. (iii) The chairperson of the CPRG of the SASP was contacted and informed of the aims of and inclusion criteria for the survey. The chairperson was asked to invite members of the CPRG to participate in the survey. Practice owners and HODs were asked to discuss the survey with their staff. The contact details of those who fitted the inclusion criteria and agreed to participate were passed on to the authors. An electronic link to the survey was sent to these physiotherapists. Alternatively, hard copies of the survey information sheet, inclusion criteria, questionnaire and self-addressed return envelopes were distributed to those who did not have access to the electronic link. All hard copy questionnaires were coded. Participants were given 3 months, from May 2013, to complete the questionnaire, and consent was implied. One and 2 months after initiation of the survey, a blanket reminder email was sent out to all participants who were initially emailed with the electronic link, to remind them to complete the survey and to thank those who had already done so. The HODs of hospitals that were sent postal questionnaires were phoned at the same intervals and asked to remind their staff to complete and return the questionnaires; those who had already completed questionnaires were thanked.

55.6%

54.6%

53.7% 48.1%

42.6%

36.1% 30.6%

30 20 10 0

ica

ica rg Su

c ra

au Tr

o th

i rd Ca

ri at

i rd Ca

i ed

ico

ica rg -su

Type of unit

Fig. 2. Type of ICU in which respondents worked.

Statistical analysis

Categorical data were summarised as frequencies and percentages in text and illustrative tables. Comparisons of findings from the current survey with those reported by van Aswegen and Potterton,[6] and Norrenberg and Vincent,[5] were made using the χ2 test or in narrative form where statistical comparisons were not possible. The denominator for the χ2 test was Yes/No, related to each treatment technique used as reported in the current survey and results reported by the other two surveys.[5,6] A p-value of ≤0.05 was considered statistically significant. SPSS version 22.0 (IBM Corp., USA) was used for statistical analyses.

Results

The authors identified 71 public hospitals that had ICUs at the time of the survey. There were 64 Life, 49 Mediclinic and 56 Netcare hospitals

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38%

CPD certificate CPT1 APDL certificate

53.7%

Master's degree PhD 5.6%

None

7.4%

0.9%

Fig. 3. Percentage of respondents who held any type of postgraduate cardiopulmonary physio therapy qualification. in SA at the time of the survey, of which 49 Life, 32 Mediclinic and 44 Netcare hospitals had ICUs with physiotherapy service provision. These 125 private hospitals were contacted by

the authors, and contact details of 154 private physiotherapy practices were obtained. A total of 319 questionnaires were sent out (n=252 electronic and n=67 postal). Eighty-

five electronic responses were received and 23 postal questionnaires were returned (response rates of 33.7% and 34.3%, respectively) with a combined response rate of 33.9% (n=108). Physiotherapists working in private sector hospitals made up 60.2% (n=65) of respondents. Responses were received from physiotherapists in all the SA provinces with the exception of Limpopo Province (Fig. 1). A large number of respondents (n=51, 47.2%) were from

Gauteng. The majority of respondents worked in medical, surgical or combined medico-surgical ICUs (Fig. 2). Fifty-six respondents (46%) held a postgraduate qualification related to cardiopulmonary physiotherapy (Fig. 3). In most cases, respondents indicated that patients in ICU were referred for physiotherapy by doctors or nurses (n=59, 54%); however, some reported that the physiotherapist working in the unit screened the patients to determine if they

Table 1. Frequency with which respondents used assessment techniques in ICU,* n Assessment technique

Never

Almost never

Sometimes

Fairly often

Very often

Auscultation

ICU chart review

Strength of cough effort

X-ray/Computed tomography scan

Arterial blood gas analysis

Thoracic expansion

Readiness for mobilisation using specific criteria

Need for humidification

Peripheral muscle strength (dynamometry or Medical Research Council scale)

Respiratory muscle strength (MIP)

Percussion note to assess quality of lung tissue

Readiness for weaning (RSBI)

Calculation of lung compliance

Calculation for the presence of hypoxaemia

MIP = maximum inspiratory pressure; RSBI = rapid shallow breathing index. *Ranked according to activities performed ‘very often’.

Table 2. Frequency with which respondents used various treatment techniques in their management of critically ill patients, n Physiotherapy technique

Never

Almost never

Sometimes

Fairly often

Very often

Manual chest clearance techniques (percussions, vibrations, shaking)

101

Mobilising a patient in bed

Positioning a patient in bed

Airway suctioning

Mobilising a patient out of bed

Deep breathing exercises

Positioning a patient out of bed

Peripheral muscle-strengthening exercises

Postural drainage/modified postural drainage

Active cycle of breathing techniques

Nebulisation

Blow bottle

Blowing up a glove

Inspiratory muscle training (threshold device/devices by other manufacturers)

Manual hyperinflation (ambubagging)

IPPB

Active involvement in weaning a patient from MV

Adjustment of MV settings for respiratory muscle training

Implementation and supervision of non-invasive ventilator support (CPAP, BiPAP)

Flutter device

IS = incentive spirometry; IPPB = intermittent positive pressure breathing; CPAP = continuous positive airway pressure; BiPAP = bilevel positive airway pressure. *Ranked according to activities performed ‘very often’.

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were suitable for physiotherapy intervention (n=49, 45%). An after-hours physiotherapy service was provided by 72% (n=78) of respondents to ICUs during weekdays. The majority of respondents (n=105, 97%) provided weekend physiotherapy services to their ICUs. Respondents were asked how often they used various methods of assessment to determine patient suitability for physiotherapy intervention and how often they used various treatment techniques in their patient management. They could select responses indicating either ‘never’, ‘almost never’, ‘sometimes’, ‘fairly often’ or ‘very often’. Responses related to assessment are summarised in Table 1 and those related to treatment in Table 2. The most frequently used assessment techniques included ICU chart assessment (n=90, 83%), chest auscultation (n=94, 82%) and assessment of strength of cough effort (n=81, 75%). Assessment techniques that were ‘almost never’ or ‘never’ used included calculation of lung compliance (n=75, 69%), calculation of hypoxaemia (n=74, 69%) and assessment of patient readiness for weaning (n=63, 58%). Objective outcome measures such as MIP, RSBI, dynamometry or Medical Research Council scale were more often not used. Treatment techniques performed by respondents ‘very often’ included manual chest clearance techniques (n=101, 94%), mobilising a patient in bed (n=91, 84%), positioning a patient in bed (n=91, 84%), airway suctioning (n=89, 82%), mobilising a patient out of bed (n=84, 78%), deep breathing exercises (n=83, 77%) and peripheral muscle-strengthening exercises (n=79, 73%). Treatment techniques that respondents ‘never’ or ‘almost never’ used included the flutter device (n=77, 71%), implementation and supervision of noninvasive ventilation support (n=77, 71%) and adjustment of mechanical ventilation (MV) settings for respiratory muscle training (n=76, 70%). Fifty-six percent (n=60) of respondents attended ward rounds in the ICU on a daily or weekly basis. Forty-five percent (n=49) of respondents had attended an ICUrelated continuous professional development activity within the last year. Thirty-four percent (n=37) of respondents were involved in student training and 33% (n=36) were involved in training of other members of the interprofessional team in the ICU. A large number of respondents were involved with the inservice training of colleagues, such

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Table 3. A comparison of physiotherapy techniques used by the respondents in the study by Norrenberg and Vincent[5] and the current study Norrenberg and Vincent (Europe, 2000)

Current study (SA, 2013)

Treatment technique

Yes, %

No, %

Yes, %

No, %

p-value

Respiratory treatment

Suctioning

0.00

IPPB/NIPPV

0.56

Intubation

0.95

Extubation

0.00

Adjustment of MV

0.02

Weaning from MV

0.06

Mobilising

100

0.32

Positioning

0.95

NIPPV = non-invasive positive pressure ventilation.

Table 4. A comparison of physiotherapy techniques used by the respondents in the study by van Aswegen and Potterton[6] and the current study Van Aswegen and Potterton (SA, 2005)

Current study (SA, 2013)

Treatment technique

Yes, %

No, %

Yes, %

No, %

p-value

Respiratory treatment

Suctioning

0.56

IPPB

0.00

Intubation

0.56

Extubation

0.46

Adjustment of MV

0.01

Weaning from MV

0.00

Mobilising

0.56

Positioning

0.10

Blow bottle

0.88

MHI

0.07

0.00

MHI = manual hyperinflation.

as training junior physiotherapists to work safely in the ICU (n=51, 47%) and training other physiotherapists at their hospital or private practice to work safely in the ICU (n=55, 50%). Comparisons were made between physiotherapy treatment techniques used in this survey and those reported by Norrenberg and Vincent[5] (Table 3). More SA respondents performed suctioning (99 v. 70%, p=0.00), extubation (60 v. 25%, p=0.00) and adjustment of MV settings (30 v. 12%, p=0.02) than their European counterparts. Similarly, comparisons were made between physiotherapy treatment techniques used in this survey and those reported by van Aswegen and Potterton[6] (Table 4). More

respondents in the current survey used IPPB (57 v. 28%, p=0.00), performed adjustment of MV settings (30 v. 15%, p=0.01), were involved with weaning patients from MV (42 v. 19%, p=0.00) and used IS (76 v. 46%, p=0.00) in patient management than reported in the 2005 survey.[5]

Discussion

Immobility, bed rest and inflammation during critical illness result in impaired ventilation, decreased lung compliance and increased airway resistance. These cond itions lead to respiratory system dysfunction, muscle protein breakdown and weakness, and subsequent neuromusculoskeletal system dysfunction.[3] As a result, physiotherapists

are involved in the prev ention and treatment of respiratory and neuromusculoskeletal conditions of patients with critical illness.[1,3] This report provides updated information on physiotherapy practice in SA adult ICU settings and is timely, in light of a recent drive to develop minimum standards for physiotherapy practice in ICU.[4] Clinical decision-making regarding rehabilitation interventions in the ICU is based on multisystem assessment of the critically ill patient to identify potential problems and precautions, and contraindications to such interventions.[7,8] Most of the respondents in this survey frequently conducted ICU chart assessment, auscultation, assessment of cough effort, thoracic expansion, assessment of radiological investigations and patient readiness for mobilisation. This is in keeping with recommendations made by others on patient assessment in ICU[4,7,8] and supports the importance of individualised patient management in ICU. Physiotherapy patient assessment was not reported on in the surveys by Norrenberg and Vincent[5] or van Aswegen and Potterton[6] and therefore comparison with current results cannot be made. Most respondents reported that they frequently performed mobilisation of patients in and out of bed and peripheral musclestrengthening exercises. This is in keeping with the statement of Hanekom et al.[4] that physiotherapists are rehabilitation experts who form an integral part of the interprofessional team in ICU. The indisputable role for physiotherapy in the ICU setting is confirmed by strong evidence that demonstrates the beneficial effects of early mobilisation and strengthening exercises on ICU and hospital length of stay, number of ventilator-free days and functional outcomes.[1,2] The use of outcome measures is important to determine patients’ responses to treatment received and evaluate the usefulness of treatment techniques employed.[9,10] Even though regular assessment of patient readiness for mobilisation was reported, it was interesting to find that respondents did not often use outcome measures such as dynamometry or the Medical Research Council scale to assess patients’ peripheral muscle strength. Calculation for the presence of hypoxaemia or decreased lung compliance was rarely done. Poor oxygenation and restricted lung ventilation is known to affect a patient’s respiratory reserve and their ability to perform exercise and mobilisation. Time constraints and lack of equipment were highlighted as factors that influence physiotherapists’ use of outcome measures in daily practice.[9] The authors speculate that these may have been contributory factors to the results of the current survey but this would require further investigation. Assessment of patient readiness to wean from MV and maximal inspiratory pressure to assess respiratory muscle strength was done less often. Respondents reported using active cycle of breathing techniques or deep breathing exercises frequently during patient management in the ICU, but only a few used inspiratory muscle trainer devices or adjustment (temporary) of mechanical ventilator settings for respiratory muscle training. They reported limited active involvement in weaning of patients from MV. This is not in keeping with the report by Plani et al.,[11] which showed that physiotherapists’ involvement in a weaning and extubation protocol implemented in the management of critically ill trauma patients in an SA ICU setting resulted in a clinically significant reduction in MV time. The use of respiratory muscle trainer devices has been shown to significantly increase maximal inspiratory pressure[12,13] and tidal volume[13] and shorten time to weaning from MV.[12] The majority of respondents reported being involved with extubation of patients and more respondents in the current survey reported involvement with adjustment of mechanical ventilator settings and weaning of patients

from MV than reported previously.[6] However, reasons for continued limited active involvement of physiotherapists in weaning of patients from MV require further exploration. Pulmonary hygiene in the form of nebulisation, manual chest clearance techniques, postural drainage/modified postural drainage positions, positioning a patient in bed and suctioning were performed frequently, whereas manual hyperinflation was performed less often. These findings are in keeping with the use of multimodality respiratory physiotherapy in the care of critically ill patients described by Stiller.[1] Multimodality respiratory physiotherapy, a combination of techniques including positioning, chest-wall vibrations, percussions, manual hyperinflation and suction,[1,14,15] has been shown to reduce the incidence of ventilator-associated pneumonia[14] and shorten duration of MV and ICU length of stay in previous reports.[15] The selective use of manual hyperinflation in patient care is in keeping with research evidence, as this technique is associated with side-effects such as marked haemodynamic changes in the form of decreased cardiac output in some critically ill patients, and increased intracranial pressure in traumatic brain injury patients.[3] Alternatively, physiotherapists’ level of confidence in the application of manual hyperinflation as part of patient management might have influenced the results and would need further exploration. Assessment of patients’ need for humidification was done less often by respondents in this survey. Patients who receive supplemental oxygen via non-invasive ventilation or through invasive ventilation via an artificial airway require adequate humidification to prevent secretions from becoming too viscous, forming mucus plugs in distal airways and resulting in lung volume loss or infection;[16,18] therefore, humidification therapy and regular assessment for changes in patient humidification needs should form part of daily practice in the ICU. Oscillatory positive expiratory pressure (PEP) in the form of a blow bottle seems to be a popular treatment intervention for physiotherapists in SA, as a large number of respondents in the current and 2005[6] surveys reported using it as a treatment strategy. Limited evidence exists to support the use of PEP over other breathing exercises in patients following abdominal or thoracic surgery.[19] More respondents in the current survey used IPPB and IS as part of patient treatment in ICU than those in the 2005 survey.[6] IS is frequently used by others in the postoperative setting for lung volume recruitment in spontaneously breathing patients.[3] A limited number of respondents used IPPB or blowing up a glove on a regular basis, which may reflect that limited research evidence exists to support their use in clinical practice, especially glove-blowing. The authors acknowledge, however, that varying availability of IPPB equipment in the clinical setting may have influenced results. Compulsory training in theoretical and clinical aspects of care of the critically ill patient is offered to all undergraduate physiotherapy students at the eight universities in SA. Postgraduate physiotherapy training in the field of critical care is voluntary,[4] which offers an explanation for the relatively low number of respondents with any type of postgraduate qualification. In the survey by Van Aswegen and Potterton,[6] 36% of respondents held a postgraduate qualification compared with 46% in the current survey, which indicates a growing interest among SA physiotherapists to build on the knowledge base obtained at undergraduate level to work safely and effectively with critically ill patients. A number of respondents indicated that they shared their knowledge through training of students, junior physiotherapists and other members of the ICU interprofessional team. The majority of respondents provided after-hours physiotherapy service to the ICU on

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weekdays. This was, however, less than the 82 - 94% of respondents who provided a weekday after-hours physiotherapy service to ICUs in the 2005 survey.[6] Reasons for this reduced service provision are unclear. Physiotherapy service provision to the ICU over the weekend remains a priority of care, as almost all respondents provided such service in the current survey, similar to previous results (96%).[6] One area of concern is that only half of the respondents were involved in training of physiotherapists in their hospital to ensure that they work safely in ICU after hours; this requires further exploration.

Study limitations

The response rate of survey-based studies may influence the standard and quality of research; therefore, it is important to know if a surveybased study has a high non-response bias. A response rate of 60% should be the goal for all survey-based studies.[20] The current study carries a 66% non-response bias and thus the results should be interpreted with caution. Recently, emphasis has been placed on the use of validated outcome measurement tools such as the Chelsea Critical Care Physical Assessment (CPAx) tool[21] and Physical Function in ICU test (PFIT)[8] to assess patient function in ICUs. The use of electrical muscle stimulation to prevent disuse muscle atrophy in critically ill patients is gaining popularity among clinicians and researchers.[1,3] Future surveys on physiotherapy practice in SA ICUs should include these.

Conclusion

The care provided by physiotherapists to adult patients in SA ICUs consists mostly of exercise therapy, mobilisation and multimodality respiratory therapy. This is in keeping with international reports in the fields of critical care and rehabilitation. Future exploration of physiotherapists’ role in weaning of patients from MV, use of functional outcome measures and electrical muscle stimulation in the critical care setting, as well as the training of staff for after-hours service provision, is recommended.

