Critical care july sep 2012

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Volume 8, Number 2

July-September 2012

Amniotic Fluid Lamellar Body Count as a Predictor of Fetal Lung Maturity Autologous Bone Marrow Stem Cell Therapy shows Functional Improvement in Hemorrhagic Stroke- A Case study Is Essential Medicine Organizations only

concept

for

Voluntary

Serum Magnesium levels in Chronic Alcoholics “Pseudo central cervical Fibroid in a Nulliparous Girl –A Case Report Surgical Treatment of Obesity and Diabetes Aneurysm of Mitral Valve Complicated by Ventricular Tachycardia Multiple Developmental A Therapeutic Challenge

Urogenital

Anomalies:

A division of

Asian Journal of

Critical Care Volume 8, Number 2, July-September 2012

An IJCP Group Publication Dr Sanjiv Chopra Prof. of Medicine & Faculty Dean Harvard Medical School Group Consultant Editor Dr Deepak Chopra Chief Editorial Advisor

Dr KK Aggarwal CMD, Publisher and Group Editor-in-Chief Dr Veena Aggarwal MD & Group Executive Editor

Contents Contents From the Desk of Group Editor-in-chief

Reflexology for Cancer Symptoms

5

KK Aggarwal

Anand Gopal Bhatnagar Editorial Anchor

Critical Care Editorial Board Dr MM Pandit Rao Prof. Anesthesia, BJ Medical College, Pune Dr Vijay Langer Head, Dept. of Anesthesia, Moolchand Medcity, New Delhi Dr Rajesh Chauhan Sr. Anesthetist, Escorts Heart Institute, New Delhi Dr A Kale Prof. Anesthesia, AIIMS, New Delhi Dr Manju Mani Director-Critical Care, Delhi Heart and Lung Institute New Delhi Dr Tarlika Doctor Associate Professor Anesthesia, BJ Medical College, Ahmedabad Dr Sunita Jain, New Delhi

IJCP Editorial Board Obstetrics and Gynaecology Dr Alka Kriplani Dr Thankam Verma, Dr Kamala Selvaraj

review article

Amniotic Fluid Lamellar Body Count as a Predictor of Fetal Lung Maturity

6

Sunanda Kulkarni, Jayamma

Autologous Bone Marrow Stem Cell Therapy shows Functional Improvement in Hemorrhagic

Stroke- A Case study

9

Cardiology Dr Praveen Chandra Dr M Paul Anand, Dr SK Parashar Paediatrics Dr Swati Y Bhave Dr Balraj Singh Yadav Dr Vishesh Kumar Diabetology Dr Vijay Viswanathan Dr CR Anand Moses, Dr Sidhartha Das Dr A Ramachandran, Dr Samith A Shetty Dentistry Dr KMK Masthan Dr Rajesh Chandna

clinical Study

Is Essential Medicine concept for Voluntary Organizations only?

12

Dixon Thomas, G. Seetharam, Y. Padmanabha Reddy, Gerardo Alvarez-Uria

Gastroenterology Dr Ajay Kumar Dermatology Dr Hasmukh J Shroff Nephrology Dr Georgi Abraham

Original article

Neurology Dr V Nagarajan

Serum Magnesium levels in Chronic Alcoholics

Journal of Applied Medicine & Surgery Dr SM Rajendran

KP Shah, HB Sirajwala, RL Shah

17

Advisory Body Heart Care Foundation of India Non-Resident Indians Chamber of Commerce & Industry World Fellowship of Religions

Advisory Body Asian Journal of Critical Care Vol. 8, No. 3, October-December 2012

3

Asian Journal of

Review Article

Critical Care Volume 8, Number 2, July-September 2012

Contents

Published, Printed and Edited by Dr KK Aggarwal, on behalf of IJCP Publications Ltd. and Published at E - 219, Greater Kailash, Part - 1 New Delhi - 110 048 E-mail: editorial@ijcp.com

case report “Pseudo central cervical Fibroid in a Nulliparous Girl –A Case Report” 22

Printed at Entire Printers Nampally, Hyderabad

N Rajamaheswari, Sugandha Agarwal, Archana Bharti Chhikara, K Seethalakshmi

© Copyright 2012 IJCP Publications Ltd. All rights reserved.

The copyright for all the editorial material contained in this journal, in the form of layout, content including images and design, is held by IJCP Publications Ltd. No part of this publication may be published in any form whatsoever without the prior written permission of the publisher.

Surgical Treatment of Obesity and Diabetes

24

PS Mahato, AS Dabhi, PB Thorat

Editorial Policies The purpose of IJCP Academy of CME is to serve the medical profession and provide print continuing medical education as a part of their social commitment. The information and opinions presented in IJCP group publications reflect the views of the authors, not those of the journal, unless so stated. Advertising is accepted only if judged to be in harmony with the purpose of the journal; however, IJCP group reserves the right to reject any advertising at its sole discretion. Neither acceptance nor rejection constitutes an endorsement by IJCP group of a particular policy, product or procedure. We believe that readers need to be aware of any affiliation or financial relationship (employment, consultancies, stock ownership, honoraria, etc.) between an author and any organization or entity that has a direct financial interest in the subject matter or materials the author is writing about. We inform the reader of any pertinent relationships disclosed. A disclosure statement, where appropriate, is published at the end of the relevant article.

Note: Asian Journal of Critical Care does not guarantee, directly or indirectly, the quality or efficacy of any product or service described in the advertisements or other material which is commercial in nature in this issue.

Aneurysm of Mitral Valve Complicated by Ventricular Tachycardia 29 Monika Maheshwari, Nirmal Vyas, Rk Gokroo

Multiple Developmental Urogenital Anomalies: A Therapeutic Challenge

32

N Rajamaheswari, Sugandha Agarwal, Archana Bharti Chhikara, K Seethalakshmi

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Asian Journal of Critical Care Vol. 8, No. 3, October-December 2012 Sr.: Senior; BM: Business Manager

From the desk of Group editor-in-chief

Reflexology for Cancer Symptoms Dr KK Aggarwal Padma Shri and Dr BC Roy National Awardee Sr. Physician and Cardiologist, Moolchand Medcity, New Delhi President, Heart Care Foundation of India Group Editor-in-Chief, IJCP Group and eMedinewS Chairman Ethical Committee, Delhi Medical Council Director, IMA AKN Sinha Institute (08-09) Hony. Finance Secretary, IMA (07-08) Chairman, IMA AMS (06-07) President, Delhi Medical Association (05-06) emedinews@gmail.com https//twitter.com/DrKKAggarwal Krishan Kumar Aggarwal (Facebook)

WA study led by a Michigan State University researcher offers the strongest evidence yet that reflexology can help cancer patients manage their symptoms and perform daily tasks.

Funded by the National Cancer Institute and published in the latest issue of Oncology Nursing Forum, it is the first large-scale, randomized study of reflexology as a complement to standard cancer treatment, according to lead author Gwen Wyatt, a professor in the College of Nursing.

Reflexology is based on the idea that stimulating specific points on the feet can improve the functioning of corresponding organs, glands and other parts of the body.

The study involved 385 women undergoing chemotherapy or hormonal therapy for advanced-stage breast cancer that had spread beyond the breast. The women were assigned randomly to three groups: Some received treatment by a certified reflexologist, others got a foot massage meant to act like a placebo, and the rest had only standard medical treatment and no foot manipulation.

They found that those in the reflexology group experienced significantly less shortness of breath, a common symptom in breast cancer patients. Perhaps as a result of their improved breathing, they also were better able to perform daily tasks such as climbing a flight of stairs, getting dressed or going grocery shopping.

Also unexpected was the reduced fatigue reported by those who received the “placebo” foot massage, particularly since the reflexology group did not show similarly significant improvement. Wyatt is now researching whether massage similar to reflexology performed by cancer patients’ friends and family, as opposed to certified reflexologists, might be a simple and inexpensive treatment option.

Asian Journal of Critical Care Vol. 8, No. 3, October-December 2012

5

Reviewarticle clinical practice

Amniotic Fluid Lamellar Body Count as a Predictor of Fetal Lung Maturity Sunanda Kulkarni*, Jayamma

Abstract Assessment of fetal lung maturity can be done with various biochemical tests on amniotic fluid. In the present study lamellar body count (LBC) was compared with the traditional shake bubble test (SBT), as LBC is simple, reliable and cost effective method to predict fetal lung maturity. This was a prospective study conducted on 50 patients with known LMP, Gestational Age (GA) >28 weeks presenting in active phase of labor with intact membranes. Amniotic fluid was collected either through vaginal route or through amniocentesis and SBT &LBC were conducted on all samples. Newborns were watched for signs of respiratory distress syndrome (RDS) Fourteen babies developed RDS. i.e. 1 out of 34 babies with positive SBT, 7 out of 10 with intermediate SBT,6 out of 6 with negative SBT developed RDS .Lamellar body count varied between 3000-28,000/mlit among the 14 babies with RDS. i.e. all cases with RDS had LBC <30000/Âľlit. This study showed that LBC with cut off value of 30,000 /mlit to predict fetal lung maturity is superior to all other tests in terms of technique and cost effectiveness..

Key words: Fetal lung, RDS, bubble test, amniotic fluid

R

DS due to prematurity is the leading cause of perinatal morbidity and mortality in obstetric practice .It is important to predict fetal lung maturity accurately with a quick cost effective method before termination of pregnancy, particularly in problem pregnancies such as previous LSCS, precious pregnancy requiring interventions for associated risks and those pregnancies with unreliable dates, irregular cycles etc. It is well known that in pathological cases fetal lung maturity deviates from that at which it occurs in normal pregnancy thereby further complicating the decision for termination. Various biochemical tests done on amniotic fluid can assess fetal lung maturity .It includes L: S ratio, detection of phosphatidyl glycerol, dipalmitoyl phosphatidyl choline estimation, Shake bubble test (SBT), fluorescence polarization, optical density at 650nm and lamellar body count (LBC). L: S ratio is the time honoured standard test for assessing fetal lung maturity, but it is expensive, laborious and time consuming. SBT is a rapid,

*Professor Dept. of Obstetrics and Gynaecology, Bowring and Lady Curzonhospital Bangalore Medical College, Bangalore.

6

inexpensive, bedside test, but it is inconclusive when test results are intermediate. Another test on amniotic fluid is lamellar body count (LBC). Lamellar bodies are storage forms of surfactant released by type II pneumocytes in to amniotic fluid. They have the same size as platelets, hence can be easily quantified using automated hematological cell counts, set for platelet quantification. Their production starts at 20-24 weeks of gestational age and are released into lung fluid at a basal rate. Secretion is stimulated by labor and initiation of air breathing. As LBC is inexpensive test this study was done with an aim to evaluate the reliability of this test as a possible cost effective alternative in assessing the fetal lung maturity.

Material and Methods.

The study was conducted on 50 patients with known LMP, gestational age >28 weeks and who delivered with in 72 hours of collection of amniotic fluid.

This included women reporting in active phase of labor with intact membranes, women presenting with threatened preterm labor, women with severe PIH or IUGR who need induction. Women with hydramnios, oligohydramnios, multiple pregnancy, anemia, heart disease, antepartum hemorrhage, chorioamniotis, intrauterine death and those women where amniotic fluid is grossly contaminated with bood, meconium and mucus were excluded from the study.

Asian Journal of Critical Care Vol. 8, No. 2, July-September 2012

review article Samples were collected through vaginal route in those who come in active phase of labour with intact bag of membranes using Sims speculum and sterile 10cc syringes. Whenever amniotic fluid could not be collected from the bag of membranes vaginal pool of liquor was aspirated. Samples were collected by amniocentesis in one case of severe PIH and two cases of threatened preterm labor. In one case amniotic fluid was collected during cesarean section.

Samples of amniotic fluid were tested within 4-6hrs of collection or preserved at 4ºC until they were taken for testing. SBT was done immediately after collection using uncentrifuged samples. LBC was done using automated hematological cell counter.

RDS was diagnosed in the newborn when all the following criteria were present. zz Physical signs-nasal flaring, grunting, cyanosis, tachypnoea, zz Supplementary oxygen requirement for more than 24hrs zz Radiographic findings of widespread lung opacities.

