volume 5, number 2, september 2017 - critical care medicine · 9/3/2018 · dr. madiha hashmi,...

Volume 5, Number 2, September 2017

CONTENTSFrom the Desk of the Editor

Chikungunya-Dengue Co-infection: the upcoming double trouble! 75 Muhammad Abdur Rahim, Khwaja Nazim Uddin

Original Article

Laparoscopic cost effective management of cholecystoduodenal fistula 77 Md Ezharul Haque Ratan, Hasina Alam, Md Abdul Karim

Microorganism profile and their resistance pattern among the patients of sepsis in an intensive care unit of a tertiary care hospital 80 Rozina Sultana, Mohammad Omar Faruq, ASM Areef Ahsan, Kaniz Fatema, Fatema Ahmed Debasish Kumar Saha, Madhurima Saha, Suraiya Nazneen, Tarikul Hamid, Ariful Islam

Ultrasound guided emergency cannulation of internal jugular vein in coagulopathic adult patients – a prospective observational pilot study 85 Gentle Sunder Shrestha, Sabin Koirala, Arjun Gurung, Prakash Chand

Frequency of Myocardial Ischaemia and Mortality in Septic Shock with Elevated Cardiac Troponin 89 Shihan Mahmud Redwanul Huq, Ahmad Mursel Anam, Jamia Ahmad, Raihan Rabbani, Mirza Nazim Uddin Mohammad Mufizul Islam Polash, Shahzadi Sayeeda Tun Nessa

Early Laparoscopic Cholecystectomy in acute cholecystitis and its sequlae- Experience in tertiary care hospital 92 Md Ezharul Haque Ratan, Hasina Alam

Review Article

Update on Management of Rhabdomyolysis - A Review 97 Shihan Mahmud Redwanul Huq, Ahmad Mursel Anam, Raihan Rabbani, Mirza Nazim Uddin M Mufizul Islam Polash, Shahzadi Sayeeda Tun Nessa

Case Report

Neuroleptic Malignant Syndrome – A medical emergency in a psychiatry patient 102 Rajib Ahsan Sumon, Eshita Majumder

Heyde’s syndrome: Rare cause of GI bleeding 105 Deepankar Kumar Basak, Richmond Ronald Gomes, Md. Samsul Arfin

First Episode Psychosis following ESRD in a 50 year old lady: A Case Report 109 Umme Salma Talukder

Heparin Induced Thrombocytopenia in a Patient Requiring Haemodialysis - A Case Report 111 M.A. Wahab Khan, Tasnova Mahin

Clinical Image

Ogilvie’s Syndrome 114 Ahmad Mursel Anam, Dipesh Kumar Barua

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Volume 5, Number 2, September 2017

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Chikungunya and dengue are the two most rapidly spreading mosquito-borne viral infections of global concern.1 In Bangladesh, dengue is endemic and chikungunya is an emerging infection.2 Since both chikungunya and dengue viruses are transmitted by Aedes spp. of mosquitos, simultaneous or sequential infections by them are possible.

Chikungunya virus belongs to Togavirus family and genus Alphavirus. The first recognized outbreak of chikungunya occurred in 1952-53 in Tanzania. Because of increased air travels, the rapidity of chikungunya spread has been increased by many folds over the past few decades. As per Center for Disease Control and Prevention (CDC) (April 22, 2016) a total of 79 countries and territories had recorded their own chikungunya outbreaks and this number is after exclusion of countries with imported chikungunya cases. The first chikungunya outbreak in Indian subcontinent was recorded in 1963-64 in Kolkata and the first outbreak in Bangladesh3 was reported in 2008. Sporadic cases of chikungunya had been occurring in Bangladesh over the preceding years but a massive outbreak occurred in 2017 claiming few deaths as well.4,5

Dengue virus is the most relevant arbovirus in terms of morbidity, mortality and socioeconomic impact threatening more than 2.5 billion individual worldwide.6 It belongs to the Flaviviridae family and genus Flavivirus and is composed of four closely related serotypes. Over the past two decades, dengue virus has been established as endemic in Bangladesh.2 Dengue has a higher rate of mortality (0.5-3.5%) than chikungunya (<0.1%).7

Chikungunya and dengue are spacio-temporally related.7

Furuya-Kanamori L, et al in a review in 2016 reported that among the 98 countries where both chikungunya and dengue were documented, only 13 countries including Angola, Gabon, India, Madagascar, Malaysia, Myanmar, Nigeria, Saint Martin, Singapore, Sri Lanka, Tanzania, Thailand and Yemen(Figure 1) had chikungunya-dengue co-infections.7,8 Reports of such co-infections are continuing to rise and included countries like Bangladesh5,9-11 and Guatemala.12

In spite of widespread distribution of chikungunya, dengue and their shared vectors, why co-infections by both have been reported from only 15 countries? Recently zika has been displaced by chikungunya outbreak in Brazil13 and in Bangladesh dengue has been displaced by few weeks. Chikungunya and dengue have many similarities in clinical presentation; both can present with fever, aches and pains, rash etc., though arthritis favours chikungunya and retro-orbital pain favours dengue.2 As both are self-limiting viral infections, they require supportive therapies only if remain uncomplicated. Clinical suspicion guided

investigations may find the one diagnosis and it is not impossible to miss the other in such a scenario.

Does chikungunya and dengue co-infection affect each other and the host adversely? It remains as an unresolved area of research interest.7 Some authors did not find adverse outcomes14-16 while others did.9,17 During an acute febrile episode attributable to an arbovirus infection, it is important to exclude dengue rather than to establish chikungunya.2 Arthritis of chikungunya may require non-steroidal anti-inflammatory drugs (NSAIDs) which is not advocated in dengue, as NSAIDs may increase bleeding risk. So, a high index of suspicion is required in appropriate clinical scenario, as an increasing number of such co-infections are predicted to occur in Bangladesh in the upcoming years and appropriate public health measures are urged to effectively reduce the burden of chikungunya and dengue infections in Bangladesh.

Dr. Muhammad Abdur RahimMBBS, FCPS (Medicine)Assistant ProfessorDepartment of NephrologyBIRDEM General Hospitaland Ibrahim Medical CollegeDhaka, Bangladesh.

References:1. Weaver SC, Lecuit M. Chikungunya virus and the global spread of

a mosquito-borne disease. N Engl J Med 2015; 372:1231-1239.

2. Rahim MA, Uddin KN. Chikungunya: an emerging viral infection with varied clinical presentations in Bangladesh: Reports of seven cases. BMC Res Notes 2017; 10:410.

3. ICDDR, B. First identified outbreak of chikungunya in Bangladesh, 2008. Health Sci Bull 2009; 7:1-6.

4. Kabir I, Dhimal M,Müller R, Banik S,Haque U. The 2017 Dhaka chikungunya outbreak. The LANCET Infectious Diseases 2017; 17(11):1118.

