Pulmonary pulmonary rehabilitation guidelines : Dr. Deepak Talwar lung cancer specialist

Volume 1.2

DECEMBER 2016 - FEBRUARY 2017

Editorial by Dr. Rajesh Chawla

I

t gives me great pleasure to present to you the second issue of Pulmonary Communications.

I have received overwhelming response appreciating this initiative of National College of Chest Physicians (NCCP). I am grateful to you for your support and encouragement.

In this issue Dr. Rohit Sarin, Director, National Institute of TB and Respiratory Diseases,

Delhi has clarified standards of TB care in India based on the revised strategies of WHO and RNTCP.  Read full editorial on page 2

Contents 1.

NCCP News Headlines

2. Editorial 3.

Secretary's Message

4.

Standards for TB Care in India

7.

Current Status of Non-Invasive Ventilation in Clinical Practice

9.

 NCCP News Headlines  Comprehensive Pulmonary Medicine eCourse being launched by National College of Chest Physicians (NCCP) in February – 2017.

Pulmonary Rehabilitation

12. NAPCON 2016

Editorial Office

12. Criticare 2017

Dr. Rajesh Chawla

13. Journal Scan

Institute of Respiratory Medicine, Critical Care and Sleep Medicine, Indraprastha Apollo Hospitals, Gate No.-2, 2nd Floor, Room No. 1223, Sarita Vihar, Delhi-Mathura Road, New Delhi - 110076

16. Advertisement

Mobile : +91 9810033395 • drchawla@hotmail.com

We request our esteemed readers to send their valued feedback, suggestions & views at drchawla@hotmail.com

Editorial

MDR TB. Cartridge-based Nucleic

want to stress here that Pulmonary

Acid Amplification Test (CB-NAAT)

rehabilitation is not limited to

is the preferred first diagnostic test

exercise training but is a combination

for Pulmonary TB in children and

of education, behavioral change

patients living with HIV (PLHIV).

designed to improve physical and

He also clarified that Probable TB

emotional condition of the patient

is the terminology now used for

with chronic respiratory disease and

patients with symptoms suggestive

to promote long term adherence

of

to health enhancing program. The

TB

without

confirmation

Dr. Rajesh Chawla Editor in Chief, Pulmonary Communications President, National College of Chest Physicians (India) drchawla@hotmail.com

www.nccpindia.com

I

t gives me great pleasure to

present

to

you

the

second issue of Pulmonary Communications.

I

have

received overwhelming response appreciating

this

initiative

of

National College of Chest Physicians (NCCP). I am grateful to you for your support and encouragement.

In this issue Dr. Rohit Sarin, Director, National Institute of TB and Respiratory Diseases, Delhi has clarified standards of TB care in India based on the revised strategies of WHO and RNTCP. In this he has clearly mentioned the importance of rapid molecular tests which are emerging as the first test of choice for

2

microbiological

(sputum

smear

goals of pulmonary rehabilitation

microscopy, culture and molecular

include

diagnosis), but with strong clinical

burden

and other evidence (e.g. X-ray, Fine

performance

Needle Aspiration Cytology (FNAC),

increased

histopathology) may be diagnosed

activities. The other goals are to

as “Probable TB”. One of the major

decrease psychological symptoms

change now recommended is the

& improve health related quality of

change in treatment strategy. Initial

life. That is why one requires the help

treatment in Intensive phase for two

of respiratory physicians, exercise

months of Rifampicin Isoniazid,

physiologists respiratory therapists,

Combutol & Pyrazinamide remains

physiotherapists,

the same but Continuation phase

nutritionist, social workers, patient

includes Rifampicin, Isoniazid and

educators & occupational therapists.

Ethambutol for four months.

Resources & lack of availability of

Once again we all need to remember

heath care professionals limits most

that TB is now a notifiable disease

of the pulmonary rehabilitation

since 7th May 2012, We should

program. But in India teammates

ensure that we notify all patients to

can take up the duel responsibility or

the District Nodal Officer & make

more roles to fill the non-availability

full use of the electronic notification

of staff members.

system called NIKSHAY. So in

We will have to escalate this initiative

this article Dr. Sarin has very

as it is very much promotable,

clearly answered everything about

provided we feel very strongly for it.

standards of TB care in India.

Non-invasive Ventilation has now

Pulmonary rehabilitation is never

acquired a definite role in the

considered important to be a part

management of patients with acute

of the treatment for most of the

and

pulmonologists. Majority of the

This is predominantly being used

stress is given to pharmacotherapy.

for acute respiratory failure. There

Dr. Deepak Talwar in his article on

is now great evidence for its use in

this subject has described in detail

acute exacerbation of COPD where

the

pulmonary

this is the standard of care unless

rehabilitation. Most of the physicians

there are contraindications. The

perceive this as exercise training, I

other conditions where its role has

components

of

minimizing &

symptom

maximizing with

autonomy

participation

chronic

exercise in

&

daily

psychologist,

respiratory

failure.

Pulmonary Communications  A quarterly Newsletter of National College of Chest Physicians

Message

D

ear Colleagues, It gives me great pleasure that the II issue of the News Letter of NCCP(I) -- Pulmonary Communications, has been published.

The First issue, which was released in the Joint meeting of NCCP(I) and ICS on 25-9-2016 was greatly appreciated. Dr. Rajesh Chawla deserve the credit for taking this initiative.

The National College of Chest Physicians (India) is having joint conference with Indian Chest Society for last 17 years - named NAPCON and this year the venue is Hotel Hyatt, Mumbai from Nov., 24-27, 2016.

The Conference will have distinguished faculty from India and Abroad.

The scientific programme has been made meticulously and covers all the aspects of Pulmonary Medicine with seperate sessions on Thoracic Surgery, Imaging, Environmental diseases, Smoking, Recent advances etc.

There are 14 workshops on the first day and I am glad to inform you that all are almost full.

This year one session on "Veterans Speak" has been added, where Veterans in the field will be giving their experience through lecture.

Prof. S. N. Gaur

I am sure that the NAPCON_2016 will be the best opportunity to interact

Secretary,

with reputed faculty and to update your knowledge on the subject.

National College of Chest Physicians (India) & Director (Acting)

I welcome you all. The website of NAPCON-2016 is http://www. napcon2016.org./

V.P. Chest Institute, University of Delhi,

I also wish you all happy reading of the news letter of NCCP(I).

Delhi-110007.

Editorial Continuous .....

been proven are acute cardiogenic

found to be associated with poor

conducted by expert faculty at

pulmonary oedema, weaning in

outcome if you delay intubation.

various medical colleges to select

COPD, acute respiratory failure

Friends, once again I request you

PG students on merit basis and

in

host.

to send in articles, case discussions

the winners have been given

Although the evidence is not very

and information about upcoming

complementary registration and

robust, but it can still be used in

conferences. We shall be happy to

travel allowance. In addition for the

some other conditions like trauma

publish it.

first time there are 15 training cum

immunocompromised

patents, mild ARDS, community acquired Pneumonia in COPD and acute respiratory failure in OSA so as to prevent endotrachial intubation in these patients. We are well aware that this modality is very useful in avoiding intubation in many patients but a word of caution that we must know when to stop NIV and when to intubate. If you delay intubation, it increases mortality. NIV should not be used in ARDS Hpatient where P/F ratio is below 150 as it has been

I take this opportunity to welcome everyone on behalf of National College of Chest Physicians (NCCP) & Indian Chest Society (ICS) to

hands on experience workshops on 24th November which have been organized at various tertiary care hospitals across Mumbai.

the NAPCON 2016. This annual

The

conference

has

excellent

conference has very unique features.

scientific program spread over 3

First time 250 Post graduate students

days. And it has been accredited

of Pulmonary Medicine, Internal

5 credit hours by Maharashtra

Medicine and allied specialties have

Medical Council.

been awarded NAPCON-2016 PG

Looking forward to welcoming

scholarship through preconference

you all!

PG QUIZ. The PG Quiz was

Pulmonary Communications  A quarterly Newsletter of National College of Chest Physicians

3

Standards for TB Care in India Tuberculosis is a very common disease in India. It is important to diagnose and treat according to the recommended standard of care to achieve the best results Standard 1: Testing and screening for TB 1.

Who should be Tested for TB ?

people with cough >2 weeks, fever >2 weeks, significant weight loss, hemoptysis etc. and any abnormality in chest radiograph must be evaluated for TB. Children with persistent fever and/or cough >2 weeks, loss of weight / no weight gain, and/ or h/o contact with pulmonary TB should be evaluated for TB

2.

Which is most common symptom of TB?

The most common symptom of pulmonary TB is prolonged cough that lasts longer than the cough with most other acute lung infections. The evidence from India suggests that cough lasting > 2 weeks is a more sensitive indicator for TB

3.

Who should be regularly screened for TB?

People living with HIV (PLHIV), malnourished, diabetics, cancer patients, patients on immunosuppressant or maintenance steroid therapy, should be regularly screened for signs and symptoms suggestive of TB.

4.

What Is enhanced case finding?

Enhanced case finding means maintaining a high index of suspicion for TB in all encounters with health provider, with proactive exclusion of TB using the appropriate combination of clinical queries, radiographic or microbiologic testing.

It should be done in People living with HIV (PLHIV), malnourished, diabetics, cancer patients, patients on immunosuppressants, health care workers, slum dwellers, Prisoners etc.

Standard 2: Diagnostic Technology 5. Which are the diagnostic technologies available for diagnosis of TB?

diagnosis of active tuberculosis.

Standardized TST may be used as a complimentary test in children.

7.

How many samples should be tested for diagnosis of pulmonary TB?

Two samples (a morning sample is better than a spot sample for detection of mycobacteria)

Standard 3: Testing for extra-pulmonary TB 8.

What should be kept in mind when Extra pulmonary TB is suspected.