Table 1. SBT, Maturity, and Birth weight in relation to RDS No of cases

RDS RDS present absent

SHAKE BUBBLE TEST Positive

34

33

1

Intermediate

10

3

7

Negative TOTAL

6

0

6

50

36

14

NEW BORN MATURITY Below 34 wks

13

-

13

Above 34 wks

17

36

1

TOTAL

50

36

14

BIRTH WEIGHT

6

Below 1.5kg

6

Above 1.5kg

44

TOTAL

50

-

8

36 36

14

Table 2. Clinical utility of LBC at various cut off levels LBC

P value Sensi- Specitivity ficity

<30,000/µlit

<0.001

100%

97.2%

93.3%

100%

Those cases classified as transient tachypnoea of newborn were also considered as RDS.

<35,000/µlit <0.0001

100%

86.1%

73.6%

100%

For both tests (SBT & LBC) sensitivity, specificity, positive and negative predictive values were calculated.

Table 3.

Results The study group of 50 patients was constituted by 29(58%) term pregnancies,8 (16%) preterm normal pregnancies,7 (14%) PIH cases,6 (12%) PIH with preterm pregnancies.

From table 1 it is seen that SBT was positive in 34 cases out of which one baby developed RDS, intermediate in 10 cases out of which 7 babies developed RDS and negative in 6 cases where all babies developed RDS. Same table shows that all 13 cases with GA less than 34 wks developed RDS, only one out of 37cases with GA more than 34wks-developed RDS. Also RDS developed in all 6 babies weighing less than 1.5kg and 8 out of 44 babies weighing more than 1.5kg.

Among 50 cases LBC was less than 30,000/µlit in 15 cases between 30,000-35,000/µlit in 5 cases and more Asian Journal of Critical Care Vol. 8, No. 2, July-September 2012

Positive Negative PV PV

Parameters in Amniotic fluid

Sensi- Speci- Positive PV tivity ficity

SBT

92.8%

91.6%

81.2%

97%

LBC

100%

97.2%

93.3%

100%

Negative PV

Table 4. Comparison of methodology of LBC&SBT Methodology

LBC

SBT

1. Simplicity

Simple

Simple

2.Duration

5min

15min

3.Quantity of amniotic fluid required

0.4 ml

2.25ml

4.Observer bias

Absent

Present

5.Accessibility

Readily accessible

Readily accessible

6.Specialised training

Not required

Not required

7.Cost

Inexpensive

Inexpensive

8.Meconeum/blood contamination

Feasible

Not feasible

7

review article than 35,000/µlit in 30 cases. Those which developed RDS had LBC between 3,000//µlit -28,000//µlit.

Sensitivity and specificity of LBC to predict RDS when cut of value of 30,000//µlit and 35,000//µlit are shown in the table below. (Table 2) Since LBC <30,000/µlit is more specific than 35,000/ µlit in predicting RDS a cut off of <30,000/µlit is taken.

Discussion From the present study we found that all the 14 babies with RDS showed LBC <30,000/µlit. Only 13 babies with RDS showed negative SBT (-ve & intermediate results are taken as negative.) Thus comparing sensitivity, specificity and predictive values of SBT and LBC from table 3 we found that LBC is more sensitive more specific and has better predictive value than SBT in predicting RDS. Comparison of methodology of SBT and LBC showed that LBC is simple, inexpensive, rapid test, requires only small quantity of amniotic fluid, contamination does not interfere with test results and no special training is needed for conducting the test.

Cacyea and co workers have claimed that at term fetal lung is more echogenic than liver. However as the perception of echogenecity is subjective, this aspect needs further work up. Todate various biochemical tests on amniotic fluid continue to be the standard tests to measure surfactant and hence predict fetal lung maturity.

Rapidness, reliability, feasibility and cost effectiveness are matters of concern in applying these tests.

Studies by Edward R Ashwood et al, Preethi Mittal et al, Caslos R Dalence et al have inferred LBC to be rapid, reliable, feasible and cost effective test for fetal lung maturity. In a study by Michael E Roche, LBC was found to be a reliable test in pregnancies complicated by diabetes mellitus.

Though Ashwood et al from his study opined that LBC should not be carried out on contaminated

8

vaginal pool sample, Dubin, Dalence et al showed that contamination did not affect LBC significantly. Our present study has also found the same.

The recommended cut off value for LBC is 30,000/m lt according to Dalence et al, Fakhory, Dowie et al studies.

35,000/mlt according to Preeti Mittal, Ashwood et al.

26,000/mlt according to Dubin et al study. 37,000/mlt according to Michael. E. Roche study. All have used different centrifugation protocols. Maternal and fetal neonatal medicine 2002 August 12(2) 95-98 quotes, optimal L: S ratio of > 3 and LBC of >50,000/mlt for predicting lung maturity in diabetic women and 30,000/mlt in nondiabetic.

As suggested by Nerhoff 2003, LBC procedure, sample preparation, equipment needs standardization to find uniform threshold values where RDS are not seen.

From the present study we found that LBC cut off of 30,000/mlt is optimum for predicting RDS.LBC is equal to SBT in simplicity and cost effectiveness and superior to SBT in reliability.

References 1. Ashwood ER, Oldroyed RG, Palmer SE, Measuring the number of lamellar body particles in amniotic fluid.

Obstet.Gynecol 1990;75:289-92.

2. Dalence CR,Bowie LJ,Dohnal JC, Farrel EE, Neerhoff MG.Amniotic fluid lamellar body count , a rapid and reliable fetal maturity test Obstet.Gynecol1995;86:23539.

3. Dubin SB. Characterization of amniotic fluid lamellar bodies by resistive pulse counting: relationship measures of fetal lung maturity. Clin Chem 1989;35:612-6.

4. Fakhoury G, Daikoku NH, Benser J, Dubin NH. Lamellar body concentrations and the prediction of fetal lung maturity .Am J Obstet.Gynecol 1994;170:72-6.

5. Michael E Roche et al .The use of lamellar body counts to predict fetal lung maturity in pregnancies complicated by diabetes mellitus. Meeting of society of maternal and fetal medicine New Orleons Jan 2002 14-19.

6. Maternal fetal neonatal medicine 2002,August 12 (2).95-98.

Asian Journal of Critical Care Vol. 8, No. 2, July-September 2012

Review article clinical practice

Autologous Bone Marrow Stem Cell Therapy shows Functional Improvement in Hemorrhagic Stroke- A Case study Abstract In hemorrhagic stroke, damage to the brain tissue is inevitable and no effective treatment for functional improvement is currently available except neurorehabilitation. Stem cell therapy is a rapidly growing field and has recently opened new avenues for brain repair strategies. We present a case study of 69 year old female treated with stem cell therapy for right sided hemiplegia caused due to left thalamic hemorrhagic stroke. Inspite of regular physiotherapy, the patient had constant residual neurodeficit, one year after the stroke, which was severely incapacitating. In view of the same, the patient was given intrathecal autologous bone marrow derived stem cell therapy as part of the NeuroRegeneration and Rehabilitation Therapy (NRRT) along with rehabilitation.

After the therapy, patient showed functional as well as neurological improvements (cognition and motor strength) without any side effects. There is accumulating experimental data showing the benefits of cell transplantation on functional recovery after hemorrhagic stroke. This case study supports the concept of Neuroregeneration with bone marrow stem cells as a novel strategy having great therapeutic potential. However, large clinical studies are needed to further investigate autologous bone marrow stem cell therapy in addition to neurorehabilitation for treating the disability in hemorrhagic stroke.

Key words: Hemorrhagic stroke, Bone Marrow Stem Cells, Autologous Transplantation, Neuroregeneration, Rehabilitation

S

troke is the leading cause of mortality and significant morbidity in India (prevalence of approximately 0.5%) and worldwide.13 It is ranked as the sixth leading cause of DALY (disability adjusted years) in 1990 and projected to rank fourth by 2020. Hemorrhagic stroke, of all strokes, is a major cause of serious long-term disability and the survivors of ischemic insults have no effective treatment available other than neurorehabilitation. To repair the human brain after hemorrhagic stroke may seem unrealistic because of the loss of many different neuronal cells.

One of the most encouraging approaches has been restorative therapy using stem cell replacement in the ischemic areas.2 Apart from their individual impact, research shows that exercise enhances the effect of stem cells by helping the mobilization of local stem cells and encouraging angiogenesis. Hence, the concept of Neuro Regenerative Rehabilitation Therapy (NRRT) endeavors to combine the impact of neuroregeneration and rehabilitation for a better therapy outcome.

Although, evidence of the beneficial effects of stem cells in animal stroke models is growing, there is lack of enough clinical data.3 Our case study is an effort towards this direction.

Source: Adapted from Am faon Physician 2011;83(3):271-280

Asian Journal of Critical Care Vol. 8, No. 2, July-September 2012

Case Study We present a 69 years old female patient with history of hemorrhagic infarct, a year ago, leading to right sided hemiplegia with impaired cognition, speech as well as bladder & bowel function. MRI revealed left thalamic bleed with intraventricular extension. Patient received standard treatment for the same and had a VP shunt in place. She also underwent neurorehabilitation for one year. Then, on our pre stem cell treatment evaluation, patient was hypertonic with spasticity of Grade 1 (According to Modified Ashworth Scale). She was hyperreflexic with reduced sensations over right half of the body and had muscle power of Grade 2/5 in right upper and lower limb and Grade 5/5 strength on the left half of her body. She was impaired cognitively with affection of orientation in time, place and person, along with hemineglect of right side of her body and emotionally labile. Functionally, she was dependent on the caregiver for all her activities of daily living (ADLs). STREAM (Stroke Rehabilitation Assessment of Movement) score was.19 Functional Independence Measure (FIM) score was 39 with severe affection in areas of self care, sphincter control, mobility & social cognition. She was given autologous bone marrow stem cells intrathecally, since she had exhausted all other treatment options.

9

review article Methods The NRRT has been designed and the patients are selected for the therapy based on the inclusion criterion as per the World Medical Associations Helsinki declaration.4 The NRRT is approved by the Institutional committee for Stem cell Research and Therapy (IC-SCRT). G-CSF (300 mcg) injections were administrated subcutaneously, 48 hours and 24 hours prior to the bone marrow aspiration. The G-CSF administered before the transplantation helped in stimulation of CD34+ cells and also in survival and multiplication of the stem cells. Bone marrow (100ml) was aspirated from the iliac bone and Mononucleocytes (MNC) were obtained after density gradient separation.

Viable count of the isolated MNCs was taken and checked for CD34+ by FACS analysis. A total of 50 x 106 MNC were then injected intrathecally in L4-L5 using a lumbar puncture needle and catheter.14 Stem cell therapy was followed by neurorehabilitation including regular physiotherapy, occupational therapy and counseling to reduce her impairment and improve functionality. The patient showed progressive improvements after the therapy as mentioned below.

Results Cognition: Prior to stem cell therapy, there was total neglect of right half of body and immediately after the stem cell therapy, awareness of the right side of the body was present and the patient tried to use it for functional activities. Emotionally, she was less labile and crying spells had reduced significantly. She had increased attention span, with ability to participate in conversations and read the clock & tell time accurately. She could identify colours, weeks and months of the year and was well oriented in time and place along with improvements in her comprehension and memory skills.

Motor System: She could move her right upper extremity voluntarily. Improvement in gross as well as fine motor activity was observed. Tightness/spasticity/ clawing of right hand had reduced and could open & close her fist. Strength in her upper extremity had grossly improved from grade 2 to 3++. Strength in her right lower limbs had improved from Grade 2 to 3++.

Also, spasticity in her muscles had reduced significantly with near normal voluntary control.

Activities of Daily Living: Independently she can now 10

tie a knot, cut vegetables, peel peas and pick up coins and marbles with her right hand, transfer from bed to wheelchair & vice versa, stand up from chair & remain standing for about 10 mins with an assistive device.

On the bed, she could shift & roll independently. On reassessment her Functional Independence Measure6 had increased from 39-84 with major improvements seen in sections of self care activities, transfer skills, social cognition & communication. STREAM7 score improved from 19-53, with an overall improvement in voluntary movements/activities using the right side of the body.