5. Nazneen S, Saha M, Hossain R, et al. Chikungunya Viral Infection Requiring Intensive Care–Experience in a Tertiary Care Hospital in Bangladesh. BIRDEM Med J 2018; 8(1):16-20.

6. Bhatt S, Gething PW, Brady OJ, et al. The global distribution and burden of dengue. Nature 2013; 496:504-507.

7. Furuya-Kanamori L, Liang S, Milinovich G, et al. Co-distribution and co-infection of chikungunya and dengue viruses. BMC Infectious Diseases 2016; 16:84.

8. Furuya-Kanamori L, Liang S, Milinovich G, et al. Erratum to: Co-distribution and co-infection of chikungunya and dengue viruses. BMC Infectious Diseases 2016; 16:188.

9. Rahim MA, Zaman S, Sultana N, Islam A, Uddin KN. Chikungunya–dengue co-infection during pregnancy requiring preterm Caesarean section: first case report from Bangladesh. Trop Doc 2017 (First Published Dec 13, 2017). DOI: 10.1177/0049475517747431.

10. Haque HF, Rahim MA, Mahiuddin N, et al. Dengue-Chikungunya Co-Infection: A Case Report from 2017- Chikungunya Outbreak in Dhaka, Bangladesh. BIRDEM Med J 2018; 8(1):72-74.

11. Rahim MA, Zaman S, Afroze SR, et al. Chikungunya virus and dengue virus coinfection: a case report from Bangladesh. IMC J Med Sci 2018; 12(1):42-43.

12. Edward T, Signor LCC, Williams C, Donis E, Cuevas LE,Adams ER. Co-infections with Chikungunya and DengueViruses, Guatemala, 2015. Emerging Infectious Diseases 2016; 22:2003-2005.

13. Magalhaes T, Braga C, Cordeiro MT, et al. Zika virus displacement by a chikungunya outbreak in Recife, Brazil. PLOS Neglected Tropical Diseases 2017;11(11):e0006055.

14. Schilling S, Emmerich P, Gunther S, Schmidt-Chanasit J. Dengue and Chikungunya virus co-infection in a German traveller. J ClinVirol 2009;45:163-164.

15. Taraphdar D, Sarkar A, Mukhopadhyay BB, Chatterjee S. A comparative studyof clinical features between monotypic and dual infection cases with Chikungunya virus and dengue virus in West Bengal, India. Am J Trop Med Hyg 2012; 86:720-723.

16. Omarjee R, Prat CM, Flusin O, et al. Importance of case definition to monitor ongoing outbreak of chikungunya virus on a background of actively circulating dengue virus, St Martin, December 2013 to January 2014. Euro Surveill 2014;19(13).pii:20753.

17. Chahar HS, Bharaj P, Dar L, Guleria R, Kabra SK, Broor S. Co-infections with chikungunya virus and dengue virus in Delhi, India. Emerging Infectious Diseases 2009;15:1077-1080.

Bangladesh Crit Care J September 2017; 5 (2): 75-76

From the Desk of the Editor

Chikungunya-Dengue Co-infection: the upcoming double trouble!Muhammad Abdur Rahim1, Khwaja Nazim Uddin2

Prof. Khwaja Nazim UddinMBBS, FCPS (Medicine)FACP (USA), FRCP (Edin)ProfessorDepartment of Internal MedicineBIRDEM General Hospital andIbrahim Medical CollegeDhaka, Bangladesh

75

Chikungunya and dengue are the two most rapidly spreading mosquito-borne viral infections of global concern.1 In Bangladesh, dengue is endemic and chikungunya is an emerging infection.2 Since both chikungunya and dengue viruses are transmitted by Aedes spp. of mosquitos, simultaneous or sequential infections by them are possible.

Chikungunya virus belongs to Togavirus family and genus Alphavirus. The first recognized outbreak of chikungunya occurred in 1952-53 in Tanzania. Because of increased air travels, the rapidity of chikungunya spread has been increased by many folds over the past few decades. As per Center for Disease Control and Prevention (CDC) (April 22, 2016) a total of 79 countries and territories had recorded their own chikungunya outbreaks and this number is after exclusion of countries with imported chikungunya cases. The first chikungunya outbreak in Indian subcontinent was recorded in 1963-64 in Kolkata and the first outbreak in Bangladesh3 was reported in 2008. Sporadic cases of chikungunya had been occurring in Bangladesh over the preceding years but a massive outbreak occurred in 2017 claiming few deaths as well.4,5

Dengue virus is the most relevant arbovirus in terms of morbidity, mortality and socioeconomic impact threatening more than 2.5 billion individual worldwide.6 It belongs to the Flaviviridae family and genus Flavivirus and is composed of four closely related serotypes. Over the past two decades, dengue virus has been established as endemic in Bangladesh.2 Dengue has a higher rate of mortality (0.5-3.5%) than chikungunya (<0.1%).7

Chikungunya and dengue are spacio-temporally related.7

Furuya-Kanamori L, et al in a review in 2016 reported that among the 98 countries where both chikungunya and dengue were documented, only 13 countries including Angola, Gabon, India, Madagascar, Malaysia, Myanmar, Nigeria, Saint Martin, Singapore, Sri Lanka, Tanzania, Thailand and Yemen(Figure 1) had chikungunya-dengue co-infections.7,8 Reports of such co-infections are continuing to rise and included countries like Bangladesh5,9-11 and Guatemala.12

In spite of widespread distribution of chikungunya, dengue and their shared vectors, why co-infections by both have been reported from only 15 countries? Recently zika has been displaced by chikungunya outbreak in Brazil13 and in Bangladesh dengue has been displaced by few weeks. Chikungunya and dengue have many similarities in clinical presentation; both can present with fever, aches and pains, rash etc., though arthritis favours chikungunya and retro-orbital pain favours dengue.2 As both are self-limiting viral infections, they require supportive therapies only if remain uncomplicated. Clinical suspicion guided

investigations may find the one diagnosis and it is not impossible to miss the other in such a scenario.

Does chikungunya and dengue co-infection affect each other and the host adversely? It remains as an unresolved area of research interest.7 Some authors did not find adverse outcomes14-16 while others did.9,17 During an acute febrile episode attributable to an arbovirus infection, it is important to exclude dengue rather than to establish chikungunya.2 Arthritis of chikungunya may require non-steroidal anti-inflammatory drugs (NSAIDs) which is not advocated in dengue, as NSAIDs may increase bleeding risk. So, a high index of suspicion is required in appropriate clinical scenario, as an increasing number of such co-infections are predicted to occur in Bangladesh in the upcoming years and appropriate public health measures are urged to effectively reduce the burden of chikungunya and dengue infections in Bangladesh.

Dr. Muhammad Abdur RahimMBBS, FCPS (Medicine)Assistant ProfessorDepartment of NephrologyBIRDEM General Hospitaland Ibrahim Medical CollegeDhaka, Bangladesh.

