Critical care jan march 2013

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Volume 9, Number 2

Urine Output: Beacon of Diagnosis Prevalence and Susceptibility Profiles of Nonfermentative Gram-negative Bacilli Infection in a Tertiary Care Hospital of Eastern India Look-alike and Sound-alike Drug Brand Names: A Potential Risk in Clinical Practice Chylous Ascites due to Tuberculosis: A Case Report and Review of Literature Oral Tertiary Syphilis Percutaneous Curettage and Allogenic Bone Grafting with Bone Marrow in Management of Simple Bone Cyst

January-March 2013

2

Asian Journal of Critical Care Vol. 9, No. 2, January-March 2013

Asian Journal of

Critical Care Volume 9, Number 2, January-March 2013

An IJCP Group Publication Dr Sanjiv Chopra Prof. of Medicine & Faculty Dean Harvard Medical School Group Consultant Editor Dr Deepak Chopra Chief Editorial Advisor Padma Shri and Dr BC Roy National Awardee

Dr KK Aggarwal Group Editor-in-Chief Dr Veena Aggarwal MD & Group Executive Editor

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

Air Pollution may Raise Risk of Stroke, Cognitive Decline

5

KK Aggarwal

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

review article

Urine Output: Beacon of Diagnosis

6

Sudivya Sharma, Prashast Jain

Dr Tarlika Doctor Associate Professor Anesthesia, BJ Medical College, Ahmedabad

IJCP Editorial Board Obstetrics and Gynaecology Dr Alka Kriplani, Dr Thankam Verma Dr Kamala Selvaraj Cardiology Dr Praveen Chandra, Dr SK Parashar Paediatrics Dr Swati Y Bhave Diabetology Dr CR Anand Moses, Dr Sidhartha Das Dr A Ramachandran, Dr Samith A Shetty ENT Dr Jasveer Singh

clinical study

Prevalence and Susceptibility Profiles of Nonfermentative Gram-negative Bacilli Infection in a Tertiary Care Hospital of Eastern India

10

Kalidas Rit, Falguni Nag, Hirak Jyoti Raj, PK Maity

Dentistry Dr KMK Masthan, Dr Rajesh Chandna Gastroenterology Dr Ajay Kumar Dermatology Dr Hasmukh J Shroff Neurology Dr V Nagarajan Journal of Applied Medicine & Surgery Dr SM Rajendran, Dr Jayakar Thomas Anand Gopal Bhatnagar Editorial Anchor Advisory Bodies

Heart Care Foundation of India Non-Resident Indians Chamber of Commerce & Industry Advisory Body Asian Journal of Critical Care Vol. 9,ofNo. 2, January-March 2013 World Fellowship Religions

drugs and devices

Look-alike and Sound-alike Drug Brand Names: A Potential Risk in Clinical Practice

15

Mukundraj S Keny, PV Rataboli

3

Asian Journal of

Review Article

Critical Care Volume 9, Number 2, January-March 2013

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

Chylous Ascites due to Tuberculosis: A Case Report and Review of Literature

Printed at Entire Printers Nampally, Hyderabad

21

Praveen Kumar, Kalpana Chandra

Š Copyright 2013 IJCP Publications Ltd. All rights reserved.

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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.

Oral Tertiary Syphilis

26

Deepa MS, Anita Balan, S Sunil, Bifi Joy

Percutaneous Curettage and Allogenic Bone Grafting with Bone Marrow in Management of Simple Bone Cyst

30

OP Lakhwani

Lighter reading

Lighter Side of Medicine

34

Editorial & Business Offices

4

Delhi

Mumbai

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Bangalore

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Dr Veena Aggarwal 9811036687 E - 219, Greater Kailash Part - 1 New Delhi - 110 048 Cont.: 011-40587513 editorial@ijcp.com drveena@ijcp.com drveenaijcp@gmail.com Subscription Dinesh: 9891272006 subscribe@ijcp.com Ritu: 09831363901 ritu@ijcp.com

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Sr. : Senior; BM: Business Manager

Asian Journal of Critical Care Vol. 9, No. 2, January-March 2013

From the desk of Group editor-in-chief

Air Pollution may Raise Risk of Stroke, Cognitive Decline 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 National Vice President, Elect IMA 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 http://twitter.com/DrKKAggarwal Krishan Kumar Aggarwal (Facebook)

C

ar exhaust and other air pollution, even at levels considered safe by federal regulations, may substantially increase the risk of a stroke, a research team from Beth Israel Deaconess Medical Center has found.

After reviewing the medical records of more than 1,700 stroke patients in the Boston area over 10 years, the researchers found a 34% increase in the risk of ischemic strokes on days with moderate air quality compared with days when the air was rated good by the US Environmental Protection Agency.

A lifetime’s exposure to air pollution may contribute to mental decline in older women, according to the study published online Feb. 13 in the journal Archives of Internal Medicine.

Exposure to fine particulate matter air pollution - <2.5 µm in diameter, or about 1/30th of the diameter of a human hair - as well as coarse particulate matter - between 2.5 and 10 µm in diameter - were associated with mental declines in women.

A second study published in the same journal, found that more people were admitted to a Boston hospital for ischemic stroke on days when levels of fine particulate air pollution were high.

The second study found that short-term exposure to fine particulate matter - even at levels allowed by the EPA can increase the risk of ischemic stroke.

The relationship between higher particulate levels and increased risk of stroke was linear, strongest within 12 hours of exposure and was seen among patients with strokes caused by large-artery atherosclerosis or smallvessel occlusion but not cardioembolism. [AMA News] n

Asian Journal of Critical Care Vol. 9, No. 2, January-March 2013

n

n

5

review article clinical practice

Urine Output: Beacon of Diagnosis Sudivya Sharma*, Prashast Jain*

Abstract Urinary output is the best marker of tissue perfusion. When intrinsic renal function is normal and the urinary tract is unobstructed, urine output is a key indicator of intravascular volume status. Real-time and accurate monitoring of urine output could improve the clinical management of patients in the intensive care unit (ICU) and enable clinicians to early recognition of kidney injury. Although resuscitation state, perioperative medications and other interventions can alter the validity of this surrogate marker for renal function, it still remains the most commonly measured variable in critically ill patient and in perioperative period.

Key words: Urine output, renal perfusion, glomerular filtration rate, acute kidney injury, sepsis

U

rinary output by definition is the total volume of urine excreted daily. This parameter is simple and accurate to measure, yet helps in diagnosis, indicates prognosis, guides management.

Urinanalysis includes microscopic evaluation of cell types and counts; biochemical evaluation of electrolytes, proteins, glucose, ketones, etc. and physical parameters like volume, specific gravity, color, etc. Our discussion limits to just the urine volume. It is the best marker of tissue perfusion. When intrinsic renal function is normal and the urinary tract is unobstructed, urine output is a key indicator of intravascular volume status.1 Renal blood flow (RBF), renal perfusion pressure (RPP), and plasma oncotic pressure influence the effective filtration pressure gradient in Bowman’s capsule of nephron. Afferent and efferent glomerular arteriole tone can further influence the glomerular capillary hydraulic pressure, while tubular cast accumulation increases the Bowman’s hydrostatic pressure decreasing the effective filtration pressure gradient. Finally, intrarenal blood flow distribution, conformational changes of tubule Na+/H+ exchanger, urea and chloride

*MBBS Address for correspondence Dr Sudivya Sharma H. No.: 123, L/R Model Town, Rewari (Haryana) - 123 401

6

channels and aquaporin-2 expression regulate water and sodium (Na+) handling of the ultrafiltrate and hence, the urine output.2 Oliguria is defined as a urine output that is <1 ml/kg/h in infants, <0.5 ml/kg/h in children and <400 ml or 500 ml/24h in adults. The decreased output of urine may be a sign of dehydration, renal failure, hypovolemic shock, hyperosmolar hyperglycemic nonketotic syndrome, multiple organ dysfunction syndrome, urinary obstruction/urinary retention, pre-eclampsia, urinary tract infections or follow use of certain medications such as anticholinergics, methotrexate and diuretics.

However, a nonsustained decrease of urine output does not necessarily imply a decrease of glomerular filtration rate (GFR) but can simply represent a physiological renal adaptation (i.e., antidiuresis and antinatriuresis) to maintain the body volume and/or electrolytes homeostasis.

Oligoanuria is usually ‘acute renal success’ rather than failure, being a sophisticated response to tubular damage caused by renal hypoperfusion or nephrotoxins, preventing life-threatening polyuria, when reabsorption of glomerular filtrate is impaired.

Increased concentration of chloride at the macula densa, however caused, is interpreted as an imbalance between filtration and reabsorption and leads via multiple mechanisms to a reduction in glomerular filtration, conserving intravascular volume.3 Asian Journal of Critical Care Vol. 9, No. 2, January-March 2013

review article Polyuria is excessive volume of urine for an adult (i.e. >3 liters/day). Itâ&#x20AC;&#x2122;s a fairly common symptom, which is often noticed when one has to get upto use the bathroom at night. The causes include diabetes insipidus, diabetes mellitus, drinking a large amount of fluids, especially fluids that contain caffeine or alcohol, kidney failure, medications, especially diuretics, psychogenic polydipsia, sickle cell anemia and tests such as CT scan, that involve injecting contrast media.

Role of Urine Output in ICU Settings Real-time and accurate monitoring of urine output could improve the clinical management of patients in the intensive care unit (ICU) and enable clinicians to early recognition of kidney injury.4 The decrease of urine output may be associated to a decrease of GFR due to decrease of renal blood flow or renal perfusion pressure, neurohormonal factors and functional changes may influence diuresis and natriuresis in critically ill patients.

Systemic inflammation can induce natriuresis and diuresis changes due to functional changes unrelated to hypoperfusion, histological or tubular damage.2 Increased vascular response of the renal microcirculation to vasoconstrictors has been proposed to elicit intense renal vasoconstriction in sepsis-induced acute kidney injury (AKI).5 Endotoxemia also can increase urine output and water clearance despite decrease in GFR due to tubular aquaporin-2 dysfunction.6 The total interruption of renal blood flow for a prolonged period of time followed by reperfusion is always associated with major tubular and microvascular damage. In this condition, cellular lesions result from a combination of cellular hypoxia-reperfusion injury and oxidative stress-associated damage, it is expected that preventing a decrease of renal blood flow may prevent or limit the occurrence of AKI in ICU patients.7 Urine Output in Perioperative Period Inhalation and intravenous anesthetics cause cardiac depression or vasodilation, therefore decrease arterial blood pressure. The sympathetic blockade associated with regional anesthesia similarly causes hypotension.

Decrease in blood pressure below the limits of autoregulation reduces RBF, GFR, urinary flow and sodium excretion. Also, sympathetic activation commonly occurs in the perioperative period as a result of light anesthesia, intense surgical stimulation, tissue Asian Journal of Critical Care Vol. 9, No. 2, January-March 2013

trauma or anesthetic-induced circulatory depression, which increases renal vascular resistance and activates various hormonal systems. Both effects tend to reduce RBF, GFR and urinary output.8 The endocrine response to surgery and anesthesia (catecholamines, renin, angiotensin II, aldosterone, antidiuretic hormone [ADH], adrenocorticotropic hormone and cortisol) is probably at least partly responsible for the transient postoperative fluid retention that is seen in many patients.8 Certain surgical procedures can significantly alter renal physiology. The pneumoperitoneum produced during laparoscopy produces an abdominal compartment syndrome-like state. The increase in intra-abdominal pressure typically produces oliguria (or anuria). Other surgical procedures that can significantly compromise renal function include cardiopulmonary bypass, crossclamping of the aorta and dissection near the renal arteries.8 Fluid overload, hypovolemia and postoperative renal failure are major causes of postoperative morbidity and mortality. Diuretics are also used intraoperatively, particularly during neurosurgical, cardiac, major vascular, ophthalmic and urological procedures. Preoperative diuretic therapy is also common in patients with hypertension and with cardiac, hepatic and renal disease.8 Urine Output in AKI per se Acute renal failure or AKI is defined by an acute decline of GFR. Occurrence of AKI is a marker of severity of the underlying acute illness but also appears as an independent factor associated with mortality in unselected critically ill patients,9 in sepsis,10 pneumonia11 or cardiac surgery.12 The Acute Dialysis Quality Initiative Group has published a consensus definition/classification system for AKI termed the Risk, Injury, Failure, Loss and End-stage kidney disease (RIFLE) criteria (Table 1).

The Acute Kidney Injury Network (AKIN) group has recently proposed modifications to this system (Table 2). It is currently unknown whether there are advantages between these criteria. Compared to the RIFLE criteria, the AKIN criteria do not materially improve the sensitivity, robustness and predictive ability of the definition and classification of AKI in the first 24-hour after admission to ICU.13 7

review article Table 1. RIFLE Criteria Stage

GFR** criteria

Urine output criteria

Probability

Risk

SCr increased × 1.5 or GFR decreased >25%

UO <0.5 ml/kg/h × 6 h

High sensitivity (risk > injury > Failure)

Injury

SCr increased × 2 or GFR decreased >50%

UO < 0.5 ml/kg/h × 12 h

Failure

SCr increased × 3 or GFR decreased 75% or SCr ≥4 mg/d; acute rise ≥0.5 mg/d

UO < 0.3 ml/kg/h × 24 h (oliguria) or anuria × 12 h

Loss

Persistent acute renal failure: Complete loss of kidney function >4 wk

ESRD*

Complete loss of kidney function >3 months

†

‡

High specificity

*ESRD = End-stage renal disease; **GFR = Glomerular filtration rate; †SCr = Serum creatinine; ‡UO = Urine output.