Discussion In hemorrhagic stroke, the ultimate aim of any therapeutic strategy is to achieve maximum possible restoration of normal function. Stem cell therapy is a cellular approach that has the potential to induce all of the neurorestorative processes essential for facilitating recovery of neurological function.5 Stem cells are undifferentiated cells that retain the capacity to proliferate and produce generations of progenitor cells, which can differentiate into virtually all cell types of the body in response to the proper stimuli.8 The main rationale to employ stem cell therapies in stroke patients is to replace infarcted brain tissue in a way that lost neurons are replaced and there is re-establishment of a functional neuronal circuitry with proper nerve conduction. It has been observed that the transplanted stem cells can act as biological mini pumps releasing a missing transmitter or secrete growth factors which can stimulate plastic responses, improve the survival and function of host neurons and restore synaptic connection by providing a local reinnervation and neuronal replacement. The stem cells can become integrated into existing neural and synaptic networks, and reestablish functional afferent and efferent connections.13,10 The non- regenerative trait of the injured adult brain has been challenged in recent years and neural plasticity has been observed experimentally in both global and focal brain ischemia in animal models. There are several sources of stem cells that may be useful in hemorrhagic stroke, embryonic stem cells derived from the inner cell mass of preimplantation embryos, neural stem cells found in specific regions of brain, bone marrow, umbilical cord blood and adipose tissue.1 In our case study, BMSC were chosen as they are easily accessible through the Asian Journal of Critical Care Vol. 8, No. 2, July-September 2012

review article aspiration of the bone marrow, can be isolated from patients themselves thereby bypassing the ethical problems and can easily be administered to the patients for auto transplantation. The MNCs obtained from bone marrow, comprises of a variety of cells like hematopoietic stem cells, tissue specific progenitor cells, mesenchymal stromal cells and specialized blood cells in different stages of development.

They produce trophic factors in host tissue after transplantation, which is beneficial to the tissue protection and restoration, alongwith a potential to differentiate into local cells in response to environmental signals and cues. They are also known to home onto the site of injury and promote angiogenesis. In a study

by Lee et al., cells of human NSC line transplanted into the brain of mice after ICH gave rise to both neurons and astrocytes and induced behavioral recovery in the rotarod and limb placing tests.8 In other study, human BMSCs transplanted in rats after ICH, showed formation of new neuronal connections and significantly improved neurological function was found 1 week after transplantation.12 Behavioral recovery in the beamwalking test was observed in the groups of rats that received intraarterial and intraventricular delivery of BMSC in a study by Zhang and coauthors,15 who used cells of rat origin. Autologous mesenchymal stem cells have been widely used in the clinical trials in brain injury diseases such as multiple sclerosis, glioma and recently with stroke.11,10 In our case study, autologous bone marrow stem cell transplantation was given intrathecally to a hemorrhagic stroke patient as part of the NRRT. After the therapy the patient showed improvements functionally due to better cognition, voluntary control and motor strength, as stated above and evident from improvements in FIMS as well as STREAM scores. The patient was not recovering with sole neurorehabilitation for 1 year and only after addition of stem cell therapy the patient showed functional improvement, suggests that BMSC played a significant role by various mechanisms as stated above.

Conclusion Autologous intrathecal transplantation of bone marrow stem cells (BMSCs) fully circumvents the problem of immune rejection and bears no ethical concerns.

Intrathecal transplantation is a non invasive and most importantly a safe method for bone marrow stem cell transplantation without any major side effects.

Asian Journal of Critical Care Vol. 8, No. 2, July-September 2012

In view of experimental data, the patient was treated with autologous bone marrow stem cells as a last resort to improve functionality thereby decreasing her disability. Post stem cell therapy, alongwith continued neurorehabilitation, the patient showed functional and neurological improvements which were progressive in nature. This case study represents one of the earliest clinical data on intrathecal delivery of autologous bone marrow derived stem cells showing functional improvement in hemorrhagic stroke, supporting laboratory experimental data. Further large clinical studies are needed to investigate functional improvement by autologous bone marrow stem cell therapy in addition to neurorehabilitation for treating the disability in hemorrhagic stroke.

Reference 1. Andres RH, Guzman R, Ducray A et al. Cell replacement therapy for intracerebral hemorrhage. Neurosurg Focus, 2008;24:1-10 2. Bliss T, Guzman R, Daadi M, Steinberg GK. Cell transplantation therapy for stroke. Stroke 38 (2): 817-826, 2007 3. Chen J, Li Y, Wang L, et al. Therapeutic benefit of intravenous administration of bone marrow stromal cells after cerebral ischemia in rats. Stroke 2001;32: 1005-1011.

4. Carlson RV, Boyd Km, Webb Dj. The Revision of The Declaration of Helsinki: Past, Present And Future. Br J Clin Pharmacol 2004;57:695-713.

5. Dharmasaroja P. Bone marrow-derived mesenchymal stem cells for the treatment of ischemic stroke. Journal of Clinical Neuroscience 2009;16:12-20.

6. Hamilton BB, Laughlin JA, Granger CV, Kayton RM. Interrater agreement of the seven level Functional Independence Measure(FIM). Arch Phys Med Rehabil .1991;72:790 7. Kathy Daley, Nancy Mayo, Sharon Wood-Dauphine´e.

Reliability of Scores on the Stroke Rehabilitation Assessment of Movement (STREAM) Measure. Physical Therapy 1999;79(1).

8. Lee HJ, Kim KS, Kim EJ, Choi HB, Lee KH, Park IH, et al: Brain transplantation of immortalized human neural stem cells promotes functional recovery in mouse intracerebral hemorrhage stroke model. Stem Cells 2007; 25:1204-1212 9. Lipska K , Sylaja PN , Sarma PS, Thankappan KR, Kutty VR, Vasan RS, et al Risk factors for acute ischaemic stroke Contâ&#x20AC;&#x2122;d on page

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Clinical Stduy clinical practice

Is Essential Medicine concept for Voluntary Organizations only?

Dixon Thomas*, G. Seetharam**, Y. Padmanabha Reddyâ&#x20AC; , Gerardo Alvarez-Uriaâ&#x20AC;Ą

Abstract Patients are not aware that there is essential list for medicines and what are the advantages of it. It is rare to see any patient asking for providing medicines from essential medicines list (EML). Moreover, patients may have concerns about the quality and efficacy of the medicines which are of low cost. EML is largely a deal of stake holders in health care. Mostly, charity or voluntary organizations are developing or maintaining EML. For the rest of the world medicines are a mode of increasing the revenue. In many parts of the world, there is significant share for the corporate hospitals in disseminating healthcare.

It becomes like pharmaceutical care with a multi-professional approach improves the healthcare delivery. EML is a tool for effective healthcare for voluntary organizations that believes in reducing the cost of medicines and make the resources available for more those who need at low budgets.

Key words: EML, cost, healthcare, WHO, evidence

C

haritable and voluntary organizations play a significant role in practicing essential medicine concept which serve majority of the world population.1

Formularies are short profiles of drugs that are preferred by a health plan or administration. The level of cost minimization needs to be studied for the compliance of prescribing from the hospital formulary.2

As medicines consume a significant portion of the hospital budget, the administration takes extra care in the handling of it. Two simple strategies are to prepare EML and reduce cost of medicines or invest higher capital on medicines for higher profit.3 In those health systems who have a EML and a good purchase policy, patients are charged much less for drugs than the marginal cost to the provider.4 WHO essential medicines list World Health Organisation (WHO) promoted the concept of essential drugs. The concept of essential drugs started in the year 1997 with publication of the first list. Since then WHO revises the model EML every two years.5 Recently World Health Organization (WHO) intimated to use Essential

1Head, Dept of Pharmacy Practice, RIPER, Anantapur, India 2PharmD Intern, RIPER, Anantapur, India 3Principal, RIPER, Anantapur, India 4Head, Dept of Infectious Diseases, RDT Hospital, Bathalapalli, India

12

Medicines List (EML) instead of Essential Drug List (EDL).6 According to the WHO, Essential medicines are those that satisfy the priority health care needs of the population.7 The medicines included in the WHO Model List of Essential Medicines are selected with regard to disease prevalence, evidence of safety and efficacy, and comparative cost-effectiveness.8 A visibly transparent and difficult process which is done by a team of experts who critically analyze the available evidence and give to the process their expertise and experience on evaluating published studies.9 Orphan Medicines Model List is used to complement the WHO List of Essential Medicines. These are the medicines for rare diseases.10,11 As costs of medicines change over time, the price of a medicine is not a reason to exclude it from the WHO Model List if it meets the other stated selection criteria.

Cost-effectiveness comparisons are made between alternative medicines within the same therapeutic group. Applications for inclusion, changes or deletions to the Model List are submitted to the secretary of the Expert Committee for the Selection and Use of Essential Medicines.8,12 Indian Essential Drug List

The state of Indiaâ&#x20AC;&#x2122;s health care is growing at a rapid pace. Health-care cost as a percentage of the gross domestic product (GDP) is 5.1% and is designated as a priority for the government. Health-care spending Asian Journal of Critical Care Vol. 8, No. 2, July-September 2012

clinical study is expected to increase from $21 billion in 2005 to $45 billion in 2012. Public spending is anticipated to grow from the present amount of 0.9% of the GDP to 2% of the GDP by 2009. India carries a mixed disease burden of infectious diseases; re-emergence of diseases like tuberculosis and malaria; dreaded diseases like cancer and AIDS; lifestyle diseases like cardiovascular (CV), diabetes, and depression. Disease burdens are projected to rise rapidly with 60% of the global CV burden by 2020 and 73 million diabetic patients by 2025. The changing disease profile therefore calls for more advanced and innovative therapies.13 While considering the drug procurement system, The Tamil Nadu Medical Services Corporation (TNMSC) which was set up in 1994 is a global benchmark for cost effective drug procurement and distribution.14 Formularies/Essential drug lists can be useful tools in managing hospitals more rationally; zz Provide impartial drug information. zz Promote the appropriate use of safe, effective and good quality medicines.

Support cost effective utilization of drug budgets and improve access.15 It is surprising that the Government of India, Ministry of Health and Family Welfare is not very keen on updating the EML. After 2003 the list was updated in 2011.9 Campaigning to improve rational use of medicines through essential drug lists would be important.

Governments should pay extra attention to this approach as medicines are important in regulating the national budget and health of people.16 Use of NLEM is expected to improve prescribing practices as well as the health outcomes. The appropriate use of medicines selected in the NLEM promotes rational use of medicines. Such rational use of medicines, especially antimicrobial drugs, reduces development of drug resistance. NEML serves as a tool for public education and training of healthcare providers.15 Since the 1970s many developing countries have started national programmes for essential drugs to promote the availability, accessibility, affordability, quality, and rational use of medicines.5 Asian Journal of Critical Care Vol. 8, No. 2, July-September 2012

The implementation of the concept of essential medicines is intended to be flexible and adaptable to many different situations; exactly which medicines are regarded as essential remains a national responsibility.7 An essential medicine has been suggested as a strong indicator of the effectiveness of health systems and there should be clear relationships between the national EML, standard treatment guidelines, and procurement practices within the country.17 The concepts of evidence based selection of medicines and cost-effective treatment protocols need to be included in the training of doctors, pharmacists, nurses and other health care professionals. Pharmacovigilance remains an important aspect of ensuring the safety of medicine used.18 In India each prescriber decides on his/her own which make or brand is to be written for the patient.

The information currently given to the patients in India does not help to make them really informed enough to make a considered choice in selecting their medicines.19 Concept of essential medicines is relatively new to India and Tamil Nadu is the first state to develop the essential medicine list as early as in 1994. Then government of Delhi too had developed its own list. The government of India and many other individual states have their own essential medicines list. Unfortunately, the list is not regularly up dated except for Tamil Nadu. The policyâ&#x20AC;&#x2122;s main objective is to improve the availability and accessibility of quality essential drugs for all those in need.20 Other countries

In Australia, formularies mainly aim to â&#x20AC;&#x2DC;recognise the importance of world-class life-enhancing drugs to patientsâ&#x20AC;&#x2122;, protect patients from higher costs and get better value from market competition between medicines with multiple brands.21 In a report of the regional meeting about the role of education in essential use of medicines in Bangkok, Thailand, it was expressed about the need to improve the use of medicines globally. It has been estimated by WHO that about half of all medicines are inappropriately prescribed, dispensed and sold and about half of all patients fail to take their medicines properly.22 13

clinical study In the health objectives of the National Drug Policy, the government of South Africa clearly outlines its commitment to ensuring availability and accessibility of medicines for all people. These are as follows: zz To ensure the availability and accessibility of essential medicines to all citizens. zz To ensure the safety, efficacy and quality of drugs. zz To ensure good prescribing and dispensing practices. zz To promote the rational use of drugs by prescribers, dispensers and patients zz Through provision of the necessary training, education and information. zz To promote the concept of individual responsibility for health, preventive care and Informed decisionmaking.18 Today, four out of every five countries, i.e., at least 156 countries in total, have adopted national essential medicines lists. National lists are widely used for public procurement systems, reimbursement schemes, training, public education, and other nation’s health.12 Clinical Pharmacy

There are lot of community out reach programs by the modern hospitals. Pharmacists should move from behind the counter and start serving the public by providing care instead of just dispensing. There is no future in the mere act of dispensing as the roles are expanding and the consumers expect more. With the emergence of automation, dispensing can and will be taken over by the internet, machines etc. Pharmacists have to fit in to the new role of a medical and health expert. Pharmacists have to emerge as health care professionals without much burden upon the dispensing services. There is a need for improvement in the dispensing service also. Patients should feel the technical quality of the service.23

14

management with medicines) may produce a major improvement in a nation’s health care needs.25 Medicines are a special type of commodity where the user/ consumer is not having the freedom to decide what to buy and at what cost. The doctor prescribes the items, the patients pay, buy and use.19 Pharmaceutical Care

Outcomes-based formularies that consider the clinical, economic, and health-related quality of life (HRQOL) aspects of medication treatment.26 “Pharmaceutical care is the responsible provision of drug therapy for the purpose of achieving definite outcomes that improve a patient’s quality of life”.