References:1. Weaver SC, Lecuit M. Chikungunya virus and the global spread of

a mosquito-borne disease. N Engl J Med 2015; 372:1231-1239.

2. Rahim MA, Uddin KN. Chikungunya: an emerging viral infection with varied clinical presentations in Bangladesh: Reports of seven cases. BMC Res Notes 2017; 10:410.

3. ICDDR, B. First identified outbreak of chikungunya in Bangladesh, 2008. Health Sci Bull 2009; 7:1-6.

4. Kabir I, Dhimal M,Müller R, Banik S,Haque U. The 2017 Dhaka chikungunya outbreak. The LANCET Infectious Diseases 2017; 17(11):1118.

5. Nazneen S, Saha M, Hossain R, et al. Chikungunya Viral Infection Requiring Intensive Care–Experience in a Tertiary Care Hospital in Bangladesh. BIRDEM Med J 2018; 8(1):16-20.

6. Bhatt S, Gething PW, Brady OJ, et al. The global distribution and burden of dengue. Nature 2013; 496:504-507.

7. Furuya-Kanamori L, Liang S, Milinovich G, et al. Co-distribution and co-infection of chikungunya and dengue viruses. BMC Infectious Diseases 2016; 16:84.

8. Furuya-Kanamori L, Liang S, Milinovich G, et al. Erratum to: Co-distribution and co-infection of chikungunya and dengue viruses. BMC Infectious Diseases 2016; 16:188.

9. Rahim MA, Zaman S, Sultana N, Islam A, Uddin KN. Chikungunya–dengue co-infection during pregnancy requiring preterm Caesarean section: first case report from Bangladesh. Trop Doc 2017 (First Published Dec 13, 2017). DOI: 10.1177/0049475517747431.

10. Haque HF, Rahim MA, Mahiuddin N, et al. Dengue-Chikungunya Co-Infection: A Case Report from 2017- Chikungunya Outbreak in Dhaka, Bangladesh. BIRDEM Med J 2018; 8(1):72-74.

11. Rahim MA, Zaman S, Afroze SR, et al. Chikungunya virus and dengue virus coinfection: a case report from Bangladesh. IMC J Med Sci 2018; 12(1):42-43.

12. Edward T, Signor LCC, Williams C, Donis E, Cuevas LE,Adams ER. Co-infections with Chikungunya and DengueViruses, Guatemala, 2015. Emerging Infectious Diseases 2016; 22:2003-2005.

13. Magalhaes T, Braga C, Cordeiro MT, et al. Zika virus displacement by a chikungunya outbreak in Recife, Brazil. PLOS Neglected Tropical Diseases 2017;11(11):e0006055.

14. Schilling S, Emmerich P, Gunther S, Schmidt-Chanasit J. Dengue and Chikungunya virus co-infection in a German traveller. J ClinVirol 2009;45:163-164.

15. Taraphdar D, Sarkar A, Mukhopadhyay BB, Chatterjee S. A comparative studyof clinical features between monotypic and dual infection cases with Chikungunya virus and dengue virus in West Bengal, India. Am J Trop Med Hyg 2012; 86:720-723.

16. Omarjee R, Prat CM, Flusin O, et al. Importance of case definition to monitor ongoing outbreak of chikungunya virus on a background of actively circulating dengue virus, St Martin, December 2013 to January 2014. Euro Surveill 2014;19(13).pii:20753.

17. Chahar HS, Bharaj P, Dar L, Guleria R, Kabra SK, Broor S. Co-infections with chikungunya virus and dengue virus in Delhi, India. Emerging Infectious Diseases 2009;15:1077-1080.


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Introduction:

Since the first successful case in 1982, laparoscopic cholecystectomy (LC) has become the favored treatment as well accepted by surgeons and patients for gall bladder lesions worldwide1. With time and increasing experience laparoscopic cholecystectomy has successfully been attempted in all kinds of benign gall bladder pathology5 and their complications. One such condition is cholecystoenteric fistula (CEF), an abnormal spontaneous tract with bile drainage from the gall bladder to one or more adjacent bowel loop. It is though uncommon, a well-recognized complication of gall stone disease (75%) but 2, 3 can be due to peptic ulcer or neoplasm 4. During acute cholecystitis adjacent serosal surface become inflamed and adherent of gall bladder. Raised

1. Dr. Md. Ezharul Haque Ratan, MS (General Surgery), Associate Professor, Surgery, Ibrahim Medical College and BIRDEM General Hospital, Dhaka

2. Dr. Hasina Alam, FCPS (General Surgery), Registrar Surgery, Ibrahim Medical College and BIRDEM General Hospital, Dhaka

3. Dr. Md. Abdul Karim, Resident Medical Officer BIRDEM General Hospital, Dhaka

Corresponding Author:

Dr. Md. Ezharul Haque RatanAssociate Professor, SurgeryIbrahim Medical College and BIRDEM General HospitalRoom no-445, BIRDEM General HospitalShahbagh, Dhaka-1000, BangladeshEmail: [email protected]

intra cholecystic pressure and gangrene of gall bladder wall leads to penetration of bile to bowel, forming cholecystoduodenal fistula 5. Its incidence has been reported as 3-5% in cholelithisasis and 0.15-4.8% among patients who undergo biliary tract surgery6. Cholecystoduodenal type (CDF) has the highest incidence (up to 80%) among cholecystoenteric fistula. The symptoms of cholecystoduodenal fistula are non-specific, often resemble those due to gall stone 3, rarely diagnosed pre-operatively and almost always discovered during cholecystectomy 6. At inception of laparoscopic surgery cholecystoduodenal fistula was considered an absolute contraindication for laparoscopic cholecystectomy. Now it is a relative contraindication to laparoscopic cholecystectomy, while it is not a contraindication to some surgeons6,8. Now increasing number of surgeons are managing cholecystoduodenal fistula laparoscopically with a conversion rate of 58.8%. Laparoscopic stapling techniques are used to seal the fistula and have been proved to be flexible and safe method2,3,9. However, stapling devices are expensive, not always available and require certain level of expertise of the surgeon. We are reporting eight cases of cholecystoduodenal fistula managed successfully by laparoscopic ligation and suture technique using traditional laparoscopic instruments. All these cases were discovered during an attempt to perform laparoscopic cholecystectomy.

Materials and methods:

From march 2008 to march 2017, 1500 patients underwent laparoscopic cholecystectomy for gall stone disease in a

Original Article

Laparoscopic cost effective management of cholecystoduodenal fistulaMd Ezharul Haque Ratan1, Hasina Alam2, Md Abdul Karim3

Abstract

Introduction: Contraindication to laparoscopic surgery is decreasing with time, expertise and innovation. One such uncommon condition is cholecystoduodenal fistula (CDF), now increasingly managed with laparoscopic technique. We are reporting eight such cases incidentally diagnosed intraoperatively, successfully managed, cost-effectively with traditional laparoscopic instruments.