Note: Patients can be classified either by GFR criteria or by UO criteria. The criteria that support the most severe classification should be used. The superimposition of acute on chronic failure is indicated with the designation RIFLE-FC; failure is present in such cases even if the increase in SCr is <3-fold, provided that the new SCr is >4.0 mg/dl (350 μmol/l) and results from an acute increase of at least 0.5 mg/dl (44 μmol/l).

When the failure classification is achieved by UO criteria, the designation of RIFLE-FO is used to denote oliguria. The initial stage, ‘risk,’ has high sensitivity; more patients will be classified in this mild category, including some who do not actually have renal failure. Progression through the increasingly severe stages of RIFLE is marked by decreasing sensitivity and increasing specificity.

Table 2. AKIN Classificationa Stage

Serum creatinine criteria

Urine output criteria

1

Increase in serum creatinine of ≥0.3 mg/dl (≥ 26.4 μmol/l) or increase to ≥ 150200% (1.5- to 2-fold) from baseline

Less than 0.5 ml/kg/hour for more than 6 hours

2b

Increase in serum creatinine to >200-300% (>2- to 3-fold) from baseline

Less than 0.5 ml/kg/hour for more than 12 hours

3c

Increase in serum creatinine to >300% (>3-fold) from baseline (or serum creatinine of ≥4.0 mg/dl [≥354 μmol/l] with an acute increase of at least 0.5 mg/dl [44 μmol/l])

Less than 0.3 ml/kg/hour for 24 hours or anuria for 12 hours

Modified from RIFLE (Risk, Injury, Failure, Loss and End-stage kidney disease) criteria. The staging system proposed is a highly sensitive interim staging system and is based on recent data indicating that a small change in serum creatinine influences outcome. Only one criterion (creatinine or urine output) has to be fulfilled to qualify for a stage.

a

b

200-300% increase = 2- to 3-fold increase.

Given wide variation in indications and timing of initiation of renal replacement therapy (RRT), individuals who receive RRT are considered to have met the criteria for stage 3 irrespective of the stage they are in at the time of RRT.

c

The AKIN and RIFLE classification systems recognized the need to include urine output measurement in smaller time intervals.

Diagnostic Criteria for AKI

An abrupt (within 48 hours) reduction in kidney function currently defined as an absolute increase in serum creatinine of ≥0.3 mg/dl (≥26.4 μmol/l), a percentage increase in serum creatinine of ≥50% (1.5-fold from baseline) or a reduction in urine output (documented oliguria of <0.5 ml/kg/hr for >6 hours).

8

Management and Measures Whereas fluid challenge can improve renal perfusion pressure and renal perfusion in hypovolemic states, the sole fluid resuscitation is unlikely to increase largely the mean arterial pressure.

The choice of the type of fluid also seems to be crucial, because colloids increase the oncotic pressure and may reduce filtration rate. Fluid administration may be found inappropriate and even harmful in numerous situations due to the inconstant relationship between Asian Journal of Critical Care Vol. 9, No. 2, January-March 2013

review article renal blood flow or renal perfusion pressure and diuresis/natriuresis due to complex neurohormonal control.2 Vasopressor infusion is therefore required to improve renal perfusion pressure in conditions with systemic inflammation.14 Infusion of low-dose dopamine can increase renal blood flow, induce renal vasodilatation and increase urine output but with no effect on creatinine clearance.15 Aggressive fluid resuscitation, although increases renal blood flow, can be ineffective in restoring renal microvascular oxygenation due to hemodilution with no increase in blood-oxygen carriage capacities.16 Also, positive fluid balance can deteriorate cell oxygenation and prolong mechanical ventilation.17 Finally, fluid overload may lead to central venous congestion and decrease of renal perfusion pressure,18 which will promote the development of AKI in patients with acute heart failure or sepsis.

Urine Output can be Misleading

Although severe acute renal failure with oliguria or anuria has been reported to be associated with a worse outcome compared with patients with preserved urine output, the use of urine output as a criterion to classify AKI severity may be misleading. It was reported that the combination of creatinine and urinary output for classifying the patientâ&#x20AC;&#x2122;s risk of death was more stringent than urinary output alone for classifying patients.9,19 Severe tubular dysfunction can lead to increased urine output despite low GFR. Similarly, increase of RBF or urine output does not necessarily translate into increase of creatinine clearance.

Conclusion Although resuscitation state, perioperative medications and other interventions can alter the validity of this surrogate marker for renal function and hemodynamic status, it still remains the most commonly measured variable in critically ill patient and in perioperative period.

References 1. Solomon AW, Kirwan CJ, Alexander ND, Nimako K, Jurukov A, Forth RJ,et al; Prospective Analysis of Renal Compensation for Hypohydration Asian Journal of Critical Care Vol. 9, No. 2, January-March 2013

in Exhausted Doctors (PARCHED) Investigators.

Urine output on an intensive care unit: case-control study. BMJ 2010;341:c6761.

2. Legrand M, Payen D. Understanding urine output in critically ill patients. Ann Intensive Care 2011;1(1):13.

3. Thurau K, Boylan JW. Acute renal success. The unexpected logic of oliguria in acute renal failure. Am J Med 1976;61(3):308-15.

4. Macedo E, Malhotra R, Claure-Del Granado R, Fedullo P, Mehta RL. Defining urine output criterion for acute kidney injury in critically ill patients. Nephrol Dial Transplant 2011;26(2):509-15.

5. Boffa JJ, Arendshorst WJ. Maintenance of renal vascular reactivity contributes to acute renal failure during endotoxemic shock. J Am Soc Nephrol 2005;16(1):117-24.

6. Chagnon F, Vaidya VS, Plante GE, Bonventre JV, Bernard A, Guindi C, et al. Modulation of aquaporin-2/ vasopressin2 receptor kidney expression and tubular injury after endotoxin (lipopolysaccharide) challenge.

Crit Care Med 2008;36(11):3054-61.

7. Legrand M, Mik EG, Johannes T, Payen D, Ince C. Renal hypoxia and dysoxia after reperfusion of the ischemic kidney. Mol Med 2008;14(7-8):502-16 8. Morgan GE, Mikhail MS, Murray MJ (Eds). Peripheral nerve blocks. In: Clinical Anaesthesiology. 4th edition, McGraw Hill: New York 2008:p.734-6.

9. Ricci Z, Cruz D, Ronco C. The RIFLE criteria and mortality in acute kidney injury: A systematic review.

Kidney Int 2008;73(5):538-46.

10. Bagshaw SM, George C, Bellomo R; ANZICS Database Management Committee. Early acute kidney injury and sepsis: a multicentre evaluation. Crit Care 2008;12(2):R47.

11. Murugan R, Karajala-Subramanyam V, Lee M, Yende S, Kong L, Carter M, et al; Genetic and Inflammatory Markers of Sepsis (GenIMS) Investigators.

Acute kidney injury in non-severe pneumonia is associated with an increased immune response and lower survival. Kidney Int 2010;77(6):527-35.

12. Dasta JF, Kane-Gill SL, Durtschi AJ, Pathak DS, Kellum JA. Costs and outcomes of acute kidney injury (AKI) following cardiac surgery. Nephrol Dial Transplant 2008;23(6):1970-4.

13. Bagshaw SM, George C, Bellomo R; ANZICS Database Management Committe. A comparison of the RIFLE and AKIN criteria for acute kidney injury in critically ill patients. Nephrol Dial Transplant 2008;23(5):1569-74.

14. Losser MR, Forget AP, Payen D. Nitric oxide involvement in the hemodynamic response to fluid Contâ&#x20AC;&#x2122;d on page 29...

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clinical study clinical practice

Prevalence and Susceptibility Profiles of Nonfermentative Gram-negative Bacilli Infection in a Tertiary Care Hospital of Eastern India Kalidas Rit*, Falguni Nag**, Hirak Jyoti Raj†, PK Maity‡

Abstract Background: Nonfermentative gram-negative bacilli (NFGB) have emerged as a major cause of nosocomial infections. This study was undertaken to know the prevalence of nonfermenters isolated from different clinical samples along with their susceptibility profile. Material and methods: Conventional bacteriological methods were used for identification and susceptibility testing of nonfermenters. Susceptibility testing was performed by methods as recommended by Clinical Laboratory Standard Institute (CLSI). Results: Out of the total 1,650 clinical samples received NFGB were found in 201 samples with an isolation rate of 12.18%. Nonfermenters isolated were Pseudomonas aeruginosa (50.24%), Acinetobacter baumannii (24.87%), Acinetobacter lowffii (5.47%), Pseudomonas fluorescens (1.49%), Pseudomonas stutzeri (1.99%), Burkholderia cepacia (6.96%), Stenotrophomonas maltophilia (2.98%), Achromobacter xylosoxidan (3.98%) and Shewanella putrefaciens (1.99%). Most of the isolated organisms were multidrug-resistant (MDR). P. aerurginosa showed good sensitivity to imipenem (91.08%), cefoperazone sulbactum (68.31%) combination, amikacin (69.30%) and colistin (100%). A. baumannii showed 90% sensitivity to imipenem and 94% to colistin. Conclusion: Our study showed that prevalence of NFGB amongst different clinical isolates is significantly high especially in this part of the world and these organisms are often MDR. In this scenario, we propose all laboratory samples should be screened for NFGB even in clinically unsuspected cases. P. aeruginosa showed good sensitivity to colistin, imipenem, amikacin and cefoperazone sulbactum combination while A. baumannii showed good sensitivity to imipenem and colistin.

Key words: Nonfermentative gram-negative bacilli, prevalence, Pseudomonas aeruginosa, Acinetobacter baumannii, nosocomial infection

T

he nonfermentative gram-negative bacilli (NFGB) are a group of aerobic, nonspore forming, gram-negative bacilli that either do not utilize carbohydrates as a source of energy or degrade them through metabolic pathways other than fermentation.1 They can be recovered from hospital environment, commonly cause device related infections, are often resistant to disinfectants and have the potential to spread from patient-to-patient via fomites or the hands of medical personnel.2,3 Nonfermenting bacteria associated with different nosocomial infections are becoming increasingly resistant to commonly used antimicrobial agents.4 NFGB are known to account for nearly 12-16%, all bacterial isolates from a clinical

*Assistant Professor, Dept. of Microbiology **Junior Resident, Dept. of Dermatology † Demonstrator ‡ Professor and Head, Dept. of Microbiology IPGME&R and SSKM Hospital, Kolkata Address for correspondence Dr Kalidas Rit Assistant Professor Dept. of Microbiology IPGME&R and SSKM Hospital, Kolkata

10

microbiology laboratory. This study was done to know the prevalence of nonfermenters isolated from different clinical samples and to assess their clinical significance.

Antimicrobial susceptibility profile of nonfermenters was also studied.

Material and Methods The present study was done from July 2011 to June 2012. The nonfermenters (201) included in this study were isolated from various clinical samples like wound, pus, sputum, blood, urine, tracheal aspirate and others (including cerebrospinal fluid [CSF] and various body fluids). All collected specimens were processed by standard techniques. Organisms that failed to acidify the butts of triple sugar iron media were considered nonfermenters and subjected to a battery of tests like morphology, motility, oxidase, catalase, indole, urease, nitrate, citrate tests and oxidation-fermentation reactions of glucose, lactose, xylose, maltose, mannitol (Hugh-Leifson method), lysine, arginine decarboxylase test and gelatine liquefaction test.1,5 Biochemical characteristics of isolated nonfermenters is shown in Table 1.

Asian Journal of Critical Care Vol. 9, No. 2, January-March 2013

clinical study Table 1. Differential Reactions of Nonfermentative Gram-negative Bacilli P. aeruginosa

A. baumannii

A. lowffii

P. fluorescens

P. stutzeri

B. cepacia

S. maltophilia

A. xylosoxidan

S. putrefaciens

Differential tests

Oxidase

+

–

–

+

+

w

–

+

+

Motility

+

–

–

+

+

+

+

+

+

Oxidation glucose

+

+

–

+

+

+

+

+

+

Oxidation lactose

–

+

–

–

–

+

+

–

v

Oxidation maltose

v

v

–

v

+

+

++

–

+

Oxidation mannitol

v

–

–

+

v

+

–

–

+

NO3 reduction

v

–

–

–

+

–

–

v

–

Arginine

+

–

–

+

–

–

–

–

–

Fluorescein

+

–

–

+

–

–

–

–

–

DNase

–

–

–

–

–

–

+

–

+

Aesculin

–

–

–

–

–

v

+

–

v

H2S (KIA)

–

–

–

–

–

+

–

–

+

Urease

v

v

v

v

v

v

–

–

–

ONPG+ Lysine+

Lysine+

Xylose+

Additional tests

Growth at 42ºC

Gelatin+

+ = Positive, – = Negative, v = Variable, w = Weakly positive, ++ = Strongly positive. ONPG = Orthonitrophenyl-β-D-galactopyranoside.