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References 1. Stiller K. Physiotherapy in intensive care: An updated systematic review. Chest 2013;144(3):825847. DOI:10.1378/chest.12-2930 2. Cameron S, Ball I, Cepinskas G, et al. Early mobilisation in the critical care unit: A review of adult and pediatric literature. J Crit Care 2015;30:664-672. DOI:10.1016/j.jcrc.2015.03.032 3. Gosselink R, Clerckx B, Robeets C, Vanhullebusch T, Vanpee G, Segers J. Physiotherapy in the intensive care unit. Neth J Crit Care 2011;15(2):66-75. 4. Hanekom S, van Aswegen H, Plani N, Patman S. Developing minimum clinical standards for physiotherapy in South African intensive care units: The nominal group technique in action. J Eval Clin Pract 2015;21(1):118-127. DOI:10.1111/jep.12257 5. Norrenberg M, Vincent JL. A profile of European intensive care unit physiotherapists. Intensive Care Med 2000;26(7):850-856. DOI:10.1007/s001340051292 6. Van Aswegen H, Potterton J. A pilot survey of the current scope of practice of South African physiotherapists in intensive care units. S Afr J Physiother 2005;61(1):17-21. 7. Gosselink R, Bott J, Johnson M, et al. Physiotherapy for adult patients with critical illness: Recommendations of the European respiratory society and European society of intensive care medicine task force on physiotherapy for critically ill patients. Intensive Care Med 2008;34(7):1188-1199. 8. Berney S, Haines K, Denehy L. Physiotherapy in critical care in Australia. Cardiopulm Phys Ther J 2012;23(1):19-25. 9. Maher C, Williams M. Factors influencing the use of outcome measures in physiotherapy management of lung transplant patients in Australia and New Zealand. Physiother Theory Pract 2005;21(4):201-217. DOI:10.1080/09593980500321093 10. Marques A, Bruto A, Barney A. Clinically useful outcome measures for physiotherapy airway clearance techniques: A review. Phys Ther Rev 2006;11:299-307. DOI:10.1179/108331906X163441 11. Plani N, Becker P, van Aswegen H. The use of a weaning and extubation protocol to facilitate effective weaning and extubation from mechanical ventilation in patients suffering from traumatic injuries: A non-randomised experimental trial comparing a prospective to retrospective cohort. Physiother Theory Pract 2013;29(3):211-221. 12. Cader SA, Vale RG, Castro JC, et al. Inspiratory muscle training improves maximal inspiratory pressure and may assist weaning in older intubated patients: A randomised trial. J Physiother 2010;56(3):171-177. 13. Condessa RL, Brauner JS, Saul AL, et al. Inspiratory muscle training did not accelerate weaning from mechanical ventilation but did improve tidal volume and maximal respiratory pressures: A randomised trial. J Physiother 2010;59(2):101-107. 14. Ntoumenopoulos G, Presneill JJ, McElholum M, Cade JF. Chest physiotherapy for the prevention of ventilator-associated pneumonia. Intensive Care Med 2002;28(7):850-856. DOI:10.1007/ s00134-002-1342-2 15. Malkoç M, Karadibak D, Yildirim Y. The effect of physiotherapy on ventilator dependency and the length of stay in an intensive care unit. Int J Rehabil Res 2009;32(1):85-88. 16. Branson RD. Secretion management in the mechanically ventilated patient. Respir Care 2007;52(10):1328-1347. 17. Solomita M, Palmer LB, Daroowalla F, et al. Humidification and secretion volume in mechanically ventilated patients. Respir Care 2009;54(10):1329-1335. 18. Esquinas Rodriguez AME, Scala R, Soroksky A, et al. Clinical review: Humidifiers during non-invasive ventilation – key topics and practical implications. Crit Care 2013;16(1):203-210. DOI:10.1186/cc10534 19. Orman J, Westerdahl E. Chest physiotherapy with positive expiratory pressure breathing after abdominal and thoracic surgery: A systematic review. Acta Anaethesiol Scand 2010;54(3):261-267. 20. Fincham JE. Response rates and responsiveness for surveys, standards and the journal. Am J Pharm Educ 2008;72(2):1-3. DOI:10.5688/aj720243 21. Corner EJ, Soni N, Handy JM, Brett SJ. Construct validity of the Chelsea critical care physical assessment tool: An observational study of recovery from critical illness. Crit Care 2014;18(2):110. DOI:10.1186/cc13801

ARTICLE

Reducing paediatric ventilator-associated pneumonia – a South African challenge! H Kunzmann,1 BCur, PG Dip (Nursing Admin), PG Dip (Critical Care Child); K Dimitriades,1,2 MB ChB, FCPaed (SA), MMed (Paeds), Cert Crit Care (Paed); B Morrow,2 BSc (Physiotherapy), PG Dip (Health Research Ethics), PhD (Paediatric Crit Care); A Argent,1,2 MB BCh, FCPaed (SA), MMed (Paed), Cert Crit Care (Paed) 1 2

Department of Critical Care, Red Cross War Memorial Children’s Hospital, Cape Town, South Africa Department of Paediatrics and Child Health, Faculty of Health Sciences, University of Cape Town, South Africa

Corresponding author: B Morrow (brenda.morrow@uct.ac.za)

There has been a decline in ventilator-associated pneumonia (VAP) in the paediatric intensive care units of developed countries. Previous studies at the Red Cross War Memorial Children’s Hospital give an incidence of VAP of >40/1 000 ventilator days, identifying VAP as a priority area for practice improvement. We outline the process and outcome of a practice improvement initiative that implemented an evidence-based bundle of care to reduce VAP. In 2011, this initiative was taken to improve healthcare-associated infections, with the support of the ‘Best Care Always’ project. A task team identified an evidence-based bundle of care aimed at reducing VAP. The bundle consisted of five elements that were adjusted practically to suit the unit. Standardised metrics to measure compliance with the bundle and outcomes of the intervention were instituted and collected prospectively throughout the study period. Following implementation in October 2011, VAP rates decreased from 55/1 000 to 19.1/1 000 ventilator days over the first 5-month period. During this period, compliance remained poor and metrics were poorly collected. With the introduction of a full-time VAP coordinator, compliance improved from 57% to a peak of 83%, with a decrease in VAP to an average of 4/1 000 ventilator days (January 2013 - July 2013). This practice improvement initiative resulted in a significant reduction in VAP. The success of this initiative is attributed equally to the introduction of the bundle of care and driving power of the VAP coordinator. S Afr J Crit Care 2016;32(1):17-20. DOI:10.7196/SAJCC.2016.v32i1.243

Ventilator-associated pneumonia (VAP) is a nosocomial pneumonia that develops in ventilated patients after 48 hours of intubation. [1] Approximately 1 400 children are admitted annually to the paediatric intensive care unit (PICU) of Red Cross War Memorial Children’s Hospital (RCWMCH), Cape Town, South Africa (SA). Many of these children (~1 000) require intubation and mechanical ventilation, which places them at risk of developing VAP. Previous studies at this study site showed the incidence of VAP to be high (>40/1 000 ventilator days), with an association between VAP and both standardised mortality and morbidity.[2,3] These findings are in contrast to reports of VAP rates between 2% and 6% from PICUs in developed parts of the world such as the USA and Europe.[4] As a result of local reports, VAP was identified as a priority focus area and a practice improvement initiative targeting VAP was commenced in the PICU in conjunction with the ‘Best Care Always’ (BCA) project, a campaign promoting the use of evidence-based practice to improve quality of care. The objective of this initiative was to develop and implement an evidence-based bundle of care to reduce VAP. It was considered important that the bundle of care should be relevant and practical for this specific PICU environment, to ensure global and sustainable implementation. An additional objective was to monitor and evaluate VAP incidence throughout the implementation period.

Context

RCWMCH is a tertiary-level academic paediatric hospital situated in Cape Town, SA, with a 22-bed PICU. A large proportion of admitted children are referred via the emergency medicine department for the management of infectious diseases such as gastroenteritis and pneumonia. The remainder of the patient load consists of a mix of postoperative patients, including neurosurgical, cardiac and general surgical patients,

and general paediatric patients. Particular challenges in implementing practice improvement initiatives in this environment include the high patient turnover and a relatively low nurse-to-patient ratio (with about 100 nurses in total). Additionally, the pool of about 13 doctors consists of 5 consultant intensivists and includes up to 5 registrars who rotate every 3 months, necessitating regular retraining and education.

Change implementation strategies and process In May 2011, the chief executive officers and management of selected tertiary and secondary hospitals in the Western Cape Province of SA attended a BCA project information session addressing hospitalacquired infections (HAIs). The project aim was to reduce HAIs using care bundles developed by the Institute of Healthcare Improvement. Subsequent to this meeting, teams were launched at individual hospitals to implement the care bundles. The team tasked with implementing VAP bundles in the RCWMCH PICU consisted of the head of the clinical unit, a clinical technologist, an operational manager and a research consultant. Initial brainstorming and discussion led to the development and testing of an adapted VAP bundle. Consensus was reached that a modification of the Clinical Pulmonary Infection Score (CPIS) would be used to measure outcome, as this tool was validated and appropriate for use in the setting.[3] This tool was subsequently used throughout the study period. A CPIS score of ≥6 was considered diagnostic of VAP if: (i) the patient was ventilated more than 48 hours; (ii) in a patient with a high CPIS score on admission, the CPIS dropped by at least 3 points for 1 day or 2 points for 2 consecutive days before rising to ≥6; or (iii) in a patient previously diagnosed with VAP, the score decreased to <5 for at least 2 days before rising to ≥6. A registered nurse (the ‘VAP Champion’) and four enrolled

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nurses formed a five-person team to drive the practice improvement initiative in the PICU. Following discussion and consensus, and using evidence from healthcare literature, it was decided that in addition to strict adherence to PICU infection control policies, the VAP bundle should consist of five elements: (i) Elevating the head of the bed to 30°, on the basis of the results of an adult random ised controlled trial by Drakulovic et al.[5] An exception to this criterion was if it was contraindicated by the medical team in postoperative cardiac or neurosurgical cases. Children nursed prone or in incubators and children receiving high-frequency oscillatory ventilation would be nursed at 10° elevation, for logistical reasons. The team approach allowed for the troubleshooting of difficulties as they arose. For example, when elevating the head of the bed children tend to slip down the bed; elevating the foot of the bed and positioning a pillow under the buttocks countered this. (ii) Appropriate mouth care provided to all children, based on previous recommendations.[6] Taking into consideration staffing levels, with an average of one registered nurse to two patients with the assistance of either an enrolled nurse or assistant nurse, the VAP team adjusted mouth care frequency to 6-hourly. Some adjustments in the use of chlorhexidine gluconate for different age groups were also made (Fig. 1). (iii) Checking naso- and orogastric tubes 3 - 4-hourly to confirm position in the stomach and marking feeding tubes to allow early detection of malpositioning, to reduce the risk of aspiration, one of the known causes of VAP.[7] Marking of feeding tubes was taught to nursing staff to be performed as standard care after confirming the tube position in the stomach. The tube position was checked by either measuring a pH of between 1 and 5 of 0.5 mL gastric aspirate using a universal pH indicator strip, or by chest X-ray (including the upper abdomen). (iv) No saline to be instilled routinely in the endotracheal tube prior to suctioning, as this may result in dispersion of contaminated material in the lower respiratory tract, increasing the risk of nosocomial infection.[8] There are no physiological benefits to using saline with suctioning, and saline instillation is associated with hypoxia.[9] Standard practice was that saline was not routinely used during endotracheal suctioning; however, this practice had not been formalised prior to the initiative. (v) The ventilator tubing positioned in such a manner that the condensed water could run freely away from the patient into the water

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Neonates and infants without teeth

Infants and children with teeth <6 years old

12-hourly gum and tongue wipe with gauze soaked in saline

12-hourly brush teeth with toothpaste and soft toothbrush (suction excess with yankauer, do not rinse mouth with water)

12-hourly gum and tongue wipe with gauze soaked in 1:5 chlorhexidine solution (chlorhexidine:sterile water)

Children ≥6 years old

Instructions for gum wipe: Soak gauze in required solution, then wrap around finger and gently wipe the gum and tongue surface

12-hourly rinse mouth with chlorhexidine mouthwash – 10 mL 0.2% chlorhexidine with 10 mL sterile water suction excess with yankauer, do not rinse mouth with water)

Fig. 1. Flowchart for oral hygiene. trap. This required ongoing inservice training and repetitive demonstration at the bedside to improve compliance. Prior to the practice improvement inter vention, children were generally nursed flat or, on rare occasions, with the head of bed raised, but this seldom reached 30°. Mouth care was performed 4-hourly on children of all ages by wiping the inside of the mouth with gauze dipped in saline. Positioning of naso- and orogastric tubes was tested prior to commencing feeds or administering medication, but they were not marked to indicate if the tube migrated. The ventilator tubing was usually placed in a position that prevented the condensed water from draining freely into the water trap. From October 2011, infection control improve ment measures and the VAP bundle were implemented through group training and teaching of all staff categories, and VAP compliance was monitored using a standard ised form. Disposable ventilator circuits were introduced into the unit and the PICU doctors were required to complete a VAP identification form (including CPIS score[3]) (Fig. 2) daily on each intubated and ventilated patient during the morning ward round. For the first 4 months of the practice improve ment initiative, data were obtained in a standardised manner, but collection was un reliable and compliance with the bundle was poor. Although the VAP rates decreased initially, they plateaued at a higher level than the target. The five-member team had little time to teach and monitor the staff owing to their own full-time patient care responsibilities. Teaching and monitoring was difficult as the shift patterns of these five

members had to coordinate to ensure that each nursing shift was covered by at least one team member. Obtaining buy-in from the whole PICU team was challenging, as there was no sense of urgency to address the unacceptably high VAP rate. This was compounded by natural resistance to change, with many nurses asking, ‘Why do we need to do it that way if we’ve been doing it this way all these years?’ It was clear that there was a need to change our implementation approach. The need for a full-time VAP coordinator, with protected time and without patient responsibilities, was identified. A coordinator would educate, monitor and observe that staff adhere to the VAP bundle and reliably report VAP incidence, developing sustainable processes. This was motivated to hospital management on the basis that preventing VAP would save costs from patient morbidity and mortality, PICU bed occupancy and staff load. In an environment where there is substantial pressure on beds, decreasing the incidence of VAP could potentially increase the number of patients the PICU could manage per annum. Management balanced this against the loss of a senior member of nursing staff from clinical duties in the context of already limited numbers of experienced critical care nurses. The motivation for a full-time VAP co ordinator was accepted and a VAP coordinator (a senior registered nurse) was appointed fulltime for an initial 4-week period in February 2011, followed by dedicated time for weekly input. With the opportunity to focus only on implementation of the practice improvement initiative and with flexible working hours, it

was possible to standardise the VAP bundle and the desired outcome of each element. The bundle elements were taught to each staff member individually, on day and night shifts, using a one-on-one teaching method at the bedside and practical assistance in executing each bundle element. In addition to one-on-one teaching, information brochures and posters advising on the extent of VAP and the bundle elements to address the problem were made widely available throughout the PICU. Feedback was obtained from nursing staff about the practical barriers to implementing the bundle elements. The VAP coordinator used the feedback to adjust the recommendations using a ‘Plan, Do, Study, Act’ (PDSA) cycle, to optimise compliance. An example of PDSA cycle use was in addressing the bundle element of raising the head of the bed to 30°. The initial planning suggested using a 40° triangle to compensate for the 10° tilt at the foot end of the bed; however, this was found to be timeconsuming and there was confusion about exactly where the angle should be measured. In addition, the reference triangles were often not returned and difficult for the next user

to locate. We found that 30° was almost always underestimated without use of the triangle and therefore compliance was not obtained. The VAP coordinator suggested using the triangle on admission to determine the correct 30° elevation and then applying a piece of string to the top crossbar of the bed, marking the string at the point obtained when the head of bed was elevated correctly. This was practically demonstrated to each nurse individually and the ability of the nurses to implement the procedure then was checked. This small adjustment ensured an improvement in compliance with the head of bed elevation element of the VAP bundle. Following the appointment of the VAP coordinator, daily compliance on every ventilated patient was assessed, using a standardised tool. This created the opportunity to identify possible obstacles to VAP compliance and made it easier to address these obstacles early. Information on VAP compliance and number of VAP cases was fed back to the unit at weekly meetings and graphic representations were posted on the notice board. For full compliance, adherence to all five bundle elements had to be maintained and a target

of 90% compliance was set, similar to previous studies.[10] VAP cases were reported, using standardised tools, at the same time each day. Initially, cases were recorded daily on one page without individual CPIS scores. However, this was not practical as it was difficult to determine the daily change in individual scores necessary to confirm the diagnosis. The form was changed to a 7-day page that was prepacked in the admission booklet and filled in on the ward round. This made it easy to compare scores for each day of the patients’ admission. The forms were removed from the pack on Fridays and new ones inserted for the following week (Fig. 2).