Materials and Methods: During March 2008 to March 2017, 1500 patient underwent laparoscopic cholecystectomy for benign gall bladder condition or their complications, eight of these having chronic dyspeptic symptoms of gallstone, were found to have cholecystoduodenal fistula, intraoperatively. All cases were managed laparoscopically using common laparoscopic instruments without any special gadgets and extra costs. Medical records of eight cases were reviewed for age, sex, operative technique, intra and post-operative complications and length of stay in hospital.

Results: Five patients were male and three female with a mean age of 63 years. All of them had gall stones at abdominal ultrasound and cholecystoduodenal fistula were found intraoperatively. Fistula tract was dissected, cleaned, sealed with combination of intracorporeal simple and transfixation ligation and interrupted stitches to invert the stump in duodenal wall in transverse fashion. All eight had uneventful postoperative course with hospital stay of 4-7 (mean 5) days.

Conclusion: In expert hands cholecystoduodenal fistula can successfully and safely be managed laparoscopically using common instruments and logistics with slight modification of open technique without extra cost.

Key words: Cholecystoduodenal fistula (CDF), Cholecystoenteric fistula (CEF), laparoscopic technique.

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surgical unit of BIRDEM general hospital, Dhaka, Bangladesh. Eight of them (0.53%) were found intraoperatively to have cholecystoduodenal fistula, abnormal communication between gall bladder and the first part of the duodenum.We, retrospectively, reviewed the medical records of eight patients of cholecystoduodenal fistula. All the patients history were recorded and underwent physical examination, ultrasonography (USG), and biochemical tests to establish a preoperative diagnosis. USG revealed, fibrosed, contracted, thick walled gallbladder with stones in all cases. In each case laboratory findings were unremarkable. Data were collected on patients’ age, sex, preoperative diagnosis, operative methods, morbidity and length of stay in hospital. Surgery was performed under general anesthesia using standard four ports technique. Cholecystoduodenal fistula was clearly demonstrated after careful blunt and sharp dissection. Gall bladder end of the fistula tract was sealed with metal clip and the duodenal end was closed with a transfixation ligature and a simple ligature proximal to that.

The cholecystoduodenal fistula was divided between ligature and clip. Duodenal end of the tract was inverted by three interrupted intracorporeal stitch in the duodenal wall in transverse fashion. Rest of the surgery was completed in usual manner of laparoscopic cholecystectomy. Oral diet was resumed 48 hours after surgery. Patients were followed up in the outpatient clinic 7 days and one month after surgery.

Results:

Cholecystoduodenal fistulas were diagnosed in 8 of 1500 patients (0.53%) over the last 9 years by a single surgeon. Five patients were male and three were femalewith age ranging from 54 to 69 years (mean 63 years). They had gall stones detected by abdominal Ultrasonography. Cholecystoduodenal fistula was found during operative treatment of gall stones. All the cases were managed laparoscopically. Cholecystoduodenal fistula was completely mobilized with a combination of blunt and sharp dissection and divided after application of metal clip at gall bladder end

and intracorporeal transfixation ligature and simple ligature. Duodenal end was inverted by intracorporeal interrupted seromuscular suture of duodenal wall in a transverse manner. After that, laparoscopic cholecystectomy was completed. There were no intraopeprative complications in any of the patients. None of the cholecystoduodenal fistula was caused by malignancy. All eight patients had uneventful post-operative course. The hospital stay of eight patients ranged from 4 to 7 days (mean 5 days). Follow up was scheduled at 7th post-operative day and at one month with an advice to report in need. None returned with a complication.

Discussion:

According to international publications, cholecystoenteric fistulas are more common in female geriatric population 6.

Contrary to this, in our study, elderly male predominate over females (5 vs. 3). There were no specific symptoms suggestive of cholecystoduodenal fistula, rather chronic dyspeptic symptoms are indistinguishable from those of non-complicated calculus chronic cholecystitis. Thus, the diagnosis is made intraoperatively unless ultrasonography shows pneumobillia or there is an indication for more advanced diagnostic exercise like CT scan, MRCP or ERCP. In pre-laparoscopic era the standard treatment for this condition was open cholecystectomy with closure of the fistula with excision. With the advancement in video laparoscopic surgery many reports have described laparoscopic approach for cholecystoduodenal fistula 6. The strategy and techniques used in open surgery are also applicable in laparoscopic operations. Prompt recognition is crucial along with meticulous preparation of the fistula site to demonstrate surrounding anatomy. The endoscopic stapling device appeared to be easy to use and effective in closure of cholecystoduodenal fistula. But it is expensive and not available in resource constrained areas where it is needed for an incidental occasion. Ligation of the fistula with an endoloop is another option. Though unreliable and loss of control over divided fistula stump may create a technical difficulty during application2,9. Making a simple ligation either intracorporeally or extracorporeally is time consuming and cannot secure fistula closure9. An alternative is applying laparoscopic intracorporeal interrupted or continuous suture closure of the fistula. Similar to those in open procedure, again there is risk of loss of control outside the laparoscopic field of view. We solved the problem by combining, a transfixation ligature and holding it for control, a simple ligature proximal to it to avoid leak though needle prick for

transfixation followed by simple interrupted seromuscular inversion suture and finally ends of transfixation ligature were cut. This technique is technically demanding but safe and effective.

Conclusion:

The standard treatment of cholecystoduodenal non-malignant fistula was open cholecystectomy and suture closure of fistula in pre-laparoscopic era. With increasing expertise contraindications of laparoscopic surgery in such rare complications of gall stone that are discovered at operation are decreasing. A little modification of technique of open surgery have been used successfully in laparoscopic surgery without intraoperative and postoperative complications with all the advantages that minimally invasive surgery offers using traditional instruments. Thus keeping the expenditure no more than laparoscopic cholecystectomy alone.

References:1. Cuschieri A, Dubois F, Movie J, Mouret P, Becker H, Buess G, et

al. The European experience with laparoscopic cholecystectomy. Am J surg 1991; 161:385-7.

2. Successful laparoscopic management of four cases of cholecystoduodenal fistula. MJAFI 2012; 68:88-9.

3. Azra L,Ferid L, Mirela D, Josip S, DarkoK, Samir D. Successful laparoscopic treatement of cholecystoduodenal fistula. MED ARH 2010; 649(6):379-80.

4. Gentileschi P, Forlini A, Rossi P, Zaffoli M, Gentileschi E. Laparoscopic approach to cholecystocolic fistula: report of a case. J laparoendosc Surg,1995;5:413-7

5. Mervyn FSC, Dilip PAK, Swati VN, Jean-louis ASM. Colecystocolic fistula: a diagnostic enigma. The Saudi journal of gastroenterology 2009;15 (1): 42-4

6. L Angrisani, F Coricione, A Tartaglia, et al. Cholecystoenteric fistula is not a contraindication for laparoscopic surgery. Surg Endosc 2001; 15:1038-41.