Appropriate specimens from the presumed sites of involvement must be obtained for microscopy/ culture/ CBNAAT/molecular test/ histopathology examination and drug sensitivity testing (DST)

Which patients should be screened as presumptive MDR

15. What is probable TB?

Patients who have failed treatment with first line drugs, paediatric nonresponders, TB patients who are contacts of MDR-TB (or R resistance), TB patients who are found positive on any follow-up sputum smear examination during treatment with first line drugs, diagnosed TB patients with prior history of antiTB treatment, TB patients with HIV co-infection and all presumptive TB cases among PLHIV.

10. What are the available tests for diagnosis of MDR-TB?

a. Rapid molecular DST (as the first choice)-LPA or CBNAAT

b. Liquid / solid culture-DST (at least for R and H; and at least for Ofloxacin (O) and Kanamycin (K), if MDR). Liquid is preferred to solid culture.

On detection of Rifampicin and isoniazid resistance, patient must be offered sputum test for second line DST using quality assured phenotypic(Liquid or solid culture) or genotypic (CBNAAT or LPA) methods, wherever available

c. CBNAAT: preferred first diagnostic test in children & PLHIV

12. What is the prevalence of HIV in TB patients in India?

What is the status of serological tests like Tuberculin Skin Test (TST) & Interferon Gamma Release Assay (IGRA) in diagnosis of TB?

13. Which TB patients should be offered counseling for HIV testing

around 5%

All TB patients with active TB should be offered HIV counselling and testing.

Patients with symptoms suggestive of TB without microbiological confirmation (sputum smear microscopy, culture and molecular diagnosis), but with strong clinical and other evidence (e.g. X-ray, Fine Needle Aspiration Cytology (FNAC), histopathology) may be diagnosed as “Probable TB”.

16. Which patients are likely to be treated for “Probable TB”?

The probable TB may be higher in Children, Patients with extra pulmonary TB or PLHIV.

Standard 6: Pediatric TB 17. What are the diagnostic tools in children who are not able to produce sputum?

11. Which patients should undergo diagnosis of Extensively Drug Resistant (XDR-TB)?

4

Prevalence of MDR-TB of 2-3% in new, untreated TB patients and around 15% in previously treated TB cases

9.

a. Microbiological confirmation on sputum

These are not recommended for the

Standard 5: Probable TB

b. Chest Xray as screening tool

14. What is the prevalence of MDR TB among New & Retreatment patients?

Standard 4: Diagnosis of HIV co-infection in TB and Diagnosis of DRTB

6.

Dr. Rohit Sarin

Director, National Institute of TB & Respiratory Diseases, Sri Arbindo Marg, Delhi

In all children with presumptive intra-thoracic TB, microbiological confirmation should be sought through examination of respiratory specimens (e.g. sputum by expectoration, gastric aspirate, gastric lavage, induced sputum, bronchoalveolar lavage or other appropriate specimens) with a quality assured diagnostic test, preferably CB-NAAT, smear microscopy or culture.

18. Can children be treated for probable TB?

YES, the diagnosis of probable TB in children should be based on the presence of abnormalities consistent with TB on radiography, a history of exposure to pulmonary TB case, evidence of TB infection (positive TST) and clinical findings suggestive of TB

19. Can TST ( Tuberculin Skin Testing) alone be used as diagnostic tool in TB?

Pulmonary Communications  A quarterly Newsletter of National College of Chest Physicians

20. What is the standard cutoff for TST in India?

IAP and RNTCP recommend 10mm as cut off

27. What are recommended weight bands for dosing of TB treatment?

The RNTCP guidelines outline dosing based on weight bands.

Suggested weight bands for adults are: 30-39kg, 40-54kg, 55-70kg and >70kg. Recommended weight bands for paediatric patients are: 6-8kg, 9-12kg, 13-16kg, 17-20Kg, 21-24kg and 25-30kg. Drug formulations are available for matching these weight bands.

34. Which patients should be screened for Surgery in M/XDR-TB patients:

Standard 8: Monitoring the treatment Response

35. What is the Treatment duration in MDR-TB patients ?

28. Should the Intensive phase of treatment be extended during the treatment?

21. Do Serodiagnostic tests or IGRA have a role in diagnosis of TB in pediatric population?

Their role is same as in TST mentioned.

Standard 7: Treatment with first line regimen 22. What is the recommended regimen for New TB Patients

The initial phase should consist of two months of Isoniazid (H), Rifampicin (R), Pyrazinamide (Z), and Ethambutol (E). The continuation phase should consist of three drugs (Isoniazid, Rifampicin and Ethambutol) given for at least four months

23. Under what conditions can the continuation phase be extended?

The duration of continuation phase may be extended by three to six months in special situations like Bone & Joint TB, Spinal TB with neurological involvement and neurotuberculosis. This can be done in consultation with the concerned specialist , relating to organ involved.

24. What is dosage frequency? Daily or Intermittent?

All patients should be given daily regimen under direct observation.

However, the country programme may consider daily or intermittent regimen for treatment of TB depending on the available resources and operational considerations as both are effective provided all doses are directly observed. All paediatric TB patients and HIV associated TB patients should be given daily regimen under direct observation.

25. What are the recommended drug formulations?

Fixed dose combinations (FDCs) of four drugs (Isoniazid, Rifampicin, Pyrazinamide, and Ethambutol), three drugs (Isoniazid, Rifampicin and Ethambutol) and two drugs (Isoniazid and Rifampicin) are recommended.

The extension of the intensive phase is not recommended

29. How to assess response to treatment in Extra Pulmonary TB?

In patients with extra-pulmonary tuberculosis, the treatment response is best assessed clinically. The help of radiological and other relevant investigations may also be taken. The specialist in the concerned system should also be consulted wherever possible.

In children, who are unable to produce sputum, the response to treatment may be assessed clinically.

The help of radiological and other relevant investigations may also be taken. If required , a pediatrician may be consulted.

31. What Is the recommendation for monitoring during treatment?

International standards recommend that a sputum sample should be collected at the end of the intensive phase (two months) and at the end of treatment (six months) to monitor the success of therapy

32. What Is the recommendation for long term follow-up after treatment is completed?

After completion of treatment the patients should be followed up with clinical and/or sputum examination at the end of six and 12 months

Standard 9: Management

33. What is the recommended treatment regimen for MDR-TB (R resistant) ?

Drug

Resistant

TB

The regimen chosen for MDR-TB may be standardized and/or based on microbiologically confirmed drug

All patients of M/XDR-TB should be evaluated for surgery at the initiation of treatment and/or during follow up.

Total treatment should be given for at least 24 months in patients newly diagnosed with MDRTB (i.e. not previously treated for MDR-TB) with recommended intensive phase of treatment being six to nine months and continuation phase of atleast 18 months after culture conversion.

The total duration may be modified according to the patient’s response to therapy.

36. When should the Second line DST be done during the treatment of MDR-TB ?

30. How to assess response to treatment in Children?

26. What is the regimen recommended for previously treated patients?

After MDR-TB (or R resistance) is ruled out by a Quality Assured test, TB patients returning after lost to follow up, relapsing from their first treatment course or new TB patients

susceptibility patterns. At least four drugs (second line) to which the organisms are known or presumed to be susceptible, should be used. Most importantly the regimen should include at least Pyrazinamide, Ethambutol, a later generation Fluoroquinolone (such as high dose Levofloxacin) and a parenteral agent (such as Kanamycin or Amikacin), Ethionamide (or Prothionamide), and Cycloserine.

failing with first treatment course may receive the retreatment regimen containing first-line drugswith an Intensive phase of three months and a continuation phase of five months: 2HREZS/1HREZ/5HRE

NO, it may be used as a complimentary test in children, in combination with microbiological investigations, history of contact, radiology, and symptoms

During the course of MDR-TB treatment, if the sputum culture is found to be positive at 6 months or later, the most recent culture isolate should be subjected to DST with second-line drugs (at least Ofloxacin and Kanamycin) to decide on further course of action.

37. What are the new drugs under consideration?

The new drugs e.g. Bedaquiline, Delaminid may be considered whenever scientific evidence for their efficacy and safety becomes available as per the national policy for newer antimicrobials.

Standard 10 : Addressing TB with HIV infection and other comorbid conditions 38. What is the treatment of HIV infected TB patients?

TB patients living with HIV infection should receive the same duration of TB treatment with daily regimen as HIV-negative TB patients.

39. How Anti-retroviral therapy and cotrimoxazole prophylactic therapy in HIV infected TB patients should be given?

Anti-retroviral therapy must be offered to all patients with HIV and TB as well as drug-resistant TB , irrespective of CD4 cell-count, as early as possible (within the first

Pulmonary Communications  A quarterly Newsletter of National College of Chest Physicians

5

eight weeks) following initiation of anti-TB treatment.

all patients. Minimum records also be maintained by Private sector.

40. Is there a need of Isoniazid preventive therapy (IPT) in HIV patients without active TB?

47. Can the anti TB drugs be bought over the counter without prescription?

People living with HIV (PLHIV) should be screened for TB using four symptom complexes (current cough or fever or weight loss or night sweats) at HIV care settings and those with any of these symptoms should be evaluated for ruling out active TB. All asymptomatic patients in whom active TB is ruled out, Isoniazid Preventive Therapy (IPT) should be offered to them for six months.

The Government of India through a gazette notification has made all anti-TB drugs under schedule H1.

These drugs should not be dispensed without a valid prescription from a qualified practitioner. A copy of the prescription should be maintained and details of the patient to be recorded by the chemist and should be made available for verification by the responsible public health authorities

providers. Every visit of the patient to the healthcare provider and visit of the health worker to the patient’s home should be utilized for health education.

Standard 21: Death audit among TB patients 54. Competent Authorities should audit which TB deaths?

Every death among TB patients should be audited by a competent authority to ascertain preventable causes.