The concept of the seven-star pharmacist, introduced

by WHO and taken up by FIP in 2000 in its policy statement on Good Pharmacy Education Practice, sees the pharmacist as a caregiver, communicator, decisionmaker, teacher, life-long learner, leader and manager.

Pharmacists already in practice were mainly educated on the basis of the old paradigm of pharmaceutical product focus. If these pharmacists are to contribute effectively to the new patient-centred pharmaceutical practice, they must have the opportunity to acquire the new knowledge and skills required for their new role.

To do this they must become life-long learners, one of the roles of the new pharmacist.27 Evidence based medicine (Clinical guidelines/standard treatment guidelines)

Continuity of care, equitable access, and quality and safety are major foci in health services management.

The introduction of clinical pharmacy services optimise medication management, improve continuity of patient care and improve patient access to medication.24

It is not compulsory that all the medicines used in the hospital should be in the hospital EML. EML/ Formulary is a continually revised compilation of pharmaceuticals (plus important ancillary information) that reflects the current clinical judgment of medical staff. Availability of brands or generics varied from single to many based on purchase policy. The drugs to be avoided or used with caution in renal failure, hepatic failure and in pregnancy were categorized and included in the formulary as additional information.

The prepared hospital formulary need to be periodically updated, which could thereby help as a tool to promote rational drug use.27

Clinical pharmacy interventions are vital parts in advanced health systems such as those in Europe, the United States, or Australia (e.g., for the better healthcare

Applications for inclusion, changes or deletions to the Model List are submitted to the secretary of the Expert Committee for the Selection and Use of Essential Asian Journal of Critical Care Vol. 8, No. 2, July-September 2012

clinical study Medicines. The Expert Committee is responsible for reviewing the evidence provided in an application and deciding whether to include or delete a medicine.8 Listing the drugs to the EDL is determined by their clinical efficacy and their relative safety, including adverse drug reactions, side effects, interactions, the potential for errors, and the risk of patient harm.1 Newly approved pharmaceutical, biological, and vaccine products should be subjected to a rigorous clinical review and periodic re-review, based on evidence from the clinical literature. Evidence-based assessment of product efficacy, safety, effectiveness, and cost-effectiveness provide the foundation for such a review.12 evidence based national clinical guidelines as the basis for training and rational prescribing; and a national medicines policy to balance conflicting policy objectives and to express government commitment to a common goal.5 The main reason for developing hospital formulary is to set standards for best practice. This should promote high quality; evidence based prescribing and reduces variation in the level of treatment provided to patients.

A formulary can be used as a tool to rationalize the range of medicines used in standard practice.27 Conclusion WHO EML remains the most accepted list of priority medicines for most of the population of the world.

From the model list different countries and healthcare settings prepare their EML. But it is of higher interest for voluntary organizations and hospitals for serving more number of people with minimal cost. The EML is highly evidence based and there is considerable compromise on quality. Clinical pharmacists along with other healthcare professionals provide pharmaceutical care and support rational use of medicines (RUM).

EML is a vital component in RUM and it is a multiprofessional approach.

2. Haiden A. Huskamp, Arnold M. Epstein and David Blumenthal, The impact of a national prescription drug formulary on prices, market share, and spending: lessons for medicare? Health Affairs, 2003;22(3):149-158.

3. Martin DK, Hollenberg D, MacRae S, Madden S, Singer P. Priority setting in a hospital drug formulary: a qualitative case study and evaluation. 2003 Dec;66(3):295-303. Available at: http://www.ncbi.nlm. nih.gov/pubmed/14637013 (Accessed on 18/9/2011).

4. Todd Olmstead and Richard Zeckhause. The MenuSetting Problem and Subsidized Prices: Drug Formulary Illustration. 1999 March 12: Available at: http://www. hks.harvard.edu/m-rcbg/research/r.zeckhauser_jhe_ menu.setting.problem.pdf (Accessed on 18/9/2011).

5. Hans V Hogerzeil. The concept of essential medicines: lessons for rich countries. BMJ, 2004 Nov; 329(7475), Available at http://www.bmj.com/ content/329/7475/1169.full (Accessed on 12/9/2011).

6. Laing R, Tisocki K,Ball DE. How to develop a national formulary based on the WHO model formulary: A practical Guide. WHO, Geneva, 2004. Available at: http://apps.who.int/medicinedocs/en/d/Js6171e (Accessed on 18/9/2011).

7. All India drug action network. Towards a people oriented, rational, drug policy! Available at: http://aidanindia. wordpress.com/2008/08/12/essential-drugs/ (Accessed on 29/08/2011).

8. WHO media center and information. Available at: http://www.who.int/mediacentre/factsheets/fs325/ en/index.html (Accessed on 25/08/2011).

9. Gitanjali B. The national essential medicines list of India: Time to revise and purgethe mistakes. Journal of pharmacology and pharmacotherapeutica, 2010 Nov: Available at: www.jpharmacol.com (Accessed on 11/9/2011).

10. E-drug. Definition essential drugs, orphan medicines list. Available at: http://www.essentialdrugs.org/ edrug/archive/200609/msg00010.php (Accessed on 25/08/2011).

11. Marcus MR. Are drugs for rare diseases are “essential”?

Bull world health organ. 2006. Sep; 84(9). Available at: http://www.who.int/bulletin/volumes/84/9/06-034447. pdf (Accessed on 29/08/2011).

Reference

12. Essential medicines list. Available at: http://www. allcountries.org/health/essential_medicines_list_eml. html (Accessed on 25/08/2011).

1. Matthew Grissinger. The Truth about Hospital Formularies, We’ve Come a Long Way—or Have We? P&T. 2008 August; 33(8): 441. Available at: http:// www.ncbi.nlm.nih.gov/pmc/articles/PMC2730104/ (Accessed on 18/9/2011).

13. Puja Kochhar, Viraj Suvarna, Sandeep Duttagupta, and Shirsendu Sarkar. Cost-Effectiveness Study Comparing Cefoperazone-Sulbactam to a Three-Drug Combination for Treating Intraabdominal Infections in an Indian Health-Care Setting. Value in heath. 2008; II(supplement

Asian Journal of Critical Care Vol. 8, No. 2, July-September 2012

15

clinical study I); Available at: http://www.ispor.org/consortiums/asia/ ViH/6-Kochhar.pdf (Accessed on 18/9/2011).

14. Manimekalai P, Zeena J. Facilitating rational drug usage-An illustrative example. 2011 March; available at: http://www.ictph.org.in/downloads/Facilitating%20 Rational%20Drug%20Usage_with%20Appendix.pdf.

(Accessed on 18/9/2011).

15. CDSCO. National list of essential medicines India 2011.

Available at: http://cdsco.nic.in/National%20List%20 of%20Essential%20Medicine-%20final%20copy.pdf (Accessed on 18/9/2011).

16. Hettihewa LM, Jayarathna KAKT. Comparison of the Knowledge in Core Policies of Essential Drug List Among Medical Practitioners and Medical Students in Galle. Sri Lanka. Online J Health Allied Scs. 2010;9(3):7.

17. Robertson J, Hill SR. The essential medicines list for a global patient population, Clin Pharmacol Ther. 2007 Nov; 82(5):498-500. (Accessed on 29/08/2011).

18. Standard treatment guidelines and essential drug list for South Africa. 2006; Available at: http://www.kznhealth. gov.za/edladult06.pdf (Accessed on 05/09/2011).

19. Veena R, Revikumar KG, Manna PK and Mohanta GP. Emerging trends in medicine procurement in government sector in India-A critical study. Int. J. res. Pharm. Sci. 2010;1(3):372-381.

20. Sitanshu Sekhar Kar, Himanshu Sekhar Pradhan and Guru Prasad Mohanta. Concept of Essential Medicines and Rational Use in Public Health. 2010 Jan;35(1),10-13.

16

21. HansLofgren, Thomas faunce. Drug price reforms.

Available at www.australianprescriber.com (Accessed on 25/08/2011).

22. The Role of Education in Rational Use of Medicine.

Report of the regional meeting. 2007 December, WHO; 12-14. Available at http://www.searo.who.int/ LinkFiles/Meetings_SEA_DRUGS_157.pdf (Accessed on 25/08/2011).

23. KarinWiedenmayer,RobS.Summers,ClareA.Mackie,Andries G. S. Gous, Marthe Everard. Developing pharmacy practice A focus on patient care. WHO, 2006: Available at: http://www. fip.org/files/fip/publications/DevelopingPharmacyPractice/ DevelopingPharmacyPracticeEN.pdf (Accessed on 12/08/2011).

24. Lynne Emmerton, Jennifer Marriott, Tracey Bessell, Lisa Nissen and Laura Dean. Pharmacists and Prescribing Rights: Review of International Developments. J Pharm Pharmaceut Sci. 2005;8(2):217-225.

25. Lisa Nissen. Current status of pharmacist influences on prescribing of medicines. American Journal of HealthSystem Pharmacy. March 2009;66(5):s29-s34.

26. Wenchen Kenneth Wu, Robert B Sause and Christopher Zacker. Use of health-related quality of life information in managed care formulary decision-making. RSAP. 2005; 1(4);579-598.

27. Dâ&#x20AC;&#x2122;Almeida RJ, Acharya LD, Rao PG, Jose J, Bhat RY. Development of hospital formulary for a tertiary care teaching hospital in south India. Indian J Pharm Sci. 2007;69:773-9.

Asian Journal of Critical Care Vol. 8, No. 2, July-September 2012

Original article clinical practice

Serum Magnesium levels in Chronic Alcoholics KP Shah, HB Sirajwala, RL Shah

Abstract Aim: To study prevalence of hypomagnesemia in alcoholic patients, serum magnesium levels in various alcohol related disorders and clinical features in hypomagnesemic alcoholic patients. Study Design: A prospective study of 100 alcoholic patients compared with non-alcoholic patients. Material and methods: The study was conducted at the Shri Sayajirao General Hospital, Vadodara, Gujarat. Hundred consecutive chronic alcoholics admitted due to different diseases formed the study group. They were compared with 100 non-alcoholics with identical diseases and demographic characteristics. Serum magnesium level was measured in both the groups and was compared. Results: Serum magnesium levels in alcoholic patients was significantly low, irrespective of the various alcohol related disorders. Conclusion: As magnesium plays magnesium influences the activity of enzymes by binding to ligands such as ATP, in ATP-requiring enzymes, and binding to the active site of the enzyme in glycolysis pathway. Hypomagnesaemia in alcoholics had more severe neurological features than alcoholics who had normal magnesium levels.

Key words: Magnesium, Alcohol, ATP

A

lcohol consumption is one of the major causes of magnesium loss from several tissues. As a result of this loss, serum magnesium tends to decrease while urinary magnesium excretion increases 2-3 fold. This decrease affects brain, liver and all muscle, including heart, to a varying extent. It has become progressively clear that magnesium loss affects energy production, protein synthesis, cell cycle, and specific functions in the various organs affected. In addition, as magnesium regulated cytokine production and secretion, especially in macrophages and leukocytes, a major role of magnesium deficiency in alcoholinduced inflammatory processes can be envisioned.

Thus, magnesium loss may represent a predisposing factor to the onset of alcohol-induced pathologies including steatohepatitis, cirrhosis, brain stroke and cardiomyopathy.