7. Sharm A, Sullivan M, English H, Folwy R. Laparoscopic repair of cholecystoduodenal fistula. Surglaparosc Endosc 1994; 4:433-5.

8. Moreno Ruiz F J ,del Rey Moreno A, Suescun Garcia RM, Martinez Ferriz JA, Hidalgo Garrido JM, Espadas Padial B, et al. Treatment of cholecystoduodenal fistula in the era of laparoscopy. Rev Esp Enferum Dig.2001 Nov; 93 (11); 715-20.

9. Wang WK, Yeh CN, Jan YY. Successful laparoscopic management for cholecystoenteric fistula. World J gastroenterol 2006; 12 (5):772-5.


1 2

3 4

Figure I:

1-Anatomy of cholecystoduodenal fistula

2-Metal clip ligation at gall bladder end, intracorporeal transfixation ligature and simple ligature at duodenal end

3-Fistula transection after ligature placement

4-Duodenal end inverted by intracorporeal interrupted seromascular suture

78

surgical unit of BIRDEM general hospital, Dhaka, Bangladesh. Eight of them (0.53%) were found intraoperatively to have cholecystoduodenal fistula, abnormal communication between gall bladder and the first part of the duodenum.We, retrospectively, reviewed the medical records of eight patients of cholecystoduodenal fistula. All the patients history were recorded and underwent physical examination, ultrasonography (USG), and biochemical tests to establish a preoperative diagnosis. USG revealed, fibrosed, contracted, thick walled gallbladder with stones in all cases. In each case laboratory findings were unremarkable. Data were collected on patients’ age, sex, preoperative diagnosis, operative methods, morbidity and length of stay in hospital. Surgery was performed under general anesthesia using standard four ports technique. Cholecystoduodenal fistula was clearly demonstrated after careful blunt and sharp dissection. Gall bladder end of the fistula tract was sealed with metal clip and the duodenal end was closed with a transfixation ligature and a simple ligature proximal to that.

The cholecystoduodenal fistula was divided between ligature and clip. Duodenal end of the tract was inverted by three interrupted intracorporeal stitch in the duodenal wall in transverse fashion. Rest of the surgery was completed in usual manner of laparoscopic cholecystectomy. Oral diet was resumed 48 hours after surgery. Patients were followed up in the outpatient clinic 7 days and one month after surgery.

Results:

Cholecystoduodenal fistulas were diagnosed in 8 of 1500 patients (0.53%) over the last 9 years by a single surgeon. Five patients were male and three were femalewith age ranging from 54 to 69 years (mean 63 years). They had gall stones detected by abdominal Ultrasonography. Cholecystoduodenal fistula was found during operative treatment of gall stones. All the cases were managed laparoscopically. Cholecystoduodenal fistula was completely mobilized with a combination of blunt and sharp dissection and divided after application of metal clip at gall bladder end

and intracorporeal transfixation ligature and simple ligature. Duodenal end was inverted by intracorporeal interrupted seromuscular suture of duodenal wall in a transverse manner. After that, laparoscopic cholecystectomy was completed. There were no intraopeprative complications in any of the patients. None of the cholecystoduodenal fistula was caused by malignancy. All eight patients had uneventful post-operative course. The hospital stay of eight patients ranged from 4 to 7 days (mean 5 days). Follow up was scheduled at 7th post-operative day and at one month with an advice to report in need. None returned with a complication.

Discussion:

According to international publications, cholecystoenteric fistulas are more common in female geriatric population 6.

Contrary to this, in our study, elderly male predominate over females (5 vs. 3). There were no specific symptoms suggestive of cholecystoduodenal fistula, rather chronic dyspeptic symptoms are indistinguishable from those of non-complicated calculus chronic cholecystitis. Thus, the diagnosis is made intraoperatively unless ultrasonography shows pneumobillia or there is an indication for more advanced diagnostic exercise like CT scan, MRCP or ERCP. In pre-laparoscopic era the standard treatment for this condition was open cholecystectomy with closure of the fistula with excision. With the advancement in video laparoscopic surgery many reports have described laparoscopic approach for cholecystoduodenal fistula 6. The strategy and techniques used in open surgery are also applicable in laparoscopic operations. Prompt recognition is crucial along with meticulous preparation of the fistula site to demonstrate surrounding anatomy. The endoscopic stapling device appeared to be easy to use and effective in closure of cholecystoduodenal fistula. But it is expensive and not available in resource constrained areas where it is needed for an incidental occasion. Ligation of the fistula with an endoloop is another option. Though unreliable and loss of control over divided fistula stump may create a technical difficulty during application2,9. Making a simple ligation either intracorporeally or extracorporeally is time consuming and cannot secure fistula closure9. An alternative is applying laparoscopic intracorporeal interrupted or continuous suture closure of the fistula. Similar to those in open procedure, again there is risk of loss of control outside the laparoscopic field of view. We solved the problem by combining, a transfixation ligature and holding it for control, a simple ligature proximal to it to avoid leak though needle prick for

transfixation followed by simple interrupted seromuscular inversion suture and finally ends of transfixation ligature were cut. This technique is technically demanding but safe and effective.

Conclusion:

The standard treatment of cholecystoduodenal non-malignant fistula was open cholecystectomy and suture closure of fistula in pre-laparoscopic era. With increasing expertise contraindications of laparoscopic surgery in such rare complications of gall stone that are discovered at operation are decreasing. A little modification of technique of open surgery have been used successfully in laparoscopic surgery without intraoperative and postoperative complications with all the advantages that minimally invasive surgery offers using traditional instruments. Thus keeping the expenditure no more than laparoscopic cholecystectomy alone.

References:1. Cuschieri A, Dubois F, Movie J, Mouret P, Becker H, Buess G, et

al. The European experience with laparoscopic cholecystectomy. Am J surg 1991; 161:385-7.

2. Successful laparoscopic management of four cases of cholecystoduodenal fistula. MJAFI 2012; 68:88-9.

3. Azra L,Ferid L, Mirela D, Josip S, DarkoK, Samir D. Successful laparoscopic treatement of cholecystoduodenal fistula. MED ARH 2010; 649(6):379-80.

4. Gentileschi P, Forlini A, Rossi P, Zaffoli M, Gentileschi E. Laparoscopic approach to cholecystocolic fistula: report of a case. J laparoendosc Surg,1995;5:413-7

5. Mervyn FSC, Dilip PAK, Swati VN, Jean-louis ASM. Colecystocolic fistula: a diagnostic enigma. The Saudi journal of gastroenterology 2009;15 (1): 42-4

6. L Angrisani, F Coricione, A Tartaglia, et al. Cholecystoenteric fistula is not a contraindication for laparoscopic surgery. Surg Endosc 2001; 15:1038-41.

7. Sharm A, Sullivan M, English H, Folwy R. Laparoscopic repair of cholecystoduodenal fistula. Surglaparosc Endosc 1994; 4:433-5.