The clinical significance of the NFGB was assessed retrospectively by analyzing the case sheets for compiling of laboratory and clinical criteria. The laboratory criteria included the presence of pus cells along with gram-negative bacilli in the stained smear from the sample, single bacterium infection, repeat isolation of same bacteria from the sample concerned, leukocytosis and relevant radiological evidence (in case of sputum and trachea bronchial aspirate sample).6 The clinical criteria included the presence of risk factors such as underlying disease (diabetes mellitus, chronic renal failure, malignancy, hepatitis, bronchiectasis, cystic fibrosis, pneumonia and other immunosuppressive conditions), presence of intravenous or urinary catheters, length of stay in intensive care unit (ICU), beginning of mechanical ventilation, history of previous antibiotic therapy, history of recent hospitalization and recent surgery.3 The sensitivity test was performed with help of the Kirby-Bauer disc diffusion method using commercially available disc (Hi-Media).7 The different antimicrobials used were cephalexin (30 ug), ampicillin (10 ug), tetracycline (25 ug), chloramphenicol (25 ug), co-trimoxazole (25 ug), norfloxacin (10 ug), Asian Journal of Critical Care Vol. 9, No. 2, January-March 2013

ciprofloxacin (5 ug), gentamycin (10 ug), amikacin (30 ug), ceftazidime (30 ug), ceftriaxone (30 ug), cefotaxime (30 ug), ticarcillin (75 ug), piperacillin/ tazobactum (100 ug/10 ug), cefoperazone/sulbactum (75 ug/10 ug), imipenem (10 ug) and colistin (10 ug).

The results were interpreted as per CLSI guidelines.8 Escherichia coli ATCC 25922 and Pseudomonas aeruginosa 27853 were used as control strains.

Results In the present study, 201 nonfermenters were isolated out of 1,650 clinical samples accounting for an isolation rate of 12.18%. A total of 188 isolates were considered significant by the criteria mentioned. The clinical specimen included tracheal aspirate (18.4%), sputum (16.41%), blood (16.41%), pus (27.86%), urine (15.92%) and remaining 4.97% from other categories.

P. aeruginosa was the predominant isolate, 101 (50.24%) followed by Acinetobacter baumannii (24.87%). Other isolated nonfermenters were Acinetobacter lowffii (5.47%), Pseudomonas fluorescens (1.49%), Pseudomonas stutzeri (1.99%), Burkholderia cepacia (6.96%), Stenotrophomonas maltophilia (2.98%), Achromobacter xylosoxidan (3.98%) and Shewanella putrefaciens (1.99%).

11

clinical study The clinical sources of these isolates are shown in Table 2. Fifty-five percent of patients were male and 45% were female. Majority of patients (72%) were adults aged above 45 years. Connection to ventilator,

history of invasive procedures, steroid and other immunosuppressive therapy and underlying disease accounted for significant decrease of antibiotic activity.

The results of susceptibility testing of the identified

Table 2. Clinical Sources of Nonfermentative Gram-negative Bacilli Organism

Pus

Sputum

Tracheal aspirate

Blood

Urine

Others

Total

P. aeruginosa

31

20

18

14

16

2

101

A. baumannii

10

9

11

10

8

2

50

A. lowffii

3

2

3

1

1

1

11

P. fluorescens

--

--

--

1

1

1

3

P. stutzeri

2

--

--

1

1

---

4

B. cepacia

5

2

2

2

2

1

14

S. maltophilia

2

--

1

1

1

1

6

A. xylosoxidan

3

--

--

2

1

2

8

S. putrefaciens

--

--

2

1

1

--

4

Total

56

33

37

33

32

10

201

Table 3. Susceptibilities of Nonfermentative Bacilli to Antimicrobial Agents P. aeruginosa (%)

A. baumannii (%)

A. lowffii (%)

P. fluorescens (%)

P. stutzeri (%)

B. cepacia (%)

S. maltophilia (%)

A. xylosoxidan (%)

S. putrefaciens (%)

Antimicrobials

8 (7.92)

4 (8)

1 (9.09)

0

1 (25)

0

0

0

1

Tetracycline

22 (21.78)

11 (22)

2 (18.2)

1 (33.33)

1 (25)

2 (14.28)

0

2 (25)

2 (50)

Chloramphenicol

23 (22.77)

14 (28)

3 (27.8)

1 (33.33)

2 (50)

3 (21.42)

0

4 (50)

75 (75)

Co-trimoxazole

11 (10.89)

3 (6)

1 (9.09)

0

0

13 (92.85)

6 (100)

2 (25)

4 (100)

Ampicillin

Cephalexin

0

0

0

0

1 (25)

3 (21.42)

0

0

0

27 (26.73)

9 (18)

3 (27.27)

1 (33.33)

2 (50)

12 (85.71)

6 (100)

6 (75)

2 (50)

Norfloxacin

4 (3.96)

0

0

0

1 (25)

4 (28.57)

3 (50)

2 (25)

1 (25)

Ceftazidime

29 (28.71)

14 (28)

2 (18.18)

0

2 (50)

12 (85.71)

4 (66.66)

2 (25)

2 (50)

Cefotaxime

17 (16.83)

7 (14)

3 (27.27)

0

0

6 (42.85)

0

0

2 (50)

Ciprofloxacin

12

Ceftriaxone

21 (20.8)

15 (30)

4 (36.36)

1 (33.33)

1 (25)

7 (50)

0

2 (25)

3 (75)

Gentamicin

24 (23.76)

12 (24)

3 (27.27)

1 (33.33)

2 (50)

0

0

4 (50)

2 (50)

Imipenem

92 (91.08)

45 (90)

10 (90.9)

3 (100)

3 (75)

13 (92.85)

0

8 (100)

4 (100)

Cefoperazone/ Sulbactum

69 (68.31)

8 (16)

4 (36.36)

2 (66.66)

2 (50)

9 (64.28

0

6 (75)

4 (100)

Piperacillin/ Tazobactum

47 (46.53)

19 (38)

4 (36.36)

1 (33.33)

2 (50)

8 (57.14)

0

4 (50)

3 (75)

Ticarcillin

49 (48.51)

12 (24)

5 (45.45)

1 (33.33)

2 (50)

4 (28.57)

0

4 (50)

3 (75)

Amikacin

70 (69.30)

32 (62)

6 (54.54)

2 (66.66)

1 (25)

2 (14.28)

0

6 (75)

4 (100)

Colistin

101 (100)

47 (94)

11 (100)

3 (100)

4 100)

0

3 (50)

4 (100)

4 (100)

Asian Journal of Critical Care Vol. 9, No. 2, January-March 2013

clinical study

35 30

Pus

25

Sputum 20

Tracheal aspirate Blood

15

Urine

10 5 0 P. aeru

A. bau

A. loef

P. stu

B. cep

S. malt

A. xylo

Figure 1. Clinical sources of nonfermentative gram-negative bacilli.

species are listed in Table 3. The most active antibiotic against P. aeruginosa was colistin (100%) followed by imipenem (91.08%), amikacin (69.30%) and cefoperazone/sulbactum combination (68.31%).

In case of A. baumannii most active drug was also colistin (94%), followed by imipenem (90%) and amikacin (62%). All isolates of S. maltophilia were susceptible to co-trimoxazole and ciprofloxacin. Susceptibility of B. cepacia to co-trimoxazole, ciprofloxacin, ceftazidime and imipenem was 92.8%, 85.7%, 87.5% and 92.8%, respectively.

Discussion NFGB, that were previously considered to be contaminants have now emerged as important nosocomial pathogens.9 P. aeruginosa and Acinetobacter species are known to be common among them.10 Our observations well corroborate with this. NFGB belonging to Pseudomonas species and Acinetobacter species together accounted for 84.06% of the isolates.

In our study, highest number of the NFGB isolates were from pus sample, similar to the observations made by others.11,12 NFGB were commonly involved in wound infections resulting from road traffic accidents and chronic nonhealing ulcers. The clinical conditions associated with NFGB infection in our study included surgical site infection (SSI), ventilator-associated pneumonia (VAP), urinary tract infection (UTI), septicemia and chronic nonhealing ulcer because of Asian Journal of Critical Care Vol. 9, No. 2, January-March 2013

endocrinopathy like diabetes mellitus. P. aeruginosa and A. baumannii were more commonly isolated from SSI and UTI, whereas majority of VAP cases were due to A. baumannii.

P. aeruginosa isolates in this study were highly susceptible to colistin, imipenem, amikacin and cefoperazone/sulbactum combination. This contrasts with the antibiotic susceptibility pattern of bacterial isolates from Chandigarh12 and Bangalore.13 In a study from Chandigarh a total of 42% strains of P. aeruginosa were found to be resistant to imipenem.12 Similarly in Bangalore P. aeruginosa showed 60-70% resistance to amikacin, ceftazidime and ciprofloxacin.13 The strains of Acinetobacter species showed higher rate of resistance to ciprofloxacin, amikacin, ceftazidime and piperacillin in a study in Bangalore when compared with the present study.14 The antibiotic susceptibility patterns may change with time and may vary from hospital to hospital. Susceptibility patterns may be altered due to resistance transfer and mutant selection from indiscriminate and excessive use of antibiotics.15,16 Furthermore, most of our patients came from rural areas without much exposure to antibiotics.

Differences in susceptibility could be attributed to these above mentioned factors. Six strains of S. maltophilia were isolated during the study. Two of isolates were from wound infections and one each from tracheal aspirate, blood, urine and CSF. Administration of co-trimoxazole promptly brought out a cure in these 13

clinical study patients.2,17 S. maltophilia is inherently resistant to aminoglycosides and β-lactum antibiotics including carbapenem. Our study showed a lower range of sensitivity of isolated strains against fluoroquinolone and this may be attributed to their widespread use particularly ciprofloxacin and norfloxacin.

5. Thong ML. Differentiation of nonfermentative gram-negative bacilli in the clinical laboratory.

Southeast Asian J Trop Med Public Health 1977; 8(1):7-12.

6. Hill EB, Henry DA, Speert DP. Pseudomonas. In: Manual of Clinical Microbiology. Vol. 1, 9th edition, Murray PR, Baron EJ, Jorgensen JH, Landry ML, Pfaller MA (Eds.), American Society for Microbiology: Washington, DC 2007:p.734-48.

From the present study, it can be concluded that nonfermenter gram-negative bacilli though regarded as contaminants are important bacteria causing both hospital- and community-acquired infections.

P. aeruginosa and A. baumannii were the most common NFGB isolated in our study. They have been associated with UTI, septicemia, SSI, VAP and other chronic wound infection and most of them were multidrug-resistant. P. aeruginosa has shown good sensitivity to colistin, imipenem, amikacin and cefoperazone/sulbactum combination. A. baumannii shows good sensitivity to colistin, imipenem and amikacin. The different species of NFGB showed varied susceptibility pattern in this study. So, the proper identification of NFGB upto the species level along with monitoring of their susceptibility patterns are important for proper management of the infection caused by them. It is also important to establish the clinical relevance of the isolated NFGB, before they can be considered as pathogens to avoid unnecessary usage of antibiotics and emergence of drug-resistant strains.

7. Bauer AW, Kirby WM, Sherris JC, Turck M. Antibiotic susceptibility testing by a standardized single disk method. Am J Clin Pathol 1966;45(4):493-6.

8. Clinical and Laboratory Standards Institute. Performance Standards for Antimicrobial Susceptibility Testing. 16th Informational Supplement (M100-S16). Vol. 26, No. 3, Clinical and Laboratory Standards Institute, Wayne, Pa; 2006.

9. Troillet N, Samore MH, Carmeli Y. Imipenem-resistant Pseudomonas aeruginosa: risk factors and antibiotic susceptibility patterns. Clin Infect Dis 1997;25(5):1094-8.

10. Yashodara P, Shyamala S. Identification and characterization of nonfermenters from clinical specimens. Indian J Med Microbiol 1977;15:195-7.

11. Mishra B, Bhujwala RA, Shriniwas. Nonfermenters in human infections. Indian J Med Res 1986;83:561-6.

12. Taneja N, Maharwal S, Sharma M. Imipenem resistance in nonfermenters causing nosocomial urinary tract infections. Indian J Med Sci 2003;57(7):294-9.

References

13. Kumari HB, Nagarathna S, Chandramuki A. Antimicrobial resistance pattern among aerobic gramnegative bacilli of lower respiratory tract specimens of intensive care unit patients in a neurocentre. Indian J Chest Dis Allied Sci 2007;49(1):19-22.

1. Winn W Jr, Allen S, Janda W, Koenman E, Procop G, Schreckenberger P, et al. (Eds.). Nonfermenting Gramnegative bacilli. In: Koneman’s Color Atlas and Textbook of Diagnostic Microbiology. 6th edition, Lippincott Williams and Wilkins Company: USA 2006:p.305-91.

14. Sinha M, Srinivasa H, Macaden R. Antibiotic resistance profile and extended spectrum beta-lactamase (ESBL) production in Acinetobacter species. Indian J Med Res 2007;126(1):63-7.

2. Steinberg JP, Rio DC. Other Gram-negative and Gram variable bacilli. In: Principles and Practice of Infectious Diseases. 6th edition, Vol. 2, Mandell GL, Bennett JE, Dolin R (Eds.), Elsevier Publication: Philadelphia, USA 2005:p.2751-68.

15. von Graevenitz A. Clinical microbiology of unusual Pseudomonas species. Prog Clin Pathol 1973;5: 185-218.

3. Quinn JP. Clinical problems posed by multiresistant nonfermenting gram-negative pathogens. Clin Infect Dis 1998;27 Suppl 1:S117-24.

16. Gilardi GL. Antimicrobial susceptibility as a diagnostic aid in the identification of nonfermenting gramnegative bacteria. Appl Microbiol 1971;22(5):821-3.