Hypomagnesemia In Alcoholics â&#x20AC;&#x201C; Mechanisms19,22 Mechanisms of magnesium deficiency in alcoholics are

**Dept. of Biochemistry GGS Govt. Medical College, Faridkot, Punjab **Dept. of Anesthesia, PGIMS Rohtak, Haryana Address for correspondence Backside Civil Vet. Hospital, Sikhan Wala Road, Prem Nagar Kotkapura, Faridkot - 151204, Punjab

Asian Journal of Critical Care Vol. 8, No. 2, July-September 2012

proposed as1. Malnutrition Magnesium depletion in alcoholism results from nutritional deficiency of magnesium and overall caloric starvation. Hypomagnesemia occurs due to inadequate magnesium intake and impaired magnesium absorption due to Vit. D deficiency since it plays a role in magnesium absorption. Phosphate deficiency also contributes to magnesium deficiency but exact mechanism is not known.

2. Acid - base disturbances Alcohol induced acidosis is a mixed acid-base disturbance. Metabolic acidosis is due to lactic acidosis and alcoholic ketoacidosis. Metabolic alkalosis is frequently present due to ethanol induced vomiting. Treatment of this acid - base disturbances includes replacement of magnesium along with other electrolytes., In acute alcohol withdrawal, respiratory alkalosis and insulin release stimulated by administration of nutrients at in concern to move phosphate in to cells. Increased ATP synthesis as a result of phosphate movement in to cells may cause increase magnesium binding and hypomagnesemia.14 3. Gastrointestinal losses The magnesium content of diarrheal fluid is high, 17

Original article ranging from 1 mg/dl to 16 mg/dl, so magnesium deficiency may occur in alcoholics with chronic diarrhea.15

zz

Previous episodes of blackouts, rumfits, delirium tremens Past history of alcohol related disorder.

4. Free fatty acidemia associated to alcohol withdrawal syndrome

Alcoholic patients were classified in four groups:

Lipolysis occurs during withdrawal of alcohol in chronic alcoholism with high levels of long chain free fatty acids. Concentrations of magnesium fall when free fatty acids increase.

Group II- Alcohol withdrawal and intoxication syndrome patients.

5. Increased urinary magnesium excretion Increased excretion might be related to increased lactate production and excretion.43 Certain organic acids accumulating after ethanol ingestion may form magnesium organic acid complexes that are not readily absorbed in renal tubules. The possibility that ethanol or one of its intermediate metabolites exert a direct toxic renal tubular effect on a cation exchange mechanism must be considered.

Aims of the Study zz To study prevalence of hypomagnesemia in alcoholic patients. zz To study serum magnesium level in various alcohol related disorders. zz To study clinical features in hypomagnesemic alcoholic patients.

Material and Methods In this prospective study, 100 chronic alcoholics admitted due to different diseases was conducted at the Shri Sayajirao General Hospital, Vadodara, Gujarat.. They were compared with 100 non-alcoholic with identical illness and demographic characteristics.

Serum magnesium level was measured in both the groups and was compared.

Inclusion criteria

Alcoholic Patients were defined and included in the study were those with history of any three of the following zz Alcoholism more than 5yrs zz Average daily alcohol intake about 120 ml zz Alcohol intake 5-6 days/wk zz Alcohol withdrawal sign/symptoms

18

zz

Group I- Alcoholic liver disease (ALD) patients.

Group III- Alcoholic patients with vascular events (cardiac/cerebral).

Group IV- Alcoholic patients with other illnesses.

Exclusion criteria

Patients excluded from study were those with: zz Presence of concomitant conditions causing magnesium depletion e.g. Intestinal cause [Malabsorption syndrome, tropical sprue, chronic diarrhea], Endocrine and Metabolic cause [hyperthyroidism, aldosteronism], Renal causes [renal tubular necrosis, glomerulus-nephritis, pyelonephritis] zz Drug related renal disorders [Patients on Diuretics, Cyclosporin, Aminoglycosides, Cisplatinum, Vancomycin etc] zz History of Magnesium containing drug intake [antacids etc] Control group

In this group, 100 non-alcoholics with identical illness and demographic characteristics were compared.

Sample collection and analysis

Blood samples from patients were collected for analysis at the time of admission to medicine wards.

Samples were analysed for estimations of Total bilirubin, Direct bilirubin and Indirect bilirubin levels.

Samples were also analysed for Alkaline Phosphatase, SGOT (Serum glutamate oxaloacetate transaminase), SGPT(Serum glutamate pyruvate transaminase) and Gamma GT. Serum urea and Creatinine levels were also done to rule out and renal disease.

Blood samples from the control subjects were also collected for similar testing.

Asian Journal of Critical Care Vol. 8, No. 2, July-September 2012

Original article Table 1. Serum Magnesium in Alcoholics and Controls Patients Magnesium

N

Mean

Standard Deviation

Standard Deviation

Alcoholics

100

1.475

0.5349

Controls

100

2.0110

0.2860

p Value <0.001

Table 2. Prevalence of hypomagnesemia according to various alcoholic group patients Hypomagnesemia Group

Normal Magnesium

No. of patients

% within subgroup

No. of patients

% within subgroup

Total

Alcoholic liver disease

40

83.3

8

16.7

48

alcohol withdrawl or intoxication

14

56

11

44.0

25

alcoholic with vascular events

6

46.2

7

53.8

13

Alcoholic Others

7

50.0

7

50.0

14

Total

67

67 %

33

33 %

100

percentage of patients

Fig. 2 Cases of Hypomagnesemia in study groups Normal Magnesium

100 90 80 70 60 50 40 30 20 10 0

Hypomagnesemia

Gamma GT estimation was done by ‘Szasz Method’.

(IFCC recommended).

Results & Statistical Analysis

Alcoholics

Normal Magnesium Hypomagnesemia

All observations were tabulated and analysed by SPSS version 17. The ‘t-test’ was applied to find out clinical significance. P value<0.05 was taken as significant.

Control

33

89

Hundred alcoholics and 100 non-alcoholics were compared in this study.

67

11

Table-I Serum magnesium levels in alcoholics and controls

Fig. 8 Incidence of signs and symptoms in alcoholic patients with hypomagnesemia 100 90 80 70 60 50 40 30 20 10 0

The mean serum magnesium level in alcoholic group patients was 1.475 mg/dl and mean serum magnesium level in control group patients was 2.0110 mg/dl. This value is statistically significant (p<0.001) calculated by statistical software SPSS 17.

Signs and Symptoms Asian Journal of Critical Care Vol. 8, No. 2, July-September 2012

Carpoped...

Nystagm...

Ataxia

Limb...

Paresthe...

Vomiting

Nausea

Anorexia

Tremor

Cramps

Delirium

Table-II Prevalence of hypomagnesemia according to various alcoholic group patients Seizure

percentage

Serum magnesium level was determined by the xylidine blue reagent , an end point method. Its normal value is 1.8 mg/100 ml to 2.6 mg/100 ml.

The alcoholic patients were further divided into subgroups Maximum number of patients (48%) had Alcoholic Liver Disease of which 40 were suffering from hypomagnesemia.

19

Original article Graph-I Cases of hypomagnesemia in alcoholics & non-alcoholics Among 100 alcoholic patients, 67% had hypomagnesemia and 33% had normal magnesium levels. The control group had 11 % cases of hypomagnesemia.

Graph-II Incidence of signs and symptoms in alcoholic patients with hypomagnesemia The neurological symptoms such as tremors and cramps were present in more than half of alcoholic patients.

Discussion Magnesium plays a role in many of energy storing & releasing reactions involved in oxidative phosphorylation. Indirectly therefore it affects all anabolic & catabolic reactions involving carbohydrates, fat, & proteins. Though its normal concentration is very low it is necessary for many critical physiologic functions and decrease in normal serum value can have serious deleterious effects.

When magnesium intake is restricted urinary excretion decreases thus kidney represents primary regulator of magnesium balance in the body. Alcoholics have the potential for exaggerated risk for morbidity and mortality in presence of magnesium deficiency. It is suggested that hypomagnesaemia may be a cause of neurological damage,7 hypertension and cardiovascular diseases8 and cancer9 in chronic alcoholism.

In the present study mean serum magnesium level in alcoholic group was 1.475 mg/dL and in control group was 2.011 mg/dL. The difference was statistically significant.

Cook C. C.et al has reported relative deficiency of magnesium while studying abnormalities of trace element & vitamins in alcoholic and control patients. Mussalo R. H et al has reported significantly lower serum magnesium concentrations in chronic drunkenness arrestees than control subjects.

In our study, prevalence of hypomagnesemia in alcoholic patients was 67 % ( 67 of 100) which was statistically significant by 5 Chi-Square test. Sullivan et al has reported 66% of alcoholics having abnormally low serum magnesium levels. Elisaf M et al studied 127 chronic alcoholic patients admitted for causes related 20

to alcohol abuse and reported hypomagnesaemia in 29.9% of alcoholic patients. Edmund et al has reported significant hypomagnesaemia in alcoholic patients.

Alcoholic patients were divided in 4 groups with the intention to study serum magnesium level in various alcohol related disorders.

In our study, 83.3% of alcoholic liver disease group patients showed serum magnesium less than the control. Waker W.E.C has shown the association of low serum magnesium levels with liver disease (cirrhosis) in the absence of alcoholic withdrawal syndrome. Sullivan et al 42 has reported 44.4 % (4 out of 9) of alcoholic cirrhotic (histology proven) patients having hypomagnesemia. Romani in his review has emphasized that magnesium loss may represent a predisposing factor to the onset of alcohol-induced pathologies including steatohepatitis and cirrhosis.

Our study showed 56% of Alcoholic withdrawal or intoxication group patients as having hypomagnesemia.

Sullivan et al 43 reported 100% hypomagnesemia in patients with delirium tremens, psychosis, coma and severe neuropathy. The difference in results may be due to the broader inclusion criteria for alcohol withdrawal patients in our study. Stasiukinene VP et al found that hypomagnesemia in alcohol withdrawal syndrome was registered in 28.7% patients. It occurred significantly more frequently (p < 0.05) in patients with a severe alcohol withdrawal syndrome Seelig MS et al 5 has stated that when magnesium deficiency exists, stress paradoxically increases risk of cardiovascular damage including hypertension, cerebrovascular and coronary constriction and occlusion, arrhythmias and sudden cardiac death.

In our Study, Neurological features like tremor (77.6 %) and cramps (80.6 %) were found in more than half of the alcoholic patients with hypomagnesemia.

Hypomagnesemia rarely shows specific signs or symptoms; its diagnosis depends on a high index of suspicion in patients with hypokalemia, especially after its correction, and in patients with unexplained hypocalcemia. Swaminathan R. in his review has stated that manifestations may depend more on the rate of development of magnesium deficiency and/or on the total body deficit rather than the actual serum magnesium concentration.13 Asian Journal of Critical Care Vol. 8, No. 2, July-September 2012

Original article In our study, out of 100 patients in alcoholic group 67 had hypomagnesemia. Tremors (54 out of 67) and cramps (52 out of 67) were observed in more than half of patients with hypomagnesemia. Carpopedal spasm occurred with profound hypomagnesemia (mean serum magnesium level 1.16 mg/dl) and is the most specific feature as 87.50% patients with carpopedal spams had hypomagnesemia. Flink et al observed that the lowest serum magnesium concentration in chronic alcoholics with delirium tremens were associated with severe neurological manifestations.

Summary and Conclusion

3. Shane SR, Flink EB. Magnesium deficiency in alcohol addiction and withdrawal. Magnes Trace Elem. 19911992;10(2-4):263-8.

4. Flink E. B. Magnesium deficiency in human subjects--a personal historical perspective. Journal of the American College of Nutrition, Vol 4, Issue 1: 17-31.

5. Cook C. C. et al. Trace element and vitamin deficiency in alcoholic and control subjects. Alcohol and Alcoholism Volume 26, Number 5-6 Pp. 541-548.

6. Helena Mussalo-Rauhamaa et al. Decreased serum selenium and magnesium levels in drunkenness arrestees.

Drug and Alcohol Dependence Volume 20, Issue 2, November 1987, Pages 95-103

Alcoholic patients had significantly lower serum magnesium levels compared to controls.

Hypomagnesemia was more common in patients with alcoholic liver disease than other alcoholic disorders.

A case control study involving large number of patients will be required to assess the effect of treatment of Hypomagnesemia with magnesium supplementation in alcoholic patients.

7. Sullivan J F et al. Magnesium Metabolism in Alcoholism.

American Journal of Clinical Nutrition 1963;13:297303.