8. Moreno Ruiz F J ,del Rey Moreno A, Suescun Garcia RM, Martinez Ferriz JA, Hidalgo Garrido JM, Espadas Padial B, et al. Treatment of cholecystoduodenal fistula in the era of laparoscopy. Rev Esp Enferum Dig.2001 Nov; 93 (11); 715-20.

9. Wang WK, Yeh CN, Jan YY. Successful laparoscopic management for cholecystoenteric fistula. World J gastroenterol 2006; 12 (5):772-5.


79


Introduction:

Sepsis is a complex condition that is often life threatening. It remains the most frequent cause of death in ICU. Septicaemia is currently ranked by the Centers for Disease Control and Prevention as the 10th leading cause of death in the United States.1 Sepsis is a clinical syndrome characterized by systemic inflammation and widespread tissue injury due to infection.2 There is a continuum of illness severity ranging from sepsis to severe sepsis and septic shock. Suspected infection may be Pneumonia, Meningitis, Intra abdominal infection, Urinary tract infection and Catheter related infections.4

In a recent report, Infectious Disease Society of America (IDSA), specifically addressed three categories of Gram Negative Bacilli, namely ESBL (Extended Spectrum Beta-Lactamase) producing Escherichia coli, and Klebsiella sp, MDR (Multi Drug Resistant) Pseudomonas sp, and carbapenem resistant Acinetobacter sp as high priority

bacterial pathogens.8 Infections with resistant strains of microorganisms in the ICUs lead to increased mortality and cost., 9 All these major reports indicate the need for obtaining data on prevalent strains in the ICU along with the susceptibility pattern, to help in revising antibiotic policy and guiding clinicians for the better management of patients. Prevalent flora and antimicrobial resistance pattern may vary from region to region depending upon the predominant antibiotic use in that locality.

The objectives of the current study were to identify the causative organisms of sepsis and determined their antibiotic resistance pattern isolated from patients admitted to the ICU

Materials and Methods:

This Prospective observational study was done from July, 2012 to December, 2012 to evaluate 100 subjects, suffering from Sepsis admitted in the Department of Critical Care Medicine, BIRDEM General Hospital, Shahbagh, Dhaka.

Original Article

Microorganism profile and their resistance pattern among the patients of sepsis in an intensive care unit of a tertiary care hospitalRozina Sultana1, Mohammad Omar Faruq2, ASM Areef Ahsan3, Kaniz Fatema4, Fatema Ahmed5, Debasish Kumar Saha6, Madhurima Saha7, Suraiya Nazneen8, Tarikul Hamid9, Ariful Islam10

Abstract

Objective: To identify the causative organisms of sepsis and determine their antibiotic resistance pattern isolated from patients admitted to the ICU.

Methodology: This prospective observational study was carried enrolling 100 subjects with sepsis, in the Department of Critical Care Medicine (CCM), BIRDEM General Hospital, Dhaka, over a period of six months from July 2012 to December 2012.

Results: Among the 100 study population, mean age was 56.85 (± SD of 13.58) years and 68% of the patients were male and 32% were female. All the subjects were presented with raised temperature. Blood, urine and respiratory secretion (Tracheal aspirate) samples were sent for culture and sensitivity in all cases. Culture from wound swab was done in 16 subjects. Out of 286 samples from 100 subjects, microorganisms were isolated from 134 samples (46.8%). Some samples revealed more than one organism growth, ultimately 207 organisms were isolated. Growth of Pseudomonas (22.2%), Acinetobactor (35.7%), Staphylococcus aueus (3.8%), Enterococcus (1.4%), E. coli (14.9%), Klebsiella (12.6%), Enterobacter (4.8%) and Citrobactor (1.9%) and Candida sp. (4.8%) were observed. Most common organisms isolated from blood were Pseudomonas (48.2%), Acinetobactor (31.0%) and E. coli (10.3%). E. coli (37.7%) and Klebsiella (17.7%) were most common organisms isolated from urine. Pseudomonas (21.3%, 18.1%) and Acinetobactor (49.1%, 18.1%) were most frequently isolated organisms from tracheal aspirate and wound swab respectively. From culture sensitivity test, it was found that majority of the isolated organisms were resistant to quinolones and 3rd generation cephalosporin. Majority of the E coli and Klebsiella were less resistant (9.6% and 14.2%) to Imipenem. Colistin resistance was seen in less than 50% in major Gram negative organisms. Piperacillin and Tazobactum combination showed less than 50% resistance in case of Acinetobactor and Klebsiella.

Conclusion: In this study majority of the isolated organisms were resistant to conventional antibiotics. As patients with sepsis admitted in ICU are already ill it would be unwise to wait for result of antibiotic sensitivity test and it is suggested that third generation Cephalosporin or Carbapenem (Meropenem or Imipenem) should be started depending on the severity of the illness and then start susceptible antibiotic after obtaining culture–sensitivity result. Colistin and Piperacillin-Tazobactum combination should be preserved for further use. However further study with a comparative prospective design is required regarding this issue.

Keywords: Antimicrobial resistance, microorganism profile, intensive care unit, sepsis.

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Demographic information was prospectively recorded and substantiated by means of inspection of medical record. Information included was the subject’s age, gender, medical and clinical history, followed by conduction of the study.

Samples included blood, urine, respiratory secretions (sputum/tracheal aspirate) and pus/wound swabs were collected from study population and cultured in standard media for isolation of potential pathogens. Isolates were identified by standard methods. For each isolat antibiotic susceptibility was performed by Kirby Bauer disk diffusion techniques. Isolates with intermediate susceptibility were considered resistant. From 100 subjects 286 samples were collected (Blood and urine 100 each, tracheal aspirate 70 and wound swab 16). Growth was found in 134 positive samples. Some samples revealed more than one organism growth, ultimately 207 organisms were isolated.

All the relevant collected data were compiled on a master chart first. Then organized by using scientific calculated and standard statistical formulas, percentage was calculated to find out the proportion of the findings. Data entry and analysis were done using SPSS for windows version 13.0. Output of data and graphical representation was done using Microsoft Office chart and Microsoft Word.