Outcomes

Data were collected from October 2011 to July 2013. After the introduction of the initiative in October 2011, an initial reduction in VAP rates was noted, from 55/1 000 to 19.1/1 000 ventilator days (Fig. 3), despite poor compliance with the bundle. This coincided with the introduction of disposable ventilator circuits to replace the reusable circuits that were in use at the time, as well as a change in the packaging of intubation equipment in

Fig. 2. CPIS chart used in the PICU at RCWMCH.

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Jul 2013

Jun 2013

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VAP rate/1 000 ventilator days

60 50 40 30 20 10 0

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Acknowledgements. We would like to thank Michele Youngleson and Gary Kantor for leading the Best Care Always initiative. References

Jul 2013

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Nov 2012

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Percentage (%)

Fig. 3. Decline in VAP rate over time. The arrow indicates the commencement of the VAP coordinator.

Fig. 4. Percentage compliance with VAP bundle. the hospital. However, this decline in VAP rates plateaued and only gradually improved following the introduction of the full-time VAP coordinator. Thereafter, VAP rates continued to decline steadily, with a noticeable reduction after June 2012 with the reappointment of the full-time VAP coord inator. In September 2012, a spike in VAP rates was noted during the unit’s routine quality assurance audit. This prompted an aggressive re-education drive by the coordinator on the VAP bundle implementation Compliance to the bundle was measured on a daily basis at each bedside. This daily measurement was commenced by the VAP coordinator and continued during the period where the coordinator was no longer present (March 2012 - June 2012) (Fig. 4). The figure indicates that with an identified VAP coordinator, compliance to the VAP bundle steadily improved and this mirrored a steady decrease in VAP incidence. Achieving optimal compliance to the VAP bundle remains a challenge. Current challenges to achieving full compliance include shortages of consumables required for mouth care, faulty beds, and high turnover of staff resulting in an ongoing need to educate new staff about the VAP bundle. It is of concern that this process requires

champion is integral in coordinating the efforts of the team responsible for implementing the components of the VAP bundle. Other duties identified in literature include setting benchmarks and continuous use of the PDSA cycle to meet the set benchmarks.[12-14] A large number of changes were made over the period under study, which resulted in significantly fewer cases of VAP. The implementation of the VAP prevention bundle required the introduction of a VAP champion to sustain these improvements.

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constant supervision and has not yet reached a self-sustaining point in the unit.

Lessons and messages

Prior to appointing a VAP coordinator, data collection was unreliable, compliance was poor and VAP rates high. Dividing attention between patient care and the VAP practice improvement process was a major obstacle to the implementation of the initiative. After a VAP coordinator with protected time was appointed, it was possible to develop processes to ensure the collection of reliable data to measure VAP bundle compliance, ventilated days and VAP identification. The proportion of beds fully compliant to all VAP bundle elements peaked at 80% (with a target of 90%) and the VAP rate dropped significantly. In a resource-constrained environment, investment in dedicated staff could be cost-effective when balanced against the considerable saving in healthcare costs and the improvements in patient outcomes achieved by sustained and marked reductions in healthcare-associated infections. This was noted by Rello et al.[11] in 2002 and used as the basis for marketing the use of a VAP ‘champion’ to hospital management by Craven[12] in 2006. The use of a VAP

1. Morrow BM, Argent AC, Jeena PM, Green RJ. Guideline for the diagnosis, prevention and treatment of paediatric ventilator-associated pneumonia. S Afr Med J 2009;99(4):255-267. 2. Morrow BM, Argent AC. Ventilator-associated pneumonia in a paediatric intensive care unit in a developing country with high HIV prevalence. J Paediatr Child Health 2009;45(3):104111. DOI:10.1111/j.1440-1754.2008.01437.x 3. Morrow BM, Mowzer R, Pitcher R, Argent AC. Investigation into the effect of closed-system suctioning on the frequency of pediatric ventilator-associated pneumonia in a developing country. Pediatr Crit Care Med 2012;13(1):e25-e32. DOI:10.1097/pcc.0b013e31820ac0a2 4. Rosenthal VD, Bijie H, Maki DG, et al. International Nosocomial Infection Control Consortium (INICC) report, data summary of 36 countries, for 2004 - 2009. Am J Infect Control 2012;40(5):396-407. DOI:10.1016/j.ajic.2011.05.020 5. Drakulovic MB, Torres A, Bauer TT, Nicolas JM, Nogué S, Ferrer M. Supine body position as a risk factor for nosocomial pneumonia in mechanically ventilated patients: A randomised trial. Lancet 1999;354(9193):1851-1858. DOI:10.1016/s0140-6736(98)12251-1 6. Johnstone L, Spence D, Koziol-McClain J. Oral hygiene care in the pediatric intensive care unit: Practice recommendations. Pediatr Nurs 2010;36(2):85-96. 7. Charles MP, Kali A, Easow JM, et al. Ventilator-associated pneumonia. Australas Med J 2014;7(8):334-344. DOI:10.4066/amj.2014.2105 8. Freytag CC, Thies FL, König W, Welte T. Prolonged application of closed in-line suction catheters increases microbial colonization of the lower respiratory tract and bacterial growth on catheter surface. Infection 2003;31(1):3137. DOI:10.1007/s15010-002-3066-1 9. Morrow BM, Argent AC. A comprehensive review of pediatric endotracheal suctioning: Effects, indications, and clinical practice. Pediatr Crit Care Med 2008;9(5):465-477. DOI:10.1097/pcc.0b013e31818499cc 10. Weireter LJ, Collins JN, Britt RC, Reed SF, Novosel TJ, Britt LD. Impact of a monitored program of care on incidence of ventilator-associated pneumonia: Results of a longterm performance-improvement project. J Am Coll Surg 2009;208(5):700-705. DOI:10.1016/j.jamcollsurg.2009.01.041 11. Rello J, Ollendorf DA, Oster G, et al. Epidemiology and outcomes of ventilator-associated pneumonia in a large US database. Chest 2002;122(6):2115-2121. DOI:10.1378/ chest.122.6.2115 12. Craven DE. Preventing ventilator-associated pneumonia in adults: Sowing seeds of change. Chest 2006;130(1):251-260. DOI:10.1378/chest.130.1.251 13. O’Keefe-McCarthy S, Santiago C, Lau G. Ventilatorassociated pneumonia bundled strategies: An evidencebased practice. Worldviews Evid Based Nurs 2008;5(4):193204. DOI:10.1111/j.1741-6787.2008.00140.x 14. Sen S, Johnston C, Greenhalgh D, Palmieri T. Ventilatorassociated pneumonia prevention bundle significantly reduces the risk of ventilator-associated pneumonia in critically ill burn patients. J Burn Care Res 2014;37(3):166171. DOI:10.1097/BCR.0000000000000228

ARTICLE

An observational study on the relationship between plasma vitamin C, blood glucose, oxidative stress, endothelial dysfunction and outcome in patients with septic shock K G H Katundu,1 MSc (Med) Nutrition, MBBS; L T Hill,2 PhD (Physiology), RD (SA); L M Davids,3 PhD (Med), MSc (Med); I A Joubert,4 MB BCh, DA (SA), FCA (SA); M G A Miller,4 MB ChB, DA (SA), FCA, Cert Crit Care (SA); J L Piercy,4 BSc (Hons), MBBS (Lond), FCA (SA), Cert Crit Care (SA); W L Michell,2 MB ChB, DA (SA), FFA (SA)

Division of Human Nutrition, Department of Human Biology, Faculty of Health Sciences, University of Cape Town, South Africa Division of Critical Care, Department of Surgery, Faculty of Health Sciences, University of Cape Town, South Africa 3 Redox Laboratory, Department of Human Biology, Faculty of Health Sciences, University of Cape Town, South Africa 4 Division of Critical Care, Department of Anaesthesia, Faculty of Health Sciences, University of Cape Town, South Africa 1 2

Corresponding author: K G H Katundu (kkatundu@gmail.com)

Background. Septic shock is associated with endothelial dysfunction and oxidative stress, against which vitamin C plays a protective role, possibly influencing clinical outcome. Hyperglycaemia may lower vitamin C. Objective. To study plasma vitamin C, oxidative stress, hyperglycaemia, endothelial dysfunction and outcome in septic shock. Methods. In a prospective, observational study of 25 adult septic shock patients, serial blood samples were analysed for vitamin C, thiobarbituric acid-reactive substances (TBARS) (a biomarker of oxidative stress), and soluble vascular cell adhesion molecule-1 (sVCAM-1) and E-selectin (markers of endothelial dysfunction). Blood glucose, Sequential Organ Failure Assessment (SOFA) scores and fluid requirements were monitored. Results. Plasma vitamin C was low, while plasma TBARS were high throughout the 7-day study period. Endothelial dysfunction markers (sVCAM-1 and E-selectin) were high at the baseline. VCAM-1 decreased significantly on day 1 and normalised on day 7. E-selectin was unchanged on day 1 compared with baseline, but increased significantly on day 7. Oxidative stress and endothelial dysfunction were associated with increased SOFA score. Increased oxidative stress was associated with increased requirements for intravenous fluids and prolonged duration of vasoconstrictor support. Nine patients died in hospital. At baseline, levels of TBARS were significantly higher in non-survivors than in the survivors of septic shock. Conclusion. In septic shock, clinically relevant oxidative stress was associated with endothelial dysfunction, low vitamin C and high glucoseto-vitamin-C ratios. Markers of oxidative stress and endothelial damage were increased and correlated with resuscitation fluid requirements, vasoconstrictor use, organ failure and mortality. S Afr J Crit Care 2016;32(1):21-27. DOI:10.7196/SAJCC.2016.v32i1.270

The third international consensus definition for sepsis and septic shock describes septic shock as ‘a subset of sepsis in which underlying circulatory, cellular, and metabolic abnormalities are associated with a greater risk of mortality than sepsis alone’.[1] Microcirculatory dysfunction is the hallmark of septic shock and its persistence is associated with poor outcome. [2] Endothelial function and the glycocalyx are deranged, resulting in increased permeability and poor reactivity to vasoactive substances.[3-5] Septic shock is accompanied by intense oxidative stress arising from the increased production of free radicals under conditions of inadequate antioxidative defences.[6] Uncontrolled oxidative stress has been associated with organ dysfunction and multiorgan failure.[7] It has been suggested that management targeting the microcirculation, distinct from the macrocirculation, could potentially decrease the burden of organ failure in sepsis.[8] Antioxidant defences during severe sepsis may be important. Vitamin C, an antioxidant that works as the first line of defence against free radical action in plasma, is considered essential for normal endothelial function.[9] Vitamin C requirement may be increased in septic shock following losses due to increased oxidative stress, redistribution of blood volume from the intravascular to the extravascular space, and urinary losses or dialysis.[4,7,10] In the endothelial cells, depletion of vitamin C may be induced in part by the intense hyperglycaemia typical of septic shock. Not only does hyperglycaemia enhance urinary losses of vitamin C[11] but, owing to the

structural similarity between glucose and dehydroascorbic acid – one of the forms of vitamin C – glucose competitively inhibits the uptake of dehydroascorbic acid by the endothelial common glucose transporters, GLUT1 and GLUT3.[9] Therefore, the ratio of plasma glucose to vitamin C may be important. In this study we investigated the possibility of a link between plasma vitamin C levels and oxidative stress, endothelial dysfunction and clinical markers in patients with septic shock.

Methods

This prospective study was conducted in the intensive care unit (ICU) of a tertiary academic hospital. Patients with septic shock expected to survive more than 24 hours were enrolled within 12 hours of the commencement of vasoconstrictor support. Septic shock was defined as two or more sys temic inflammatory response syndrome criteria, a proven or presumed source of sepsis and a systolic blood pressure of <90 mmHg, or the need for vasoconstrictors after adequate volume resuscitation. Exclusion criteria applied at screening included the following: underweight (body mass index (BMI) <18 kg/m2), patients unlikely to survive more than 24 hours, parenteral nutritional support, pregnancy, gastrointestinal fistula or other considerable exudative losses, renal dialysis, or more than 100 mg vitamin C supplementation during the previous 7 days. The study was approved by the Human Research Ethics Committee of the Faculty of Health Sciences, University of Cape Town (UCT) (Ref. UCT/FHS/HREC 528/2011). Due

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to the observational nature of the study and the minimal risk to the participants, we were permitted to utilise a deferred informed consent procedure where patients were enrolled in the study when they met the eligibility criteria. Blood samples and collected data were stored until the patient was well enough to give written informed consent for the use of such data. If the patient declined participation, all data and derived data were excluded from the study and destroyed. If a patient died before deferred written informed consent could be obtained, informed consent was waived and we were permitted to use the data. The patients were managed according to the Surviving Sepsis Cam paign international guidelines.[12] Crystalloid fluids were used for resuscitation using dynamic endpoints, and adrenaline was used as the vasoconstrictor. An insulin infusion was used if blood glucose exceeded 10 mmol/L. No vitamin C was administered during the study period. Clinical, demographic and outcome data were collected from the patients’ clinical records and from their charts during their admission. Sequential Organ Failure Assessment (SOFA) was scored daily, Acute Physiology and Chronic Health Evaluation (APACHE II) levels were calculated from data collected in the first 24 hours of admission, and daily mean blood glucose and ranges were taken from the clinical records. Blood sampling for plasma thiobarbituric acid-reactive substances (TBARS), vitamin C, soluble vascular cell adhesion molecule-1 (sVCAM-1) and E-selectin was done on enrolment and thereafter daily until vasoconstrictor cessation and on the 7th day following cessation of vasoconstrictors. For each assay, 5 mL of whole blood was drawn into a chilled heparinised/ ethylenediaminetetraacetic acid (EDTA) vacutainer, which was kept on ice for transport to the laboratory. All samples were centrifuged at 1 000 rpm for 10 minutes, and the plasma was drawn off into 1.5 mL Eppendorf (Axygen Inc., US) tubes, which were coded and stored at –20 –80°C until batch analysis. The TBARS assay was performed according to a modified method devised by Jentzsch et al.[13] and then developed and optimised at the Lipidology Research Laboratory, UCT. Plasma concentration of vitamin C was determined using a ferric reducing ascorbate (FRASC) assay kit (#K671-100, BioVision Research Products, USA). The sVCAM-1 was determined using a commercial human sVCAM-1 enzyme-linked immunosorbent assay (ELISA) kit (RayBiotech, USA). ELISA for E-selectin was performed using the Human E-selectin ELISA kit (RayBiotech, USA). Blood glucose values were obtained from the routine ICU blood glucose monitoring assessments. Using an alpha error of 5% and power of 80%, the sample size required to detect at least a 40% prevalence of deficient vitamin C status was calculated to be 23 participants. Statistical analysis of the data was done using Stata version 12 (StataCorp, USA) and Statistica version 11 (Statsoft, USA). The Shapiro-Wilks normality test was used to test the data for normality. Descriptive statistics were expressed as mean (SD) and median (IQR) for the continuous data, depending on whether the data were parametric or non-parametric. The Wilcoxon rank-sum test (or Mann-Whitney U-test) was used to test the null hypothesis that two populations (survivors and non-survivors of septic shock or males and females) had equal medians in terms of investigating differences in the measured variables. Testing the differences between the means and the medians of the measured variables at different points in time (i.e. the baseline (day 0), day 1 and day 7), the Wilcoxon rank-sum test and the repeated measures for analysis of variance (ANOVA) or the Friedman test (K-related samples) were used. To measure the associations between the variables vitamin C, TBARS, sVCAM-1, E-selectin and the clinical outcomes of interest, Spearman’s test of association was used. A p-value of <0.05 was considered statistically significant.

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Results

Eighty patients were screened and 25 sequential patients who fitted the study criteria were enrolled (Fig. 1). The baseline characteristics of the study population are given in Table 1. The mean (SD) baseline SOFA score was significantly lower in survivors compared with non-survivors of septic shock (9.8 (2.7) v. 12.2 (2.1), p=0.014). The median (IQR) vitamin C levels were low compared with the normal reference range (11 - 114 nmol/mL)[14] with no significant Patients with septic shock and on vasopressors screened, N=80

Included in study?

Yes, n=25

No, n=55

Reasons for exclusion: - Not timeously referred, n=20 - On dialysis, n=11 - On parenteral nutrition, n=7 - BMI <18 kg/m2, n=10 - Not expected to survive >24 hours, n=1 - On vitamin C supplementation, n=4 - No consent provided, n=2

Fig. 1. Flowchart of patients who met inclusion/exclusion criteria for the study population.

Table 1. Characteristics of the study population (N=25) Gender, n (%) Male

7 (28)

Female

18 (72)

Age (years), mean (SD)

49.0 (15.6)

Source of sepsis, n (%) Intra-abdominal

8 (32)

Respiratory

7 (28)

Necrotising fasciitis and soft tissue

7 (28)

Polytrauma with secondary infection

3 (12)

BMI (kg/m ), mean (SD)

28.2 (6.4)

APACHE II score, mean (SD)

20.1 (10.5)

Baseline SOFA score, mean (SD)

10.6 (2.8)

Lowest MAP (mmHg), mean (SD)

54.9 (10.9)

Survivors, n (%)

16 (64)

Length of ICU stay (days), median (IQR)

6 (4 - 10)

MAP = mean arterial pressure.