Standard 22 : Information prevention and care seeking

on

TB

Standard 11 : Treatment adherence

Standard 15 : Contact investigation

41. How to promote adherence?

48. Which contacts of TB patients be prioritized for screening of TB?

55. Which group of people should receive information on TB Prevention?

Trained treatment supporter which may include identification and training of a treatment supporter (for tuberculosis and, if appropriate, for HIV, Diabetes Mellitus etc.) who is acceptable, accessible and accountable to the patient and to the health system.

42. What are newer modalities for promoting treatment adherence?

Use of SMS reminders and call center linkages between patients, providers and pharmacists, use of ICT to promote treatment literacy and adherence.

Standard 12 : Public health responsibility

Standard 16 : Isoniazid Prophylactic therapy 49. Who should be considered for IPT?

43. What is the public health responsibility of a private/Govt. physician treating tuberculosis?

The practitioner must not only diagnose as per standard of care and prescribe an appropriate regimen, but when necessary, also utilize local public health services / community health services, and other agencies including NGOs to assess the adherence of the patient and to address poor adherence when it occurs

The highest priority contacts for active screening are: Persons with symptoms suggestive of tuberculosis, Children aged less than six years , Contacts with known or suspected immune-compromise, particularly HIV infection, Contacts with Diabetes Mellitus , other higher risks including pregnancy, smokers and alcoholics etc. and Contacts of patients with DR-TB.

Children less than 6 years of age who are close contacts of a TB patient, after excluding active TB, should be treated with isoniazid for a minimum period of six months and should be closely monitored for TB symptoms

Standard 17 : Airborne infection control 50.

What measures should be implemented for Air borne infection control measures in facilities treating TB?

Standard 13: Notification of TB cases

Administrative, environmental and personal protective measures should be implemented in all health care facilities as per national airborne infection control guidelines

44. Since when is the TB a notifiable disease in India and to whom the cases should be notified?

51. Which is the most cost effective infection control measure?

Since 7th May’2012 and the cases should be notified to District Nodal officer

45. What is the name of electronic notification system of TB in India?

NIKSHAY

6

A written record of all medications given, bacteriologic response, adverse reactions and clinical outcome should be maintained for

Standard 23 : Free and quality services 56. Which patients should receive free and quality services?

All patients

Standard 24 : Respect, confidentiality and sensitivity 57. Health system should be sensitive to which group of patients?

All people seeking or receiving care for TB should be received with dignity and managed with promptness, confidentiality and gender sensitivity

Standard 25 : Care and support through social welfare programmes 58. Which social health programmes can help in supporting the TB patients?

Social welfare support systems such as RSBY, nutritional support programmes, national rural employment guarantee scheme etc. to mitigate out of pocket expenses such as transport and wage loss incurred by people affected by TB and post TB sequelle.

Standard 18: Quality assurance systems

Standard 26: Addressing counseling and other needs

52. What is covered under Quality assurance?

59. To whom and at what interval should counseling be provided?

Standard 14 : Maintain records for all TB patients 46. What records are to be maintained for TB patients?

Administrative measures

All individuals especially women, children, elderly, differently abled, other vulnerable groups and those at increased risk should receive information related to TB prevention and care seeking.

All diagnostic tests used for diagnosis and all anti-TB drugs used in the country are subjected to stringent quality assurance mechanisms at all levels (from manufacturer to patients)

Standard 20 : Health education 53. Which patients should be given counseling?

Every TB symptomatic should be properly counseled by the healthcare

Persons affected by TB and their family members should be counselled at every opportunity, to address information gaps and to enable informed decision-making.

60. What issues should be addressed during counseling?

Counseling should address issues such as healthcare, physical, financial, psycho-social and nutritional needs

Pulmonary Communications  A quarterly Newsletter of National College of Chest Physicians

Current Status of Non-Invasive Ventilation in Clinical Practice

N

oninvasive ventilation (NIV) refers to the delivery of mechanical ventilation to lungs using techniques that do not require an endotracheal airway ie either an endotracheal tube or a tracheostomy tube. The concept of NIV is not new and the initial ventilators like iron lung were non- invasive ones. Initially the concept of non-invasive negative pressure ventilation (NINPV) was the one which was utilized for ventilation. In this an iron tank or chest wrap device was used to create negative pressure around patient’s chest wall and thus helping in ventilation. But NINPV now almost been given up (except in case of neuromuscular diseases) and non-invasive positive pressure ventilation (NIPPV) has come to an extensive use. Presently the term NIV is used synonymously with NIPPV. NIV is being used for an array of indications and is now a well established therapy for many respiratory disorders.

Initially NIV was used for hypercapnic respiratory failure associated with chronic obstructive airway disease (COPD) but now it has gained acceptance as first line ventilation modality for numerous conditions and clinical indications for which efficacy of NIV has been proven.

It has become an integral tool in the management of both acute and chronic respiratory failure, in both home setting and in the critical care unit. Currently it is strongly recommended for acute hypercapnic respiratory failure due to COPD, cardiogenic pulmonary edema, pneumonia in immunocompromised host and respiratory failure secondary to neuromuscular disorders. (Table 1) Table 1. Current evidence to support use of NIV 1. Level A (Multiple controlled trials) • Chronic obstructive pulmonary disease • Cardiogenic pulmonary edema • Immunocompromised patients 2. Level B (Single controlled trial or multiple case seires) • Weaning from mechanical ventilation in COPD patients • Community - acquired pneumonia (COPD) • Asthma • Postoperative respiratory distress and respiratory failure • Avoidance of extubation failure • Do not Intubate patients • Neuromuscular respiratory failure • Decompensated obstructive apnea/cor pulmonale

sleep

3. Level C (Few case series or case reports or failure to demonstrate benefit in controlled trials ) • Cystic fibrosis • Acute respiratory distress syndrome • Community-acquired pneumonia in non-COPD patients • Upper airway obstruction • Mild Pneumocysis Carnii pneumonia • Trauma

NIV has gained popularity as it offers many advantages over invasive mechanical ventilation when used judiciously. It has lower financial cost, reduced rates of infections and reduces hospital and ICU stay. Risks of intubation like tracheal injuries, stenosis and cardiac arrest during intubation are also reduced with use of NIV. It allows gradual weaning and most patients are able to eat, drink and communicate while getting ventilation through NIV and recovering from their primary illness. It also allows for better nebulistaion, physiotherapy, mobilisation and coughing out expectoration. NIV can also be used for patients who are poor risk for intubation or who are unwilling for intubation.

Careful patient selection, appropriate interface selection, close monitoring especially in initial few hours and readiness to intubate as and when required are few important issues while initiating NIV in an intensive care setting. The use of NIV for acute care is not recommended in settings where immediate intubation is not feasible. However, NIV should not be used indiscriminately as it may be harmful for the patients who require endotracheal intubation at the outset. It is essential that NIV is applied in an appropriate clinical area by appropriately trained staff using the optimal ventilator mode, settings, and interface for that patient with adequate monitoring. An adequate knowledge of arterial blood gas (ABG) is essential for NIV use.

The equipments required include ventilator (or portable machine), tubing, humidifiers and interface. Several types of masks are available and a well-fitting appropriate mask is must. Air leaks from mask undermine the benefits of NIV. NIV can be used through ICU ventilators or via portable NIV machines using appropriate interfaces. The choice depends upon availability, the level of support required, users’ familiarity and further advantages and disadvantages of each machine.

Poratable NIV machines have a singlecircuit gas delivery system that has an intentional leak port to allow exhalation.

They are pressure limited, time and flow triggered and flow cycled. Most machines allow for an IPAP from 2 to 30 cm of H2O while EPAP of 2 to 20 cm H2O. The various modes in these machines include: CPAP, spontaneous (S) and S/T (spontaneous/ timed). In CPAP mode patient breathes spontaneously at a baseline pressure.

The rate and tidal volume delivered is determined by the patient. In spontaneous mode, the operator sets IPAP and EPAP, the gap between two determines the level of support that will be given to each breath thus determining tidal volume to a certain extent. In this mode cycling occurs when flow reduces to a certain pre-fixed value usually 40-60%. In S/T mode the operator has to set a respiratory rate in addition to IPAP and EPAP. If patient triggers a breath then it works as a spontaneous mode but if patient fails to trigger then machine will give a breath to the assigned IPAP level. Thus this mode has a backup rate and is especially useful in patients with central apnoea, commonly seen in heart failure. These portable ventilators have

Prof. G.C. Khilnani

Chairman, Critical Care Section, NCCP Professor in the Department of Pulmonary Medicine & Critical Care All India Institute of Medical Science, Delhi better leak compensation as compared to adult ICU ventilators. The other important term to understand in this regard is rise time ie the time required to reach the IPAP. Using appropriate rise time control improves patient comfort and reduces work of breathing. But these machines have variable oxygen delivery as delivered FiO2 depends upon oxygen flow, airflow, pressure applied and interface. CO2 rebreathing may also occur as these ventilators have exhalation port in the mask itself. The washing of exhaled gases depends upon flow in the circuit, if flow is low and respiratory rate is high then rebreathing may occur. At EPAP settings more than 4 cm H2O the chances of rebreathing are minimal.

Adult ICU ventilators have an advantage of delivering desired FiO2 with no chances of rebreathing and allow better monitoring especially in acute care setting. In ICU ventilators, CPAP as well as PSV with a backup rate can be used but if required (though seldom) volume-controlled or pressure controlled ventilation can also be achieved through NIV interface. In acute care setting, if available, ICU ventilators offer advantage of closer monitoring and are usually preferred. The use of a proper interface remains the cornerstone to success of NIV therapy. The various interfaces available include nasal masks, oronasal masks, total facemasks, helmets, nasal pillows and mouthpieces with lip seals. A correct interface selection ensures patient comfort and thus improves compliance.

Total face mask covers the entire face and has less chances of pressure necrosis due to even pressure distribution all around the face. Special masks in form of helmet are also available, it covers entire head and is secured with straps under armpits.

Recently helmets have been shown to reduce intubation rates in patients with ARDS as compared to using face mask.

Mouthpieces and lip seals are also available and are used mostly in long term NIV use like in patients with neuromuscular diseases.