Reference

10. Romani A M.P. Magnesium homeostasis ad alcohol consumption Magnesium Research 2008:21(4):197-204

1. Bringhurst F. R. hormone and disorder of mineral metabolism in Williams Textbook of Endocrinology, 11th Ed. Saunders 2009:1249-1256.

2. Hristova Elena N. et al. Serum ionized magnesium in chronic alcoholism: is it really decreased? Clinical Chemistry 43: 394-399, 1997

8. Elisaf M et al. Pathogenetic mechanisms of hypomagnesemia in alcoholic patients. J Trace Elem Med Biol. 1995 Dec;9(4):210-4.

9. Edmund B et al. Magnesium Deficiency in Alcoholism.

Alcoholism: Clinical and Experimental Research-Jun 2007 Volume 10 Issue 6, Pages 590

11. Stasiukinene VP et al. Hypomagnesemia in patients with chronic alcoholism in the course of alcohol withdrawal syndrome Ter Arkh. 2004;76(11):97-9.

12. Kingston ME. Clinical manifestations of hypomagnesemia: Critical Care Medicine 1986;14:950-954.

...Contâ&#x20AC;&#x2122;d from page 11 in young adults in South India. J Neurol Neurosurg Psychiatry 2007;78:959-963.

10. Mondana Moheyeddin et al. Autologous In Vitro Expanded Mesenchymal stem cell therapy for human old Myocardial infarctions. Arch Iranian Med 2007; 10(4):467-473 11. Prakash. N .Tandon. Transplantation and stem cell research in neurosciences: Where does India stand?

Neurology India 2009; 57 (6):706-714.

12. Seyfried D, Ding J, Han Y, Li Y, Chen J, Chopp M: Effects of intravenous administration of human bone marrow stromal cells after intracerebral hemorrhage in rats. J Neurosurg 2006;104:313-318

Repairing brain after stroke: a review on post-ischemic neurogenesis. Neurochem Int. 2007;50(7-8):1028-41.

14. Yoon SH, Shim YS, Park YH et al. Complete Spinal Cord Injury Treatment Using Autologous Bone Marrow Cell Transplantation and Bone Marrow Stimulation with Granulocyte Macrophage-Colony Stimulating Factor: Phase I/II Clinical Trial.stemcells 2007;25:2066-2073.

15. Zhang H, Huang Z, Xu Y, Zhang S: Differentiation and neurological benefit of the mesenchymal stem cells transplanted into the rat brain following intracerebral hemorrhage. Neurol Res 2006; 28:104-112

13. Wiltrout C, Lang B, Yan Y, Dempsey RJ, Vemuganti R.

Asian Journal of Critical Care Vol. 8, No. 2, July-September 2012

21

Case Report clinical practice

“Pseudo central cervical Fibroid in a Nulliparous Girl – A Case Report” N Rajamaheswari*, Sugandha Agarwal**, Archana Bharti Chhikara**, K Seethalakshmi†

Abstract Cervical fibroids are classified as true and false. True cervical fibroids are further subdivided into anterior, posterior, lateral, central and multiple Key words: fibroids, cervix, intra-ligamentary, retroperitoneal,

F

ibroids are benign (non-cancerous) growths on the uterus. There is an overall incidence of 20% in women more than 30yrs of age. The incidence of cervical fibroids is much lower at 1-2%1. They arise either from the portio vaginalis presenting as a fibroid polyp or from the supravaginal cervix presenting either as an interstitial or subserous or submucus fibroid.

Case History A 21 year old unmarried girl from West Bengal presented with complaints of difficulty in passing urine, lower abdominal pain and spasmodic dysmenorrhea for 4 months. She was evaluated at her hometown and told to have a 15 x 10cm subserosal fibroid.

Systemic examination was normal. Per abdomen there was a firm, non tender midline mass arising from the pelvis corresponding to 20 weeks size gravid uterus with restricted mobility. Per vaginal examination with consent was done and a polypoidal mass measuring 10 x 8 cm was found filling the entire vagina. Cervix could not be felt. Ultrasonographic examination showed 10.2 x 10.7 cm fibroid in the posterior wall. There were no adnexal masses. Minimal bilateral hydronephrosis was also seen.

*Professor and Head **Dept. of Urogynecology † Assistant Professor, Dept. of Urogynecology Govt. Kasturba Gandhi Hospital and Institute of Social Obstetrics Madras Medical College,Triplicane, Chennai Address for correspondence Dr Archana Bharti Chhikara H.No.: 1398, Sector-15, Sonepat, Haryana - 131 001 E-mail: archanachhikara@gmail.com

22

She was planned for examination under anesthesia and laparotomy with consent taken for hysterectomy if required and blood was arranged. Intra-operatively, a huge fibroid polyp was seen vaginally. It was not possible to get above the swelling, the cervix could not be felt and the tumor did not have any plane to enucleate and thus it was decided to proceed to laparotomy. On laparotomy, both tubes and ovaries were normal. The uterus was sitting like a lantern on the dome of St. Paul’s Cathedral. A 25 × 18 cm pseudo central cervical fibroid, partly intramural, partly sub mucous was seen to arise from the posterior cervico isthmic region.

Bonney’s rubber shod clamps were applied along the uterine vessels and a myomectomy was performed.

There were no other fibroids felt and the cervix was felt to be normal at the end of the laparotomy. Since the cavity was entered into, she was advised low dose combined oral contraceptive pills for 3 cycles and to have elective LSCS during pregnancy.

Discussion Cervical fibroids are classified as true and false.

True cervical fibroids are further subdivided into anterior, posterior, lateral, central and multiple. False cervical fibroids are classified into intra-ligamentary, retroperitoneal, non-capsulated.2 The size, growth, number and progression of cervical fibroids are unpredictable and rarely do they become cancerous (less than 0.1%).3 they are unlikely to shrink or disappear on their own until after menopause. Those arising from portio vaginalis usually present as cervical fibroid polyp and are easily felt as mass protruding from Asian Journal of Critical Care Vol. 8, No. 2, July-September 2012

case report the cervix.4 Central tumor expands the cervix equally in all directions and the uterus is elevated on top of the large tumor. Diagnosis is by ultrasonogram and HSG.5 Management in cervical fibroid of supravaginal portion is hysterectomy if fertility is not desired and myomectomy if the patient is young and fertility is desired.6 When one faces a case of nulliparous cervical fibroid the following steps are mandatory including an extensive pre-operative workup along with exclusion of a concurrent adnexal disease, an informed consent for probable hysterectomy, anticipation of blood loss and operative challenges are to be considered.

2. Rein MS, Barbieri RL, Friedman AJ. Progesterone: A critical role in the pathogenesis of uterine myomas. Am J Obstet Gynaecol 1995;172: 14.

References

6. Dorsey JH, Steinberg EP, Holtz PM. Clinical indications for hysterectomy route: patient characteristics or physician preference? Am J Obstet Gynecol 1995;173: 1452–1460.

1. Myomectomy and the Management of Fibroids in Pregnancy, Bonney’s Gynecological Surgery (Tenth Edition), Pgs 87-94.

Asian Journal of Critical Care Vol. 8, No. 2, July-September 2012

3. Dicker RC, Greenspan JR, Strauss LT, et al. Complications of abdominal and vaginal hysterectomy among women of reproductive age in the United States. Am J Obstet Gynecol 1982; 144:841– 848.

4. Thompson JD, Warshaw JS. Hysterectomy Rock JA, Thompson JD. Telinde’s Operative Gynecology 8th edition 1997 Philadelphia:Lippincott-Raven.

5. Leiomyomata uteri and myomectomy John D Thompson, John A Rock in TeLinde’s textbook of operative gynecology 9th edition.

23

case report clinical practice

Surgical Treatment of Obesity and Diabetes PS Mahato*, AS Dabhi**, PB Thorat**

Abstract Low BMI patients may not fully benefit by these surgeries. After malabsorptive surgeries, patient has to be on life-long vitamin supplement and often after bariatric surgery patient has to take small 4-6 frequent meals as large meal ingestion will lead to vomiting and intense abdominal pain.

Key words: micronutrient, bariatric surgery, BMI

S

urgery for obesity is the last option but is most effective.

Life-long medical surveillance is needed to prevent micronutrient and vitamin deficiencies after surgery. Conservative treatment is less effective than bariatric surgery in terms of weight reduction.

Criteria for selection for Bariatric Surgery BMI - 35 to 40 kgs/m2 with significant co-morbid diseases or obesity with BMI > 40 kgs/m2; well informed, mostivated patient who understands and accepts risk of surgery; long-time commitment to life-style changes and follow-up; supportive social environment and absence of psychosis or depression are the usual criteria for selection for bariatric surgery.

Types of weight-loss surgeries Mal absorptive

Restrictive

Jejuno ileal bypass

Vertical banded gastroplasty

Bilio pancreatic diversion & duodenal switch

Laparoscopic adjustable gastric band Gastric bypass

*Third Year Resident **Associate Professor Dept. of Medicine Medical College and SSG Hospital, Vadodara Address for correspondence Dr Ajay S Dabhi 38, Alkanagar, Near Priyalaxmi Mill, Old Alembic Road, Vadodara - 390 003 E-mail: dr_ajay_44@yahoo.co.in

24

Laparoscopic Adjustable Gastric Banding (LAGB) Widely practiced simple surgery with less complications and low mortality (0.05%).1 Weight is lost slowly but for prolonged period. Restrictive procedures, hence vitamin deficiency is not common as there is intact GI tract. Folic acid deficiency has been seen due to different eating habits after surgery viz. taking less fruits, vegetables and whole-meal bread. Patient has to take 4-6 small feeds to avoid vomiting or intense pain which usually occurs if one eats a heavy meal.

Re-operation is less, results are good. Complications of this surgery are - prolapse of gastric wall through the band with acute stromal obstruction and vomiting.

Devise erosion and devise malfunction.

Laparoscopic Gastric Bypass Surgery (RNY) Complex and major surgery for those whose BMI is over 40. Significant weight loss occurs in 18 months.

There is evidence that surgery can help to achieve complete remission, especially in morbid obese patients with diabetes. It is not effective in T2 DM with low BMI.2 Elderly patients with T2 DM with a prolonged duration were less likely to achieve euglycemia at 12 months. Higher rates of remission is seen in diabetic patients with shorter duration. Complete remission was observed with BMI above 32.3 This surgery carries a mortality rate of 0.4. Rouen Y Gastric Bypass in women with polycystic ovarian syndrome is effective in alleviating symptoms.4 Asian Journal of Critical Care Vol. 8, No. 2, July-September 2012

case report Mechanism of DM Control in RYGB (Rouxen-Y Gastric Bypass)

Effect of Bariatric Surgery on Weight loss (EWL)

Distal bowel hypothesis

All types of surgery

61.2

Gastric banding

47.5

Gastric bypass

61.2

Gastroplasty

68.2

Nutrients reach the distal ileum within 5 minutes of ingestion of food and this stimulates the secretion of GLP1 by L cells located in this area.5 Sleeve Gasterectomy (Gastric Sleeve or Sleeve Resectomy, VSG) Done in patients with BMI over 35. Involves removing a major portion of the stomach. Once done, this surgery is not reversible. It is a type of restrictive surgery. First described by Hess in 1988. It provides acceptable percentage of weight loss (70-80%). Late nutritional complications occur after this surgery.6 Main complications are diarrhoea, hepatic failure, metabolic derangement, protein malnutrition, iron deficiency anaemia, vitamin deficiency and metabolic bone diseases.

Vertical Banded Gastroplasty (VBG)7 A small pouch of stomach, is created with gastric banding (stomach stapling). Revisional surgery is needed in VBG due to stoma, stenosis, pouch enlargement or stapler dysfunction. Long-term weight loss and improved co-morbidities occur. In 65% of cases, there is failure of surgery and need revision and conversion surgeries.

Jejuno ileal bypass

7

JIB is created by division of proximal jejuno distal to ligament of Terez, creating anaestomosis to Ileum 10 cm from ileocaecal valve.

Procedure creates short-gut syndrome. It becomes a malabsorptive procedure and results in weight loss.

Patient develops nephrolithiasis, dental caries, renal failure, bypass enteritis, cirrhosis, hepatic failure, arthritis and severe metabolic deficiency.