A 4 500 4 000

Plasma sVCAM-1 (ng/mL)

3 500

p=0.08

p=0.0008

3 000 2 500 2 000 1 500 1 000 500 0

n=25

n=19

n=15

1 Days

B p=0.01 4 000

Baseline VCAM-1 level (ng/mL)

change from baseline to day 7 (baseline: 5.7 (2.3 - 8.0) nmol/mL, day 1: 5.9 (3.7 - 14.2) nmol/mL, day 7: 5.6 (3.7 - 9.4) nmol/mL, p=0.83). Compared with the normal reference range of 1.9 - 3.9 nmol/mL,[15] the median TBARS level in the patients as a marker of oxidative stress was high at baseline (19.5 (14.0 - 37.0) nmol/mL) and continued to be high at day 1 (20.4 (13.0 - 64.0) nmol/mL), with no statistically significant reduction at day 7 (13.3 (9.0 - 18.0) nmol/mL, p=0.52). At baseline, non-survivors of septic shock had higher median TBARS levels (mmol/ mL) than survivors (16.9 (11.9 - 21.7) v. 43.8 (23.6 - 47.7) mmol/mL, p=0.008). The median (IQR) plasma sVCAM-1 levels were raised at baseline and day 1 but decreased significantly at day 7 (p<0.001) (Fig. 2A). When further analysed, the sVCAM-1 levels at baseline in survivors were significantly lower than those of non-survivors (Fig. 2B). Fig. 3A indicates the elevated median (interquartile range (IQR)) plasma E-selectin levels at baseline. The E-selectin levels significantly increased from day 1 to day 7 (p=0.003). Comparing survivors and nonsurvivors at baseline, the levels were found to be significantly higher in survivors than nonsurvivors (13.1 (7.8 - 24.1) v. 7.1 (6.2 - 15.3) ng/mL, p=0.04) (Fig. 3B). Since oxidative stress may influence endothelial dysfunction, the association between TBARS as a marker of oxidative stress and the biomarkers of endothelial function was tested. These results are presented in Table 2. A moderate but significant positive correlation was found between sVCAM-1 and TBARS at all the time points. However, no significant correlation was observed between E-selectin and TBARS at any of the time points. The median (IQR) blood glucose from the routine records was highest at baseline (8.8 (7.3 - 10.1) mmol/L), but decreased to within the ICU target range of 5 - 8 mmol/L on the subsequent research days (day 1: 7.8 (6.0 - 8.6) mmol/L, day 7: 7.2 (6.4 - 7.8 mmol/L). Similarly, intravenous fluid volume infused per 24 hours in the patients was highest at baseline (1 870 (1 410 - 2 615) mL) but decreased significantly on day 1 (1 046 (500 - 1 680) mL, p=0.0004) and did not change significantly at day 7 (704 (0 - 2 250) mL, p=0.7). The median (IQR) duration on vasoconstrictors during ICU admission was 30 (24 - 38) hours. Fig. 4 indicates the association between oxidative stress and intravenous fluid requirements at baseline and inotrope-free days at day 7. It was found that increased

3 000

2 000

1 000

Survivors

Non-survivors

Fig. 2. sVCAM-1 levels in the patients. (A) Plasma sVCAM-1 concentrations over the study period. At baseline, the sVCAM-1 levels were higher than reference values with no statistically significant change at day 1 but significantly decreased from day 1 to day 7. (B) Comparison of baseline sVCAM1 between survivors and non-survivors. Non-survivors of septic shock had statistically significantly higher levels at baseline than survivors. Normal reference range is 72 - 349 ng/mL. oxidative stress was associated with increased requirement for intravenous fluid at baseline and fewer inotrope-free days. The associations between oxidative stress (TBARS) and severity of illness as indicated by SOFA score, and between SOFA and sVCAM-1 scores, were also determined (Fig. 5). A positive correlation was found between TBARS and SOFA score. Baseline high sVCAM-1 levels were also associated with high SOFA scores.

The ratio of glucose to vitamin C was calculated and found to be high at all time points compared with the expected reference physiological ratio, with no statistically significant change over the period (Fig. 6).

Discussion

This is the first study in a South African (SA) setting to investigate vitamin C status, oxidative stress levels, hyperglycaemia and

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A 240

p=0.03

220 200

Plasma E-selectin (ng/mL)

180 160 140 120 100 80

p=0.67

60 40 20 0

n=25 0

n=19

n=15

1 Days

B 50

Baseline E-selectin (ng/mL)

40 p=0.04 30

0 Survivors

Non-survivors

Fig. 3. E-selectin levels in the patients. (A) shows plasma E-selectin concentrations over the study days. E-selectin levels were higher than reference range at baseline and day 1 but increased significantly at day 7. (B) shows the comparison of baseline plasma E-selectin levels between survivors and non-survivors at baseline. At baseline, survivors had statistically significantly higher values than non-survivors. Normal reference range for E-selectin is 0.9 - 2.8 ng/mL.

Table 2. Association between endothelial function markers and TBARS as a marker of oxidative stress sVCAM-1 v. TBARS Study day

Spearmanâ&#x20AC;&#x2122;s rho

p-value

E-selectin v. TBARS Spearmanâ&#x20AC;&#x2122;s rho

p-value

Baseline

0.45

0.02

0.08

0.70

Day 1

0.57

0.01

0.16

0.50

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their association with endothelial dysfunction in patients with septic shock. This study has shown that septic shock is associated with low levels of plasma vitamin C, which persisted until day 7 after the cessation of inotropic support. There was also evidence of oxidative stress in the patients, marked by increased levels of TBARS, and there was no significant reduction in these levels at day 7 of the study. Non-survivors had increased levels of oxidative stress and organ failure compared with survivors. The results also showed that the plasma glucoseto-vitamin-C ratios were higher than the normal expected ratio on all of the study days. Both plasma biomarkers of endothelial dysfunction (sVCAM-1 and E-selectin) were high at baseline. However, sVCAM-1 levels were significantly higher in non-survivors than in survivors, although this difference was not observed for E-selectin levels. Furthermore, the sVCAM-1 levels fell significantly at day 1, and normalised at day 7, while the E-selectin levels were constantly raised at day 1, as at baseline, and further increased significantly at day 7. Both sVCAM-1 and TBARS associated positively to SOFA score, and increased TBARS levels were associated with increased requirements for intravenous fluids for resuscitation and an increased number of days on vasoconstrictors. The study group had extremely low vitamin C levels, with plasma levels reaching only approximately 50% of the lower limit of reference range. These levels are comparable with those reported in a similar study where, without intervention, plasma ascorbic acid levels were borderline normal or below normal reference values at baseline and continued to decline during ICU admission, in a similar patient population.[16,17] There are a number of reasons for such low levels. Firstly, there is profound oxidative stress and consequent antioxidant utilisation associated with critical illness,[6,7,16] and excess losses of plasma antioxidants via circulating volume redistribution to the extravascular space. Secondly, although study patients received enteral nutritional support, it has previously been shown that it is not possible to restore normal plasma levels while in ICU through nutritional support alone, without the addition of parenteral high-dose vitamin C.[18] Thirdly, in our patient collective, the very low levels could be due to low plasma vitamin C prior to the onset of septic shock, since low vitamin C status is known to be common in the healthy SA population owing to low micronutrient intake.[19,20] This patient population may, therefore, be predisposed to low vitamin C levels in acute illness because of a pre-existing

Inotrope-free days at day 7

Inotrope-free days r=−0.48, p=0.0015 Intravenous fluid requirements r=0.75, p=0.02 7

4 500

4 000 3 500

3 000

2 500 3 2 000 2

1 500

1 000

Intravenous fluids at baseline (mL)

500

–1 –10

Baseline TBARS (nmol/mL)

Fig. 4. Correlation between baseline TBARS and inotrope-free days at day 7, and baseline TBARS and baseline intravenous fluid requirements. 90

8 000 TBARS r=0.47, p=0.02 VCAM-1 r=0.57, p=0.003

7 000

Baseline TBARS (nmol/mL)

6 000

5 000

50 4 000 40 3 000 30 2 000

Baseline VCAM-1 (ng/mL)

nutritional compromise in the diet, which is worsened by the increased demands during septic shock.[21] Patients also had high plasma glucose-tovitamin-C ratios, above the reference value of 88 calculated from the expected physiological levels of both glucose and vitamin C. The increased ratio was mainly contributed to by the very low plasma vitamin C levels and to a lesser extent the high blood glucose levels at baseline. This unfavourably high ratio could partly explain the increased oxidative stress through the glucose-mediated induction of inflammatory response,[22,23] as well as competitive inhibition of cellular vitamin C uptake.[22,24] Lax management of sepsisrelated stress hyperglycaemia together with the common clinical practice of administering systemic steroids in vasopressor-dependent patients, which worsens glucose control, may contribute to oxidative stress in this population. Importantly, TBARS levels at baseline were positively associated with increased organ dysfunction and/or failure, as measured by SOFA score, and an increase in sVCAM-1 (a marker of endothelial damage). The association between oxidative stress and increased endothelial and organ dysfunction in this study is of clinical relevance. Previous literature has shown that oxidative stress causes damage to the endothelial glycocalyx.[25] Damage to the glycocalyx disrupts its shielding function to the vascular walls from direct exposure to blood flow, while serving as a vascular permeability barrier.[26] Disruption of the glycocalyx therefore causes capillary leakage and predisposes the endothelial cells to oxidative stress-induced disruption, when endothelial cell tight junctions may be damaged by mechanisms such as protein modification, thiol-oxidation, phosphorylation, nitration and carboxylation during sepsis.[27] Endothelial dysfunction in sepsis has been demonstrated to cause microvascular dysfunction, the motor for sepsis-induced organ dysfunction and failure that may be reflected by SOFA score.[28-30] The baseline oxidative stress marker in this study was significantly higher in the non-survivors, who also had increased organ dysfunction when compared with survivors. These results, therefore, demonstrate that increased oxidative stress is a marker of increased risk of death; this finding supports previous similar findings of other researchers.[31,32] Contrary to the hypothesis, no significant correlation was found between E-selectin and TBARS. The lack of correlation could be a consequence of the effect of increased oxidative damage to the endothelial cells, a factor known

1 000

0 2

Baseline SOFA score

Fig. 5. Correlation between baseline TBARS and SOFA score, baseline SVCAM-1 and SOFA score. to negatively affect E-selectin expression.[33] This would also explain the findings of this study that E-selectin levels were higher in the survivors than in the non-survivors. The non-survivors of septic shock in the current study had increased levels of oxidative stress, with increased levels of sVCAM-1, marking endothelial damage. Since endothelial cell damage and necrosis do not induce E-selectin expression,[34,35] it is not unexpected to find higher E-selectin levels in the survivors, who may have relatively less endothelial damage than the non-survivors. Further to this, it has been suggested that

increased E-selectin levels may reduce collateral damage to the host.[35] Indeed, one study in children with sepsis found that those with the highest levels of E-selectin exhibited the best outcome and survival rates.[36] In survivors, sVCAM-1 levels decreased at day 1 and decreased to within a normal range within 7 days of stopping vasoconstrictors. This demonstrates that there was less cellular damage and recovery in endothelial functions, as septic shock resolved. This was an expected result. However, the plasma E-selectin levels remained relatively stable from baseline to

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8 000

biomarkers was considered a suitable proxy for the observational purposes of this baseline study. This study was conducted prior to the publication of the new consensus definition of septic shock, but the majority of our participants also complied with this definition.

p=0.2

Plasma glucose-to-vitamin C ratio

7 000 6 000

Conclusions

5 000 4 000 p=0.6 3 000 2 000 1 000 0 n=25 0

n=19

n=15

1 Days

Fig. 6. Glucose-to-vitamin-C ratios over the study period. day 1 but increased significantly at day 7. It is known that in addition to being stimulated by inflammatory mediators, increased E-selectin expression has been described as a marker of proliferating endothelium and is known to be involved in angiogenesis.[37-39] Increased E-selectin expression at day 7 may therefore reflect increased endothelial proliferation in repair and regeneration, post resolution of septic shock. This study has demonstrated that increased oxidative stress at baseline is associated with an increased requirement for intravenous fluids for resuscitation and more days on inotropic support. One of the major organs affected in septic shock is the cardiovascular system and it is not surprising that such patients require large amounts of intravenous fluids for resuscitation and inotropic support, to restore macrovascular haemodynamics.[12] It may be hypothesised that reducing oxidative stress may result in the reduction of intravenous fluid requirements in this patient group. A randomised study of vitamin C supplementation in burns patients[40] demonstrated that high doses of vitamin C resulted in reduced oxidative stress levels and lower requirements of resuscitation fluids in the patients who received vitamin C supplementation, compared with controls. Although septic shock and burns are different disease conditions, they have common factors, as they both exhibit a profound inflammatory response and are associated with increased oxidative stress. A recent review on the possible use of vitamin C in critically ill

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patients has emphasised the need for future research to focus on the prompt use of shortterm, high-dose intravenous vitamin C as a resuscitation drug.[41] Vitamin C may intervene in the oxidant cascade for optimisation of the macro- and microcirculation and limitation of cellular injury.[41] Another interesting finding of this study is that increased oxidative stress was associated with more days on inotropic support. This demonstrates that increased oxidative stress in septic shock is somehow associated with circulatory dysfunction, so that this patient group requires more time on vasoconstrictors, presumably due to lingering endothelial dysfunction. Use of vasoconstrictors is very important clinically because it reflects illness severity and, therefore, the need for organ support and ICU resources. Early liberation from vasoconstrictors is an indication of an accelerated improvement and response to the other critical aspects of sepsis control such as source control and antibiotic responsiveness.

Study limitations

Limitations of this study include its design as a cross-sectional study. The study can only report associations between variables and cannot demonstrate any cause-and-effect relationship. Our sample size was 25 patients; although a relatively small sample, we met the sample size required for the planned statistical analysis. Because of the study design, in vivo assessment procedures were not indicated for assessment of the endothelium and the use of circulating

The results of the study demonstrate clinically relevant oxidative stress-associated endothelial dysfunction in a context of profoundly low vitamin C plasma levels and high plasma glucose-to-vitamin-C ratios. Markers of oxidative stress and endothelial damage were increased and correlated with resuscitation fluid requirements, vasoconstrictor use, organ failure and death. Strategies to limit oxidative damage in septic shock, such as short-term, high-dose vitamin C supplementation, merit further research attention. Ac k n ow l e d g em ent s . We a ck n ow l e d ge Shaheen Mowla, Dee Blackhurst and Fahima Adams for their assistance with the laboratory aspects of the study, and the SA Consortium for Research Excellence (SACORE) and UCT for financial support. References 1. Singer M, Deutschman CS, Seymour CW, et al. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA 2016;315(8):801-810. DOI:10.1001/ jama.2016.0287 2. Hernandez G, Bruhn A, Ince C. Microcirculation in sepsis: New perspectives. Curr Vasc Pharmacol 2013;11(2):161-169. DOI:10.2174/1570161111311020006 3. De Backer D, Orbegozo Cortes D, Donadello K, Vincent J. Pathophysiology of microcirculatory dysfunction and the pathogenesis of septic shock. Virulence 2014;5(1):73-79. DOI:10.4161/viru.26482 4. Wilson JX. Evaluation of vitamin C for adjuvant sepsis therapy. Antioxid Redox Signal 2013;19(17):2129-2140. DOI:10.1089/ars.2013.5401 5. Donati A, Damiani E, Botticelli L, et al. The aPC treatment improves microcirculation in severe sepsis/ septic shock syndrome. BMC Anesthesiol 2013;13(1):25. DOI:10.1186/1471-2253-13-25 6. Doise J, Aho LS, Quenot J, et al. Plasma antioxidant status in septic critically ill patients: A decrease over time. Fundam Clin Pharmacol 2008;22(2):203-209. DOI:10.1111/j.14728206.2008.00573.x 7. Heyland D, Muscedere J, Wischmeyer PE, et al. A randomized trial of glutamine and antioxidants in critically ill patients. N Engl J Med 2013;368(16):1489-1497. DOI:10.1056/ NEJMoa1212722 8. Trzeciak S, McCoy JV, Phillip Dellinger R, et al. Early increases in microcirculatory perfusion during protocoldirected resuscitation are associated with reduced multiorgan failure at 24 h in patients with sepsis. Intensive Care Med 2008;34(12):2210-2217. DOI:10.1007/s00134-0081193-6 9. Wilson JX. Mechanism of action of vitamin C in sepsis: Ascorbate modulates redox signaling in endothelium. Biofactors 2009;35(1):5-13. DOI:10.1002/biof.7 10. Raimann JG, Levin NW, Craig RG, Sirover W, KotankoÂ P, Handelman G. Is vitamin C intake too low in dialysis patients? Semin Dial 2013;26(1):1-5. DOI:10.1111/sdi.12030 11. Will JC, Byers T. Does diabetes mellitus increase the requirement for vitamin C? Nutr Rev 1996;54(7):193-202. DOI:10.1111/j.1753-4887.1996.tb03932.x 12. Dellinger RP, Levy MM, Rhodes A, et al. Surviving sepsis campaign: international guidelines for management of severe sepsis and septic shock: 2012. Crit Care Med 2013;41(2):580637. DOI:10.1097/CCM.0b013e31827e83af 13. Jentzsch AM, Bachmann H, FĂźrst P, Biesalski HK. Improved analysis of malondialdehyde in human body fluids. Free Radic Biol Med 1996;20(2):251-256. DOI:10.1016/08915849(95)02043-8