Adequate ventilation and oxygenation with patient tolerance and comfort are the primary goals of noninvasive ventilation.

Initial settings should aim at tidal volumes in the range of 5-7 mL/kg and reduce the respiratory rate to < 25 breaths/minute.

Oxygen is adjusted to achieve adequate oxygenation, with a pulse oximetery goal of greater than 90%. Serial arterial blood gases measurements should monitor and guide further adjustments. There is no recommended protocol for initiation of NIV but gradually escalating pressures as

Pulmonary Communications  A quarterly Newsletter of National College of Chest Physicians

7

per patients tolerance helps. We should start with inspiratory positive pressure (IPAP) of 8 and expiratory positive pressure (EPAP) of 4. IPAP should be increased by 2 cm water if hypercapnia is persistent.

Increase IPAP and EPAP by 2 cm water if hypoxemia is persistent. Maximal IPAP is limited to 20-25 cm water and EPAP to 1015 cm water. Injury to bridge of nose due continuous pressure leading to facial skin necrosis may occur in some cases. Ill fitting mask with significant air leak can lead to eye irritation and conjunctivitis. Gastric bloating can be prevented by keeping IPAP below 25 cm of water. Dry mucus membranes and thick secretions can occur in cases with prolonged NIV use without humidifier.

Patients with respiratory failure should be carefully selected for NIV. Patients with respiratory failure in the absence of any other organ involvement benefit the most.

The current status for recommendations of NIV is detailed in Table 1. Those selected, should be able to voluntarily synchronize respiration with ventilator. NIV is effective only if patient is able to cooperate. Patient has to be conscious for being able to cooperate with NIV but COPD patients with altered sensorium due to hypercapnia may be given a trial of NIV for a period 30 to 60 minutes and if the sensorium improves,NIV may be continued.

Several randomized controlled trials have proven efficacy of NIV in acute hypercapnic exacerbation of COPD. It has been shown to reduce mortality, duration of hospital in ICU stay and morbidity in acute exacerbation of COPD. The largest review concluded that NIV decreased the intubation rate by 28%, in-hospital mortality rate by 10%, and absolute reduction in length of stay by 4.57 days.

The benefit is most pronounced in patients with more severe COPD exacerbations with initial pH of less than 7.30. In these patients intubation rates decreased by 34%, mortality reduction of 12%, and absolute reduction in the length of hospital stay was by 5.59 days. Investigations with less severely affected patients did not demonstrate benefits in any of these outcomes.

NIV has also been found to be useful in patients with cardiogenic pulmonary oedema. CPAP therapy has been used for years for treatment of acute cardiogenic pulmonary edema (ACPE). CPAP helps in improving oxygenation and improves lung compliance and reduces intubation rates. It reduces both preload and afterload and reduces work of breathing. Multiple studies have shown similar success with NIV use especially in patients with hypercapnia. Current recommendation is to start CPAP therapy with standard medical management and start NIV (Bilevel positive pressure) if patients do not improve or develop hypercapnia.

In immunocompromised patients (like solid organ or bone marrow transplant recipients) pneumonia can be severe and NIV can be used initially to prevent intubation as incidence of ventilatorassociated pneumonia is high in this population and has poor prognosis. In these patients NIV reduces intubation rates, mortality and ICU length of stay.

In such patients, if undergoing diagnostic bronchoscopy, NIV can be used preprocedure and thus preventing intubation.

8

NIV has been tried in ARDS and acute lung injury with various out comes and is a debatable indication.

Multiple observational studies have suggested ARDS as a strong predictor of NIV failure.

NIV may be useful in mild ARDS as per Berlin definition. In patients with shock, metabolic acidosis and greater hypoxemia the chances of failure are very high. NIV in patients with ARDS should be used with utmost caution as it may increase mortality if used for longer than necessary leading to delayed endotracheal intubation. If after one hour of NIV trial, the PaO2/FiO2 ratio is less than 15o , then the patient should be intubated. Recently a randomized trial using helmet as interface showed reduced intubation rate with use of NIV. This study may be a game changer in use of NIV in patients with ARDS. NIV has been successfully used in hypercapnic exacerbation of diseases other than COPD. In patients with bronchiecatsis having an infective exacerbation NIV may be useful adjunct to standard medical therapy. Other diseases like obesity hypoventilation syndrome and cystic fibrosis may be treated with NIV during an exacerbation.

NIV is becoming increasingly popular for prevention and treatment of post-operative complications. In post lung resection patients use of NIV (as compared to mechanical ventilation) reduces atelecatsis and infections preventing intubations.

Similar findings have been seen in cardiac surgery patients. In abdominal surgery patients, NIV improves gas exchange, reduces atelecatsis and incidence of sepsis and pneumonia. NIV is commonly used for management of patients with do-not intubate instructions. Patients who have a high risk of complications with intubation like very old age, severely debilitated or advanced malignancy are commonly managed with NIV. NIV may be used as highest level of care for them or as palliative measure to treat dyspnea at endof-life. They have good improvement with NIV but overall survival depends upon primary illness. NIV or CPAP can be used during bronchoscopy to prevent procedure related hypoxemia and intubation. But this indication needs more studies to have a better recommendation. During intubation most patients develop hypoxemia and it is recommended to pre-oxygenate with bag and mask. In some patients preoxygenation can not be achieved through bag and mask even with high FiO2. In such patients using NIV in a controlled mode with high FiO2 helps in achieving better oxygenation prior to intubation.

Restrictive disorders including chest wall deformities and neuromuscular diseases result in progressive muscle weakness which eventually involves respiratory muscles causing hypoventilation and eventually respiratory failure. This one indication of NIV use was earliest to be studied and continues o be class 1 indication. NIV improves gas exchange and respiratory muscle function in these patients thus improving quality of life and psychosocial function.

NIV is also used as a method of weaning from invasive mechanical ventilation.

It can be used in three situations in this aspect: 1. Extubation to NIV after few days of mechanical ventilation (without following the standard weaning criteria): This in-

dication has not shown any advantage over standard weaning methods and thus is not recommended to shorten the period of invasive mechanical ventilation 2. Extubation to NIV after following standard weaning criteria, to prevent respiratory failure: This approach is useful to prevent reintubation in high risk patients which include COPD patients who remain hypercapnic at the time of extuabtion.

3. Using NIV as a treatment of post-extubation respiratory failure: This leads to delay in reintubation and increases ICU and hospital length of stay and mortality, so currently not recommended.

Conclusion To summarize, over last two decades, NIV has emerged as an indispensible respiratory modality in critical care due to many advantages over conventional ventilation. It has an irrefutable role in the management of acute respiratory failure supported by many clinical trials.

It is worthwhile to remember that this modality is not for all patients and should be used only by trained personnel with sound knowledge of instrument and its use. NIV utilization is variable in different areas with variable knowledge of indications and use among physician and intensivists. NIV should be integral part of care in all ICUs. Proper training of nurses, physicians and respiratory therapist for use of NIV is extremely important for optimum utilization of this modality of assisted ventilation.

References: 1. Nava S, Hill N: Non-invasive ventilation in acute respiratory failure. Lancet 2009, 374(9685):250-259.

2. Khilnani GC, Banga A: Noninvasive ventilation in patients with chronic obstructive airway disease. Int J Chron Obstruct Pulmon Dis 2008, 3(3):351357.

3. Khilnani GC, Saikia N, Banga A, Sharma SK: Non-invasive ventilation for acute exacerbation of COPD with very high PaCO(2): A randomized controlled trial. Lung India, 27(3):125-130.

4. Masip J, Roque M, Sanchez B, Fernandez R, Subirana M, Exposito JA: Noninvasive ventilation in acute cardiogenic pulmonary edema: systematic review and meta-analysis. Jama 2005, 294(24):3124-3130.

5. Girault C, Bubenheim M, Abroug F, Diehl JL, Elatrous S, Beuret P, Richecoeur J, L'Her E, Hilbert G, Capellier G et al: Noninvasive ventilation and weaning in patients with chronic hypercapnic respiratory failure: a randomized multicenter trial. Am J Respir Crit Care Med, 184(6):672-679.

6. Ward S, Chatwin M, Heather S, Simonds AK: Randomised controlled trial of non-invasive ventilation (NIV) for nocturnal hypoventilation in neuromuscular and chest wall disease patients with daytime normocapnia. Thorax 2005, 60(12):1019-1024.

7. Patel BK, Wolfe KS, Pohlman AS, Hall JB, Kress JP. Effect of noninvasive ventilation delivered by helmet vs face mask on the rate of endotracheal intubation in patients with acute respiratory distress syndrome: a randomized clinical trial. JAMA. 2016;315(22):24352441.

Pulmonary Communications ď&#x201A;&#x2021; A quarterly Newsletter of National College of Chest Physicians

Pulmonary Rehabilitation

P

ulmonary rehabilitation is an integral part of the clinical management and health maintenance of those patients with chronic respiratory disease who remain symptomatic or continue to have decreased function despite standard medical treatment. Pulmonary Rehabilitation (PR) is a complex multidisciplinary intervention with variable composition as per needs and requirements of the respiratory patient. Components of PR e.g. breathing techniques, walking exercises, bronchial hygiene, and respiratory medications including oxygen have been included for many centuries as a part of good medical care.1 In 1974, American Collage of Chest Physicians gave its name and in 1981, ATS published first official statement on PR. Six minute walk test and respiratory related quality of life questionnaires led to clinical trails demonstrating effectiveness in patients particularly in COPD.2 In 1991, Casaburi demonstrated dose dependent effect of exercise training on physiological benefit in COPD and subsequently it was shown to improve exertional dyspnea.3 In 2001 on the basis of unequivocal impact of PR in COPD not only on exercise capacity and QOL but also on subsequent need for healthcare, it was recommended in management of COPD in all stages.4 Over last decade use of PR has been recognized in non-COPD respiratory conditions with an aim to reduce symptom of dyspnea.5 Also as physical inactivity is related to shortened survival and recurrent hospitalizations, PR targets in improving activity with collateral benefit.