Risk of T2DM and CAD risk factors reduced after gastric bypass and not after restrictive surgery Benefits of Bariatric Surgery zz zz

8

Appetite decreases Weight loss of 70% of excess of body weight* occurs

Asian Journal of Critical Care Vol. 8, No. 2, July-September 2012

Type of Surgery

Percentage weight loss (EWL)

BPD/DS

70

Effect of Bariatric Surgery on Weight Loss and Amelioration of Comorbid Conditions7 Type of Bariatric Surgery

Weight Loss after 2 Yrs

RYGB

30%

GB

20%

BPT

35%

Comorbid Conditions Corrected after JIB 70% dyslipidemia 70% hypertension Obstructive sleep apnoea improved 90% T2DM reverted Gastro oesophageal reflex Cured in 100%

Hormonal changes after Bariatric Surgery9 Hormone/Peptide

Changes Seen Post Bariatric Surgery

Obesity

Ghrelin

Increased1

Increased

Post Prandial PYY

Increased

Decreased

GLP-1

Increased

Increased

Enteroglucagon

Increased

Decreased

GIP

Decreased

Increased

C-Peptide

Decreased

Increased

Adiponectin

Increased

Decreased

Leptin

Normalises

Increased

Resistin

Decreased

Increased

TNFA

Decreased

Increased

IL-6

Decreased

Increased

Plasminogen Activator Decreased Inhibitor-I (PAI-I)

Increased

Long-term complications of Bariatric Surgery10 LAGB

VBG

RYGB

Reflux

Complications

6%

6%

0%

Vomiting

42%

41%

0%

Dysphagea

2%

6%

4%

Port related problem

10%

0%

0%

Re-operation

33%

26%

8%

Conversion

10%

63%

0%

Second re-operation

5%

8%

0%

25

case report Comorbidity Resolution11 Resolution criteria EWL

Gastric banding

Gastroplasty

Gastric bypass

BPD and DS

Total

47%

68%

62%

70%

61%

Mortality

0%

0.1%

0.5%

1.1%

Resolution of DM

48%

72%

84%

99%

77%

Resolution of hyper-lipidemia

50%

74%

97%

99%

79%

Hypertension

43%

69%

68%

83%

62%

Sleep apnea syndrome

95%

78%

80%

92%

86%

Resolution of fatty liver

Improved with all surgeries

Improved with all surgeries

Improved with all surgeries

Improved with all surgeries

Improved with all surgeries

Comorbidities resolved or improved after laparoscopic sleeve gastrectomy12 Comorbidity

No.of Patients

Resolved

Improved

%

Hypertension

119

81

35

97.5

DM

58

41

16

98.3

Hyperlipidemia

98

47

48

96.3

Depression

103

41

61

99.0

Obstructive sleep apnea

73

53

18

97.3

GERD

113

43

69

99.1

Arthritis

72

37

34

98

Chronic joint pains

44

26

18

100

Stress inconvinence

44

41

3

100

Asthma

34

21

13

100

Comparison between life-style modification and bariatric surgery13 Features Cost

Bariatric Surgery

No cost

Costly

Side effects

Nil

Vitamin deficiency and malabsorption. With LGB, problems are less

Weight loss

Long term results, moderate loss

Severe weight loss in short time

Weight loss maintenance

Not maintained. Weight gain occurs after few years

Forever

Nutrient deficiency

No

Usually occurs

Effect on comorbid disorders

Mild to moderate

Marked amelioration to cure

No

Can occur

Needed, motivated to continue life-style modification for ever

Not needed

Must learn to eat healthy foods

Must learn to eat slowly and 4-6 small feeds to prevent vomiting and epigastric pain

Not applicable

Can develop. Needs revision or redo surgeries at times

In all age groups

Not much effective with low BMI, oldage and with long-duration of comorbid disorders

Psychological problems Patients cooperation Food habits Post-operative complications Useful

26

Life-style Modification

Asian Journal of Critical Care Vol. 8, No. 2, July-September 2012

case report zz zz

zz zz zz zz

70% patients can stop blood pressure medication Lipids come to normal in 70% of patients with dyslipidemia GERD is completely cured 90% of type-2 DM become euglycemic Sleep apnea syndrome is completely cured Long-lasting effect on weight and co-morbidities

*Percentage excess weight loss is - weight loss/total weight - normal weight (EWL). Expected EWL after bariatric surgery is 50-70%.

Complications of Gastric Bypass zz zz zz zz

zz zz zz

zz

zz

Anastomosis leakage, stricture and ulcer Dumping syndrome Nutritional deficiencies Iron, Zinc, B1, Vitamin B12 (due to lack of intrinsic factor), Pica develop due to iron deficiency Infection Haemorrhage Hypo parathyroidism is due to inadequate calcium absorption Hypochlorohydria leads to positive hydrogen breath test which is due to bacterial overgrowth in small bowel Muscle weakness due to protein deficit Psychological problems like depression

Systolic/Diastolic BP, Plasmaglucose, HbA1C, Total cholesterol and triglyceride, all above parameters decreased to normal after bariatric surgery Clinically beneficial weight loss in patients with morbid obesity is possible with conservative non-surgical interventions particularly residential intermittent program and weight loss camps. Despite much larger weight loss observed in surgical group, small weight losses of 5-15% achieved through life-style intervention can result in similar reduction in risk factors and resolution of comorbidities at one year.12 Cardiovascular Outcomes after Bariatric Surgery14,15,16 Swedish obese subject study looked into cardiovascular outcomes after bariatric surgery. Patients have followed Asian Journal of Critical Care Vol. 8, No. 2, July-September 2012

for 2-10 years. There were 2000 surgically treated patients for obesity who are compared with 2000 controlled subjects with life-style modification. In surgically treated cases, normalization of Triglyceride, Hyperglycemia of Diabetes, Hyperuricemia were seen.

Despite reduction in disease related deaths after gastric bypass, surgery risk of non disease related deaths such as accidents and suicides increased as compared to control group due to psychological problems.17 Conclusion Various types of surgeries done in morbid obesity are described with their merits ad demerits. Resolution of comorbid diseases with obesity occurs depending upon the amount of weight loss, age of the patients, duration of comorbid disorders. Low BMI patients may not fully benefit by these surgeries. After malabsorptive surgeries, patient has to be on life-long vitamin supplement and often after bariatric surgery patient has to take small 4-6 frequent meals as large meal ingestion will lead to vomiting and intense abdominal pain. Even in restrictive surgery, patient needs folic acid supplement. Hormonal changes after bariatric surgery are described. Bariatric surgery is compared with lifestyle modification.

References 1. Chapman AE, Kiroff G, Game P, et al. Laparoscopic adjustable gastric banding in the treatment of obesity: a systematic literature review. Surgery 2004;135:326-351.

2. Hussain A, Mahonad H, Elltasan S, Can Roux en Y gastric by pass provide a life-long solution for diabetes mellitus - Canadian Journal of Surgery, 2009, 52, 269-75.

3. Chihkun Huang, Asim Shobin CH, Hsir-N Lo et al, Laparoscopic Rouxen Y, Gastric by pass for the treatment of type-2 DM in Chinese patients with BMI of 25-35 Journal of Metabolic Surgery and Allied Care, 2011.

4. Georg M Eid, Daniel R Cottam, Laura M Veleu & et al - Surgery for Obesity and related disorders I (2005) 77-80.

5. Mason E, â&#x20AC;&#x153;Mechanism of Surgical Treatment of Type-2 DMâ&#x20AC;?, Obesity Surgery 2005, 15, 459-461 6. Hess DS, Hess DW - Bilio-pancreatic diversion with a duodenal switch - Obesity Surgery, 1998 - 8-267-82.

7. Strain GW, Gagner M, Pomp A, et al; Comparison of weight loss and body composition changes with four surgical procedures. Surg Obes Relat Dis. 2009 Apr 14.

27

case report 8. Gunn Singh Jakobsen, Daghofsa, Jo Roislien, Rune Sandbu & Joran Hjel Mesaeth -Morbid obesity patientswho undergoes bariatric surgery? The Journal of Metabolic Surgery & Allied Care, 2009

14. Athyros VG,Tziomalos K,Karagiannis A,Mikhailidis DP: Cardiovascular benefits of bariatric surgery in morbidly obese patients, Obesity Review, Year 2011, Vol.12, Issue 7, Pg.515, 524

9. Marie Guldstrand: Hormonal changes after bariatric surgery, Endocrine Abstracts (2010) 22 S23.3

15. Batsis JA, A. Romero-Corral, ML Collazo-Clavell, MG Sarr, V Somers, L Brekke, F. Lopez-Jimenez. Effect of Bariatric Surgery on Cardiovascular Risk Factors and Predicted Effect on Cardiovascular Events and Mortality in Class II-III Obesity. J Am Coll Card 2006 Feb;47(4) (Suppl 1): 358A

10. Poitou Bernert, C., Ciangura, C., Coupaye, M., Czernichow, S., Bouillot, J.L., & Basdevant, A. (2007), “Nutritional deficiency after gastric bypass: diagnosis, prevention and treatment.”, Diabetes & Metabolism 33 (1): 13–24, doi:10.1016/j.diabet.2006.11.004.

11. Brlan G Luck, Blake Movitz, Shannan Jansma et al, Laparoscopic Sleeve Gastrecomy is safe and effective Bariatric Procedure for the lower BMI population - The Journal of Metabolic Surgery and Allied Care, 2010 12. Buchwald H, Avidor Y, Braunwald E, et al; Bariatric surgery: a systematic review and meta-analysis. JAMA. 2004 Oct 13;292(14):1724-37.

13. Bjorvell H, Rossner S. A ten-year follow-up of weight change in severely obese subjects treated in a combined behavioural modification programme. Int J Obes.

1992;16:623–5.

28

16. Lars Sjöström, Anna-Karin Lindroos, Markku Peltonen, Jarl Torgerson, Claude Bouchard, Björn Carlsson, Sven Dahlgren, Bo Larsson, Kristina Narbro, Carl David Sjöström, Marianne Sullivan, and Hans Wedel, Swedish Obese Subjects Study Scientific Group, N Engl J Med 2004; 351:2683-2693, December 23, 2004 17. Ted D. Adams, Richard E. Gress, Sherman C. Smith, R. Chad Halverson, Steven C. Simper, Wayne D. Rosamond, Michael J. LaMonte, Antoinette M. Stroup and Steven C. Hunt: “Long term mortality after gastric bypass surgery”, N Engl J Med 357;8 August 23, 2007.

Asian Journal of Critical Care Vol. 8, No. 2, July-September 2012

Case Report clinical practice

Aneurysm of Mitral Valve Complicated by Ventricular Tachycardia Monika Maheshwari*, Nirmal Vyas, Rk Gokroo

Abstract An interesting case of mitral valve aneurysm secondary to myxomatous valvular degeneration presenting with ventricular tachycardia in emergency department is described herein.

Key words: Mitral valve aneurysm, myxomatous valvular degeneration, ventricular tachycardia

A

neurysm is an echolucent space that is contiguous with the cavity of origin and is completely bounded by a thin layer of tissue extending from the cavity of origin.1 Aneurysms of cardiac valves are usually secondary to infective endocarditis.2 Rarely, such aneurysms can occur without any evidence of infection, in the presence of connective tissue disorders, Marfanâ&#x20AC;&#x2122;s syndrome, pseudoxanthoma elasticum or myxomatous valvular degeneration.3 We report herein one such case of noninfective mitral valve aneurysm complicated by ventricular tachycardia.

secondary to myxomatous degeneration of mitral valve.

On Doppler color flow mapping presence of eccentric mitral regurgitation jet further supported the etiology of mitral valve prolapse.

Case Report A 28-year-old female presented in emergency department with complaints of sudden-onset of palpitation and breathlessness. On examination, her systolic blood pressure was 70 mmHg, with pulse rate of 160/minute regular, temperature 98°F and respiratory rate - 30/minute. Jugular venous pressure was raised upto the angle with cold and sweaty extremities. There was pallor but no cyanosis, icterus, pedal edema or lymphadenopathy. Electrocardiogram showed regular wide QRS ventricular tachycardia (Fig. 1). Echocardiography demonstrated small fluttering echoes on the mitral valve and a localized saccular bulge of the anterior mitral leaflet protruding into the left ventricle during systole measuring 2.2 x 3.1 cm (Fig. 2) suggestive of mitral valve aneurysm

*DM(Cardio) 2nd Year Resident Dept. of Cardiology JLN Medical College, Ajmer, Rajasthan Address for correspondence Dr Monika Maheswari Navin Niwas, 434/10, Bapu Nagar, Ajmer - 305 001, Rajasthan E-mail: opm11@rediffmail.com

Asian Journal of Critical Care Vol. 8, No. 2, July-September 2012

Figure 1. Electrocardiogram showing ventricular tachycardia.