14. Blanchard J. Depletion and repletion kinetics of vitamin C in humans. J Nutr 1991;121(2):170176. 15. Miller E, Markiewicz L, Saluk J, Majsterek I. Effect of short-term cryostimulation on antioxidative status and its clinical applications in humans. Eur J App Physiol 2012;112(5):1645-1652. DOI:10.1007/s00421-011-2122-x 16. Long CL, Maull KI, Krishnan RS, et al. Ascorbic acid dynamics in the seriously ill and injured. J Surg Res 2003;109(2):144-148. DOI:10.1016/S0022-4804(02)00083-5 17. Nathens AB, Neff MJ, Jurkovich GJ, et al. Randomized, prospective trial of antioxidant supplementation in critically ill surgical patients. Ann Surg 2002;236(6):814-822. DOI:10.1097/00000658-200212000-00014 18. Berger MM. Vitamin C requirements in parenteral nutrition. Gastroenterology 2009;137(5 Suppl):S70-S78. DOI:10.1053/j.gastro.2009.08.012 19. Segal I, Gut A, Schofield D, Shiel N, Braganza JM. Micronutrient antioxidant status in black South Africans with chronic pancreatitis: Opportunity for prophylaxis. Clin Chim Acta 1995;239(1):7179. DOI:10.1016/0009-8981(95)06102-J 20. MacIntyre UE, Kruger HS, Venter CS, Vorster HH. Dietary intakes of an African population in different stages of transition in the North West Province, South Africa: The THUSA study. Nutr Res 2002;22(3):239. DOI:10.1016/S0271-5317(01)00392-X 21. Berger MM. Antioxidant micronutrients in major trauma and burns: Evidence and practice. Nutr Clin Pract 2006;21(5):438-449. DOI:10.1177/0115426506021005438 22. Ceriello A, Esposito K, Ihnat M, Thorpe J, Giugliano D. Effect of acute hyperglycaemia, long-term glycaemic control and insulin on endothelial dysfunction and inflammation in Type 1 diabetic patients with different characteristics. Diabet Med 2010;27(8):911-917. DOI:10.1111/j.14645491.2009.02928.x 23. Gordin D, Forsblom C, Rönnback M, et al. Acute hyperglycaemia induces an inflammatory response in young patients with type 1 diabetes. Ann Med 2008;40(8):627-633. DOI:10.1080/07853890802126547 24. Dungan KM, Braithwaite SS, Preiser J. Stress hyperglycaemia. Lancet 2009;373(9677):1798-1807. DOI:10.1016/S0140-6736(09)60553-5 25. Marechal X, Favory R, Joulin O, et al. Endothelial glycocalyx damage during endotoxemia coincides with microcirculatory dysfunction and vascular oxidative stress. Shock 2008;29(5):572576. DOI:10.1097/shk.0b013e318157e926 26. Van den Berghe G, Wilmer A, Hermans G, et al. Intensive insulin therapy in the medical ICU. N Engl J Med 2006;354(5):449-461. DOI:10.1056/NEJMoa052521 27. Rao R. Oxidative stress-induced disruption of epithelial and endothelial tight junctions. Front Biosci 2008;13:7210-7226. DOI:10.2741/3223

28. Gomez H, Ince C, De Backer D, et al. A unified theory of sepsis-induced acute kidney injury: Inflammation, microcirculatory dysfunction, bioenergetics, and the tubular cell adaptation to injury. Shock 2014;41(1):3-11. DOI:10.1097/SHK.0000000000000052 29. Piagnerelli M, Ince C, Dubin A. Microcirculation. Crit Care Res Pract 2012;867176. DOI:10.1155/2012/867176 30. Ren J. Wide spectrum of presentation and variable mechanisms of compromised cardiac function in multiple organ dysfunction syndrome. J Organ Dysfunct 2008;4(4):239-248. DOI:10.1080/17471060701200394 31. Costa NA, Gut AL, De Souza D, et al. Serum thiamine concentration and oxidative stress as predictors of mortality in patients with septic shock. J Crit Care 2013;29(2):249-252. DOI:10.1016/j.jcrc.2013.12.004 32. Huet O, Obata R, Aubron C, et al. Plasma-induced endothelial oxidative stress is related to the severity of septic shock. Crit Care Med 2007;35(3):821-826. DOI:10.1097/01.ccm.0000257464.79067.af 33. Harrington EO, Stefanec T, Newton J, Rounds S. Release of soluble E-selectin from activated endothelial cells upon apoptosis. Lung 2006;184(5):259-266. DOI:10.1007/s00408-005-2589-5 34. Pigott R, Dillon LP, Hemingway IH, Gearing AJ. Soluble forms of E-selectin, ICAM-1 and VCAM-1 are present in the supernatants of cytokine activated cultured endothelial cells. Biochem Biophys Res Commun 1992;187(2):584-589. DOI:10.1016/0006-291x(92)91234-h 35. Zonneveld R, Martinelli R, Shapiro NI, Kuijpers TW, Plötz FB, Carman CV. Soluble adhesion molecules as markers for sepsis and the potential pathophysiological discrepancy in neonates, children and adults. Crit Care 2014;18(1):204. DOI:10.1186/cc13733 36. Briassoulis G, Papassotiriou I, Mavrikiou M, Lazaropoulou C, Margeli A. Longitudinal course and clinical significance of TGF-beta1, sL- and sE-Selectins and sICAM-1 levels during severe acute stress in children. Clin Biochem 2007;40(5-6):299-304. DOI:10.1016/j.clinbiochem.2006.11.015 37. Kräling BM, Razon MJ, Boon LM, et al. E-selectin is present in proliferating endothelial cells in human hemangiomas. Am J Pathol 1996;148(4):1181-1191. 38. Läubli H, Borsig L. Selectins promote tumor metastasis. Semin Cancer Biol 2010;20(3):169-177. DOI:10.1016/j.semcancer.2010.04.005 39. Smadja DM, Mulliken JB, Bischoff J. E-selectin mediates stem cell adhesion and formation of blood vessels in a murine model of infantile hemangioma. Am J Pathol 2012;181(6):2239-2247. DOI:10.1016/j.ajpath.2012.08.030 40. Tanaka H, Matsuda T, Miyagantani Y, Yukioka T, Matsuda H, Shimazaki S. Reduction of resuscitation fluid volumes in severely burned patients using ascorbic acid administration: A randomized, prospective study. Arch Surg 2000;135(3):326-331. DOI:10.1001/archsurg.135.3.326 41. Oudemans-van Straaten M, Spoelstra-de Man A, De Waard MC. Vitamin C revisited. Crit Care 2014;18(4):460. DOI:10.1186/s13054-014-0460-x

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ARTICLE

Incidence and risk factors for thrombocytopenia in the intensive care units of a tertiary hospital in northern India C Mehta,1 MBBS, DNB, FNB; J V George,1 RN/RM; Y Mehta,1 MBBS, MD, MNAMS, FRCA; M T Ali,1 MBBS, MD, EDIC; M K Singh,2 MSc (Biostatistics) 1 2

Institute of Critical Care and Anesthesia, Medanta – The Medicity, Gurgaon, Haryana, India Institute of Clinical Research, Medanta – The Medicity, Gurgaon, Haryana, India

Corresponding author: J V George (jobygeorge05@hotmail.com)

Background. In Western countries, incidence of thrombocytopenia in intensive care units (ICUs) has been found to be 13 - 44%. We chose to study the incidence, risk factors and transfusion requirements of thrombocytopenia in tertiary care ICUs in northern India. Objective. To study the incidence and risk factors of thrombocytopenia in a mixed ICU. Methods. This prospective observational 6-month cohort study was conducted in two 22-bedded medical-surgical ICUs. Patients aged 18 years or older with an ICU stay of at least 2 days were included. Results. Thrombocytopenia (<150 000/dL) occurred in 190 (38%) of the 500 patients studied. Thrombocytopenia was present on admission in 41 (8%) patients. Of the remaining patients, 149 (32%) developed new-onset thrombocytopenia (NOT) – thrombocytopenia developing in patients with platelet count more than 150 000/U on admission – during ICU stay. Incidence and prevalence were 30% and 38%, respectively. ICU mortality was 13%. Thrombocytopenia was commonly associated with sepsis, disseminated intravascular coagulation, heparin and certain antibiotics. Cause could not be established in 10 patients. Underlying coronary artery disease and sepsis correlated with thrombocytopenia. Mortality was higher in patients with NOT (15.4 v. 8.7%, p=0.003). Compared with non-thrombocytopenic patients, patients with NOT required more blood product transfusions (57.7 v. 38.4%, p=0.000) and mechanical ventilation (23.5 v. 13.5%, p=0.008). No difference was observed in length of hospital stay and bleeding risk between the two groups. Conclusion. We found incidence and prevalence of thrombocytopenia in the ICU comparable with internationally reported figures. NOT was associated with higher mortality and morbidity and may be considered as a marker of disease severity. S Afr J Crit Care 2016;32(1):28-31. DOI:10.7196/SAJCC.2016.v32i1.234

Thrombocytopenia is one of the most commonly observed laboratory abnormalities in the intensive care unit (ICU),[1] with incidence ranging from 13% to 44%.[1] Thrombocytopenia has been found to predispose patients to increased bleeding risk, increasing morbidity and mortality.[2] It is also considered a marker of disease severity.[3] The aetiology of thrombocytopenia in the ICU is multifactorial. Sepsis, malignancy, presence of invasive catheters and various medications such as heparin and antibiotics have been found associated with thrombocytopenia. Because of the many confounding factors, establishing the cause of thrombocytopenia in critically ill patients is challenging.[4,5] Different aspects of thrombocytopenia have been examined in various studies. The majority of these studies are Western, retrospective or have a small sample size. Until now, Indian literature has been silent on the prevalence of thrombocytopenia in the ICU. A Korean group recently evaluated thrombocytopenia in the ICU,[6] the sole study from Asian countries so far. This prompted us to study the incidence, risk factors and impact on outcome of thrombocytopenia in the mixed ICU of our tertiary, multispecialty hospital in northern India.

Methods

This was a prospective, observational cohort study. Consecutive patients aged 18 years or older admitted to our medical-surgical ICU for at least 2 days were included. The study was conducted over a period of 6 months (October 2012 - March 2013). Patients were excluded if they had history of cardiac surgery, pregnancy, platelet disorders, haematological malig nancy, recent chemotherapy, splenectomy, ICU stay of <48 hours, were <18 years of age or had a history of readmission to the ICU during the same

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hospital stay. Platelet counts were measured daily from ICU admission to ICU discharge. The necessary approvals were obtained from the Medanta Institutional Review Board (Ref. no.: 198/2012). Informed consent was obtained from the patients or their relatives prior to data collection. The study was registered at the Clinical Trial Registry of India (CTRI) (Ref. no.: CTRI/2012/05/002620). The primary study objective was to assess thrombocytopenia incidence and associated risk factors. Secondary objectives were to study the effect of thrombocytopenia on bleeding risk and transfusion requirements in the ICU. The outcomes of length of hospital stay, ICU discharge and mortality were also studied.

Definitions

Thrombocytopenia was defined as two or more consecutive platelet counts <150 000/µL, obtained at least 12 hours apart. Lowest platelet count during the ICU stay was considered the nadir platelet count. Disseminated intravascular coagulation (DIC) was defined by presence of elevated D-dimer along with two of the following criteria: prolonged prothrombin time, increased fibrinogen degradation products, and decreased fibrinogen or platelet counts. Drug-induced thrombocytopenia was considered present if there was resolution of thrombocytopenia after discontinuation of the suspected drug. Heparin-induced thrombocytopenia (HIT) was diagnosed using 4T scoring (Table 1) and if there was recovery in platelet count after discontinuation of unfractionated heparin or low-molecular-weight heparin. Major bleeding was defined as any intracranial bleed or any bleed associated with a fall in haemoglobin by at least 2 g/dL.

Data collection

parameters satisfying normality assumptions, the independent Student’s t-test was used to draw inferences between groups. Cross-tables were generated to illustrate the relationships between parameters and comparisons were made using the χ2 test. Stepwise multiple logistic regressions were performed for parameters. A p-value of <0.05 was considered statistically significant. The entire statistical analysis was performed using SPSS software version 19.0 (IBM Corp., USA).

The following variables were recorded: general demographic character istics including age, gender, comorbidities, reason for ICU admission; severity of illness by APACHE (Acute Physiology and Chronic Health Evaluation) II score calculation; biochemical parameters of complete blood count, liver function tests, kidney function tests, coagulation assays and any other special blood investigations if conducted; a comprehensive list of drugs patients were receiving in ICU; various interventions performed in ICU such as mechanical ventilation and haemodialysis; frequency and products of blood transfusions, if any; complications such as bleeding episodes or thromboembolic events; and any use of vasopressors.

Results

A total of 500 patients were enrolled in the study. Of these, 41 (8.2%) had thrombocytopenia on admission. Of the remaining 459 patients, 149 (32.5%) had new-onset thrombocytopenia (NOT) during their ICU stay. The median APACHE II score at the time of ICU admission was 11.0 (interquartile range (IQR) 1 - 32), and the predicted death rate was 5 - 10%. Median length of ICU stay was 4 days (IQR 1 - 35). Median length of hospital stay was 11 days (IQR 1 - 149). Thrombocytopenia incidence was 30% and prevalence during the study period was 38%. ICU mortality was 13%. The baseline patient demographic profile is shown in Table 2.

Statistical analysis

Analysis included profiling of patients for different demographic and clinical parameters, comorbidity and risk factors. Descriptive analysis of quantitative data was expressed as means and standard deviations (SDs). Ordinal data were expressed as percentages, medians and ranges. Data normality was tested using the Kolmogorov-Smirnov test. For quantitative

Table 1. The 4T scoring system of HIT[7] 2

Thrombocytopenia

>50% platelet fall to nadir ≥20

30 - 50% platelet fall or nadir 10 - 19

<30% platelet fall or nadir <10

Timing* of onset of platelet fall (or other sequelae of HIT)

Days 5 - 10, or ≤day 1 with recent heparin (past 30 days)

>day 10 or timing unclear; or <day 1 with recent heparin (past 31 - 100 days)

<day 4 (no recent heparin)

Thrombosis or other sequelae

Proven new thrombosis, skin necrosis, or acute systemic reaction after intravenous unfractionated heparin bolus

Progressive or recurrent thrombosis, erythematous skin lesions or suspected thrombosis (not proven)

None

Other cause(s) of platelet fall

None evident

Possible

Definite

HIT: The ‘Four Ts’ (2, 1 or 0 for each of four categories: maximum possible score = 8). Pretest probability score: 6 - 8 indicates high; 4 - 5 intermediate; and 0 - 3 low. *First day of immunising heparin exposure considered day 0.

Table 2. Baseline characteristics of patients (N=500) Parameters

n (%)

Age (years), mean (SD)

56.8 (16.6)

Male

330 (66.0)

APACHE II score, mean (SD)

12.0 (7.1)

10 (6.7%) 3 (2.0%)

15 (10.1%)

Medical history Hypertension

222 (44.4)

Diabetes mellitus

91 (18.2)

Cardiovascular disease

70 (14.0)

Chronic renal failure

33 (6.6)

Chronic liver disease

15 (3.0)

Chronic obstructive pulmonary disease

31 (6.2)

Neurological disorders

20 (4.0)

89 (59.7%)

32 (21.5%)

Reason for ICU admission Respiratory

90 (18.0)

Sepsis

301 (60.2)

Fluid overload

28 (5.6)

Cardiovascular problem

41 (8.2)

Postoperative

19 (3.8)

Others

21 (4.2)

ICU length of stay (days), mean (SD)

5.8 (5.5)

ICU mortality

65 (13.0)

DIC Drug-induced thrombocytopenia Heparin-induced thrombocytopenia Liver disease Unknown Fig. 1. Causes of new-onset thrombocytopenia.