4. McGowan JE Jr. Resistance in nonfermenting gramnegative bacteria: multidrug resistance to the maximum.

Am J Infect Control 2006;34(5 Suppl 1):S29-37; discussion S64-73.

n

14

17. Nag F, De A, Banerjee K, Chatterjee G. Non healing leg ulcer infected with Stenotrophomonas maltophilia: first reported case from India. Int Wound J 2012 Jan 31.

n

n

Asian Journal of Critical Care Vol. 9, No. 2, January-March 2013

drugs and devices clinical practice

Look-alike and Sound-alike Drug Brand Names: A Potential Risk in Clinical Practice Mukundraj S Keny*, PV Rataboli**

Abstract Objective: Indiaâ&#x20AC;&#x2122;s pharmaceutical industry is now the third largest in the world in terms of volume. With this growth, various drugs with catchy brand names have been introduced. The potential for error due to confusing drug names amongst the healthcare personnel is significant. Numerous case reports and studies have thrown light on the confusion over similar drug names. Despite these efforts, new names that are similar to the existing names continue to be approved. Aim: The study was carried out to isolate confusing brand names, which are used currently in the Indian market and to categorize these names depending on their effect on therapeutic success. Material and methods: The March to April 2011 issue of the drug formulary Indian Drug Review (IDR) (Vol. XVII Issue No. 2) was referred to and all the potentially confusing brand names were analyzed. Results: Many of the brand names were similar looking (orthographic) and similar sounding (phonetic).

Certain observations regarding brand naming techniques and their possible implications were noted. Conclusion: The Indian pharmaceutical industry is growing at a fast pace. Hence, India needs a competent Medication Error Reporting Program to report the brand name confusion. Also, we need to create more awareness about confusing brand names and their implications.

Key words: Drug name, look-alike, sound-alike, therapeutic success, implications, confusing

I

ndiaâ&#x20AC;&#x2122;s pharmaceutical industry is now the third largest in the world in terms of volume. The Indian Pharmaceutical sector is highly fragmented with more than 20,000 registered units. Following the delicensing of the pharmaceutical industry, industrial licensing for most of the drugs and pharmaceutical products has been done away with. Manufacturers are free to produce any drug duly approved by the Drug Control Authority.1 With this growth, various drugs with catchy brand names have been introduced. With tens of thousands of drugs currently on the market, the potential for error due to confusing drug names amongst the practicing doctors, pharmacists and patients is significant. Confusion over the similarity of prescription and over-the-counter (OTC) drug names has accounted for as many as 25% of all reports to the United States Pharmacopeia Medication Errors Reporting (USP MER) Program.2

*Postgraduate Student **Director-Professor, Dept. of Pharmacology Goa Medical College, Bambolim, Goa Address for correspondence Dr Mukundraj S Keny H. No. 881, Abhyudaya Apartments, Vidyanagar Margao, Goa - 403 601 E-mail: mukundkeny@yahoo.com

Asian Journal of Critical Care Vol. 9, No. 2, January-March 2013

The proposed names are subjected to pre-approval screening by the pharmaceutical manufacturers to various organizations like US Pharmacopeia (USP) and US Food and Drug Administration (US FDA).

Numerous case reports and studies have thrown light on the confusion over similar drug names.3-10 Despite these efforts, new names that are similar to the existing names continue to be approved. We carried out the study to isolate confusing brand name products, which are used currently in the Indian market and to describe potential effect of this confusion on the therapeutic success.

Material and Methods The March to April 2011 issue of the drug formulary Indian Drug Review (IDR) (Vol. XVII Issue No. 2) was referred to and all the potentially confusing brand names were analyzed.11 The brand names were presented in the form of tables along with the generic names and the manufacturer of the drug. The possible implication of this confusion was assessed.

Results The IDR lists more than 10,000 brands. Many of the brand names were similar looking (orthographic) and similar sounding (phonetic). The brand names were 15

Drugs and devices Table 1. Major Effect on Therapeutic Success

16

Brand name

Generic name

Manufacturer

Benzol

Danazol 100 mg

Solitaire

Benzole

Albendazole 400 mg/Ivermectin 6 mg

Flamingo

Alparazole

Alprazolam 0.5 mg

Laborate

Adprazole

Omeprazole 20 mg

Admac

Amsat

Ampicillin 250 mg/Cloxacillin 250 mg

Vensat

Amset

Amlodipine 5 mg

Pulse

Adcom

Telmisartan 40 mg

Intel Pharma

Adcon

Fluconazole 150 mg

Admac

Alflox

Norfloxacin 400 mg

Alkem

Alfox

Oxcarbazepine 300 mg

Medi Health

Bromolin

Amoxycillin 500 mg/Bromhexine 8 mg

Cipla

Bromotin

Bromocriptine 2.5 mg

RPG LS

Dialox

Tinidazole 300 mg/Diloxanide 375 mg/ Methyl polysiloxane 25 mg

Aglowmed

Diamox

Acetazolamide 250 mg

Wyeth

Dazolic

Ornidazole 500 mg

Sun

Dazolin

Sertraline 50 mg

Daksh

Depik

Imipramine 25 mg

Aarpik

Depin

Nifedipine 5 mg

Zydus Cadila

Felix

Cefpodoxime 100 mg

Positif

Feliz

Citalopram 10 mg

Torrent

Flex

Ofloxacin 400 mg

Siomond

Flexi

Ondansetron 4 mg

Adley

Flunat

Fluoxetine 10 mg

Sun

Flunaz

Fluconazole 150 mg

BMV

Glucar

Acarbose 50 mg

Glenmark

Glucart

Glucosamine 500 mg

Juggat

Hycin

Roxithromycin 150 mg

Saga Labs

Hymin

Albendazole 400 mg

Intra Labs

Lodol

Haloperidol 5 mg

Symbiosis

Lodoz

Bisoprolol 2.5 mg/Hydrochlorothiazide 6.25 mg

Merck

Lorvan

Lorazepam 1 mg

Cipla

Lorvas

Indapamide 2.5 mg

Torrent

Norten

Propranolol 10 mg

Baroda

Nortin

Nortriptyline 25 mg

La Pharma

Ocimix

Ciprofloxacin 500 mg/Ornidazole 500 mg

Panacea

Ocimax

Omeprazole 20 mg

Pidek

Rispod

Cefpodoxime 100 mg

Symbiosis

Rispond

Risperidone 2 mg

Microsynapse

Topdep

Citalopram 10 mg

Orchid

Topdip

Amlodipine 10 mg

RPG LS

Zolep

Zolpidem 5 mg

Taj Pharma

Zolet

Letrozole 2.5 mg

United Biotech

Wypan

Pantoprazole 40 mg

YACCA

Wypar

Nimesulide100 mg/Paracetamol 500 mg

YACCA

Asian Journal of Critical Care Vol. 9, No. 2, January-March 2013

Drugs and devices Table 2. Minor Effect on Therapeutic Success Aquamide

Furosemide 50 mg/Spironolactone 20 mg

Sun

Aquazide

Hydrochlorothiazide 12.5 mg

Sun

Disprin

Aspirin 350 mg/Calcium carbonate 105 mg

Reck and Benckiser

Dospin

Aspirin 75 mg/Clopidogrel 75 mg

Ajanta

Epitab

Phenytoin 100 mg

East west

Epitan

Phenobarbitone 60 mg

Reliance

Glide

Glipizide 5 mg

Franco indian

Gliden

Gliclazide 80 mg

BMW

Heal gel

Silver sulfadiazine/Chlorhexidine/Metronidazole

ORDAIN

Healin ointment

Povidone iodine/Metronidazole

Speciality Meditech

Moxycarb

Amoxycillin 500 mg/Carbocisteine 150 mg

AHPL

Moxycare

Amoxycillin 500 mg/Clavulanate 125 mg

TRITAG

Ostofit

Glucosamine/Chondroitin

Torrent

Ostrobit

Calcium carbonate 500 mg/Vitamin D3

Cubit

Serip

Diclofenac 50 mg/Serratiopeptidase 10 mg

Bennet

Serit

Serratiopeptidase 5 mg

Sunrise

Wormnil

Mebendazole 100 mg

Wings Pharma

Wormonil

Albendazole 400 mg

PDC

Table 3. No Significant Effect on Therapeutic Success Avcif

Cefixime 200 mg

Positif

Avcip

Ciprofloxacin 500 mg

Positif

Atmox

Amoxycillin 250 mg

A To Z

Atrox

Roxithromycin 150 mg

A To Z

Afcal

Calcium carbonate 1250 mg/Vitamin D3 250 IU

Alcure

Atcal

Calcium carbonate 625 mg/Vitamin D3 125 IU

A To Z

Cefit

Cefixime 200 mg

Cubit

Cefiz

Cefpodoxime 200 mg

Medi Health

Ceftab

Cefuroxime 250 mg

Sienna

Ceftas

Cefixime 200 mg

Intas

Cufex syrup

Chlorpheniramine/codeine/menthol

Ind-Swift

Cuffix syrup

Terbutaline/Ambroxol/Guaiphenesin/Menthol

Amra

Oflomil

Ofloxacin 200 mg

Glenmark

Oflomix

Cefixime 200 mg

Orion

Recocef

Cefetamet 250 mg

Zydus Cadila

Recocif

Ciprofloxacin 250 mg

Zydus Cadila

Deplin

Sertraline 50 mg

Sykocure

Depnil

Clomipramine 25 mg

Cipla

Biolex

Cephalexin 500 mg

Cubit

Biolexi

Amoxycillin 250 mg/Dicloxacillin 250 mg

Biochemix

Asian Journal of Critical Care Vol. 9, No. 2, January-March 2013

17

Drugs and devices divided into three categories based on their effect on therapeutic success (Tables 1-3).

zz

Discussion Branding is so crucial to the success of a new drug that pharmaceutical companies spend years and millions just to come up with a name. The branding agencies strive to create a name that consumers will find comforting, fast-acting and miraculous. Above all, they want it to be easy to remember and pronounce.

Many drug names look or sound-like other drug names leading to confusion errors. Databases of anonymously reported errors are maintained jointly by the Institute of Safe Medication Practices (ISMP), the USP MERP and the FDA’s MedWatch program.12,13 According to the eighth annual MEDMARX Data Report published by the USP, 1,470 different drugs are implicated in medication errors due to similarities between their brand or generic names. Based on a review of more than 26,000 records submitted to the MEDMARX database from 2003 to 2006, USP compiled a list of 3,170 look-alike and sound-alike drug name confusions. This list contains nearly twice as many medication name errors as the last MEDMARX report, which was issued in 2004.14 In India, the extent of this problem is unknown.

In a study, the effect of orthographic and phonetic similarity on the probability of making recognition memory errors (i.e., false recognitions) was examined.

It was concluded that these similarities increase the probability that experts will make false recognition errors when trying to remember drug names.15 Contributing to this confusion are illegible handwriting, incomplete knowledge of drug names, similar packaging or labeling, similar clinical use, similar strengths, dosage forms, frequency of administration and the failure of manufacturers and regulatory authorities to recognize the potential for error for drug names, prior to approving new product names.9

18

zz

zz

zz

Certain pharmaceutical companies try to use a fancy brand name to depict the effect of drug; creating confusion. For example, the word ‘Aqua’ has been used to depict diuresis.

Aquamide-/Furosemide 50 mg/Spironolactone 20 mg/Sun

Aquazide-/Hydrochlorthiazide 12.5 mg/Sun Certain companies use initial letters of the disease for which the drug is used in the brand names; creating confusion. For example, the word ‘Epi’ has been used from the disease epilepsy.

Epitab/Phenytoin 100 mg/East West

Epitan/Phenobarbitone 60 mg/Reliance To take advantage of name recognition among consumers and doctors, manufacturers like to give their new products names that are similar to the names of well-established brands. This practice can confuse users of these drugs.

Wormnil - Mebendazole 100 mg - Wings Pharma

Wormonil - Albendazole 400mg - PDC Another potential problem arises when manufacturers include certain letters in the proprietary name that differentiates their company from others and/or indicates a particular product range (e.g., antibiotic group). For example:

Avcif cefixime 200 mg POSITIF/Avcip Ciprofloxacin 500 mg/Positif

Atmox Amoxycillin 250 mg A to Z/Atrox Roxithromycin 150 mg/A to Z

Recocef Ceftamet 250 mg Zydus Cadila/ Recocif Ciprofloxacin 250 mg/Zydus Cadila

Cefit Cefixime 200 mg CUBIT/Cefiz Cefpodoxime 200 mg/Medi Health

Ceftab Cefuroxime 250 mg SIENNA/Ceftas Cefixime 200 mg/Intas

Various methods have been used to categorize the brand names in the previous studies. In our study, we have categorized the names into three categories based on the effect they will have on the treatment and progression of the disease. The brand names were correlated with the drug action.

It was noted that since the drugs forming the pair had strikingly different indications, different doses and schedule, there is less chance of drug name confusion.

But, in case the drug dose is not specified, it can create confusion. And, although some drug names and symbols may not necessarily sound-alike or look-alike, they could cause confusion in prescribing errors when handwritten or communicated verbally.

The brand naming techniques used by the branding agencies, which are evident in our study are as follows:

It was noted that drug pairs, which can have a major effect on therapeutic success included drugs-acting Asian Journal of Critical Care Vol. 9, No. 2, January-March 2013

Drugs and devices on central nervous system in most of the examples (Sertraline, imipramine, zolpidem, risperidone, nortriptyline, haloperidol and lorazepam). This category has highest risk of therapeutic failure, drug toxicity and aggravation of disease. So, practitioners should be more careful while prescribing these drugs.

Another important observation was that the drug pairs, which belong to the ‘no significant effect on therapeutic success’ category were mostly antibiotics (in bold font).

Hence, there is a risk that the antibiotics not indicated for a particular condition may be administered or that a stronger antibiotic is used for a minor infection without patient noticing any difference. The patients harmed by a medical error may never learn of the error.