Definitio n of Pulmonary rehabilitation In 2013, ATS/ERS statement on PR is closest to workable definition of PR. It’s a comprehensive intervention based on a thorough patient assessment followed by patient tailored therapies, which include, but are not limited to, exercise training, education and behavioral change, designed to improve physical and emotional condition of persons with chronic respiratory disease and to promote the long term adherence to health enhancing behaviors5. In short, PR is a entity on its own though it combines different therapies delivered by different professionals with relevant expertise e.g. respiratory physician, respiratory therapist, dietician, education counselor, exercise physiologist, etc. also, PR as intervention is given to the patient at multiple times in disease trajectory of chronic lung disease.

• Promote autonomy • Increase participation in everyday activities • Decrease psychological symptoms • Improve health-related quality of life • Effectuate long-term 1health-enhancing behavior change Pulmonary Rehabilitation Team Pulmonary rehabilitation is implemented by a dedicated, interdisciplinary team, which includes generally following specialists depending upon availability and resource utilization:7 • Respiratory Physicians • Exercise physiologists • Respiratory therapists • Physiotherapists • Psychologists / behavioral specialist • Nutritionists • Occupational therapists • Social workers • Patient Educator or Nurse practitioner Resources and availability of health care professionals limit most of PR programs and hence, some of the teammates play dual or more roles to fill in for nonavailable staff members.

Indications and Contraindications of Pulmonary Rehabilitation Although conventionally any COPD patient who is symptomatic is to be referred to PR but indications are broadening with more research in this area with beneficial effects being reported in patients beyond COPD. Pragmatic approach would be to refer any patient with persistent respiratory symptoms e.g. dyspnea, fatigue and / or functional impairment despite optimized available therapy and hence to restricting

Dr. Deepak Talwar

Director & Chair, Pulmonary, Sleep & Critical Care Medicine, Metro Group of Hospitals, Noida

Dr. Mir Shad Ali

Head Pulmonary Rehabilitation & Exercise Lab, Metro Center for Respiratory Diseases, Noida to COPD or Obstructive lung disease.

Patients with restrictive lung diseases secondary to any cause including ILD with above said clinical indications should also be referred to PR.8 Complementing these general recommendations, there are indications where PR should be prescribed without any hesitation i.e. patients recently discharged from hospital with COPD-AE and patients with MRC grade 3 dyspnea or greater regardless of lung functions impairment Broadly absolute contraindication would be a completely demotivated patient or if exercise would be painful / potentially dangerous, but still risk versus benefit should be considered in each such case.

Co morbidities are no longer considered as CI to PR and adaptation in PR may be required to address such issues e.g depression or anxiety by incorporating psychiatrist or psychologist or associate CAD requiring physician for assessment and planning. Other concurrent conditions which may interfere with PR process or places patient at substantial risk during exercise should be stabilized prior to taking them in PR.1

Table 1: Indications and contraindications of pulmonary rehabilitation INDICATIONS

CONTRAINDICATIONS

Persistent respiratory symptoms, especially dyspnea

Conditions that substantially increase risk during rehabilitation, e.g., unstable angina

Limitation of functional status despite optimal medication

Conditions that substantially interfere with rehabilitative process

Impaired health related quality of life

Uncontrolled diabetes

Decreased occupational performance

Psychiatric illness, e.g. Dementia

Goals of Pulmonary Rehabilitation

Psychosocial problems attendant on the underlying respiratory illness

Severe exercise-induced hypoxemia, not correctable with oxygen supplementation

The goals of PR are dependent on patients needs depending upon functional limitations and disabilities and hence have to be individualized for each patient6. The main goals are to:

Difficulty with medical regimen

Inability to exercise due to orthopaedic or other reasons

• Minimize symptom burden

Increased use of medical resources

• Maximize exercise performance

Gas exchange abnormalities

Difficulty performing day-to-day activities Nutritional depletion

Pulmonary Communications  A quarterly Newsletter of National College of Chest Physicians

9

Patient Selection in Pulmonary Rehabilitation This depends upon the patients who are likely to benefit from PR and since results of rehabilitation may improve many dimensions, patient referral will vary.

As improvement in exercise capacity is major positive outcome, any respiratory patient who is breathlessness on exertion, would be an ideal candidate for PR but challenge is to identify responders, which too will vary at different dimensions.9 Patients with reduction in functional capacity, quality of life or occupational / daily activities related performance, may indicate good responders as clear and achievable goals are known prior to initiation of PR. Generally, patients with pre existing skeletal muscle weakness, poor exercise capacity with better ventilator parameters and are relatively young, do better in PR.10 These points are useful as PR is labor intensive and time consuming with financial implications.

Patient Assessment in Pulmonary rehabilitation At the begining of PR, it’s crucial to have patient-physician interaction with clear dialogue where patient is to be clarified about limitations of pharmacotherapy and goals to be set by chest physician on the basis of expectations by the patient and realistic outcomes possible as per the current knowledge of PR. Patient assessment is ongoing process & done even if done on previous visits.

Complete assessment of patient begins with checking medical history with particular reference to respiratory as well as neuromuscular and orthopedic problems, comorbidities, smoking or other addictions as they may pose challenge during PR.11 Baseline literacy, hearing, vision and cognitive ability requires to be looked into as these would influence outcomes of PR. Symptom assessment of dyspnea, fatigue, cough, chest pain or sputum allows PR team to know the burden of disease to set outcome expectations. Medication history is needed not only to see if its optimized to the disease but also if any special care in PR to be provided e.g. corticosteroids, bronchodilators or diuretics, insulin, etc.

Physical examination findings of respiratory distress, breathing pattern and oxygenation status is to be recorded as would need to be addressed during PR. Diagnostic tests results to be reviewed include spirometry, oximetry both at rest as well as at walk, CXR and if available 6 minute walk test or cardio-pulmonary exercise test report. It’s important to note BMI, Serum albumin, fluids intake or restrictions and detailed dietary history with Fat free mass estimation to target skeletal muscle strengthening in PR and baseline EKG and ECHO to know cardiac limitations during PR if any. Exercise capacity assessment include physical limitations if any, gait and balance, exercise tolerance and related hypoxia, etc factors which would influence exercise training plan in PR. Pain chest, limbs, or back is also worth noting as may become limiting factors in exercise programme.

Finally a breif history of activities of daily living with reference to functional task performance e.g. bathing, washing, changing clothes, leisure activities and use of supplemental oxygen during day to day work. Some PR programmes include questionares (SGRQ, SF36, Bode Index etc) at baseline to document improvement at the end of the program. Anxiety or depression assessment using simple questionaires (PHQ-2 and 3) are included to identify any significant psychological imapirment which would require special assisstance.

At the end of this global assessment, depending upon rehabilitation potential PR team formulates goals both short term as well as long term which are individulaized, measurable, patient centred and realistic and being graded from Excellent to Poor.12 Its suffice to say that such exhaustive assessment would need multidisciplinary team work and cordination as everything needs to be done in limited time with limited discomfort to the patient Components of Pulmonary Rehabilitation: Pulmonary rehabilitation is not exercise training as includes many other aspects to improve overall functional capacity of the

Figure 1: Showing various assessments required prior to initiation of pulmonary rehabilitation in an individual patient.

10

patients. A good PR program includes, optimized medications and delivery, smoking cessation, education about disease and prognosis, self management plan for AE and daily situations, nutritional support, energy conservation techniques, psychological counseling, behavior change, ADL training, home adaptation and aids, oxygen and NIV therapy, mucus handling and bronchial hygiene, hormonal supplements, inspiratory muscle training, etc.12 Duration of Pulmonary Rehabilitation Program Ideally rehabiliation should continue as long as gains are being made. There is no concensus on optimal duration of PR but it’s ideally set by continued progress towards goals and optimization of benefit.

In reality it’s also influenced by finacial resources and traveling burden. Generally longer programs are considered to produce greater gains and maintenance of benefits achieved on short term. But a minimum of 8 weeks is recommended to gain substantial benefit.5 Our study showed that as short as 3 weeks after discharge from hospital for COPD AE is effective considering difficulties in sustaining long term programs.13 Also, length of PR is also dependent on the setting i.e. hospital based, community based or home based and if one can be followed by the other as per convience and teams decisions. Two to three visits per week are recommended during PR. Location and Settings of Pulmonary Rehabilitation Although programs have been conventionally developed where patient visits PR center in the hospital or clinic 2 or 3 times a week but PR has been shown to be effective inpatient settings too. Recently sucessful PR programs have demonstrated to be delivered in other settings e.g. primary care (physiotherapists clinic), home or secondary care (community or nursing homes) and systemic review has confirmed beneficial effects of home based PR14 but such programs are to be considered for most severely disabled provided supervision by experts is available which is rare.

Figure 2: Essential components of pulmonary rehabilitation indicating that PR is not a exercise program alone but has many other facets.

Pulmonary Communications  A quarterly Newsletter of National College of Chest Physicians

Compliance to Pulmonary rehabilitation As with any therapy in medicine long term compliance rate are not excellent in PR also. Nearly 23% drop outs are reported with primary issues related to travel, familiy, finances or due to exacerbations or hospitalization related to primary disease or unrelated helath problems.15 Exercise Training in Pulmonary Rehabilitation This is one of the most important component of PR and is based on following principles : • Intensity: Higher intensity produces greater results(e.g, > 60% of VO2MAX or at 60% TO 80% Wmax)5 • Specificity: Only muscles produce the desired effect

trained

• Reversibility: Stopping regular exercise training decreases the effect • Exercise regimen is to endurance, strength or both.

improve

Duration, frequency, mode and intensity of exercise prescription is based on severity of disease, degree of conditioning and initial exercise capacity.16 Aerobic Endurance training whether given as high or low intensity would improve patient’s ability to perform activities which require continous effort for long periods e.g. walking and optimal exercise paln would include cycle ergometry and treadmill walking. Generally biking induces less exercise induced hypoxia and hence more suitable for hypoxic patients.