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Causes of NOT

A total of 149 patients developed throm bocytopenia during their ICU stay. Thrombo cytopenia was diagnosed secondary to sepsis with disseminated intravascular coagulation in 89 patients (59.7%) and drug-induced thrombocytopenia was thought to be present in 31 (21.5%) patients Thrombocytopenia was due to underlying liver disease in 15 (10.1%) patients. HIT was diagnosed, based on 4T scoring, in 3 (2.0%) patients. Cause of thrombocytopenia could not be ascertained in 10 (6.7%) patients. During the work-up for NOT, 41 patients refused to give consent for bone marrow examination. Causes of NOT and drug-induced thrombocytopenia are shown in Fig. 1 and Table 3, respectively. Use of antibiotics, including meropenem, cefuroxime, cefepime, tazobactam, vanco mycin, levofloxacin, linezolid, and lowmolecular-weight heparin, correlated with thrombocytopenia, as did underlying coronary artery disease and sepsis (p<0.05). APACHE II score was significantly higher in patients with NOT compared with those without thrombocytopenia (13 v. 11, p=0.003). Patients with NOT required significantly more packed red-cell and platelet transfusions (5.4 v. 2.3%, p=0.000) and had significantly higher ICU mortality (15.4 v. 8.7%, p=0.003). The majority of transfusions were given prophylactically before procedures in the thrombocytopenia group. Blood products transfused were mainly fresh-frozen plasma and platelets. Patients with NOT required mechanical ventilation and inotropes more frequently (57.7 v. 38.4%, p=0.000; 23.5 v. 13.5%, p=0.008, respectively). There was no difference in duration of ICU and hospital stay or bleeding risks between the two groups. Use of invasive devices such as central-line and arterial-line catheters was not different between the groups and haemodialysis requirements also did not vary. Comparison between patients with or without NOT is depicted in Table 4.

Table 3. Causes of drug-induced thrombocytopenia (N=32) Cause

n (%)

p-value

Carbapenem

12 (8.05)

0.002*

Cephalosporin

5 (3.35)

0.000*

Fluoroquinoles

3 (2.01)

0.000*

Glycopeptides

6 (3.35)

0.002*

Oxazolidinone

5 (3.35)

0.040*

β-lactamase/ β-lactamase inhibitors

1 (0.67)

0.277

*p-value <0.05, statistically significant.

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Discussion

Thrombocytopenia is one of the most common haematological disorders seen in critically ill patients. Prevalence has been found to be around 50% and incidence varies between 13% and 44%.[8,9] In our cohort, 41 patients (8.2%) had pre-existing thrombocytopenia at the time of ICU admission and 149 patients (32.4%) developed thrombocytopenia during their ICU stay. Our incidence of 30% and prevalence of 38% were consistent with observations made internationally.[6,10,11] This is despite our study definition for thrombocytopenia of two platelet count readings <150 000/µL at least 12 hours apart. This is unlike previous investigations with thrombocytopenia defined as platelet count <150 000/µL, or fall in platelet count by at least 50% from the time of ICU admission. The majority of studies of thrombocytopenia in ICU are from North America or Europe. Among studies from Asian countries, a prospective study was conducted in Singapore, examining thrombocytopenia incidence in septic critically sick patients only.[12] A study from Korea reported an incidence of 37.1%. Therefore, this is the first prospective study of thrombocytopenia incidence in a general ICU on the Asian subcontinent. As discussed earlier, our figures were comparable with those found internationally. We discovered underlying coronary artery disease and sepsis on admission as major risk factors for developing thrombocytopenia in

critically ill patients. Unlike previous studies, blood transfusions, postoperative status, pulmonary artery catherisation and respiratory failure were not identified as risk factors.[11,13] The association of thrombo cytopenia with sepsis can be explained on the basis of an underlying DIC process. Other mechanisms implicated in sepsis-induced thrombocytopenia are immune-mediated platelet destruction and haemophagocytic syndrome.[14,15] An association between coronary artery disease and thrombocytopenia has not been reported before and the underlying pathophysiological mechanism for this observation needs further consideration. It may be related to the use of antiplatelet medication in these patients; however, this needs further investigation. Systematic and extensive investigations are required to establish the cause of thrombocytopenia in ICU, the aetiology of which is multifactorial and complicatedly linked. The work-up of thrombocytopenia in our study left scope for improvement, as 41 (27.5%) patients refused bone marrow examination. Within these constraints, sepsis with DIC was the most common cause, occurring in 59.7% of patients. The second-most common cause was drug-induced thrombo cytopenia, occurring in 21.4% of patients. Implicated drugs were mainly antibiotics such as teicoplanin, levofloxacin, cefuroxime, meropenem, vancomycin, line zolid, and cefepime and tazobactam combinations.

Table 4. Comparison between patients with or without NOT Variable

Patients with NOT (N=149), n (%)

Patients without NOT (N=310), n (%)

p-value

Age (years), mean (SD), median

57.3 (16.9), 59

56 (16.4), 58

0.454

Male

99 (66.4)

201 (64.8)

0.673

ICU stay (days), mean (SD), median

6.1 (5.6), 4

5.3 (5.2), 3

0.151

Hospital stay (days), mean (SD), median

15.0 (10.9), 12

17.9 (19.4), 11

0.086

APACHE II score, mean (SD), median

13.0 (7.3), 13

10.9 (6.8), 11

0.003*

Haemodialysis

6 (4.0)

20 (6.5)

0.530

ICU mortality

37 (15.4)

23 (8.7)

0.003*

Mechanical ventilation

86 (57.7)

119 (38.4)

0.000*

Bleeding risk

8 (5.4)

7 (2.3)

0.079

Transfusion requirement

33 (22.1)

29 (9.4)

0.000*

Inotropes

35 (23.5)

42 (13.5)

0.008*

Invasive catheters

103 (69.1)

218 (70.3)

0.539

Dialysis

6 (4.0)

20 (6.5)

0.239

Coronary artery disease

15 (10.1)

46 (14.8)

0.043*

Sepsis

101 (67.7)

154 (49.6)

0.004*

Respiratory failure

39 (26.2)

36 (11.6)

0.617

Postoperative status

2 (1.3)

14 (4.5)

0.132

*p-value <0.05, statistically significant.

However, we did not find any associations between thrombocytopenia and anticonvulsants, diuretics or H2 blockers, as reported in previous studies.[6,11] Establishing drug-induced thrombocytopenia remains difficult, as the diagnostic criteria are based on the recovery of platelet count after the drug is discontinued and there is no gold standard for its diagnosis. HIT was considered separately from drug-induced thrombocytopenia in our study. Its incidence was found to be 2%, which is in tandem with an internationally reported incidence of 1% - 5%.[16] We employed 4T scoring for diagnosing HIT because of non-availability of the functional and antigen assays used for detecting HIT antibodies.[17,18] All these tests have moderate to high negative predictive value and a low positive predictive value similar to the 4T scoring system. A 4T score of 5 - 8 on a scale of 0 - 8 reflects intermediate to high probability of HIT. The magnitude of HIT in Asian countries has not been systematically studied so far although there have been occasional case reports of HIT from the area. In our study, thrombocytopenia patients did not have any bleeding episodes. They required more platelet and fresh-frozen plasma transfusions compared with the non-thrombocytopenia group, and these were mostly prophylactic transfusions carried out if any surgical procedures or interventions were planned. Previous studies have reported increased bleeding episodes and more transfusion requirements in critically sick patients with thrombocytopenia.[9,11,19-21] As observed in previous studies,[22] our thrombocytopenia patients had more frequent need for mechanical ventilation and inotropes. We observed a higher ICU mortality among thrombocytopenia patients compared with the non-thrombocytopenia group (15.4 v. 8.7%, p=0.03); this may be because thrombocytopenia patients were much more sick than those who did not develop thrombocytopenia. This correlates with the observation that the APACHE II score at the time of ICU admission was higher in those who eventually developed thrombocytopenia during their ICU stay (13 v. 11, p=0.003). Thus, thrombocytopenia may reflect severity of critical illness. Many previous studies have observed poor outcomes with thrombocytopenia.[20,23-27] There have been reports indicating that the rate of platelet decline or recovery from thrombocytopenia may have important prognostic value in diseases such as sepsis and acute respiratory distress syndrome (ARDS).[21,22,24,26] Our study had several limitations. Firstly, this study was conducted at a single tertiary care centre in a northern part of India. Figures may not be truly representative of the entire country. The need for a robust work-up for thrombocytopenia cannot be over-emphasised. This was the second drawback of the study, as evaluation of cause of thrombocytopenia could have been more extensive and systematic. A third limitation was the non-availability of HIT antibody detection tests, which could have influenced the diagnosis. Major strengths of this study were its prospective nature and adequate sample size.

Conclusions

Thrombocytopenia occurs frequently in critically ill patients. It should be viewed generally as an indicator of illness severity, and also has prognostic significance because of its association with increased morbidity, hospital resource utilisation and increased mortality. Its

potential as a predictor of complications of ARDS and hospital-acquired pneumonia needs to be explored further. However, it remains necessary to evaluate this disorder at the earliest opportunity, as about 25% of cases are drug-associated and can be rapidly reversed with withdrawal of the offending drug, especially heparin. Rate of decline and delayed count recovery need further evaluation but may prove useful as urgently needed prognostic indicators. Declaration. The authors declare that an abstract of this study was published in the Indian Journal of Critical Care Medicine as part of a poster presentation at CRITICARE-2015, Bengaluru, India. References 1. Bonfiglio MF, Traeger SM, Kier KL, Martin BR, Hulisz DT, Verbeck SR. Thrombocytopenia in intensive care patients: A comprehensive analysis of risk factors in 314 patients. Ann Pharmacother 1995;29(9):835-842. 2. Hine LK, Gerstman BB, Wise RP, Tsong Y. Mortality resulting from blood dyscrasias in the United States, 1984. Ann J Med 1990:88(2):151-153. 3. Drews RE. Critical issues in hematology: Anemia, thrombocytopenia, coagulopathy, and blood product transfusions in critically ill patients. Clin Chest Med 2003;24(4):607-622. DOI:10.1016/ s0272-5231(03)00100-x 4. Brooks AP. Thrombocytopenia during treatment with ampicillin. Lancet 1974;2(7882):723. DOI:10.1016/s0140-6736(74)93302-9 5. Kaplan R, Sahn S, Petty T. Incidence and outcome of the respiratory distress syndrome in gram negative sepsis. Arch Intern Med 1979;139(8):867-869. 6. Lim SY, Jeon EJ, Kim H-J, et al. The incidence, causes, and prognostic significance of new-onset thrombocytopenia in intensive care units: A prospective cohort study in a Korean hospital. J Korean Med Sci 2012;27(11):1418-1423. DOI:10.3346/jkms.2012.27.11.1418 7. Warkentin TE. Heparin-induced thrombocytopenia diagnosis and management. Circulation 2004;110(18):e454-e458. DOI:10.1161/01.cir.0000147537.72829.1b 8. Priziola JL, Smythe MA, Dager WE. Drug-induced thrombocytopenia in critically ill patients. Crit Care Med 2010;38(6 Suppl):S145-S154. DOI:10.1097/ccm.0b013e3181de0b88 9. Strauss R, Wehler M, Mehler K, Kreutzer D, Koebnick C, Hahn EG. Thrombocytopenia in patients in the medical intensive care unit: Bleeding prevalence, transfusion requirements and outcome. Crit Care Med 2002;30(8):1765-1771. DOI:10.1097/00003246-200208000-00015 10. Cawley MJ, Wittbrodt ET, Boyce EG, Skaar DJ. Potential risk factors associated with thrombocytopenia in a surgical intensive care unit. Pharmacotherapy 1999;19(1):108-113. DOI:10.1592/phco.19.1.108.30518 11. Shalansky SJ, Verma AK, Levine M, Spinelli JJ, Dodek PM. Risk markers for thrombocytopenia in critically ill patients: A prospective analysis. Pharmacotherapy 2002;22(7):803-813. DOI:10.1592/ phco.22.11.803.33634 12. Lee KH, Hui KP, Tan WC. Thrombocytopenia in sepsis: A predictor of mortality in the intensive care unit. Singapore Med J 1993;34(3):245-246. 13. Gupta LK, James B. S74 incidence and analysis of risk factors for thrombocytopenia in critically ill patients. Thorax 2012;67(Suppl 2):A37-A38. DOI:10.1136/thoraxjnl-2012-202678.080 14. Neame PB, Kelton JG, Walker IR, Stewart IO, Nossel HL, Hirsh J. Thrombocytopenia in septicemia: The role of disseminated intravascular coagulation. Blood 1980;56(1):88-92. 15. Stéphan F, Thiolière B, Verdy E, Tulliez M. Role of hemophagocytic histiocytosis in the etiology of thrombocytopenia in patients with sepsis syndrome or septic shock. Clin Infect Dis 1997;25(5):1159-1164. DOI:10.1086/516086 16. Warkentin TE, Cook RJ, Marder VJ, et al. Anti-platelet factor 4/heparin antibodies in orthopedic surgery patients receiving antithrombotic prophylaxis with fondaparinux or enoxaparin. Blood 2005;106(12):3791-3796. DOI:10.1182/blood-2005-05-1938 17. Parker RI. Etiology and significance of thrombocytopenia in critically ill patients. Crit Care Clin 2012;28(3):399-411. DOI:10.1016/j.ccc.2012.04.007 18. Sakr Y. Heparin-induced thrombocytopenia in the ICU: An overview. Crit Care 2011;15(2):211219. DOI:10.1186/cc9993 19. Chakraverty R, Davidson S, Peggs K, Stross P, Garrard C, Littlewood TJ. The incidence and cause of coagulopathies in an intensive care population. Br J Haematol 1996;93(2):460-463. DOI:10.1046/j.1365-2141.1996.5101050.x 20. Vanderschueren S, De Weerdt A, Malbrain M, et al. Thrombocytopenia and prognosis in intensive care. Crit Care Med 2000;28(6):1871-1876. DOI:10.1097/00003246-200006000-00031 21. Moreau D, Timsit J-F, Vesin A, et al. Platelet count decline: An early prognostic marker in critically ill patients with prolonged ICU stays. Chest 2007;131(6):1735-1741. DOI:10.1378/chest.06-2233 22. Venkata C, Kashyap R, Farmer JC, Afessa B. Thrombocytopenia in adult patients with sepsis: Incidence, factors, and its association with clinical outcome. J Intensive Care 2013;1(1):9. DOI:10.1186/2052-0492-1-9 23. Crowther MA, Cook DJ, Meade MO, et al. Thrombocytopenia in medical-surgical critically ill patients: Prevalence, incidence, and risk factors. J Crit Care 2005;20(4):348-353. DOI:10.1016/j. jcrc.2005.09.008 24. Oguzulgen IK, Ozis T, Gursel G. Is the fall in platelet count associated with intensive care unit acquired pneumonia? Swiss Med Wkly 2004;134(29-30):430-434. DOI:2004/29/smw-10670 25. Mokhtari M, Koochak M, Miri M, et al. The incidence of thrombocytopenia and mortality in ICU patients of Imam Hossein hospital. Pejouhesh 2012;36(2):93-99. 26. Wang T, Liu Z, Wang Z, et al. Thrombocytopenia is associated with acute respiratory distress syndrome mortality: An international study. PLoS One 2014;9(4):e94124. DOI:10.1371/journal. pone.0094124 27. Sprung CL, Peduzzi PN, Shatney CH, et al. Impact of encephalopathy on mortality in the sepsis syndrome. The Veterans Administration Systemic Sepsis Cooperative Study Group. Crit Care Med 1990;18(8):801-806.

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CASE REPORT

Post-tracheostomy tracheo-oesophageal fistula – an unusual presentation C Deepa, MD; S Kamat, MD; V Ravindran, MD

Goa Medical College, Goa, India Corresponding author: C Deepa (drdeepac2007@gmail.com)

Tracheostomy, one of the oldest known surgical procedures in the history of medicine, is regularly performed in modern intensive care units. Acquired ulcerative tracheo-oesophageal fistula (TOF) is an uncommon but potentially fatal complication of tracheostomy. We report a case of ulcerative TOF with an unusual yet characteristic presentation, in a ventilator-dependent tracheostomised patient with Guillain-Barré syndrome. It presented as sudden progressive severe abdominal distension that was rhythmic with each ventilator breath. The predisposing factors, clinical features and preventive measures of post-tracheostomy TOF are discussed in this case report. Regular monitoring of tracheal tube cuff pressures and volumes, along with avoidance and treatment of various predisposing factors, are advisable for the prevention of this serious consequence. S Afr J Crit Care 2016;32(1):32-33. DOI:10.7196/SAJCC.2016.v32i1.232

But that life may … be restored to the animal, an opening must be attempted in the trunk of the trachea, in which a tube of reed or cane should be put; you will then blow into this, so that the lung may rise again and the animal take in air … (Andreas Wesele Vesalius, 1543) Tracheostomy is one of the oldest surgical procedures known to mankind. It was mentioned in the ancient Sanskrit script Rigveda, dating as far back as 2000 BC. The first successful elective human tracheostomy was performed in 1869 for the administration of general anaesthesia.[1] It is a commonly performed bedside procedure in the modern intensive care unit (ICU); however, it is not devoid of complications. Acquired ulcerative tracheo-oesophageal fistula (TOF) is a rare, but potentially fatal, complication of tracheostomy. We report a case of ulcerative TOF with an unusual yet characteristic presentation, in a ventilator-dependent tracheostomised patient with Guillain-Barré syndrome (GBS).

normal cuff air shadow. On the 83rd post-tracheostomy day, we noticed rapidly progressive abdominal distension with each mechanical breath from the ventilator. The epigastric distension was relieved immediately on opening the proximal end of the NG tube. A clinical diagnosis of TOF was made. A bedside radiograph showed a TT cuff air shadow extending beyond the confines of the trachea and a grossly distended stomach (Fig. 1).