Some antibiotics whose doses are same are more likely to be confused. For example, Oflomil = Ofloxacin 200 mg/Oflomix = Cefixime 200 mg. These factors can lead to antibiotic resistance.

Also, there is some crossover between the above three categories for e.g. Epitab and Epitan mentioned in the minor effect category could also be included in the major effect category depending on the type of epilepsy they are used for.

The treatment of the side effect of the wrong drug may in turn lead to increased cost on medications required to rectify the error.

Thus wrong drug administration can lead to therapeutic failure, aggravation of the disease, serious toxicity, antibiotic resistance and increased cost on medications.

The limitation of this study is that it has included the brand names only from one drug formulary (IDR).

Brand names from other drug formularies and which are not mentioned in these formularies but are still available with the pharmacist are not included.

The above mentioned categorization has been done without any scale to quantify the risk of particular drug pair confusion. Further studies are needed to assign a particular confusing drug pair to the appropriate category using risk assessment scales.

Steps for Reducing Drug Name Confusion Errors16,17 Role of Prescribers zz

Doctors should be well-versed with generic name and the brand names that are available in their local setting.

Asian Journal of Critical Care Vol. 9, No. 2, January-March 2013

zz

zz

zz

zz zz zz

Clearly specify dosage form, drug strength and complete directions on prescriptions.

Use both brand and generic names when writing a prescription.

Include the purpose of the medication in the prescription.

Avoid verbal orders. Do not prescribe over the phone.

Avoid the use of confusing drug mnemonics.

Write in legible handwriting.

Role of Organizations zz

zz

zz

The FDA uses computer software to analyze how close the name is to drugs already on the market.

Potentially confusing names are rejected. To minimize confusion between drug names that look or sound-alike, the FDA reviews about 300 brand names a year before they are marketed. About onethird are rejected.18 The FDA encourages pharmacists and other health professionals to report any actual or potential medication errors to the agency’s Adverse Event Reporting System.

The licensing authorities and regulatory agencies should exercise more control over the naming of a new formulation.

Role of Pharmacists zz

zz

zz

zz

Dispensers should refer back to the doctor if there is confusion and should have basic knowledge of dosing regimens, at least for commonly used drugs.

According to the MEDMARX report, “pharmacists as a group identified, prevented and reported” more errors than any other health providers.

Install a computerized reminder for the most serious confusing name pairs so that an alert is generated when entering prescriptions for either drug.

Affix ‘name alert’ stickers to areas where look or sound-alike products are stored.

Role of Patients zz

zz

Confirm the name and strength of prescribed drugs before leaving the doctor’s office.

Illiterate patients should verify the drug names and instructions.

Role of Manufacturers zz zz

Proper packaging labels and color code.

OTC drugs should be given unique names.

19

Drugs and devices zz zz

Take reports of confusion seriously.

Use of mixed-case or enlarged letters to emphasize the differing portions of two drug names: E.g.

DOBUTamine/DOPamine.

It is very important that we circulate the list of confusing brand names among the practicing doctors, pharmacists and also to the drug manufacturers. The general practitioners should be the major target as they deal with a greater variety of brand names.

4. Dooley M, Van de Vreede M. Proprietary names for glaucoma drugs: potential for error. Lancet 2006;368(9545):1419-20.

5. Rataboli PV, Garg A. Confusing brand names: nightmare of medical profession. J Postgrad Med 2005;51(1):13-6.

6. Damodaran RT. Brand confusion causes allergic dermatitis. J Postgrad Med 2005;51(3):242.

Preventing confusion between already marketed products typically involves collecting voluntary reports of names involved in confusion errors, posting warnings and alerts both electronically and in areas where drugs are used.19

7. Aronson JK. Medication errors resulting from the confusion of drug names. Expert Opin Drug Saf 2004;3(3):167-72.

The fear of malpractice lawsuits and public embarrassment has made the physicians and nurses reluctant to report medication errors. It is more important to create the open environment that encourages the reporting of errors than to develop less meaningful comparative error rates.

9. Hoffman JM, Proulx SM. Medication errors caused by confusion of drug names. Drug Saf 2003;26(7):445-52.

One possible approach to improving medical error reporting involves the use of anonymous standardized reporting systems. This type of system should also enable internal tracking, trending and comparative analyses. We need to have such systems in India.

Besides those listed above there could be many more confusing brand names available in the Indian drug market with or without being listed in the drug formularies. Therefore, we need a well-structured Medication Error Reporting Program and an organizational surveillance over drug naming in India. This program should be at par with the Pharmacovigilance program of India. A combined effort from prescribers, pharmacists, organizations and manufacturers is required.

References 1. Indian Pharmaceutical Industry http://www. pharmaceutical-drug manufacturers.com/pharmaceuticalindustry/. Accessed April 2, 2012.

2. National Coordinating Council for Medication Error Reporting and Prevention: Recommendations to reduce medication errors associated with verbal medication orders and prescriptions. Feb. 20, 2001. http://www. nccmerp.org/council/council2001-02-20.html. Accessed April 2, 2012.

20

3. Chiche L, Thomas G, Canavese S, Branger S, Jean R, Durand JM. Severe hemorrhagic syndrome due to similarity of drug names. Eur J Intern Med 2008;19(2): 135-6.

8. Gremillion L, Hogan DJ. Dermatologic look- or soundalike medications. J Drugs Dermatol 2004;3(1):61-4.

10. Lilley LL, Guanci R. Sound-alike cephalosporins. How drugs with similar spellings and sounds can lead to serious errors. Am J Nurs 1995;95(6):14.

11. Indian Drug Review (Vol. XVII Issue No. 2, MarchApril 2011) published by UBM Medica India Pvt ltd.

12. MedWatch, the FDA safety information and adverse reporting program. Available at: http://www.fda.gov/ Safety/MedWatch/default.htm. Accessed April 7, 2012.

13. USP Transitions Medication Error Reporting Programs. Available at: http://www.usp.org/search/site/ medication%20error%20reporting. Accessed April 7, 2012.

14. U.S. Pharmacopeia 8th Annual MEDMARX Report Indicates Look-Alike/Sound-Alike Drugs Lead to Thousands of Medication Errors Nationwide. Available at: http://www.usp.org/search/site/medication%20 error%20reporting. Accessed April 7, 2012.

15. Lambert BL, Chang KY, Lin SJ. Effect of orthographic and phonological similarity on false recognition of drug names. Soc Sci Med 2001;52(12):1843-57.

16. ISMP. Whatâ&#x20AC;&#x2122;s in a name? Ways to prevent dispensing errors linked to name confusion. ISMP Medication Safety Alert! 7(12) June 12, 2002.

17. JCAHO. Sentinel Event Alert. Issue 19 - May 2001.

18. Strategies to Reduce Medication Errors: Working to Improve Medication Safety, The US Food and Drug Administration [Website] Accessed October 26, 2009. http://www.fda.gov/Drugs/ResourcesForYou/ Consumers/ucm143553.htm. Accessed April 3, 2012.

19. Lambert BL, Lin SJ, Tan H. Designing safe drug names.

Drug Saf 2005;28(6):495-512.

Asian Journal of Critical Care Vol. 9, No. 2, January-March 2013

Case report clinical practice

Chylous Ascites due to Tuberculosis: A Case Report and Review of Literature Praveen Kumar*, Kalpana Chandra**

Abstract Chylous ascites (CA) is an uncommon clinical condition and occurs as a result of disruption of abdominal lymphatics either due to trauma or secondary to obstruction. We report a case of CA associated with disseminated tuberculosis.

Key words: Chylous ascites, disseminated tuberculosis, chylous ascites in tuberculosis

C

hylous ascites (CA) is the extravasation of milky chyle into the peritoneal cavity. The incidence of CA in 1950 was one case in 1,87,000 hospital admissions but in 1980s, the incidence increased to one case in 11,584 hospital admissions and this increase in cases was probably due to aggressive retroperitoneal and cardiothoracic surgery and longer survival of cancer patients. It commonly affects adults in 50-60 years of age but can even occur in pediatric populations. It affects males and females equally but a study conducted on 28 patients of chylous ascites at Massachusetts General Hospital found 75% of patients affected to be females.

In adults, the most common causes are abdominal malignancies and cirrhosis, which account for more than two-thirds of the cases in developed countries, whereas infectious diseases such as tuberculosis and filariasis are prevalent in developing countries. Other causes include congenital, inflammatory, postoperative, traumatic and miscellaneous disorders.

Case Report A 52-year-old man of Uttarakhand was admitted in our hospital with chief complaints of fever and cough for five months and distension of abdomen for four months.

*Associate Professor, Dept. of General Medicine **Associate Professor, Dept. of Pathology Shri Ram Murti Smarak Institute of Medical Sciences Bhojipura, Bareilly, UP Address for correspondence Dr Praveen Kumar Associate Professor, Dept. of General Medicine Shri Ram Murti Smarak Institue of Medical Science Bhojipura, Bareilly - 243 202, UP E-mail: praveen_kmr_23@yahoo.com

Asian Journal of Critical Care Vol. 9, No. 2, January-March 2013

He was apparently alright five months back when he developed continuous low-grade fever and cough. He was diagnosed as a case of pulmonary tuberculosis and DOTS regime for tuberculosis started. Patient had partial relief in fever and cough but he developed ascites. He was revaluated and ascitic fluid showed total count (TC) - 1,700 cells/mm3, differential count (DC) - N10 L90, red blood cell (RBC) + protein - 3.6 g/dl, sugar - 100 mg/dl and adenosine deaminase (ADA) levels - 179 IU/l. He was labeled as a case of disseminated tuberculosis and DOTS regime for tuberculosis continued. But his ascites progressed gradually with mild relief in fever and cough. There was no significant past, personal and family history. On examination, he was febrile with scattered crepitations in respiratory system and evidence of free fluid in abdomen.

Laboratory investigation reports were hemoglobin 12.8 g/dl, total leukocyte count (TLC) 3,000/cumm, DLC - N65L33E1M1, platelets - 2.95 lacs, prothrombin - N, partial thromboplastin time - N, erythrocyte sedimentation rate (ESR) - 44 mm/hr, total protein 6.0 mg% with A/G ratio of 0.9 mg%, serum bilirubin - 0.4 mg%, aspartate aminotransferase (AST) - 38 IU/l, alanine transaminase (ALT)-16 IU/l, serum alkaline phosphatase (ALP) - 162 IU/l, serum cholesterol 178 mg/dl and serum triglycerides 148 mg/dl.

Enzyme-linked immunosorbent assay (ELISA) test for human immunodeficiency virus (HIV) and hepatitis B surface antigen (HBsAg) were nonreactive. Analysis of ascitic fluid revealed grossly milky fluid with glucose level of 146 mg/dl, total protein 6.3 g/dl, amylase 62 IU/l, triglycerides -1,576Â IU/l, cholesterol 120 mg/dl and an ADA level of 27 IU/l. The cell count of ascitic fluid was 21

case report 850 cells/mm3 with DC of 98% lymphocytes and 02% polymorphs. Culture of fluid was sterile and cytological examination was negative for malignant cells. Contrast-enhanced computed tomography (CECT) of chest showed clustered nodular opacities in bilateral lung fields with minimal left pleural effusion and small area of consolidation in left lung. CECT abdomen showed gross ascites with mild omental thickening, few discrete lymph nodes in pre/left paraaortic region, largest measuring 14Â mm. Diagnostic laparoscopy was done, which showed gross CA but mesenteric lymphadenopathy/omental thickening was not seen. The patient was started on daily regime of antitubercular drugs (ATT). Further management was done by large volume paracentesis, diuretics and low salt diet. He was discharged and was called up for follow-up. Patient received total of nine months of ATT with full clinical response and complete recovery.

Discussion Chylous ascites is defined as the extravasation of milky or creamy appearing peritoneal fluid rich in triglycerides, caused by the presence of thoracic or intestinal lymph in the abdominal cavity. It is a manifestation of underlying pathology and is not a disease by itself.

Morton, in 1691, performed paracentesis in an 18-month boy with disseminated tuberculosis and noted the presence of CA. Trauma was recognized as the most common cause in the 17th century.

Later on multiple causes have been described, which are abdominal surgery, blunt abdominal trauma, malignant neoplasm, spontaneous bacterial peritonitis, cirrhosis, pelvic irradiation, peritoneal dialysis, abdominal tuberculosis, carcinoid syndrome and congenital defects of lacteal formation.

In tropical countries tuberculosis and filariasis are one of the leading causes. Congenital abnormalities of the lymphatics system and trauma should be considered as the most important etiological factors in children.

A study was conducted on 35 patients to know the etiology and prognosis of CA. More than 90% cases were due to malignancy, which included mainly lymphomas and abdominal carcinoma; cirrhosis and retroperitoneal surgery were the other causes.

The cases of malignant CA chiefly presented with extensive tumor dissemination with one year mortality 22

rate of 80%. Cases of CA with cirrhosis were refractory to treatment in 13 out of 15 cases with a mortality rate of 69%.9 Mycobacteria spp. is the most common cause of CA in HIV-infected patients.

The possible mechanisms of CA are lymph node fibrosis or infiltration by malignancy obstructing the flow of chyle, leaking of chyle through a fistula into the peritoneal cavity due to congenital lymphangiectasis and acquired thoracic duct obstruction with a lymphoperitoneal fistula causing chyle leakage from subserosal lymphatics. Paradoxical immune reconstitution inflammatory syndrome (IRIS) has also been documented in development of CA. Fibrosis of lymph nodes secondary to tuberculosis is the possible mechanism in our case. But as the CA developed and progressed even after DOT regime for tuberculosis was started, paradoxical immune reconstitution inflammatory syndrome may also be a possible contributory mechanism of development of CA in our case.