Results:

This cross sectional study was carried out to identify the causative organisms of sepsis and determine their antibiotic

1. Dr. Rozina Sultana, Medical Officer, Dept. of Critical Care Medicine, BIRDEM General Hospital

2. Prof Mohammad Omar Faruq, Consultant, Intensive Care Unit, United Hospital Limited, Dhaka

3. Prof. A.S.M. Areef Ahsan, Head, Dept. of Critical Care Medicine, BIRDEM General Hospital

4. Dr. Kaniz Fatema, Associate Professor, Dept. of Critical Care Medicine, BIRDEM General Hospital

5. Dr. Fatema Ahmed, Associate Professor, Dept. of Critical Care Medicine , BIRDEM General Hospital

6. Dr. Debasish Kumar Saha, Junior Consultant, Dept. of Critical Care Medicine , BIRDEM General Hospital

7. Dr. Madhurima Saha, Registrar, Dept. of Critical Care Medicine, BIRDEM General Hospital

8. Dr. Suraiya Nazneen, Registrar, Dept. of Critical Care Medicine, BIRDEM General Hospital

9. Dr. Tarikul Hamid, Medical Officer, Dept. of Critical Care Medicine , BIRDEM General Hospital

10. Dr. Ariful Islam, Medical Officer, Dept. of Critical Care Medicine, BIRDEM General Hospital


Dr. Rozina Sultana FCPS (Medicine), MD (Critical Care Medicine)Dept. of Critical Care Medicine BIRDEM General Hospital122, Kazi Nazrul Islam Avenue, Dhaka 1000E-mail: [email protected]

resistance pattern isolated from patients admitted to the ICU on 100 subjects with sepsis in the Department of CCM, BIRDEM General Hospital, Dhaka.

A total of 100 cases were included in the study. Their age ranged from 36 to 69 years. Age distribution of the patients is shown in table I. Majority (39%) of the respondents were found in the age group of 50-59.

Table I: Age distribution of the study population

Age group (Years) Number Percentage

40 and below 16 16

40-49 18 18

50-59 37 37

60 and above 29 29

Mean± SD 56.85±13.58

Age range 36-69

Sixty eight percent (n= 68) of the patients were male and thirty two percent (n=32) were female in the study population (fig 1). The clinical presentations have been shown in table II.

Figure 1: Pie diagram showing gender distribution of the study subjects

Table II: Clinical presentations of the study subjects

Clinical presentations Number Percentage

Raised temperature 100 100

Increased heart rate 89 89

Increased respiratory rate 76 76

*Multiple responses were elicited.

Blood and urine samples were sent for culture and sensitivity from all study patients; Tracheal aspirate culture sensitivity were done in 70 patients Cultures from wound swab (Pus, collection etc.) were done in 16 patients. Out of 286 samples from 100 subjects, microorganisms were isolated from 134 samples (46.8%).

81


Table III: Sample profile and rate of positive culture from different sample

Sample Total number Growth of organism of sample Number Percentage

Blood 100 13 13%

Urine 100 45 45%

Tracheal secretion 70 65 92.8%

Wound swab 16 11 68.7%

Total 286 134

Table IV showed growth of different organisms from different samples. Most common organisms isolated from blood were Pseudomonas (48.2%), Acinetobactor (31.0%) and E. coli (10.3%). E. coli (37.7%) and Klebsiella (17.7%) were most common organisms isolated from urine. Pseudomonas (21.3%, 18.1%) and Acinetobactor (49.1%, 18.1%) were most frequently isolated organisms from tracheal aspirate and wound swab respectively.

From culture sensitivity test, it was found that majority of the isolated organisms were resistant to quinolones and 3rd generation cephalosporin. Majority of the E coli and Klebsiella were less resistant (9.6% and 14.2%) to Imipenem.

Colistin resistance was less than 50% in major Gram negative organism. Piperacillin and Tazobactum combination showed less than 50% resistance in case of Acinetobactor and Klebsiella.

Table IV: Microorganism isolated from different Samples

Name of the Blood Urine Tracheal Wound TotalOrganism Secretion Swab

Pseudomonas sp. 14 04 26 02 46 (22.2)Acinetobactor sp. 09 03 60 02 74 (35.7)Staphylococcus aureus 00 03 05 00 08 (3.8)Enterococcus 00 01 02 00 03 (1.4)E. coli 03 17 10 01 31 (14.9)Klebsiella sp. 02 08 08 03 21 (12.6)Enterobacter sp. 00 04 05 01 10 (4.8)Citrobacter 00 00 02 02 04 (1.9)Candida sp. 01 05 04 00 10 (4.8)Total 29 45 122 11 207

* Some samples revealed more than one organism growth. Total 207 growths were found

Table VIII: Antibiotic resistant pattern of the major organism isolated from samples

Antiboitics Acinetobactor Pseudomonas E. coli Klebsiella

ß-lactamPiperacillin 100 89.9 - -Piperacillin+Tazobactum 42.4 65.2 67.7 42.8Ceftriaxone 90.9 95.6 85.2 71.4Ceftazidime 100 84.7 93.5 90.4Cefotaxime 87.1 97.8 74.1 95.2Aztreonam 90.9 84.7 - -Imipenem 69.6 54.3 9.6 14.2AminoglycosidesAmikacin 45.4 63.2 48.3 47.6Netilmicin 57.5 82.6 74.1 80.9Gentamicin 90.9 86.9 87.7 76.1QuinolonesCiprofloxacin 87.8 82.6 96.7 85.7OthersCo-trimoxazole 100 95.6 74.1 95.2Colistin 36.3 32.6 12.9 9.5Tetracycline 100 97.8 93.5 95.2

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Discussion:

With the aim to identify the causative organisms of sepsis and determine their antibiotic resistance pattern isolated from patients admitted to the ICU with sepsis this present study was carried out on 100 subjects with sepsis in the Department of CCM, BIRDEM General Hospital, Dhaka. The findings of the study are discussed on basis of related previous studies concerning the objective of the study.

The mean age was 56.8 (± SD of 13.5) years ranging from 36 to 69 years. Majority (39%) of the respondents were found in the age group of 50-59. All the subjects were presented with raised temperature. Leukocytosis was observed in 91% subjects. Increased heart and respiratory rates were seen in 89% and 76% subjects respectively. Similar features of sepsis were described in other study.8

Among 100 subjects, blood, urine and respiratory secretion (Tracheal aspirate) samples were sent for culture and sensitivity in all cases. Culture from wound swab (Pus, collection etc.) were done in 16 subjects. Microorganisms were isolated from 46.8% cases. Another study found that culture was positive in 70% infected subjects.14

In case of blood sample, growth was found from 13% samples, 45% from urine, 65% from tracheal aspirate and 68.7% from wound swab. Some samples revealed more than one organism growth. So from 134 positive samples, ultimately 166 organisms were isolated. In a comparable study in Dhaka city19 , it was observed that major organisms is isolated from blood were Pseudomonas sp. (51.7%) and Acinetobacter sp. (18.4%) while from urine it was Candida sp (43.3%) and E. coli (19.3%). The most frequently isolated organisms from both respiratory secretions and pus were Acinetobacter sp. (40.9% and 27% respectively) and Pseudomonas sp. (32.9% and 27% respectively).