29

case report

Figure 2. Echocardiograph (parasternal long-axis view) demonstrating localized saccular bulge of the anterior mitral leaflet.

Figure 4. Right coronary angiogram showing normal right coronary artery.

ruled out ischemic cause of VT. For definitive treatment and further management, we advised the patient surgical excision of the aneurysm followed by mitral valve repair. However, she did not give consent and was discharged on b-blockers and antiarrhythmics.

Discussion

Figure 3. Left coronary angiogram showing normal left anterior descending and left circumflex artery.

The ventricular tachycardia (VT) was reverted to normal sinus rhythm with 100 Joules of synchronized direct current (DC) shock. Following reversion to sinus rhythm coronary angiogram was performed, which revealed normal coronary vessels (Figs. 3 and 4) and 30

Aneurysms of the mitral valve are rare complications of aortic valve endocarditis. The cause of the aneurysm is most likely a combination of occult infection of the mitral valve leaflets by migration via the intervalvular fibrosa1 or by seeding of the anterior mitral valve leaflet from the aortic valve regurgitation jet in combination with leaflet weakening due to the high velocity regurgitant jet.4 Rarely aneurysms of the mitral valve can occur in association with connective tissue disorders.3 Mitral valve aneurysms can be confused with several abnormalities including flail mitral leaflets, papillofibroelastomas or myxomas involving the mitral valve, and nonendothelialized cysts of the mitral valve.5 Although TTE may occasionally identify subtle valvular abnormalities, the better resolution provided by TEE yields a more definitive identification. Color flow Doppler distinguishes the aneurysm from these other abnormalities by demonstrating direct communication between the aneurysm and the left ventricle.6 Early detection and prompt intervention are important Asian Journal of Critical Care Vol. 8, No. 2, July-September 2012

case report to prevent the complications of valvular aneurysms, which include rupture, embolism and endocarditis.

Aneurysmectomy with mitral valve repair is the procedure of choice; replacement should be reserved for those cases where repair would compromise valvular function.7 References 1. Sachdev M, Peterson GE, Jollis JG. Imaging techniques for diagnosis of infective endocarditis. Infect Dis Clin North Am 2002;16(2):319-37, ix.

2. Lee CH, Tsai LM. Transesophageal echocardiographic recognition of mitral valve aneurysm. J Ultrasound Med 2005;24(8):1141-4.

3. Chua SO, Chiang CW, Lee YS, Chang CH, Hung JS. Perforated

Asian Journal of Critical Care Vol. 8, No. 2, July-September 2012

aneurysm of the anterior mitral valve. A Doppler and twodimensional echocardiographic report. Chest 1990;97(3):753-4.

4. Rachko M, Safi AM, Yeshou D, Salciccioli L, Stein RA. Anterior mitral valve aneurysm: a subaortic complication of aortic valve endocarditis: a case report and review of literature. Heart Dis 2001;3(3):145-7.

5. Mollod M, Felner KJ, Felner JM. Mitral and tricuspid valve aneurysms evaluated by transesophageal echocardiography. Am J Cardiol 1997;79(9):1269-72.

6. Changlani M, Lieb D, Kaczkowski D, Moss S. The role of color flow Doppler in the echocardiographic diagnosis of mitral valve aneurysm. J Am Soc Echocardiogr 1993;6(6):610-2.

7. Ruparelia N, Lawrence D, Elkington A. Bicuspid aortic valve endocarditis complicated by mitral valve aneurysm. J Card Surg 2011;26(3):284-6.

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case report clinical practice

Multiple Developmental Urogenital Anomalies: A Therapeutic Challenge N Rajamaheswari*, Sugandha Agarwal**, Archana Bharti Chhikara**, K Seethalakshmiâ&#x20AC;

Abstract Case report: In cases of atretic lower vagina, drainage of hematocolpos per se is inadequate as recurrent hematocolpos from re-stenosis is common. Surgical reconstruction in these cases should be directed to relieve obstruction and ensure continued vaginal patency. A 14-year-old girl reported with primary amenorrhea and recurrence of cyclical lower abdominal pain due to re-stenosis following a primary intervention for hematocolpos. Evaluation identified an atretic lower vagina and multiple associated urinary tract anomalies like unascended right kidney, malrotated left duplex collection system, ureteric diverticula and bladder diverticulum with left ureter opening into it. Though associated Grade IV vesicoureteral reflux (VUR) posed a management dilemma, drainage of hematocolpos and restoration of vaginal continuity by pull through of the proximal vagina and approximating its edges to fourchette relieved the patient of pain, restored menstruation, resolved the VUR and obviated the need for extensive urinary reconstructive procedures. Conclusion: In case of atretic lower vagina, drainage of hematocolpos per se is inadequate as recurrent hematocolpos from re-stenosis is common and surgical reconstruction should be directed to relieve obstruction and ensure continued vaginal patency. Coexisting developmental urinary tract anomalies may not require immediate surgical intervention.

Key words: Multiple developmental urogenital anomalies, hematocolpos, vaginal atresia, vesicoureteral reflux

O

cclusive vaginal anomaly is identified after puberty, with onset of menstruation when accumulation of menstrual blood causes pain. Surgical management of combined multiple developmental anomalies may appear to be complex with prospect of multiple surgical corrections.

Case Report This manuscript was prepared after obtaining written informed consent from father of the patient.

A 14-year-old girl presented with primary amenorrhea and lower abdominal pain with cyclical increase in severity for three months. Patient did not have any voiding difficulty.

Occurrence of acute abdominal pain at her 14th year (1.12.2010) prompted her to consult the local gynecologist, who recognized hematocolpos and let

*Professor and Head **Dept. of Urogynecology â&#x20AC; Assistant Professor, Dept. of Urogynecology Govt. Kasturba Gandhi Hospital and Institute of Social Obstetrics Madras Medical College,Triplicane, Chennai Address for correspondence Dr Archana Bharti Chhikara H.No.: 1398, Sector-15, Sonepat, Haryana - 131 001 E-mail: archanachhikara@gmail.com

32

out 100 ml of altered blood by vaginal incision. It temporarily relieved her of pain, however, menstruation did not resume. Hence, she approached our institute on 15.2.11 for further treatment. Clinical examination revealed a firm, nontender, mobile, midline, abdominal mass of 10 x 6 cm, which appeared to be of uterine origin. Tanner stage for secondary sexual characters corresponded to her age. Local examination under anesthesia revealed normal external genitalia, a hypospadiac urethral meatus, absent vaginal lumen without obvious vaginal bulge due to hematocolpos (cryptomenorrhea).

Ultrasound imaging revealed a 12 x 4 cm mass suggestive of hematocolpos and an unascended right kidney. Intravenous urography confirmed the unascended right kidney in midline at L3-L4 level and revealed a duplex collecting system with malrotation on the left side. Both ureters appeared grossly normal and bladder contour revealed extrinsic compression due to pelvic mass. Micturating cystourethrogram revealed a Grade IV vesicoureteral reflux (VUR) on the left side. Magnetic resonance (MR) urogram revealed the following: zz Posteroinferior bladder diverticulum measuring 37.9 x 13.8 mm with left ureter opening into it (Fig. 1). zz Distal left ureteric diverticulum measuring 14.9 x 13.6 mm (Fig. 1).

Asian Journal of Critical Care Vol. 8, No. 2, July-September 2012

case report zz

A bicornuate uterus with hyperintense fluid collection in cervix and vagina confirming the hematocolpos (Fig. 2).

Cystoscopy showed a hypospadiac meatus with short urethra. The trigone was severely distorted and both ureteric orifices were displaced laterally due to the pelvic mass. A wide open left ureteric orifice was entering into the diverticulum of bladder. Further examination revealed an atretic distal vagina and a huge globular mass palpable (rectally) above the atretic vaginal segment.

Left ureter 3

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2 Ureteral diverticulum 4 Bladder Figure 1. MR urogram showing left ureter opening into the bladder diverticulum (arrow 1) and left distal ureteric diverticulum (arrow 2).

Also shown are left ureter (arrow 3) and bladder (arrow 4).

On 28.3.11 (four months after first attempt) surgical exploration was done. A staged surgical protocol was considered in view of multiple developmental urogenital anomalies.

A U-shaped incision was made between the perineum and hypospadiac meatus and sharp dissection was required through the hard fibrotic tissue for a distance of 5 cm from the fourchette to gain access to the hematocolpos (huge globular mass with thick fibrotic wall). Reaching the hematocolpos through atretic vagina (fibrotic) without injuring the rectum was challenging especially following an unsuccessful past attempt. Per rectal finger guidance facilitated the dissection.

The close proximity of the bladder diverticulum with insertion of left ureter into it forewarned about the possibility of inadvertent injury to bladder or lower ureter during the intervention. To safeguard the left ureter, a preoperative retrograde ureteric stenting was attempted which could not be accomplished due to extensive anatomical distortion caused by the mass.

MR urogram 3

Guidance with Foleyâ&#x20AC;&#x2122;s catheter enabled dissection without injuring urinary tract. The hematocolpos was drained by incising its thick fibrotic wall and about 300 ml of altered blood was drained.

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2 Urethra 4 Figure 1. MR urogram showing large hematocolpos (arrow 1), bladder diverticulum (arrow 2). Also shown are right unascended kidney (arrow 3) and urethra (arrow 4).

Asian Journal of Critical Care Vol. 8, No. 2, July-September 2012

Postoperatively, the patient was relieved of abdominal pain and resumed her first menstruation 45 days after the surgery. Re-examination during menstruation established the patency of vagina. Postoperative micturating cystogram revealed no VUR on left side.

Discussion Obstructive lesions leading to hematocolpos require prompt action to relieve pain, retrograde menstruation and pressure effect on adjacent viscera. Re-stenosis 33

case report with recurrent mass and pain is a frequent sequel following any vaginal reconstructive surgery which may make future attempts more difficult. During the primary surgical intervention emphasis should be laid on achieving persistent vaginal patency, else recurrent hematocolpos and its associated symptoms would demand repeated surgical interventions. Considering the past surgical failure, an extensive mobilization of proximal vagina was carried out, which facilitated tension-free pull-through of proximal vagina through the space created by the lengthy dissection and approximation of its edges to fourchette to form the introitus. Progressive hematocolpos in unobstructed upper vagina resulted in the chronic stretching, distension and elongation of upper vagina and provided adequate length that further enabled the approximation of its edges.

Hematocolpos is a rare cause of external mass compression on the lower urinary tract causing acute urinary retention most likely due to distal vaginal occlusions. However, a long atretic lower vagina even with massive collection only in upper vagina may not feature with urinary retention as it may not compress the outflow tract.

Coexisting bicornuate uterus (mullerian duct anomaly) categorizes her as Class III of the American Fertility Society classification.

The management dilemma in the patient was to combine vesical divertculectomy and ureteric re-implantation of the left ureter (due to significant VUR) in a single sitting during the drainage of the hematocolpos versus

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a staged approach. VUR in this case may be congenital or secondary to distortion of the vesicoureteral junction due to bladder diverticula. The vaginal obstruction and hematocolpos is likely to aggravate the distortion and displacement of the lower urinary tract which may be reversible.

VUR could be managed conservatively initially due to the absence of urinary tract infections. Diverticulectomy was not considered as the voiding function was not compromised due to diverticulae. Considering the benefits over risks, staged management strategy was adopted. Persistence of reflux or infection will warrant the re-implantation of ureter in future and at the time of re-implantation ureteral and bladder diverticulum will be surgically excised even if it remains asymptomatic.

Usually, surgical management of combined multiple developmental anomalies may appear to be complex with prospect of multiple surgical corrections. At times, drainage and restoration of continuity and ensuring continued vaginal patency may be adequate to cure the patient. However, patient must be well-counseled for sequel like re-stenosis leading to amenorrhea, pelvic mass and need for further reconstructive surgical interventions.

References 1. Yu TJ, Lin MC. Acute urinary retention in two patients with imperforate hymen. Scand J Urol Nephrol 1993;27(4):543-4.

2. Rock JA, Breech LL. Surgery for anomalies of the mullerian ducts. In: Lindeâ&#x20AC;&#x2122;s Operative Gynecology. 10th edition, Lippincott: Philadelphia 2008:p.539-84.

Asian Journal of Critical Care Vol. 8, No. 2, July-September 2012