Interval tarining is an option for those who can not sustain extended continous high intensity exercise in the form of rest periods in between or alternating periods of high and low intensity exercises.

Strength or Resistance training is used for explosive activities which require excessive strength in bursts for short period of time e.g. sprinting, jumping and lifting weights. Exercise targets local muscle groups with reduced mass and strength of peripheral muscles required to perform these activities and as collateral benefit improves bone mineral density.

This training improves muscle mass and results in improved exercise tolerance as patient experiences less dyspnea. Training is done using free weights, squating, stair climbing,elastic resistive bands, machine weights or simply repeated sit and stand from chair. Lesser weights and more repitions improves endurance and higher weights with fewer repetitions improve muscle mass.17 Exercise plan targets both upper and lower limb muscles as upper limb muscles are required for daily activities like

dressing bathing and performing house hold activities while lower limbs muscle dysfunction is main cause of exercise limitation in respiratory patients and provides best physiological gains in PR. Inspiratory muscle training (IMT)is needed as there weakness leads to more perception of dypnea and hence imapired exercise tolerance. Training includes voluntary isocapnic hperventilation, inspiratory threshold or resistive loading. This is more useful if patient has undelying COPD or reduced respirstory muscle strength demonstrated by measurement of maximum inspiratory pressures.18 Nutritional Support in Pulmonary Rehabilitation Weight as well as Fat Free Mass (FFM) estimates of the patient needs consideration in PR. Caloric supplementation is provided to meet the extra demands for energy from PR and if any deficit pre existing (BMI < 21).19 Iindian guidelines also recommend to monitor BMI periodically to see the effect of nutritional support as it has also been shown to improve QOL Psychological Support in Pulmonary Rehabilitation Prevalance of anxiety and depression in COPD is 36% and 40% respectively20 and depression is known to increase the risk of AE and hospitalizations in COPD. Patient may be provided with vocational counselling, education strategies to cope stress and involvement of family members to resove conflicts. However patients with severe psychological problems need formal evaluation by psychiatrist.

Education in Pulmonary Rehabilitation Patient education is an important part of PR and topics includes but not limited to them are, normal lungs structure and function, disease aspects, smoking cessation, avoidance of potential risk factors of irritants and allergens, clearanc eof secretions, Energy conservation techniques, appropriate inhaler technique,breathing strategies, benfits of drugs prescribed and compliance, recognition of worsening of disease and intial self management plan.21

Long Term Maintenace of Benefits of Pulmonary rehabilitation Benfits appear to diminish over 6 -12 months after discontinuation of PR. And is due to : • Decrease in treatment adherence, especially to long-term regular exercise • Progression of underlying disease • Development of co-morbidities • Acute exacerbations Benefits can be maintained by establishing ongoing communication of the patient with PR team through: • Weekly telephone calls and monthly reinforcement visits • Weekly supervised outpatient-based exercise plus unsupervised home exercise23 Pulmonary Rehabilitation: Future Directions PR addresses the systemic effects of chronic respiratory disease, which are complex and involve peripheral muscle dysfunction. Although in COPD role of PR has been established beyond doubt and has been shown to be far superior to any other therapy at patient oriented multiple outcome areas, its role is in other chronic respiratory diseases is evolving.

Recently role of PR has been extended from stable patients to patients in hospitals and immediately after discharge while being traeted for exacerbation. PR has also been recommeded early in critical illness with neuromuscular stimulation started in mechanically ventilated patients.24 Also data from pooled clinical trials in COPD showed that physical inactivity is also reported in mild and early COPD, PR is being recommended in these patients also. Realizing difficulties of traveling to PR centers, home bases and community based programs are being developed to circumvent these problems and extend benefit to many more patients.

Also, internet and telemonitoring has advanced scope of PR futher where it can be assissted remotely.

References 1. Casaburi RA. Brief history of pulmonary rehabilitation. Respir Care 2008; 53:1185-9

Outcome Assessment of Pulmonary Rehabilitation

2. ZuWallack RA. History of pulmonary rehabilitation back to future. Pneumonol Alergol Pol 2009; 77:298-301

Outcome of PR is done either on real time or during the course of the program or at the end of the program by recall.

Generally QOL, dyspnea indices and functional status parameters ( 6 MWT, BODE index, CAT, etc ) are evaluated.22

3. Casaburi R, Patessio A., Ioli F. et al. Reduction in exercise Lactic acidosis and ventilation as a result of exercise training in patients with obstructive lung disease. Am Rev Respir Dis 1991; 143:918

Pulmonary Communications  A quarterly Newsletter of National College of Chest Physicians

11

4. Griffiths TL, Phillips CJ, Davies S, et al.

Cost effectiveness of an outpatient multidisciplinary pulmonary rehabilitation program. Thorax 2001; 56:779-84

ties on the outcomes of pulmonary rehabilitation programs in patients with COPD; a systematic review. Biomed Res Int 2013; 2013:146148

5. Spruit MA, Singh SJ, Garvey C, et al.

Key concepts and advances in pulmonary rehabilitation based on the official 2013 American thoracic Society/European Respiratory Society statement on pulmonary rehabilitation. Amer J respire Crit Care Med 2013; 188:e13-64.

12. Parshall MB, Schwartzstein RM, Adams L, et al. An official American Thoracic statement: update on the mechanisims, assessment and management of dyspnea. Am J Respir Crit Care Med 2012; 185:435-52

6. American Association of Cardiovascular and Pulmonary Rehabilitation.

Guidelines for pulmonary rehabilitation programs, 3rd. Ed. 2004. Available at: www.HumanKinetics.com 7. Spruit MA, Pitta F, Garvey C, et al. Differences in content and organizational aspects of pulmonary rehabilitation programs. Eur Respir J 2014; 43:1326-37 8. Bolton CE, Bevan-Smith EF, Blakey JD, et al. British Thoracic Society guidelines on pulmonary rehabilitation in adults.

Thorax 2013; 68:ii1-30 9. Young P, Dewse M, Fergusson W, et al.

Respiratory rehabilitation in chronic obstructive pulmonary disease : predictors of nonadherance. Eur Respir J 1999; 13:855-9.

10. ZuWallack RL. Selection criteria and outcome assessment in pulmonary rehabilitation. Monaldi Archives for Chest Dis 1998; 53:429-437.

11. Hornikx M, Van Remoortel H, Demeyer H, et al. The influence of co morbidi-

13. Ali MS, Talwar D and Jain SK. The Effect of a Short- Term Pulmonary Rehabilitation on Exercise Capacity and Quality of Life in Patients Hospitalised with Acute Exacerbation of Chronic Obstructive Pulmonary Disease. Indian J Chest Dis Allied Sci 2014; 56:13-19 14. Mendes de Oliveriera JC, Studart Leitao Filho FS, Malosa Sampaio LM, et al.

Outpatient vs home based pulmonary rehabilitation in COPD: a randomized controlled trial. Multidiscip Respir med 2010; 5:401-8 15. Nici L. Adherence to a pulmonary rehabilitation program: start by understanding the patient. COPD 2012; 9:44557 16. Puhan MA, Schunemann HJ, Frey M, et al. How should COPD patients exercise during respiratory rehabilitation ?

Comparison of exercise modalities and intensities to treat skeletal muscle dysfunction. Thorax 2005; 60:367-75 17. Gloecki R, Marinov B, Pitta F, et al.

Practical recommendations for exercise

Welcome Faculty & Delegates NAPCON -2016 Dr. Rajesh Chawla Dr. S. N. Gaur President NCCP (India)

12

Secretary NCCP (India)

training in patients with COPD. Eur Respir Rev 2013; 22:178-86 18. Smith K, Cook D, Guyatt GH, et al. Respiratory muscle training in chronic airflow limitation: a meta-analysis. Am Rev Respir Dis 1992; 145:533-9 19. Debigare R, Marquis K, cote CH, et al.

Catabolic/anabolic balance and muscle wasting in patients with COPD. Chest 2003; 124:83-9.

20. Maurer J, Rebbapragada V, Borson S, et al. Anxiety and depression in COPD: current understanding, unanswered questions, and research needs. Chest 2008; 134:43S-56S 21. Monninkhof E, van der Valk P, van der Palen J, et al. Self management education for patients with chronic obstructive pulmonary disease:a systematic review. Thorax 2003; 58:394-8.

22. Mahler DA, and Jones PW. Measurement of dyspnea and quality of life in advanced Lung disease. Clin Chest Med 1997; 18:457-469.

23. Reis AL, Kaplan RM, Myers R, et al.

Maintenance after pulmonary rehabilitation in chronic lung disease; a randomized trial. Am J Respir Crit Care Med 2003; 167:880-8 24. Rochester CL. Rehabilitation in the intensive care unit. Semin Respir Crit Care Med 2009; 30:656-69.

KOCHI CRITICARE 2017 23rd Annual Conference of Indian Society of Critical Care Medicine Come! Witness the modern techniques to treat your Critical Patients in a better way.

Workshop : 1st, 2nd February 2017 Conference : 3rd, 4th, 5th February 2017

Venue : Le. Meridean Convention Centre Thomas Mathew

Suresh Nair

K. Vinodan

(Organizing Charman)

(Organizing Secretary)

(Scientific committee Chairman)

Mob. : 9447076652

Mob. : 9847040849

Mob. : 9846011922

Visit for Details

www. conference.isccm.org

Pulmonary Communications ď&#x201A;&#x2021; A quarterly Newsletter of National College of Chest Physicians

Journal Scan Efficacy and safety of benralizumab for patients with severe asthma uncontrolled with high-dosage inhaled corticosteroids and long-acting β2agonists (SIROCCO): a randomised, multicentre, placebo-controlled phase 3 trial.