The clinical presentation of CA is characterized by progressive and painless abdominal distension, weight gain, sign of malnutrition along with symptoms and signs of underlying conditions. Patient may also have chylothorax due to reflux of chyle across the diaphragm into the pleural cavities. Rarely, patients may have acute onset of chylous ascites with rapid weight gain and dyspnea especially in a patient who has undergone abdominal and thoracic surgery.

Patients of CA should be advised for complete blood count, renal function test, liver function tests, triglycerides, cholesterol, amylase, lipase and lactate dehydrogenase (LDH). Ascitic fluid examination such as total and DC, biochemical examination, cytology for malignant cells, triglycerides level, cholesterol level, LDH, serum ascitic albumin gradient (SAAG) ratio, Gram staining, ADA, acid-fast bacillus (AFB) and mycobacterial culture. CT of the abdomen is useful in identifying pathological intra-abdominal lymph nodes and masses. Lymphangiography is the gold standard to define causes of lymphatic obstruction, abnormal retroperitoneal nodes, leakage from dilated lymphatics and fistulization but has several complications related to the volume and type of contrast used. Lymphoscintography is a less invasive alternative to lymphangiography and can confirm an active lymphatic leak into the peritoneal cavity. These Asian Journal of Critical Care Vol. 9, No. 2, January-March 2013

case report tests may be useful in selecting patients for surgery.

Other investigations, which are useful in CA are lymph node biopsy, laparascopy/or laparotomy, bone marrow examination and intravenous pyelography.

Chyle is grossly milky in appearance like the peripheral lymph. In vitro characteristics of chylous fluid are its separation into a creamy layer on standing, alkaline pH, specific gravity between 1.010-1.054, total protein varies from 1.4 to 6.4 g/dl, fat content of 0.4 to 4%, total solids 14%, positive staining of fat globules with Sudan red stain and normal glucose, amylase and cholesterol. CA contain high triglycerides usually higher than 200 mg/dl, although some use a cut-off value of 110 mg/dl. Some authors have identified an elevated ascites: Plasma triglyceride ratio (between 2:1 to 8:1) as being indicative of CA. CA is differentiated from pseudochyle and chyliform ascites by presence of high triglyceride content, which is low in pseudochyle and chyliform ascites. Chyliform ascites contain lecithin - globulin complex due to fatty degeneration of cells and pseudochylous ascites fluid is milky in appearance due to presence of pus.

A study conducted on 22 patients of CA (11 cirrhotic and 11 noncirrhotic) by Casafont et al to know characteristics of fluid in cirrhotic and non-cirrhotic patients. The cirrhotic patients with CA showed lower protein (1.3 ± 0.74 mg/dl, p = 0.002) and cholesterol concentrations (46.0 ± 45.2 mg/dl, p = 0.02) in ascitic fluid than noncirrhotic patients (3.1 ± 1.09 mg/dl and 100.85 ± 41.7 mg/dl, respectively). In addition, the cellularity in the ascitic fluid was also lower in cirrhotic patients (209.09 ± 113.96 cell/mm3) versus (831.8 ± 945.08 cell/mm3; p < 0.05). This difference was proposed because of dilutional mechanism due to the combination of ‘clear’ ascites secondary to portal hypertension and CA. Four patients (18.18%) presented high ADA in the ascitic fluid in the absence of tuberculous peritonitis.

Furthermore, CA could be the cause of an elevation in ADA in the absence of tuberculous peritonitis.

Management of CA is management of underlying cause, nonpharmacological treatment, pharmacological treatment and surgical treatment. In most conditions management of underlying condition especially infective, inflammatory or hemodynamic causes will result in complete resolution of CA. Asian Journal of Critical Care Vol. 9, No. 2, January-March 2013

Nonpharmacological treatments include dietary modification with salt and water restriction, elevation of legs and wearing of stockings. Dietary modifications include high protein diet and use of a low-fat diet with medium-chain triglyceride supplementation, which reduces the production and flow of chyle. This is because medium chain triglycerides are absorbed directly into intestinal cells and transported as fatty acids and glycerol directly to liver via the portal vein, whereas long chain triglycerides need conversion to monoglycerides and free fatty acids, which are transported as chylomicrons to the intestinal lymph ducts. Orlistat can be tried when patients have difficulty in complying with a low-fat diet. Dietary modification is effective in 50% cases and should be maintained for several months after resolution of CA. If CA persists despite dietary management, the next step may involve bowel rest and the institution of total parenteral nutrition. Bowel rest and total parenteral nutrition are postulated to be beneficial in patients with post-traumatic or postsurgical chylous ascites and is effective by fulfilling the nutritional requirement of these patients and decreasing the production of lymph and allowing bowel rest. Total protein nutrition (TPN) is effective in 60-80% cases of CA not responding to dietary modification but it should be given for 2-6 weeks. Pharmacological management includes diuretics, somatostatin or octretide and etilefrine. Somatostatin or octreotide have been reported to be useful in some cases and help in closing fistula more rapidly and also help in inhibition of lymph fluid excretion through specific receptor found in the normal intestinal walls of lymphatic vessels. Mincher et al reported 100% resolution of CA in seven patients treated with subcutaneous octreotide and a fat-free diet. Etilefrine, a sympathomimetic drug, which acts by contracting the smooth muscles of the thoracic duct thereby decreasing the flow of chyle is also effective in management of CA. Embolization of cisterna chyle by fibered endovascular coil, gelatin, sponge and doxycycline can be tried for management of CA. Surgery is beneficial in patients with postoperative, neoplastic and congenital causes after identifying the site of leakage or the presence of fistula by a lymphangiogram or lymph scintigraphy.

Aalami et al conducted a study on 51 cases and found 41% effectivity of surgical management and is dependent on accurate localization of defect. The optimal timing of surgery remains controversial, but 23

case report most authors recommend a trial of conservative measures for at least 4-8 weeks before surgical intervention.

Paracentesis should be performed to relieve abdominal discomfort in large and symptomatic ascites and can be repeated as needed especially in end-stage disease not amenable to medical or surgical management. But, paracentesis has been implicated in prolongation of leaks, worsening of protein loss, nutritional depletion and infectious complications. Peritoneovenous shunt (LeVeen or Denver shunt) is indicated in patients of refractory CA who are too ill to undergo surgical exploration for direct repair but it is associated with high rate of complications such as sepsis, disseminated intravascular coagulopathy, electrolyte imbalance, small bowel obstruction, risk for air embolism and high rate of shunt closure in majority of cases because of the high viscosity of the chyle.

So, management of CA gradually increases in invasiveness, escalating from dietary manipulation to radiographic intervention and, ultimately, surgical options. In a large review of 156 cases, 67% resolved after conservative measures and 33% required surgery.

CA is associated with nutritional depletion, immunological depletion and septicemia out of which sepsis is the most common complication leading to sudden death of a patient.

Conclusion Chylous ascites is a challenging clinical condition commonly associated with abdominal malignancy and cirrhosis in developed countries and tuberculosis and filariasis in developing countries.

It is associated with high morbidity and mortality due to the associated co morbid condition. The outcome depends on early diagnosis and prompt treatment of underlying condition especially in the context of a treatable cause such as tuberculosis, which is very common in our country.

Suggested Reading 1. Nix JT, Albert M, Dugas JE, Wendt DL. Chylothorax and chylous ascites; a study of 302 selected cases. Am J Gastroenterol 1957;28(1):40-53; discussion, 53-5.

2. Press OW, Press NO, Kaufman SD. Evaluation and management of chylous ascites. Ann Intern Med 1982;96(3):358-64.

3. Wolf DC, Katz J. Chylous ascites. http://emedicine. medscape.com/article/18777-overview

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4. Aalami OO, Allen DB, Organ CH Jr. Chylous ascites: a collective review. Surgery 2000;128(5):761-78.

5. Sathiravikarn W, Apisarnthanarak A (corresponding author) Division of infectious diseases, Faculty of Medicine, Thammasart University Hospital, Pathumthani 12120, Thailand.

6. Manson Bahr PEC, Bell JR. Filariasis. In: Manson Bahr’s Textbook of Tropical Disease. ELBS 1977.

7. Frick E, Scholmerich J. Etiology, diagnosis and management of noncirrhotic ascites. In: Ascites and Renal Dysfunction in Liver Disease. Arroyo V, Gine’s P, Rode’s J, Schrier RW (Eds.) Blackwell Science: Malden 1999:p.116-25.

8. Browse NL, Wilson NM, Russo F, al-Hassan H, Allen DR. Aetiology and treatment of chylous ascites. Br J Surg 1992;79(11):1145-50.

9. Sultan S, Pauwels A, Poupon R, Levy VG. Chylous ascites in adults: etiological, therapeutic and prognostic aspects. Apropos of 35 cases. Ann Gastroenterol Hepatol (Paris) 1990;26(5):187-91.

10. Keaveny AP, Karasik MS, Farber HW. Successful treatment of chylous ascites secondary to Mycobacterium avium complex in a patient with the acquired immune deficiency syndrome. Am J Gastroenterol 1999;94(6):1689-90.

11. Ekwcani CN. Chylous ascites, tuberculosis and HIV/ AIDS: a case report. West Afr J Med 2002;21(2):170-2.

12. Rabie H, Lomp A, Goussard P, Nel E, Cotton M. Paradoxical tuberculosis associated immune reconstitution inflammatory syndrome presenting with chylous ascites and chylothorax in a HIV-1 infected child. J Trop Pediatr 2010;56(5):355-8.

13. Chylous Ascites Andre’s Ca’rdenas, M.D., and Sanjiv Chopra, M.D. Divison of Gastroenterology and Hepatology, Beth Israel Deaconess Medical Centre Harvard Medical School, Boston, Massachusetts.

14. Vettoretto N, Odeh M, Romessis M, Pettinato G, Taglietti L, Giovanetti M. Acute abdomen from chylous peritonitis: a surgical diagnosis. Case report and literature review. Eur Surg Res 2008;41(1):54-7.

15. Runyon BA. Care of patients with ascites. N Engl J Med 1994;330(5):337-42.

16. Uriz J, Cárdenas A, Arroyo V. Pathophysiology, diagnosis and treatment of ascites in cirrhosis. Baillieres Best Pract Res Clin Gastroenterol 2000;14(6):927-43.

17. Pui MH, Yueh TC. Lymphoscintigraphy in chyluria, chyloperitoneum and chylothorax. J Nucl Med 1998;39(7):1292-6.

18. Casafont F, López-Arias MJ, Crespo J, Dueñas C, Sánchez-Antolín G, Rivero M, et al. Chylous ascites in cirrhotic and non-cirrhotic patients. Gastroenterol Hepatol 1997;20(6):291-4.

19. Weinstein LD, Scanlon GT, Hersh T. Chylous ascites.

Asian Journal of Critical Care Vol. 9, No. 2, January-March 2013

case report Management with medium-chain triglycerides and exacerbation by lymphangiography. Am J Dig Dis 1969;14(7):500-9.

20. Leibovitch I, Mor Y, Golomb J, Ramon J. The diagnosis and management of postoperative chylous ascites. J Urol 2002;167(2 Pt 1):449-57.

21. Baniel J, Foster RS, Rowland RG, Bihrle R, Donohue JP. Management of chylous ascites after retroperitoneal lymph node dissection for testicular cancer. J Urol 1993;150(5 Pt 1):1422-4.

22. Chen J, Lin RK, Hassanein T. Use of orlistat (xenical) to treat chylous ascites. J Clin Gastroenterol 2005;39(9):831-3.

23. Petrasek AJ, Ameli FM. Conservative management of chylous ascites complicating aortic surgery: a case report. Can J Surg 1996;39(6):499-501.

24. Nakabayashi H, Sagara H, Usukura N, Yoshimitsu K, Imamura T, Seta T, et al. Effect of somatostatin on the flow rate and triglyceride levels of thoracic duct lymph in normal and vagotomized dogs. Diabetes 1981;30(5):440-5.

25. Dreznik Z, Dinbar A, Wolfstein I, Tulcinsky DB. Acute chylous peritonitis. A case report with a review of the literature. Isr J Med Sci 1973;9(1):89-91.

n

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26. Shah SS, Ahmed K, Smith R, Mallina R, Akhbari P, Khan MS. Chylous ascites following radical nephrectomy: a case report. J Med Case Reports 2008;2:3.

27. Cope C. Diagnosis and treatment of postoperative chyle leakage via percutaneous transabdominal catheterization of the cisterna chyli: a preliminary study. J Vasc Interv Radiol 1998;9(5):727-34.

28. Bauwens K, Jacobi CA, Gellert K, Aurisch R, Zieren HU. Diagnosis and therapy of postoperative chyloperitoneum. Chirurg 1996;67(6):658-60.

29. Pabst TS 3rd, McIntyre KE Jr, Schilling JD, Hunter GC, Bernhard VM. Management of chyloperitoneum after abdominal aortic surgery. Am J Surg 1993;166(2): 194-8; discussion 198-9.

30. Ablan CJ, Littooy FN, Freeark RJ. Postoperative chylous ascites: diagnosis and treatment. A series report and literature review. Arch Surg 1990;125(2):270-3.

31. Voros D, Hadziyannis S. Successful management of postoperative chylous ascites with a peritoneojugular shunt. J Hepatol 1995;22(3):380.