Case report

A 28-year-old man with marfanoid habitus was admitted to our ICU with GBS. He was intubated and mechanically ventilated due to respiratory failure. His muscle power did not improve despite intravenous immunoglobulin and he continued to be ventilator-dependent. Surgical tracheostomy using a size 8.0 Portex (Smiths Medical, USA) polyvinylchloride (high volume, low pressure cuff ) tracheostomy tube (TT) was performed after 2 weeks. He had anaemia and weight loss despite enteral nutrition through a 12F nasogastric (NG) tube. He developed a bronchopleural fistula on the right side following intercostal drain insertion for spontaneous pneumothorax. He acquired ventilatorassociated tracheobronchitis and pneumonia, and worsened into septic shock. His airway pressures were continually maintained below 30 cm H2O. The tracheostomy tube was changed every 3 weeks as per the ICU protocol. As there was no cuff pressure manometer available in our ICU, we were unable to monitor the TT cuff pressure accurately. His mode of communication with the unit staff and relatives was through lip, head and neck movements. From the 76th post-tracheostomy day onwards, there was an audible air leak around the TT cuff and increasing volumes of air seal (10 mL, increasing to 14 mL) were required daily. This raised suspicion of tracheal dilatation; however, bedside radiograph of the neck showed a

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Fig. 1. Radiograph showing: (A) TT cuff air shadow extending beyond the confines of the trachea; and (B) grossly distended stomach. Fibreoptic bronchoscopy (FOB) revealed a TOF (3 cm long and 1 cm wide) in the right posterolateral tracheal wall, situated distal to the equator of the cuff and extending almost to the tip of the TT (Fig. 2). After removal of the TT, orotracheal intubation with endotracheal tube (ET) size 8.0 was performed under FOB guidance and the cuff was positioned distal to the TOF. The tracheostomy stoma was then closed by suturing. Definitive surgical repair was planned once sepsis was treated. Unfortunately, the patient succumbed to septic shock 10 days after diagnosis of TOF.

Fig. 2. FOB view of the TOF.

Discussion

TOF is observed in <1% of patients undergoing tracheostomy. [2] Traumatic TOF following injury to the posterior tracheal wall during tracheostomy usually manifests in the first 48 hours following the procedure. Ulcerative TOF that occurs in patients with cuffed TT in situ for prolonged periods usually becomes symptomatic within 4 weeks. It results from tracheal mucosal ischaemia and erosion. This may be due to TT cuff pressures exceeding tracheal mucosal perfusion pressure or due to abrasion of the tracheal wall from movement of the tip of the TT during ventilatory movements, tracheal suctioning and excessive neck movements. The concomitant use of a rigid, wide-bore NG tube can aggravate the injury to the posterior tracheal wall, which gets sandwiched between the inflated cuff and the feeding tube along with the anterior oesophageal wall.[3] Other compounding factors include gastro-oesophageal reflux, tracheobronchitis, malnutrition, hypotension, hypoxaemia, anaemia, diabetes mellitus, metabolic acidosis and steroid therapy.[4] In mechanically ventilated patients, the usual manifestations are copious production of respiratory secretions, pneumonia, persistent air leak around the TT cuff, pneumothorax, pneumomediastinum and subcutaneous emphysema. The symptoms and signs will also depend on the situation of the TOF in relation to the TT cuff. A rare but characteristic sign of TOF is the rapid onset of severe epigastric distension, which may be rhythmical with each positive pressure breath from the ventilator.[5] This usually occurs when the TOF is situated below the level of the cuff. This can result in massive abdominal distension with devastating consequences. The need for high cuff

inflation pressures, increasing minimal occluding cuff volumes (more than 10 mL of air) and unexplained persistent air leak around the TT cuff should raise concerns about tracheal dilatation and TOF. FOB is the gold standard for the diagnosis of TOF. Postero-anterior radiographs of the neck and superior mediastinum may show marked bulging of the cuff beyond the normal confines of the trachea. A special TT with the cuff positioned distal to the fistula may help to re-establish adequate ventilation and prevent soiling of the tracheobronchial tree.[6] Feeding can be managed through gastrostomy or jejunostomy tube. Regular monitoring of tracheal tube cuff volume and pressure is important. It is advisable to maintain cuff pressures below 20 cm H2O[7] and avoid using more than 8 mL of air for cuff inflation.[8] Routine cuff deflation and re-inflation are no longer recommended.[7,9] Proper placement of the tracheostomy and tracheostomy tube, use of thin-walled cuffs to minimise movement of the tracheostomy tube relative to the trachea and initiation of weaning as early as possible may help in curtailing trauma to the trachea. Conscious and well-orientated tracheostomised patients should be educated and advised about avoiding excessive neck movements. Measures to minimise gastro-oesophageal reflux, such as head-end elevation to 30Â°, post-pyloric feeding, administration of enteral feeds as continuous infusion and use of prokinetics, should be implemented. NG tubes, if used, should be small and soft and removed as soon as they are no longer indicated. Predisposing factors such as hypotension, hypoxaemia, anaemia, infection, malnutrition and metabolic acidosis should be prevented and, if present, addressed early.

Conclusion

TOF is a rare but potentially fatal complication of tracheostomy. Rhythmic and rapid distension of the epigastrium, though unusual, is a dangerous manifestation of TOF. Regular monitoring of tracheal tube cuff pressures and cuff volumes is advisable for the prevention and early recognition of this adverse event. References 1. Delaney A, Bagshaw SM, Nalos M. Percutaneous dilatational tracheostomy versus surgical tracheostomy in critically ill patients: A systematic review and meta-analysis. Crit Care 2006;10(2):1-13. DOI:10.1186/cc4887 2. Epstein SK. Late complications of tracheostomy. Respir Care 2005;50(4):542-549. 3. Diddee R, Shaw IH. Acquired tracheo-oesophageal fistula in adults. Cont Educ Anaesth Crit Care Pain 2006;6(3):105-108. DOI:10.1093/bjaceaccp/mkl019 4. Sanwal MK, Ganjoo P, Tandon MS. Posttracheostomy tracheoesophageal fistula. J Anaesthesiol Clin Pharmacol 2012;28(1):140-141. DOI:10.4103/0970-9185.92478 5. Harley HR. Ulcerative tracheo-oesophageal fistula during treatment by tracheostomy and intermittent positive pressure ventilation. Thorax 1972;27(3):338-352. DOI:10.1136/thx.27.3.338 6. Hydri AS. A modified endotracheal tube serving as a long tracheostomy tube. Internet J Otorhinolaryngol 2006;6(1). 7. Hameed AA, Mohamed H, Al-Mansoori M. Acquired tracheoesophageal fistula due to high intracuff pressure. Ann Thorac Med 2008;3(1):23-25. DOI:10.4103/1817-1737.37950 8. Make BJ, Hill NS, Goldberg AI, et al. Mechanical ventilation beyond the intensive care unit: Report of a consensus conference of the American College of Chest Physicians. Chest 1998;113(5):289S-344S. DOI:10.1378/chest.113.5_supplement.289s 9. Powaser MM, Brown MC, Chezem J, Woodburne CR, Rogenes P, Hanson B. The effectiveness of hourly cuff deflation in minimizing tracheal damage. Heart Lung 1976;5(5):734-741.

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Marketing Code Authority Member

ABSTRACTS

Abstracts of scientific presentations at the 2016 Annual National Conference of the Critical Care Society of Southern Africa Does prone positioning recruit dorsal lung regions in children with acute respiratory distress syndrome (ARDS)? A Lupton-Smith,1* A Argent,1 P Rimensberger,2 B Morrow1 1 School of Child and Adolescent Health, Faculty of Health Sciences, University of Cape Town, South Africa 2 Paediatric and Neonatal Intensive Care Unit, University Hospital of Geneva, Switzerland *aluptonsmith@gmail.com Background. Prone positioning is commonly used in patients with acute lung injury (ALI)/ARDS to improve oxygenation. Improved oxygenation is thought to occur due to recruitment of collapsed dorsal lung regions and improved ventilation homogeneity. Objective. To determine the effects of prone turning on regional ventilation distribution and homogeneity in children with ALI/ARDS. Methods. Thoracic electrical impedance tomography (EIT) measurements were taken in the supine position (baseline) and 5, 20 and 60 minutes after being turned into the prone position. Arterial blood gas measurements were obtained at baseline and after 60 minutes of being in the prone position. Repeated measures analysis of variance (ANOVA) was used to determine the difference in mean relative impedance change and ventilation homogeneity between responders and non-responders. Results. Fourteen participants (n=9, 64% male) with a median (interquartile range) age of 20 (11.6 - 26.2) months were studied. Seven (50%) participants showed an improved PaO2 of 2.1 (1.5 - 3.3) kPa (‘positive responders’), while seven showed a reduction of 1.1 (0.5-1.8) kPa (‘negative responders’) after 60 minutes. Proportion of ventilation in the dorsal lung was no different between responders and non-responders (p=0.59). Responders showed significantly more variability in ventilation inhomogeneity at baseline compared with non-responders (p=0.005). After 60 minutes, ventilation inhomo geneity was significantly less variable in the responders (p=0.02). Conclusion. Prone positioning did not result in recruitment of the dorsal lung regions, but rather more homogenous ventilation. Children who responded to prone positioning had more variable ventilation inhomogeneity at baseline, compared with those who did not respond.

Background. Perioperative myocardial infarction (PMI) is the most common major cardiovascular complication in non-cardiac surgery, and increases perioperative mortality. Prognostically relevant myocardial injury following non-cardiac surgery (MINS) was shown to be an independent predictor of 30-day mortality. The VISION, POISE and MINS studies have highlighted the need for routine troponin surveillance in high-risk non-cardiac surgery. Studies in vascular patients show an increased incidence and mortality from perioperative myocardial infarction. Objectives. The primary objective was the incidence of PMI and MINS in patients admitted to intensive care following vascular surgery, and the in-hospital mortality in those who experienced a PMI or MINS. The secondary objective was to identify perioperative predictors of PMI or MINS. Methods. A retrospective review was conducted of all patients aged at least 45 years between 1 January 2011 and 31 December 2013 admitted to Inkosi Albert Luthuli Central Hospital intensive care unit 2B following vascular surgery. A total of 140 patients were included in the final analysis. Demographics, cardiovascular risk factors, troponin I levels for 3 days following surgery, perioperative brain natriuretic peptide (BNP), electrocardiogram and echocardiogram findings were extracted. The third universal definition was used for diagnosis of myocardial infarction. Patients who had a troponin level above normal but below the diagnostic threshold for a myocardial infarction were classified as MINS. Alternative or non-ischaemic causes of a troponin elevation below the myocardial infarction diagnostic threshold were not classified as MINS. Results. A total of 24.3% of the patients had a PMI and a further 25% had MINS. Compared with the in-hospital mortality of 18.3% in patients without troponin elevation, PMI was associated with significantly increased in-hospital mortality of 58.8% (p<0.01) while MINS was not (17.1%, p=1.00). Increasing age, the highest postoperative BNP and a blood transfusion within the first 3 days postoperatively were independent predictors of PMI. PMI and a history of congestive cardiac failure were independent predictors of in-hospital mortality. Conclusion. Perioperative myocardial infarction and MINS were present in nearly half the study population. A vascular surgical patient with a PMI, but not MINS, had significantly increased in-hospital mortality.

Prognosis of myocardial infarction and myocardial injury following vascular surgery

Postoperative outcome of intensive care unit (ICU) surgical patients at a Zimbabwean hospital

T Kisten,1* B M Biccard2 Discipline of Anaesthesia and Critical Care, School of Clinical Medicine, Nelson R Mandela Medical School, University of KwaZulu-Natal, Durban, South Africa 2 Department of Anaesthesia and Perioperative Medicine, Faculty of Health Sciences, University of Cape Town, South Africa

C Tadyanemhandu,1* D Shoko,1 C Nhunzvi,1 S Chengetanai,2 V Chikwasha1 1 Department of Rehabilitation, College of Health Sciences, University of Zimbabwe, Harare 2 Division of Basic Medical Sciences, Faculty of Medicine, National University of Science and Technology, Bulawayo, Zimbabwe

*toshiekis@gmail.com

*cathytadya@gmail.com

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Background. About 10 - 15% of hospital admissions in developing countries are due to diseases amenable to surgical treatment. It is estimated that surgical conditions account for 11% of the total global burden of disease and 25 million disability-adjusted life years (DALYs) in Africa, the region with the highest concentration of surgical DALYs (38/1 000 population). HIV infection has increased the burden of surgical practice by overloading the practice and increasing related surgical diseases, which have resulted in more challenges being faced in surgical interventions of HIV-infected patients and methods used to improve their outcomes. Objectives. To describe the demographic characteristics of postsurgical patients admitted to the ICU, the associated comorbidities in the patients and the outcomes. Methods. A retrospective review of records of patients who were admitted into Parirenyatwa ICU from the operating room between 1 January 2015 and 30 September 2015 was done. The following data were collected: demographic data, surgery history, comorbidities and complications that developed. Results. Out of the 119 patients’ records accessed, the majority (n=62, 52.1%) were males and the mean age of patients was 42.8 years (standard deviation (SD) 18.3). The reason for ICU admission was mainly for cardiopulmonary support using invasive and non-invasive ventilation (n=71, 59.7%). The majority of the patients were from general surgery (n=52, 43.7%), followed by neurosurgery patients (n=32, 26.9%). The most performed surgery was laparotomy, in 62 of the patients (52.1%), followed by craniotomy, in 29 of the patients (24.4%). The majority were elective surgeries (n=70, 58.8%), with the reasons for surgery tumours (n=49, 41.1%), infection (n=29, 24.4%) and trauma (n=19, 16.0%). Respiratory complications were noted in the majority of the patients (n=61, 51.3%) post surgery. Fourteen (11.8%) of the patients were HIV-positive. The other common comorbidities were hypertension and diabetes. The mean (SD) length of stay in ICU was 3.8 (3.8) days. The mortality rate was 21.8%. Mortality was associated with HIV-positive status (p=0.001), emergency surgery (p=0.001), respiratory complications (p<0.001) and ICU admission for cardiopulmonary support (p<0.001). Conclusion. The postoperative management of surgical patients is further challenged by comorbidities such as hypertension, diabetes and HIV. Strategies to reduce surgical morbidity and mortality have to be formulated to improve outcome of patients.

Yellow fever outbreak: Experience in an Angolan intensive care unit (ICU) N Velez,* F Rodriguez, R Alfredo, D Gaspar, E Viegas, E Filipe, E Tomás Clínica Sagrada Esperança – Ilha do Cabo, Luanda, Angola *velez.nadia@gmail.com Background. On 21 January 2016, Angola notified the World Health Organization of a yellow fever outbreak. The first case, with onset date 5 December 2015, was identified in Viana municipality. By 17 April 2016, 1 708 suspected cases, including 238 deaths (case fatality rate 13.9%), had been reported from 16 provinces. Objectives. To determine clinical characteristics and outcomes of yellow fever among critically ill patients admitted to Clínica Sagrada Esperança’s intensive care unit. Methods. A retrospective review of patient records was conducted. Patients admitted with laboratory confirmation of yellow fever were included in the study. The diagnostic tests performed were

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IgM antibody capture enzyme-linked immunosorbent assay (MACELISA) and polymerase chain reaction (PCR). The demographic and clinical characteristics, laboratory parameters and survival were analysed. Results. From the 39 suspected cases admitted, 16 had laboratory confirmation of yellow fever. Eleven were adults and five were infants, mainly males (68%). On admission, mean (standard deviation) sequential organ failure assessment (SOFA) was 9.56 (2.70), and simplified acute physiology score (SAPS) 3 was 63.87 (7.17), with a mean predictive death rate of 44%. On examination, all the patients presented with fever, shivers, headaches, weakness, nausea, vomiting, jaundice and consciousness disorders. Eight (56.2%) had haemorrhagic manifestations. Half of them were coinfected with Plasmodium falciparum malaria, 4 (25%) with dengue fever, 1 with leptospirosis and 1 with hepatitis B virus. Mean length of stay was 6 (5.9) (range 1 - 20) days. On the first day, 87.5% presented with bilirubin above 6 mg/dL and creatinine above 4 mg/dL. During their stay, 93.75% (n=15) required ventilatory and vasopressor support, and 53.75% (n=9) required renal support. From the 12 (75%) who died, six deaths occurred in the first 48 hours. Conclusion. Yellow fever is a hyperacute disease with a very high mortality, even with advanced life support. Therefore, the only way to avoid this fatal outcome is prevention.