Bleecker ER, FitzGerald JM, Chanez P, Papi A et al SIROCCO study

Lancet. 2016 Sep 2. pii: S0140-6736(16)31324 Eosinophilia is associated with worsening asthma severity and decreased lung function, with increased exacerbation frequency. This study assessed the safety and efficacy of benralizumab, a monoclonal antibody against interleukin-5 receptorα that depletes eosinophils by antibodydependent cell-mediated cytotoxicity, for patients with severe, uncontrolled asthma with eosinophilia.

This randomised, double-blind, parallelgroup, placebo-controlled phase 3 study was done at 374 sites in 17 countries.

They recruited patients (aged 12-75 years) with a physician-based diagnosis of asthma for at least 1 year and at least two exacerbations while on high-dosage inhaled corticosteroids and long-actingβ2agonists (ICS plus LABA) in the previous year. Patients were randomly assigned (1:1:1) by an interactive web-based voice response system to benralizumab 30 mg either every 4 weeks (Q4W) or every 8 weeks (Q8W; first three doses every 4 weeks) or placebo Q4W for 48 weeks as add on to their standard treatment.

Patients were stratified 2:1 according to blood eosinophil counts of at least 300 cells perμL and less than 300 cells perμL. All patients and investigators involved in patient treatment or clinical assessment were masked to treatment allocation. The primary endpoint was annual exacerbation rate ratio versus placebo, and key secondary endpoints were pre bronchodilator forced expiratory volume in 1 s (FEV1) and total asthma symptom score at week 48, for patients with blood eosinophil counts of at least 300 cells perμL. Efficacy analyses were by intention to treat (based on the full analysis set); safety analyses included patients according to study drug received.

Between Sept 19, 2013, and March 16, 2015, 2681 patients were enrolled, 1205 of whom met the study criteria and were randomly assigned: 407 to placebo, 400 to benralizumab 30 mg Q4W, and 398 to benralizumab 30 mg Q8W. 267

patients in the placebo group, 275 in the benralizumab 30 mg Q4W group, and 267 in the benralizumab 30 mg Q8W group had blood eosinophil counts at least 300 cells perμL and were included in the primary analysis population. Compared with placebo, benralizumab reduced the annual asthma exacerbation rate over 48 weeks when given Q4W (rate ratio 0.55, 95% CI 0.42-0.71; p<0.0001) or Q8W (0.49, 0.37-0.64; p<0.0001). Both benralizumab dosing regimens significantly improved prebronchodilator FEV1 in patients at week 48 compared with placebo (leastsquares mean change from baseline: Q4W group 0.106 L, 95% CI 0.016-0.196; Q8W group 0.159 L, 0.068-0.249). Compared with placebo, asthma symptoms were improved by the Q8W regimen (leastsquares mean difference -0.25, 95% CI -0.45 to -0.06), but not the Q4W regimen (-0.08, -0.27 to 0.12). The most common adverse events were worsening asthma (105 [13%] of 797 benralizumab-treated patients vs 78 [19%]of 407 placebo-treated patients) and nasopharyngitis (93 [12%]vs 47 [12%]).

75 years with severe asthma uncontrolled

These results confirm the efficacy and safety of benralizumab for patients with severe asthma and elevated eosinophils, which are uncontrolled by high-dosage ICS plus LABA, and provide support for benralizumab to be an additional option to treat this disease in this patient population.

Between Aug 21, 2013, and March 16,

by medium-dosage to high-dosage inhaled corticosteroids plus long-actingβ₂-agonists (ICS plus LABA) and a history of two or more exacerbations in the previous year.

Patients were randomly assigned (1:1:1) to receive 56 weeks of benralizumab 30 mg every 4 weeks (Q4W), benralizumab 30 mg every 8 weeks (Q8W; first three doses 4 weeks apart), or placebo (all subcutaneous injection). Patients were stratified (2:1) by baseline blood eosinophil counts 300 cells perμL or greater and less than 300 cells perμL, respectively. Patients and study centre staff were masked to treatment allocation. The primary endpoint was annual exacerbation rate ratio versus placebo for patients receiving high-dosage ICS plus LABA with baseline blood eosinophils 300 cells perμL or greater (intention-to-treat analysis). Key secondary endpoints were pre-bronchodilator forced expiratory volume in 1 s (FEV1) and total asthma symptom score. This study is registered with ClinicalTrials.gov, number NCT01914757.

2015, 2505 patients were enrolled, of whom 1306 patients were randomised; 425 patients were randomly assigned to and received benralizumab 30 mg Q4W, 441 to benralizumab 30 mg Q8W, and 440 to placebo. 728 patients were included in

Benralizumab, an anti-interleukin-5 receptorαmonoclonal antibody, as addon treatment for patients with severe, uncontrolled, eosinophilic asthma (CALIMA): a randomised, double-blind, placebo-controlled phase 3 trial.

FitzGerald JM, Bleecker ER, Nair P et al CALIMA study investigators Lancet. 2016 Sep 5. pii: S0140-6736(16)31322 8 Benralizumab is a humanised, afucosylated, anti-interleukin-5 receptorαmonoclonal antibody that induces direct, rapid, and nearly complete depletion of eosinophils.

This study aimed to assess the efficacy and safety of benralizumab as add-on therapy for patients with severe, uncontrolled asthma and elevated blood eosinophil counts.

In this randomised, double-blind, parallelgroup, placebo-controlled, phase 3 study (CALIMA) undertaken at 303 sites in 11 countries, They enrolled patients aged 12-

the

primary

analysis

population.

Benralizumab resulted in significantly lower annual exacerbation rates with the Q4W regimen (rate 0.60 [95% CI 0.48-0.74], rate ratio 0.64 [95% CI 0.49-0.85], p=0.0018, n=241) and Q8W regimen (rate 0.66 [95% CI 0.54-0.82], rate ratio 0.72 [95% CI 0.54-0.95], p=0.0188, n=239) compared with placebo (rate 0.93 [95% CI 0.77-1.12], n=248).

Benralizumab also significantly improved pre-bronchodilator FEV1 (Q4W and Q8W) and total asthma symptom score (Q8W only) in these patients. The most common adverse events were nasopharyngitis (90 [21%] in the Q4W group, 79 [18%]in the Q8W group, and 92 [21%]in the placebo group) and worsening asthma (61 [14%] in the Q4W group, 47 [11%]in the Q8W group, and 68 [15%]in the group).

Benralizumab annual

significantly

exacerbation

rates

reduced and

was

generally well tolerated for patients with severe, uncontrolled asthma with blood eosinophils 300 cells perμL or greater. Their data further refine the patient population

Pulmonary Communications  A quarterly Newsletter of National College of Chest Physicians

13

likely to receive the greatest benefit from benralizumab treatment.

Effect of Postextubation High-Flow Nasal Cannula vs Conventional Oxygen Therapy on Reintubation in Low-Risk Patients: A Randomized Clinical Trial.

Hernández G, Vaquero C, González P et al JAMA. 2016;315(13):1354 Studies of mechanically ventilated critically ill patients that combine populations that are at high and low risk for reintubation suggest that conditioned high-flow nasal cannula oxygen therapy after extubation improves oxygenation compared with conventional oxygen therapy.

To determine whether high-flow nasal cannula oxygen therapy is superior to conventional oxygen therapy for preventing reintubation in mechanically ventilated patients at low risk for reintubation.

Multicenter randomized clinical trial conducted between September 2012 and October 2014 in 7 intensive care units (ICUs) in Spain. Participants were 527 adult critical patients at low risk for reintubation who fulfilled criteria for planned extubation. Low risk for reintubation was defined as younger than 65 years; Acute Physiology and Chronic Health Evaluation II score less than 12 on day of extubation; body mass index less than 30; adequate secretions management; simple weaning; 0 or 1 comorbidity; and absence of heart failure, moderate-tosevere chronic obstructive pulmonary disease, airway patency problems, and prolonged mechanical ventilation.

Patients were randomized to undergo either high-flow or conventional oxygen therapy for 24 hours after extubation.

The primary outcome was reintubation within 72 hours, compared with the CochranMantel-Haenszelχ2 test.

Secondary outcomes included postextubation respiratory failure, respiratory infection, sepsis and multiorgan failure, ICU and hospital length of stay and mortality, adverse events, and time to reintubation.

Of 527 patients (mean age, 51 years [range, 18-64]; 62% men), 264 received high-flow therapy and 263 con ventional oxygen therapy. Reintubation within 72 hours was less common in the high-flow group (13 patients [4.9%]vs 32 [12.2%]in the conventional group; absolute difference, 7.2% [95% CI, 2.5% to 12.2%]; P = .004).

14

Postextubation respiratory failure was less common in the high-flow group (22/264 patients [8.3%]vs 38/263 [14.4%]in the conventional group; absolute difference, 6.1% [95% CI, 0.7% to 11.6%]; P = .03).

Time to reintubation was not significantly different between groups 19 hours [interquartile range, 12-28]in the high-flow group vs 15 hours [interquartile range, 9-31]in the conventional group; absolute difference, -4 [95% CI, -54 to 46]; P = .66].

No adverse effects were reported.

Among extubated patients at low risk for reintubation, the use of high-flow nasal cannula oxygen compared with conventional oxygen therapy reduced the risk of reintubation within 72 hours.

Effect of Hydrocortisone on Development of Shock Among Patients With Severe Sepsis: The HYPRESS Randomized Clinical Trial.

Keh D, Trips E, Marx G, Wirtz SP et al JAMA 2016 Nov;316(17):1775-1785 Adjunctive hydrocortisone therapy is suggested by the Surviving Sepsis Campaign in refractory septic shock only.

The efficacy of hydrocortisone in patients with severe sepsis without shock remains controversial.

This study was done to determine whether hydrocortisone therapy in patients with severe sepsis prevents the development of septic shock.

This study was double-blind, randomized clinical trial conducted from January 13, 2009, to August 27, 2013, with a follow-up of 180 days until February 23, 2014. The trial was performed in 34 intermediate or intensive care units of university and community hospitals in Germany, and it included 380 adult patients with severe sepsis who were not in septic shock.