32. Leibovitch I. Postoperative chylous ascites - the urologistâ&#x20AC;&#x2122;s view. Drugs Today (Barc) 2002;38(10):68797.

n

n

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case report clinical practice

Oral Tertiary Syphilis Deepa MS*, Anita Balan**, S Sunil†, Bifi Joy‡

Abstract A case of benign tertiary syphilis presenting as a solitary hypertrophic lesion on the dorsum of the tongue is described.

The oral aspects of tertiary syphilis and the need for dentists to be aware of changing trends in relevant infectious diseases are highlighted. Currently, tertiary syphilis is very rarely seen, however, this case emphasizes that it still exists and must be considered in the differential diagnosis of oral lesions.

Key words: Spirochete, tertiary syphilis, infection, oral lesions

S

yphilis is a complex systemic illness, because of defects in cell caused by the spirochete Treponema pallidum. The term ‘Syphilis’ came from a poem written in 1530 by the Italian poet Hiero Fracastor.

Transmission of syphilis occurs via close contact with an infected lesion, which usually occurs on the genitals or through blood.

Following contact, T pallidum penetrates the genital or oral mucosa, multiplies at the site of entry and systematically spreads through the lymphatics and blood. The oral mucosa is commonly affected as a consequence of orogenital contact.1,2

Case Report A 65-year-old lady was referred to the Dept. of Oral Medicine and Radiology for the evaluation of a solitary painless ulcer on the dorsum of tongue from the Dept. of Venereology, Medical College, Trivandrum, Kerala.

*Professor and Head, Dept. of Oral Medicine Azeezia College of Dental Sciences and Research, Kollam, Kerala **Professor and Head, Dept. of Oral Medicine and Radiology Govt. Dental College, Calicut, Kerala † Professor, Dept. of Oral and Maxillofacial Pathology Azeezia College of Dental Sciences and Research, Kollam, Kerala ‡ Postgraduate Student, Dept. of Dermatology Medical College, Trivandrum, Kerala Address for correspondence Dr Deepa MS Nandhanam,TC 1/955 (3), TLRA-59/A Thoppil Lane, Medical College, Trivandrum, Kerala - 695 011 E-mail: docdeepams@yahoo.co.in

26

She had increased salivation for the past five years.

There were no active skin or genital lesion at the time of presentation nor did she have a history of any skin lesions in the past. She had no systemic complaints at the time of presentation. Her husband had died 17 years back. She had four healthy children. She had no history of recurrent abortions or early neonatal deaths.

She didn’t have any significant illness in the past or any habituation.

On examination, she had a solitary painless 2 × 2 cm well-defined ulcer in the middle of dorsum of tongue (Fig. 1). Pale granulation tissue formed the base.

There was no fluid exudation on pressure. Cervical and generalized lymphadenopathy was not present.

Systemic examination revealed no abnormality.

Subsequent hematological, serological and histopathological investigations were carried out.

Figure 1. Clinical photograph showing ulcer on the dorsum of tongue.

Asian Journal of Critical Care Vol. 9, No. 2, January-March 2013

case report

Figure 2. Photomicrograph showing nonspecific inflammation of the connective tissue (H&E section, 10X).

Figure 3. Photomicrograph showing dense collection of inflammatory cells in the area of ulceration (H&E section, 10X.)

Hematological examinations were within normal limits. Blood serologic test for syphilis (STS) showed positivity in one in 32 dilutions. Blood T. pallidum hemagglutination (TPHA) was positive; hepatitis B surface antigen (HBsAg) and enzymelinked immunosorbent assay (ELISA) for human immunodeficiency virus (HIV) were negative.

Histopathological examination revealed only a chronic nonspecific inflammation (Figs. 2 and 3).

Gummas tend to arise on the hard palate and tongue although very rarely they may occur on the soft palate, lower alveolus and parotid gland.

Table 1. Describing the Orofacial Manifestations of Different Stages of Syphilis Stage of disease

Orofacial manifestations

Primary

Chancre Nontender cervical lymphadenopathy

Based on the results of serological examination patient was diagnosed as having a gummatous ulcer on the tongue and was put on injection PP12 lakh units deep intramuscular (IM) daily for 12 consecutive days.

There was resolution of the lesion two weeks after the initiation of penicillin therapy and blood STS become nonreactive after three months.

Secondary

Discussion

Tertiary

‘Rubbery’ cervical lymphadenopathy Maculopapular eruptions, moth-eaten alopecia Leukoderma patches of hypopigmentation Condylomata lata, ulceronodular disease (lues maligna) Nodular disease

Asian Journal of Critical Care Vol. 9, No. 2, January-March 2013

Gumma (palate and tongue) Osteomyelitis, atrophic and interstitial glossitis

Infective syphilis is caused by the spirochete T. pallidum. Transmission occurs via close contact with an infected lesion, which usually occurs on the genitals.

Following contact, T. pallidum penetrates the genital or oral mucosa, multiplies at this site of entry and systemically spreads via the lymphatics and blood.

Syphilis gives rise to a wide-spectrum of orofacial manifestations.3-5 However, the exclusive oral localization not associated with general manifestations is uncommon.6 The various orofacial manifestations of the different stages of syphilis are shown in Table 1.7

Mucous patch

Syphilitic leukoplakia, syphilitic sialadenitis Trigeminal neuropathy (Hitzig’s syndrome) Argyll-Robertson pupil Congenital syphilis

Moon’s/Mulberry molars Hutchinson’s incisors Facial deformity - High arched or gothic palate Maxillary hypoplasia.

Bulldog jaw, saddle-shaped deformity of nose Frontal bossing, mucous patches Rhagades, cranial neuropathies

27

case report The signs and symptoms of primary and secondary syphilis resolve spontaneously and patients then enter the latent stage of infection.8,9 Manifestations of tertiary syphilis may appear after several years of nontreatment with cardiovascular and neurologic involvement including severe manifestation of general paresis and aneurysm of aorta.

Benign tertiary syphilis is characterized by the tissue immunological reaction that leads to a specific lesion designed as gumma. These lesions are destructive granulomatous inflammation that may develop in any organ.10 In the present case, the lesion observed in the dorsum surface of the tongue was of ‘gummatous inflammation’ of tertiary syphilis. Patients with tertiary syphilis may have not remembrance of lesions during earlier stages of the disease.11 Conclusive diagnosis of syphilis infection is based on confirmation of the clinical signs and symptoms with laboratory test.9 T. pallidum can be identified in lesions by dark field microscopy or direct immunofluorescence, but usually serological confirmation is necessary. The diagnostic serologic tests for syphilis include those detecting antibodies to nonspecific treponemal antigens - the Rapid Plasma Reagin (RPR) and Venereal Disease Research Laboratory (VDRL) and those detecting antibodies specific to T. pallidum - the TPHA and fluorescent treponema antibodies absorbed assay (FTA-Abs). The nonspecific antibody tests are inexpensive, rapid screening tools and markers of disease activity. The specific tests are more sensitive than the nonspecific assay. FTA-Abs defects antibodies to T. pallidum in the early stages of infection.12,13 In the secondary stage microorganisms may be detected by special silver impregnation techniques and direct fluorescent antibody testing.

Meyer and Shklar reported the features of 1° and 2° syphilis to be essentially nonspecific and the 3° lesion to be the most obviously granulomatous and populated with Langhans-type giant cells.14 The histopathologic features in the primary lesions consist of an ulcerated epithelium. The underlying connective tissue may show moderate vascularity with intense chronic inflammatory cell infiltration, predominantly lymphocytes and plasma cells with perivascular pattern. In secondary syphilis, the 28

features include hyperplastic epithelium and the connective tissue shows perivascular infiltration with chronic inflammatory cells. In tertiary lesions, ulcerated epithelium with inflammation of connective tissue and foci of granulomatous inflammation with histiocytes and giant cells are noticed.14-16 This is in general agreement with the findings reported by Barrett et al17 who reviewed the histopathology of five oral lesions in patients with serologically proven syphilis, whereas contradictory to the findings reported by Jefferies et al.18 Features of granulonatous inflammation without significant necrosis are typical of early nodular lesions of 3° syphilis and the sparse numbers of plasma cells can mask the diagnosis.19 Tertiary lesions are only sparsely populated with spirochetes.20 Easy, consistent and reliable identification of T. pallidum, however remains problematic.

Conclusion The importance of this case report is to stress the importance of keeping alive the dentist’s knowledge of syphilis, as its tertiary stages could easily be the cause of embarrassing misdiagnosis, leading to the patient being treated for the wrong disease, sometimes for decades.

References 1. Laskaris G. Oral manifestations of infectious diseases.

Dent Clin North Am 1996;40(2):395-423.

2. Edwards S, Carne C. Oral sex and transmission of nonviral STIs. Sex Transm Infect 1998;74(2):95-100.

3. Aloi F. Lip syphilitic chancre in a child. Pediatr Dermatol 1987;4(1):63.

4. Bhatt AP. Case of the mouth. Primary chancre of the lower lip. Indian Dent Assoc 1986;58:1.

5. Hart G. Syphilis tests in diagnostic and therapeutic decision making. Ann Intern Med 1986;104(3):368-76.

6. Aquilina C, Viraben R, Denis P. Secondary syphilis simulating oral hairy leukoplakia. J Am Acad Dermatol 2003;49(4):749-51.

7. Carlesimo M, Palese E, Mari E, Feliziani G, La Pietra M, De Marco G, et al. Isolated oral erosions: an unusual manifestation of secondary syphilis. Dermatol Online J 2008;14(2):23.

8. Anderson J, Mindel A, Tovey SJ, Williams P. Primary and secondary syphilis, 20 years’ experience. 3: Diagnosis, treatment, and follow up. Genitourin Med1989;65(4):239-43.

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case report 15. Little JW. Syphilis: an update. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2005;100(1):3-9.

16. Montone KT. Infectious diseases of the head and neck: a review. Am J Clin Pathol 2007;128(1):35-67.

17. Barrett AW, Villarroel Dorrego M, Hodgson TA, Porter SR, Hopper C, Argiriadou AS, et al. The histopathology of syphilis of the oral mucosa. J Oral Pathol Med 2004;33(5):286-91.

18. Jefferies SD, Ord RA. An unusual presentation of oral syphilis. Br J Oral Maxillofac Surg 1985;23(5):376-80.

19. Mckee P. Infections diseases in skin pathology. Churchill Livingstone: Edinburgh 1997:p.549-54.

20. Siegel MA. Syphilis and gonorrhea. Dent Clin North Am 1996;40(2):369-83.

9. Hutchinson CM, Hook EW 3rd. Syphilis in adults. Med Clin North Am 1990;74(6):1389-416.

10. Hook EW 3rd, Marra CM. Acquired syphilis in adults.

N Engl J Med 1992;326(16):1060-9.

11. Aarestrup FM, Vieira BJ. Oral manifestation of tertiary syphilis: case report. Braz Dent J 1999;10(2):117-21.

12. Alam F, Argiriadou AS, Hodgson TA, Kumar N, Porter SR. Primary syphilis remains a cause of oral ulceration.

Br Dent J 2000;189(7):352-4.

13. Young H. Syphilis. Serology. Dermatol Clin 1998;16(4):691-8.

14. Meyer I, Shklar G. The oral manifestations of acquired syphilis. A study of eighty-one cases. Oral Surg Oral Med Oral Pathol 1967;23(1):45-57.

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resuscitation in endotoxic shock in rats. Crit Care Med 2006;34(9):2426-31.

15. Di Giantomasso D, Morimatsu H, May CN, Bellomo R. Increasing renal blood flow: low-dose dopamine or medium-dose norepinephrine. Chest 2004;125(6): 2260-7.

16. Legrand M, Mik EG, Balestra GM, Lutter R, Pirracchio R, Payen D, et al. Fluid resuscitation does not improve renal oxygenation during hemorrhagic shock in rats. Anesthesiology 2010;112(1):119-27.

17. National Heart, Lung, and Blood Institute Acute Respiratory Distress Syndrome (ARDS) Clinical Trials Network, Wiedemann HP, Wheeler AP, Bernard GR, Thompson BT, Hayden D, deBoisblanc B, et al.

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Comparison of two fluid-management strategies in acute lung injury. N Engl J Med 2006;354(24):256475.

18. Kastner PR, Hall JE, Guyton AC. Renal hemodynamic responses to increased renal venous pressure: role of angiotensin II. Am J Physiol 1982;243(3):F260-4.

19. Cruz DN, Bolgan I, Perazella MA, Bonello M, de Cal M, Corradi V, et al; North East Italian Prospective Hospital Renal Outcome Survey on Acute Kidney Injury (NEiPHROS-AKI) Investigators. North East Italian Prospective Hospital Renal Outcome Survey on Acute Kidney Injury (NEiPHROS-AKI): targeting the problem with the RIFLE Criteria. Clin J Am Soc Nephrol 2007;2(3):418-25.

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case report clinical practice

Percutaneous Curettage and Allogenic Bone Grafting with Bone Marrow in Management of Simple Bone Cyst OP Lakhwani

Abstract Introduction: Simple bone cyst or unicameral bone cysts are benign osteolytic lesions seen in metadiaphysis of long bones in growing children. Various treatment modalities with variable outcomes has been described in the literature. Case report shows novel surgical technique of minimally invasive method of treatment with better outcome. Case study: A 14-year-old boy diagnosed as active simple bone cyst proximal humerus with pathological fracture. Patient was treated by minimally invasive percutaneous curettage with curved titanium elastic nail (TENS) and allogenic bone grafting mixed with bone marrow under image intensifier guidance. Results: Pathological fracture was healed and allograft filled in the cavity well taken-up. Patient achieved full range of motion with successful outcome. Conclusion: Minimally invasive percutaneous method using elastic intramedullary nail give benefit of curettage cyst decompression and stabilization of fracture. Allogenic bone graft fills the cavity and healing of lesion occurs by osteointegration. This method may be considered with advantage of minimally invasive technique in treatment of benign cystic lesions of bone. Level of evidence: Therapeutic level IV. Key words: Unicameral bone cyst, simple bone cyst, allogenic bone graft

S

imple bone cysts1 (SBC) or unicameral bone cysts1 (UBC) are benign osteolytic cystic lesions of unknown etiology seen at meta-diaphyseal region of long bone in growing children. This lesion was first described by Virchow R in 1876.2 These lesions are usually asymptomatic and patients frequently present with pathological fractures3 at the time of diagnosis.