Paediatric cardiac critical care admissions to a tertiary paediatric intensive care unit (PICU) B Rossouw,* M Wege, A C Argent, B Morrow Division of Critical Care and Children’s Heart Diseases, Red Cross War Memorial Children’s Hospital, University of Cape Town, South Africa *beyra.rossouw@uct.ac.za Background. Paediatric cardiac critical care (PCCC) in South Africa is not well described. Objectives. This is the first study describing the patient profiles and treatment of PCCC admissions to a South African tertiary mixed medical and surgical PICU. Methods. A prospective review was conducted of consecutive patients admitted to the Red Cross War Memorial Children’s Hospital PICU with a cardiac discharge diagnosis from January 2015 to December 2015. Results. A total of 472 PCCC PICU admissions of 409 patients were included. Of these, 274 admissions followed elective cardiac surgery, 37 were post elective general surgery and 161 admissions were unplanned emergency admissions. Indications for emergency admission included: shock (28%), respiratory support required (22%), cyanosis (18%), decompensated cardiac failure (18%), post cardiac arrest (8%) and life-threatening arrhythmias (3%). Comparing elective admissions with emergency admissions: the median age of admission was 24 v. 5 months (p<0.0001); length of PICU stay 3 v. 6 days (p<0.0001); length of ventilation 1 v. 2 days (p=0.13), length of inotrope use 1 v. 2 days (p=0.08); and median maximum inotrope score 1 v. 9 (p=0.46). A cardiac diagnosis was made for the first time in the PICU in 57 patients. A total of 85 emergency theatre procedures (32 cardiac surgical) were undertaken from the PICU. Eighty-one patients needed PICU readmissions and 19 needed redo cardiac surgery during this study period. PICU complications in the elective admission group v. the emergency admission group included failed extubation in 5.7% v. 13% (p=0.006), chest infection on admission in 20.6% v. 45.0%

(p<0.0001), bloodstream infection in 3.8% v. 17.4% (p<0.0001), acute kidney injury in 17.4% v. 32.9% (p=0.001), liver impairment in 3.5% v. 19.3% (p<0.0001), neurological sequelae in 1.9% v. 14.9% (p<0.0001) and PICU readmission in 10.3% v. 30.4% (p<0.0001). In both the elective and emergency admission groups 4.1% of suffered a cardiac arrest during PICU stay (p<0.0001). PICU mortality for the elective v. emergency admission group was 1.6% v. 12.4% (p<0.0001) and standardised mortality 0.25 v. 0.80. Conclusions. Overall, 34.9% of all PICU admissions during 2015 were PCCC admissions. Emergency PCCC admissions have a higher morbidity and mortality in our setting.

ALCAPA in children: Single-centre perioperative outcome B Rossouw,* M Wege, A C Argent, B Morrow, J Lawrenson Division of Critical Care and Children’s Heart Diseases, Red Cross War Memorial Children’s Hospital, University of Cape Town, South Africa *beyra.rossouw@uct.ac.za Background. A 1970s report on anomalous left coronary artery to pulmonary artery (ALCAPA) patients from our institution documented 50% hospital mortality. Current outcomes are not clear. Objectives. To document perioperative management and outcome of children with ALCAPA, admitted to Red Cross War Memorial Children’s Hospital PICU. No mechanical cardiac support was available. Methods. A retrospective 10-year longitudinal study between July 2004 and August 2015 was conducted. Results. A total of 46 patients were included, of which 45% presented in cardiogenic shock requiring immediate PICU admission. Forty-three underwent coronary artery reimplantation surgery. Median length of PICU stay, postoperative inotropic support and ventilation were 9.9, 8.3, and 7 days, respectively. Perioperative morbidity included community-acquired infection (27%), nosocomial infection (40%), arrhythmias (24%), cardiac arrest (13%) and acute kidney injury needing dialysis (6%). PICU mortality was 24% (n=7). A total of 39 (85%) patients survived to hospital discharge, with 5 deaths after discharge. No independent predictors of mortality could be identified on multivariate analysis. Fourteen (30%) patients needed PICU readmission/s and six (13%) required cardiac reintervention surgery. For survivors, the median time to ejection fraction recovery was 15.5 months. Conclusions. Coronary reimplantation is a successful procedure in our institution. Perioperative infection remains a major morbidity. Mechanical cardiac support could alter these findings.

The impact of echocardiography in a paediatric intensive care unit (PICU) B Rossouw,* M Wege, A C Argent, B Morrow, J Lawrenson Division of Critical Care and Children’s Heart Diseases, Red Cross War Memorial Children’s Hospital, University of Cape Town, South Africa *beyra.rossouw@uct.ac.za Background. Echocardiography has become an important tool to assess critical ill adults. The influence of echocardiography on the management of critical ill children is not well described. Objectives. To review the impact of echocardiography in a singlecentre tertiary PICU.

Methods. A prospective review of all echocardiographic studies was done in a combined 22-bed medical and surgical tertiary PICU between February 2015 and January 2016. Results. During this 1-year study period 15% of the total PICU population received an echocardiographic assessment during PICU stay. A total of 379 echocardiograms (ECGs) were done on 211 PICU patients, of whom 88 were known to have a cardiac condition prior to PICU admission. Sixty-three per cent (n=238) of the ECGs were done by the cardiology department and 37% (n=141) by ICU staff formally trained in echocardiography. Indications for ECGs were: assessment of cardiac function, anatomical anomalies, pulmonary pressure, infective endocarditis and pericardial effusion in 146, 101, 54, 19 and 5 studies, respectively. Postcardiac surgery ECGs were performed to assess cardiac function, residual lesions and pulmonary pressure in 118, 137 and 21 studies, respectively. New congenital heart lesions were diagnosed in 47 PICU patients for the first time in PICU. The newly diagnosed congenital heart lesions included right ventricular outflow tract obstructions in 12 patients, 6 left ventricular outflow tract obstructions and shunt lesions in 27 patients. Newly acquired heart lesions were diagnosed in 10 patients, in whom 5 were dilated cardiomyopathy and 5 infective endocarditis. Normal hearts were confirmed in 14%, and 26% of the ECGs confirmed new pathology that did not require PICU treatment change. Overall, 39% of the ECGs identified new anatomical or functional pathology that subsequently altered PICU management. Treatment modification included surgical intervention (n=41), change in inotropes (n=47), pulmonary hypertension treatment (n=21), anti-failure treatment (n=22), fluid management (n=13), prostaglandin (n=6) and infective endocarditis treatment change (n=5). Four patients were found to have inoperable cardiac lesions and were palliated. Conclusions. Echocardiography is a valuable diagnostic tool in PICU and often contributes to treatment modification.

Children with fulminant dilated cardiomyopathy or myocarditis B Rossouw,* A C Argent, B Morrow, J Lawrenson Division of Critical Care and Children’s Heart Diseases, Red Cross War Memorial Children’s Hospital, University of Cape Town, South Africa *beyra.rossouw@uct.ac.za Background. Mechanical cardiac support and transplantation have improved long-term outcome of cardiomyopathy and myocarditis in children internationally. Objectives. To review the outcome of children with fulminant dilated cardiomyopathy (DCMO) or myocarditis in a setting without readily available mechanical cardiac support and transplantation. Methods. A retrospective 5-year review of consecutive PICU admissions of children with fulminant DCMO and myocarditis to Red Cross War Memorial Children’s Hospital PICU between January 2010 and July 2015 was conducted. Results. A total of 95 children with a median age of 27.8 months were included. All presented in Ross stage 4 cardiac failure (77% in cardiogenic shock). Admission median lactate was 6.5 mmol/L. Admission left ventricular ejection fraction was <30% in 79% of patients, and 9 developed intracardiac clots. Aetiology was presumed viral myocarditis in 87% and idiopathic DCMO in 13%. Adenovirus polymerase chain reaction (PCR) was positive in 28, parvovirus in 19 and multiple positive viral studies in 32. The median number of ICU

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admissions per patient was 1.5 (range 1 - 5) and length of ICU stay was 14.9 days (1 - 69). Overall, 55% required ventilation for a median of 8.1Â days; 100% required inotropic support for a median of 8.2 days; 82% received milrinone, 78% dobutamine and 33% adrenaline infusions. The median maximum inotrope score was 21.9. Complications during ICU stay included acute kidney injury in 68%, of which two patients needed dialysis, liver derangement in 43%, neurological events in 25% and 34% suffered a cardiac arrest episode. Thirty-three per cent had arrhythmias, of which 27% needed electrical cardioversion and 57% needed drug treatment. A total of 63 (66%) children survived to ICU discharge. The overall hospital survival was 47%. Of the ICU survivors, the median number of ward readmissions was 3.7 (range 1 - 19). Total median length of ward stay was 23.2 days (1 - 138). Conclusions. In our setting without transplantation availability, DCMO and myocarditis are associated with significant duration of hospital stay, morbidity and mortality.

Factors associated with survival to discharge of newborns in a tertiary hospital D E Ballot,* T Chirwa University of the Witwatersrand, Johannesburg, South Africa *daynia.ballot@wits.ac.za Background. Neonatal deaths contribute significantly to mortality in children under 5 years of age. Measures to reduce neonatal mortality have become a health priority in South Africa. Information obtained through clinical and mortality audit is an essential part of quality improvement in healthcare, in order to develop targeted interventions to improve outcome. Objective. To determine predictors of short-term survival in neonates. Methods. This was a retrospective review of an existing database. Binary logistic regression considering the outcome survived/died was done to determine predictors of survival. Results. A total 5 018 neonates >400 g admitted to a tertiary hospital (Johannesburg, South Africa) between 1 January 2013 and 31 December 2015 were analysed. Mean birth weight was 2 148 g (standard deviation (SD) 972) and mean gestational age was 34.2 (4.8) weeks. Overall survival was 85.6% (4 294/5 018). The most common causes of death were prematurity (46.2%), hypoxia (19.5%) and infection (17.2%). The strongest predictors of outcome were birth weight (odds ration (OR) 1.0, 95% confidence interval (CI) 1.0 - 1.01) and gestational age (OR 1.1, 95% CI 1.05 - 1.17). Other predictors of survival included metabolic acidosis (OR 0.14, 95% CI 0.09 - 0.20), hyperglycaemia (OR 0.31, 95% CI 0.23 0.41), mechanical ventilation (OR 0.35, 95% CI 0.28 - 0.46), major birth defect (OR 0.12, 95% CI 0.08 - 0.18), resuscitation at birth (OR 0.39, 95% CI 0.31 - 0.49) and caesarean section (OR 1.8, 95% CI 1.44 - 2.25). Conclusion. Measures to improve neonatal outcome should focus on delivery room management of neonates, care of preterm neonates and infection control.

The role of the intensive care unit (ICU) nurse in antimicrobial stewardship in a private hospital J Rout,* P Brysiewicz School of Nursing and Public Health, College of Health Sciences, University of KwaZulu-Natal, Durban, South Africa *joanrout@worldonline.co.za

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Background. The care of the critically ill patient has become progressively challenging across the world, with increasingly resistant pathogens resulting in difficult-to-treat infections. This is compounded by the decreasing effectiveness of many antibiotics. Severe infection increases the length of time spent in an ICU, increases morbidity and mortality and increases healthcare costs. Antimicrobial stewardship has the aims of slowing resistance and protecting patients and the wider community through the promotion of correct antimicrobial use by education and guidelines. Infection control measures are an essential part of antimicrobial stewardship in preventing emergent resistant pathogens and hospital-acquired infections. This has become a large part of nursing responsibilities in the ICU but the nurse does not yet have clear responsibilities with regards to antimicrobial therapy and the role that the nurse should play in antimicrobial stewardship. Objectives. To identify of the role of the ICU nurse in an antimicrobial stewardship team. Methods. A qualitative approach was used to obtain meaningful contributions that a questionnaire may not have been able to provide. Purposeful sampling was used to identify participants in a general ICU in the private healthcare sector. Semistructured interviews were conducted with 15 participants, namely ICU nurses, nursing management, surgeons, anaesthetists, physicians, microbiologists and pharmacists. Data were analysed and categorised using content analysis. Trustworthiness was demonstrated by meeting the required qualitative criteria of credibility, transferability, dependability and confirmability. Results. Perspectives of the members of the multidisciplinary antimicrobial stewardship team identified the role of the ICU nurse in an antimicrobial stewardship team as being organisational, advocatory, clinical and collaborative. Suggestions were made to further develop this nursing role by supporting proactive behaviour, teaching and learning, and teamwork. Concerns were raised about this role relating to resource barriers, knowledge deficit, poor attitude towards work, ineffective teamwork, working in isolation and economic pressures. Conclusion. The ICU nursesâ&#x20AC;&#x2122; role in antimicrobial stewardship should be recognised, developed and supported by all healthcare stakeholders as it is essential for the successful implementation of an antimicrobial stewardship programme within this acute healthcare setting. The factors affecting the development of this role need to be further explored.

Elevated lactate from three different mechanisms â&#x20AC;&#x201C; a case series S Omar,* K Naidoo, R Gheevarghese Intensive Care Unit, Baragwanath Academic Hospital and University of the Witwatersrand, South Africa *shahedicu@gmail.com Background. Traditionally considered due to tissue hypoxia, lactate is an important marker for shock and poor prognosis in critically ill patients. Biochemically, lactate production is associated with proton generation. Using a quantitative physicochemical approach, others have argued that unmeasured anions rather than lactate account for the majority of the metabolic acidosis in patients with elevated lactate. Objective. To characterise the different components of the metabolic acidosis as lactate increases and/ or decreases from three different causes of elevated lactate-associated metabolic acidosis. Methods. A case series with three patients found to have metabolic acidosis and increased blood lactate concentration was studied. The first case was from cardiogenic shock, the second from metformin

toxicity and the third from septic shock. We evaluated simultaneous blood gas, electrolytes, calcium, magnesium, phosphate, creatinine and lactate concentrations over the 24-hour period from onset to resolution of the problem. Using a quantitative physicochemical approach described previously, we calculated apparent strong ion difference (SIDa), effective strong ion difference (SIDe) and the strong ion gap (SIG). Next we calculated the total standard base deficit (SBD) acid and its individual components, namely SBD chloride, SBD H2O, SBD lactate and SBD SIG. Results. The three patients all developed significant metabolic acidosis with a median pH of 7.17 and SBD of 20.1 meq/L. At a pH below 7.25 there was a significant increase in the total SBD acid (p=0.000). SBD chloride and SBD lactate increased significantly (p<0.05). There was a nonsignificant decrease in SBD SIG and SBD H2O. Unmeasured anions, estimated by SBD SIG, contributed a maximum of 9.75% to the total SBD acid and were reduced to zero at the peak lactate concentration, which coincided with minimum pH and maximum SBD in all three cases. Although the absolute SBD chloride concentration increased as the acidosis worsened, the proportion/% of SBD chloride was inversely related to the proportion/% of SBD lactate (Spearman’s rho=0.92, p<0.05). Conclusion. Lactate, not unmeasured anions, was the major contributor to the metabolic acidosis, irrespective of the mechanism of elevation. Chloride’s contribution to the acidosis also increased, except for the patient undergoing renal replacement therapy.

Development of a paediatric simulation programme R Gillespie, A C Argent, M du Plessis, A Tshibanda, C Nelson, M McCulloch* Red Cross War Memorial Children’s Hospital, University of Cape Town, South Africa *mignon.mcculloch@uct.ac.za Background. Simulation (Sim) is a form of interactive training which can be used for technical skills teaching, human factors interaction, and improving clinical governance and patient safety.

Objective. To describe a new paediatric Sim programme, which commenced in February 2014 and is now a regular event in our hospital training programme. Methods. Initial training of instructors was done by an international team during a 1-week interactive session in February 2014 (supported by funding from the Critical Care Society of Southern Africa). Local faculty (including doctors, nurses and clinical technologists) was developed with no additional resources. Intermediate fidelity equipment was available initially, while high-fidelity equipment was donated. The concept was presented at a ‘grand rounds’ to get ‘buy-in’ from hospital and administrators before introducing simulations into the hospital environment. Results. Over 2 years, simulation provided training in three areas: (i) technical skills and human factors in the paediatric intensive care unit (including nitric oxide use, ventilation and continuous veno-venous haemodialysis); (ii) ‘Sim on request’ from the rest of the hospital including resuscitation training, emergency case management in emergency departments and ‘how to manage angry parents’; and (iii) anaesthetist-run Sims in theatre performing specific orchestrated case scenarios on a regular basis. Simulation was used to develop plans and prepare an oncology ward for the introduction of desensitisation therapy for asparaginase allergy. It was used by a nurse-led team to develop processes for ‘turning the complex patient while connected to monitors’. There has been an increased demand for simulation as a development and training tool. Our experience suggests that this is a powerful tool to develop appropriate processes at clinical level, to train new personnel, and to help personnel (and managers) understand the dynamics of clinical care. Conclusion. After initial investment in staff training and equipment, it has been possible to establish a paediatric Sim programme that appears to be an effective tool for addressing a range of issues in clinical practice, including: protocol development, staff training (in both technical and non-technical skills) and staff debriefing. Further analysis is needed to assess sustainability of this programme and the results thereof.

SAJCC July 2016, Vol. 32, No. 1

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