Patients were randomly allocated 1:1 either to receive a continuous infusion of 200 mg of hydrocortisone for 5 days followed by dose tapering until day 11 (n = 190) or to receive placebo (n = 190).

The primary outcome was development of septic shock within 14 days. Secondary outcomes were time until septic shock, mortality in the intensive care unit or hospital, survival up to 180 days, and assessment of secondary infections, weaning failure, muscle weakness, and hyperglycemia (blood glucose level>150 mg/dL [to convert to millimoles per liter, multiply by 0.0555]).

The intention-to-treat population consisted of 353 patients (64.9% male; mean [SD]age, 65.0 [14.4]years). Septic shock occurred in 36 of 170 patients (21.2%) in the hydrocortisone group and 39 of 170 patients (22.9%) in the placebo group . No significant differences were observed between the hydrocortisone and placebo groups for time until septic shock; mortality in the intensive care unit or in the hospital; or mortality at 28 days .In the hydrocortisone vs placebo groups, 21.5% vs 16.9% had secondary infections, 8.6% vs 8.5% had weaning failure, 30.7% vs 23.8% had muscle weakness, and 90.9% vs 81.5% had hyperglycemia.

Among adults with severe sepsis not in septic shock, use of hydrocortisone compared with placebo did not reduce the risk of septic shock within 14 days.

These findings do not support the use of hydrocortisone in these patients.

Effect of Noninvasive Ventilation Delivered by Helmet vs Face Mask on the Rate of Endotracheal Intubation in Patients With Acute Respiratory Distress Syndrome: A Randomized Clinical Trial.

Patel BK, Wolfe KS, Pohlman AS, Hall JB, Kress JP JAMA. 2016;315(22):2435.

Noninvasive ventilation (NIV) with a face mask is relatively ineffective at preventing endotracheal intubation in patients with acute respiratory distress syndrome (ARDS). Delivery of NIV with a helmet may be a superior strategy for these patients.

The objective of this study was to determine whether NIV delivered by helmet improves intubation rate among patients with ARDS. This was a single-center randomized clinical trial of 83 patients with ARDS requiring NIV delivered by face mask for at least 8 hours while in the medical intensive care unit at the University of Chicago between October 3, 2012, through September 21, 2015.

Patients were randomly assigned to continue face mask NIV or switch to a helmet for NIV support for a planned enrollment of 206 patients (103 patients per group). The helmet is a transparent hood that covers the entire head of the patient and has a rubber collar neck seal. Early trial termination resulted in 44 patients randomized to the helmet group and 39 to the face mask group.

Pulmonary Communications  A quarterly Newsletter of National College of Chest Physicians

The primary outcome was the proportion of patients who required endotracheal intubation. Secondary outcomes included 28-day invasive ventilator-free days (ie, days alive without mechanical ventilation), duration of ICU and hospital length of stay, and hospital and 90-day mortality.

intention-to-treat analysis cohort.

has not been validated in clinical practice.

Intervention included administration of aspirin, 325-mg loading dose followed by 81 mg/d (n = 195) or placebo (n = 195) within 24 hours of emergency department presentation and continued to hospital day 7, discharge, or death.

This study was done to assess whether a conservative protocol for oxygen supplementation could improve outcomes in patients admitted to intensive care units (ICUs).

Eighty-three patients (45% women; median age, 59 years; median Acute Physiology and Chronic Health Evaluation [APACHE] II score, 26) were included in the analysis after the trial was stopped early based on predefined criteria for efficacy. The intubation rate was 61.5% (n = 24) for the face mask group and 18.2% (n = 8) for the helmet group (absolute difference, -43.3%; P < .001). The number of ventilator-free days was significantly higher in the helmet group (28 vs 12.5, P < .001). At 90 days, 15 patients (34.1%) in the helmet group died compared with 22 patients (56.4%) in the face mask group (absolute difference, -22.3%; 95% CI, -43.3 to -1.4; P = .02).

Adverse events included 3 interfacerelated skin ulcers for each group (ie, 7.6% in the face mask group had nose ulcers and 6.8% in the helmet group had neck ulcers).

The primary outcome was the development of ARDS by study day 7. Secondary measures included ventilator-free days, hospital and intensive care unit length of stay, 28-day and 1-year survival, and change in serum biomarkers associated with ARDS. A finalαlevel of .0737 (α = .10 overall) was required for statistical significance of the primary outcome.

This study was among patients with ARDS, treatment with helmet NIV resulted in a significant reduction of intubation rates.

There was also a statistically significant reduction in 90-day mortality with helmet NIV. Multicenter studies are needed to replicate these findings.

Effect of Aspirin on Development of ARDS in At-Risk Patients Presenting to the Emergency Department: The LIPS-A Randomized Clinical Trial.

Kor DJ, Carter RE, Park PK, et al: Lung Injury Prevention with Aspirin Study JAMA. 2016;315(22):2406.

Management of acute respiratory distress syndrome (ARDS) remains largely supportive. Whether early intervention can prevent development of ARDS remains unclear.

The objective of this study was to evaluate the efficacy and safety of early aspirin administration for the prevention of ARDS. This multicenter, double-blind, placebocontrolled, randomized clinical trial was conducted at 16 US academic hospitals.

Between January 2, 2012, and November 17, 2014, 7673 patients at risk for ARDS (Lung Injury Prediction Score≥4) in the emergency department were screened and 400 were randomized. Ten patients were excluded, leaving 390 in the final modified

Among 390 analyzed patients (median age, 57 years; 187 [48%]women), the median (IQR) hospital length of stay was 6 3-10) days. Administration of aspirin, compared with placebo, did not significantly reduce the incidence of ARDS at 7 days (10.3% vs 8.7%, respectively.No significant differences were seen in secondary outcomes: ventilator-free to day 28, mean (SD), 24.9 (7.4) days vs 25.2 (7.0) days; ICU length of stay, 5.2 (7.0) days vs 5.4 (7.0) days , hospital length of stay, mean (SD), 8.8 (10.3) days vs 9.0 (9.9) days or 28-day survival, 90% vs 90% or 1-year survival, 73% vs 75%, Bleeding-related adverse events were infrequent in both groups (aspirin vs placebo, 5.6% vs 2.6%); Among 390 analyzed patients (median age, 57 years; 187 [48%] women), median (IQR) hospital length of stay was 6 (3-10) days. Administration of aspirin, compared with placebo, did not significantly reduce the incidence of ARDS at 7 days.

No significant differences were seen in secondary outcomes or adverse events.

Among at-risk patients presenting to the ED, the use of aspirin compared with placebo did not reduce the risk of ARDS at 7 days. The findings of this phase 2b trial do not support continuation to a larger phase 3 trial.

Effect of Conservative vs Conventional Oxygen Therapy on Mortality Among Patients in an Intensive Care Unit: The Oxygen-ICU Randomized Clinical Trial.

Girardis M, Busani S, Damiani Eet al JAMA. 2016 Oct 18;316(15):1583-1589 Despite suggestions of potential harm from unnecessary oxygen therapy, critically ill patients spend substantial periods in a hyperoxemic state. A strategy of controlled arterial oxygenation is thus rational but

Patients Oxygen-ICU was a single-center, open-label, randomized clinical trial conducted from March 2010 to October 2012 that included all adults admitted with an expected length of stay of 72 hours or longer to the medical-surgical ICU of Modena University Hospital, Italy. The originally planned sample size was 660 patients, but the study was stopped early due to difficulties in enrollment after inclusion of 480 patients.

Patientswere randomly assigned to receive oxygen therapy to maintain Pao2 between 70 and 100 mm Hg or arterial oxyhemoglobin saturation (Spo2) between 94% and 98% (conservative group) or, according to standard ICU practice, to allow Pao2 values up to 150 mm Hg or Spo2 values between 97% and 100% (conventional control group).

The primary outcome was ICU mortality.

Secondary outcomes included occurrence of new organ failure and infection 48 hours or more after ICU admission.

Results A total of 434 patients (median age, 64 years; 188 [43.3%]women) received conventional (n = 218) or conservative (n = 216) oxygen therapy and were included in the modified intent-to-treat analysis.

Daily time-weighted Pao2 averages during the ICU stay were significantly higher (P < .001) in the conventional group (median Pao2, 102 mm Hg [interquartile range, 88-116]) vs the conservative group (median Pao2, 87 mm Hg [interquartile range, 79-97]). Twenty-five patients in the conservative oxygen therapy group (11.6%) and 44 in the conventional oxygen therapy group (20.2%) died during their ICU stay (absolute risk reduction [ARR], 0.086 [95% CI, 0.017-0.150]; relative risk [RR], 0.57 [95% CI, 0.37-0.90]; P = .01). Occurrences were lower in the conservative oxygen therapy group for new shock episode (or liver failure and new bloodstream infection Among critically ill patients with an ICU length of stay of 72 hours or longer, a conservative protocol for oxygen therapy vs conventional therapy resulted in lower ICU mortality. These preliminary findings were based on unplanned early termination of the trial, and a larger multicenter trial is needed to evaluate the potential benefit of this approach.

Pulmonary Communications  A quarterly Newsletter of National College of Chest Physicians

15

Published By : National College of Chest Physicians (India) For Free Circulation Amongst Medical Professionals Vallabhbhai Patel Chest Institute, University of Delhi 110007.

Mobile : +91 9810033395 • e-mail : drchawla@hotmail.com Printed at : urvi compugraphics • 022-2494 5863 • email : urvi@urvi.cc

16

Editorial Office

Dr. Rajesh Chawla

Institute of Respiratory Medicine, Critical Care and Sleep Medicine, Indraprastha Apollo Hospitals, Gate No.-2, 2nd Floor, Room No. 1223, Sarita Vihar, Delhi-Mathura Road, New Delhi - 110076 • Mobile : +91 9810033395

drchawla@hotmail.com

Pulmonary Communications  A quarterly Newsletter of National College of Chest Physicians