Various methods of treatment of unicameral bone cysts have been proposed, generally supervised neglect treatment in asymptomatic incidentally discovered lesion in not weight-bearing bone may be adopted, but when patient presents with pathological fracture it requires urgent treatment. A successful treatment should give a higher healing rate and a short time to union and no recurrence. This can be achieved by open curettage with bone-grafting.4 Intralesional injection of steroids,5,6 autologous bone marrow7,8 percutaneous injection of allogenic

Associate Professor, Dept. of Orthopedics ESIC- Post Graduate Institute of Medical Sciences and Research ESI Hospital, Basai Darapur, Ring Road, New Delhi Address for correspondence Dr OP Lakhwani Associate Professor, Dept. of Orthopedics ESI Hospital, ESI PGIMSR Basai Darapur, Ring Road, New Delhi - 110 015 E-mail: orth365@gmail.com

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demineralized bone matrix and percutaneous curettage and bone grafting was described by Killian9 with widely variable success rate. As minimally invasive technique preserves periosteum, muscles and blood supply hence, we propose a novel surgical technique of curettage cyst decompression and use of allogenic bone graft. The technique gives easy and effective approach and successful outcome.

Case Study A 14-year-old boy presented with chief complaints of pain, swelling over right upper arm and difficulty to move it for three days. Mild pain at the right upper arm had been present for around two months for which he did not bother. Pain was suddenly increased three days back while he was trying to lift water bucket. On general physical examination, patient had adequate built and nutritional status for his age with no abnormality in general examination. In local examination, tenderness, bony irregularity and crepitus were present over right proximal humerus. Range of motion was painful at the right shoulder. Plain radiographs of right upper arm and shoulder revealed a central multiloculated lytic lesion with well-defined margins at proximal meta-diaphysis with transverse fracture line running through lytic lesion with no Asian Journal of Critical Care Vol. 9, No. 2, January-March 2013

case report new bone formation or parosteal reaction. Laboratory evaluation including complete blood counts with peripheral smear, erythrocyte sedimentation rate (ESR), serum electrolyte with calcium and phosphate, serum albumin and globulin, renal function tests, hepatic function tests, urinalysis, parathyroid hormone were all within normal limits. As per the criteria defined by Chang et al10 ratio of the cyst length to the physeal width it was 3.75 and located 8 mm from the physeal margin less than 10 mm is active. With these clinical and radiological findings, diagnosis of simple bone cyst with pathological fracture was made and patient was planned for surgical intervention.

Surgical Technique

Patient was planned for percutaneous cyst curettage and filling of the cyst cavity with deep freezed gammairradiated allogenic cancellous bone graft under image intensifier guidance under general anesthesia.

The patient was taken in supine position under general anesthesia. A small longitudinal skin incision 1.5 cm is made proximal in the upper arms and fenestration was created in outer cortex of proximal humerus with 3.2 mm drill bit percutaneously under the guidance of image intensifier. An infant feeding tube was inserted to aspirate out the contents of the cyst, which were sent for tissue analysis, a larger suction catheter was introduced and copious irrigation of the bone cyst was carried out. A flexible titanium elastic nail of 3 mm was passed through the curved end to break the septae and curette the cyst wall, serosanguineous material

a

content of cyst was aspirated and collected through a suction catheter. Tip of the nail was advanced distally in the medullary canal to further decompress the cyst.

Finally allogenic morselized cancellous bone graft was prepared and mixed with aspirated bone marrow and packed into the cyst cavity through the drill sleeve under the guidance of image intensifier till whole of the cyst was visibly filled with bone graft. Wound was closed with skin suture and stabilized with â&#x20AC;&#x2DC;Uâ&#x20AC;&#x2122; Slab.

Biopsy report confirmed the cyst to be a simple bone cyst. Patient was followed up at regular intervals, at 10 weeks follow-up plain skigram and CT-scan showed healing of fracture and resolution of lesion with the patient able to attain full range of motion at both the shoulder and elbow joint.

Discussion Cystic bone lesions in the first two decades of life constitute common cause for pathological fractures.

Two most important differential diagnoses of cystic lesions in children include unicameral bone cyst and aneurysmal bone cyst.

Proposed pathogenesis1 of simple bone cyst include increased production inflammatory markers as described by Komiya et al.11 Increased levels of prostaglandin E2, interleukin-1 and gelatinase induce bone resorption and high intraosseous pressure occurs due to venous obstruction. Hence, local steroids and curettage of the cyst lining are commonly used method in treatment. K-wire, cannulated screw12 and flexible intramedullary nail13 have also been used to

b

c

d

Figure 1. (a) Preoperative skigram showing lytic lesion with pathological fracture; (b) Intraoperative image intensifier skigram showing filling of cavity with allogenic bone graft; (c) Follow-up skigam at 6 months and (d) Follow-up skigram at most recent follow-up at 1 year showed complete healing (>95% opacification).

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case report

a

b

c

d

Figure 2. (a) Deep freezed gamma irradiated allogenic bone graft stored in double jar container; (b) intraoperative picture of graft preparation (c) allobone graft before and after mixing with bone marrow and (d) percutaneous packing of bone graft after curettage and decompression.

a

b

c

Figure 4. Diagram showing (a) approach for curettage; (b) percutaneous bone grafting and (c) titanium flexible nail with curved end.

Figure 3. Follow-up CT scan showing healing of lesion.

provide continuous cyst decompression and to dilute inflammatory markers and assist healing. High rate of recurrence14 after steroid injections has led to use of other methods including bone marrow and bone graft and bone substitute substitutes like calcium sulfate,15 hydroxyapatite, etc. to fill the cavity.

Open curettage and bone grafting have significant surgical morbidity4 and recurrence rates of 35-45%.4,16 Similarly, corticosteroids also have high recurrence rates and need for multiple injections has been reported. Use of allogenic bone graft is a comparatively newer method. Spence et al17 used the freezed dried cancellous bone allograft to fill the cystic cavity.

Current surgical techniques used are minimally invasive using the curved end of flexible titanium nail introduced percutaneously for curettage of cyst lining and decompression of cyst. Simultaneously, it can be used for stabilization of fracture. Allogenic grafts obtained after proper screening and gamma sterilization when used with minimally invasive 32

method appears to be a better alternative to the conventional methods of treatment.

The outcome of method this minimally invasive procedure (as determined radiographically by Chang et al,10 which include >95% of opacification of lesion to be considered as healing was determined. In the current case, lesion healed by 10 weeks as seen in follow-up skigram and CT scan. With the use of this technique, the time to achieve healing is very short as compared to other methods of treatment and patient regains full functional activities early.

In summary, percutaneous method under image intensifier guidance using flexible nail for curettage cyst decompression along with allogeneic bone graft is one of the treatment options, which may be considered although, the method and its results need further trials, larger series and comparison with other available treatments to establish its effectiveness.

References 1. Cohen J. Etiology of simple bone cyst. J Bone Joint Surg Am 1970;52(7):1493-7.

2. Virchow R. On the formation of bony cysts. In: Uber die bildung von knochencysten S-B Akad Wiss: Berlin 1876:p.369-81.

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case report trepanation and studies on bone resorptive factors in cyst fluid with a theory of its pathogenesis. Clin Orthop Relat Res 1993;(287):204-11.

3. Campanacci M, Capanna R, Picci P. Unicameral and aneurysmal bone cysts. Clin Orthop Relat Res 1986;(204):25-36.

4. Neer CS 2nd, Francis KC, Marcove RC, Terz J, Carbonara PN. Treatment of unicameral bone cyst.

A follow-up study of one hundred seventy-five cases.

J Bone Joint Surg Am 1966;48(4):731-45.

5. Oppenheim WL, Galleno H. Operative treatment versus steroid injection in the management of unicameral bone cysts. J Pediatr Orthop 1984;4(1):1-7.

6. Hashemi-Nejad A, Cole WG. Incomplete healing of simple bone cysts after steroid injections. J Bone Joint Surg Br 1997;79(5):727-30.

7. Lokiec F, Ezra E, Khermosh O, Wientroub S. Simple bone cysts treated by percutaneous autologous marrow grafting. A preliminary report. J Bone Joint Surg Br 1996;78(6):934-7.

8. Yandow SM, Lundeen GA, Scott SM, Coffin C. Autogenic bone marrow injections as a treatment for simple bone cyst. J Pediatr Orthop 1998;18(5):616-20.

9. Killian JT, Wilkinson L, White S, Brassard M. Treatment of unicameral bone cyst with demineralized bone matrix.

J Pediatr Orthop 1998;18(5):621-4.

10. Chang CH, Stanton RP, Glutting J. Unicameral bone cysts treated by injection of bone marrow or methylprednisolone. J Bone Joint Surg Br 2002;84(3):407-12.

11. Komiya S, Minamitani K, Sasaguri Y, Hashimoto S, Morimatsu M, Inoue A. Simple bone cyst. Treatment by

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12. Brecelj J, Suhodolcan L. Continuous decompression of unicameral bone cyst with cannulated screws: a comparative study. J Pediatr Orthop B 2007;16(5):367-72.

13. Roposch A, Saraph V, Linhart WE. Flexible intramedullary nailing for the treatment of unicameral bone cysts in long bones. J Bone Joint Surg Am 2000;82A(10):1447-53.

14. Cho HS, Oh JH, Kim HS, Kang HG, Lee SH. Unicameral bone cysts: a comparison of injection of steroid and grafting with autologous bone marrow. J Bone Joint Surg Br 2007;89(2):222-6.

15. Dormans JP, Sankar WN, Moroz L, Erol B. Percutaneous intramedullary decompression, curettage, and grafting with medical-grade calcium sulfate pellets for unicameral bone cysts in children: a new minimally invasive technique. J Pediatr Orthop 2005;25(6):804-11.

16. Norman-Taylor FH, Hashemi-Nejad A, Gillingham BL, Stevens D, Cole WG. Risk of refracture through unicameral bone cysts of the proximal femur. J Pediatr Orthop 2002;22(2):249-54.

17. Spence KF, Sell KW, Brown RH. Solitary bone cyst: treatment with freeze-dried cancellous bone allograft. A study of one hundred seventy-seven cases. J Bone Joint Surg Am 1969;51(1):87-96.

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lighter reading clinical practice

Lighter Side of Medicine

An Inspirational Story

Laugh a While

The Story of a Woodcutter

New Teeth

Once upon a time, a very strong woodcutter asked for a job in a timber merchant and he got it. The pay was really good and so was the work condition. For those reasons, the woodcutter was determined to do his best.

Our local minister had all of his remaining teeth pulled and new dentures made a few weeks ago.

Very motivated by these words, the woodcutter tried harder the next day, but he could only bring 15 trees.

The third day he tried even harder, but he could only bring 10 trees. Day after day he was bringing less and less trees. “I must be losing my strength”, the woodcutter thought. He went to the boss and apologized, saying that he could not understand what was going on. “When was the last time you sharpened your axe” the boss asked. “Sharpen? I had no time to sharpen my axe. I have been very busy trying to cut trees.”

Reflection: Our lives are like that. We sometimes get so busy that we don’t take time to sharpen the “axe”. In today’s world, it seems that everyone is busier than ever, but less happy that ever.

Why is that? Could it be that we have forgotten how to stay “sharp”? There’s nothing wrong with activity and hard work. But we should not get so busy that we neglect the truly important things in life, like our personal life, taking time to get close to our Creator, giving more time for our family, taking time to read, etc.

We all need time to relax, to think and meditate, to learn and grow. If we don’t take the time to sharpen the “axe”, we will become dull and lose our effectiveness.

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I asked him about this. He then told me “well, John, that first Sunday, my gums were so sore it hurt to talk.

The second Sunday, my dentures were still hurting a lot. Now the third Sunday, I accidentally grabbed my wife’s dentures and I couldn’t stop talking!”

Mind Trivia 1. What is special about the following number sequence?

8, 5, 4, 9, 1, 7, 6, 10, 3, 2, 0

2. Stands ---------- 0_2345 3. How can you alter the following equation by a single stroke to make it correct?

5 + 5 + 5 = 550

4. Add a diagonal line on the top left of the first plus sign to convert + into a 4.

1. It’s the numbers 0 through 10 in alphabetical order. 2. No one understands 3. 5 4. 5 + 5 = 550

His boss gave him an axe and showed him the area where he was supposed to work. The first day, the woodcutter brought 18 trees. “Congratulations,” the boss said. “Go on that way!”

The first Sunday, his sermon lasted 10 minutes. The second Sunday, he preached only 20 minutes. But, on the third Sunday, he preached for an hour and a half.

Quotes “Insan Kehta Hai Agar Paisa Ho To Mai Kuch Kar Ke Dikhau aur Paisa Kehta He Tu Kuch Kar Ke Dikha To Mai Aau .... Create Success....” Dr GM Singh

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