In similar previous study it was seen that most frequently reported micro-organisms were Enterobacteriaceae (34.4%), Staphylococcus aureus (30.1%), Pseudomonas (28.7%), Staphylococci (19.1%)17 . Another study found that major organism isolated were Pseudomonas sp. (29.1%), Acinetobacter sp. (27.5%), Candida sp. (12.8%), Escherichia coli (10.3%) and Klebsiella sp. (9.7%). Staphylococcus aureus, Enterobacter sp, Citrobacter sp, Enterococcus sp, Providencia sp and Serratia sp accounted for 10.6% of the isolates.19 Another study showed among the 8,072 isolates, Staphylococcus aureus (1,858), Escherichia coli (1,634), and S. pneumoniae (725) were the most common organisms. The numbers of S. aureus, Enterococcus faecalis, Bacteroides fragilis, E. coli, and Serratia marcescens increased annually during the 4-year period.20 In a study in an Indian ICU, the most common organisms were Acinetobacter sp, Escherichia Coli, Klebsiella sp, Pseudomonas aeruginosa, Staphylococcus aureus, Streptococcus pyogenes.6 But in an European ICU , Staphylococcus aureus was found as the most frequently isolated organism (30.1%), followed by Pseudomonas aeruginosa (28.7%), Coagulase negative Staphylococcus (19.1%) and Yeast (17.1%).7

Most common organisms isolated from blood were

Pseudomonas (48.2%), Acinetobactor (31.0%) and E. coli (10.3%). E. coli (37.7%) and Klebsiella (17.7%) were most common organisms isolated from urine. Pseudomonas (21.3%, 18.1%) and Acinetobactor (49.1%, 18.1%) were most frequently isolated organisms from tracheal aspirate and wound swab respectively. These findings reflected that if an intubated ICU patient develops pneumonia, a suspicion of Acinetobactor should be kept in mind and antibiotic should be started accordingly. If the patient is not intubated, then antibiotic should be started which may cover Pseudomonas, E. coli and Klebsiella.

Another finding in this present study, although small in percentage (4.8%) but striking that growth of Candida was seen in sepsis subjects. In a previous study it was observed that growth of Candida in 19% samples.14 Another comparable previous study revealed growth of fungi (17.1%) in sepsis patient admitted in ICU.15 This finding was important because antibiotic has no role against the fungal infection and if antibiotic is prescribed in these subjects there would be no control of sepsis. High number of Candida isolation might be due to the presence of underlying conditions like poor nutritional status, diabetes mellitus and the use of steroids and broad spectrum antibiotics.

From culture sensitivity test, it was found that majority of the isolated organisms were resistant to quinolones and 3rd generation cephalosporin. Majority of the E coli and Klebsiella were less resistant (9.6% and 14.2%) to imipenem. Colistin resistance was less than 50%. Piperacillin and Tazobactum combination showed less than 50% resistance in case of Acinetobactor and Klebsiella. Previous study17 revealed that in the 2-year study period the rise in the number of gram negative isolates was proportionally high along with increase in their resistance pattern. Dramatic rise in ESBL's has led to multidrug resistant E. coli and Klebsiella pneumoniae. Also organisms like Acinetobacter sp. and Pseudomonas aeruginosa are multiresistant making optimal therapy selection difficult. Imepenem, Piperacillin-Tazobactum and Amikacin were still highly active against Acinetorbacter and Enterobacteriacea.17 A similar study showed that isolates were highly resistant (>80%) to cephalosporins and fluoro quinolones which was a similar comparable findings with this present study.19 The frequency of third generation cephalosporin resistant E.coli, Klebsiella and imipenem resistant Pseudomonas and Acinetobacter were >50%. Acinetobacter was remarkably resistant to most antibiotics including imipenem (>70% resistant), but most of the members of the Enterobacteriacae group showed maximum sensitivity to imipenem (50%-94%).

Conclusion :

From the study result it could be concluded that patient with clinically suspected sepsis should be treated with antibiotic to which the organism is sensitive. As patients with sepsis admitted in ICU are already ill, it would be unwise to wait for result of antibiotic sensitivity test and it is suggested that third generation Cephalosporin or Carbapenem (Meropenem or Imipenem) should be started depending on the severity of the illness and then start suitable antibiotic after obtaining

83


culture–sensitivity result. Colomycin & Piperacillin+Tazobactum combination should be preserved for further use. However further study with a comparative prospective design is required regarding this issue.

References:1. Kathy M, Sharon C. O’Donoghue, et al. Development and

Implementation of a Multidisciplinary Protocol. Critical Care Nurse 2006; 26: 66-70.

2. Dellinger Rp, Levy MM, Carlet, JM et al. Surviving sepsis campaign: International guidelines for management of severe sepsis and septic shock: Crit Care Med 2008; 36:296-327.

3. Sibbald WJ, Mandel J. Management of septic shock. In: UpToDate in Pulmonary and Critical Care Medicine [CD-ROM]. Wellesley (MA): UpToDate, Inc; 1998-2004.

4. Scott K. Fridkin, Robert P. Gaynes; Antimicrobial resistance in Intensive Care Units. Clinics in Chest Medicine. 1999; 20 (2): 199-204.

5. Jamshdi M, Javadpour S, Eftekhari T E, et al. Antimicrobial resistance pattern among Intensive Care Unit patients. African Journel of Microbiology Research 2009; 3 (10): 590-4.

6. Patwardhan RB, Dhakephalkar PK, Niphadkar KB, et al. A study on nosocomial pathogens in ICU with special reference to multiresistant Acinetobacter baumannii harbouring multiple plasmids.Indian J Medcine Res 2008; 128: 178-87.

7. Spencer RC . Predominant pathogens found in the Europian prevalence of infection in Intensive care study. Eur J Clin Microbial Infect Dis 1996; 15:281-5.

8. Talbot GH, Bradley J, Edwards JE Jr, et al. Bad bugs need drugs: An update on the Development pipeline from the antimicrobial availability Task Force of the Infectious Diseases Society of America. Clin Infect Dis 2006; 42:657-68.

9. Kaul S, Bahmadathan KN, Jagannati M, et al. One year trends in the gram negative bacterial antibiotic susceptibility patterns in a medical intensive care unit in South India. Indian J Med Microbiology 2007; 25: 230-5.

10. Colle JG, Miles RS, Watt B. Tests for the identification of bacteria. In: Mackie & McCartney Practical Medical Microbiology, 14th edn. New York. Churchill Livingstone Inc, 1996; 131-49.

11. Bauer AW, Kirby WMM, Sherris JC, et al. Antibiotic susceptibility testing by a standardized sigle disc method. Am J Clin Pathol 1966; 45: 493-9.

12. Kahn JM, Goss CH, Heagerty PJ, et al. Hospital volume and the outcomes of mechanical ventilation. New England Journal of Medicine 2006; 355 (1): 41–50.

13. Gallesio A.O, Ceraso D, Palizas F. Improving quality in the intensive care unit setting. Crit Care Clin.2006; 22 (3): 547–71.

14. Vincent JL, Rello J, Marshall J, et al. EPIC II Group of Investigators: International study of the prevalence and outcomes of infection in intensive care units. JAMA 2009; 302: 2323-9.

15. Vincent JL, Bihari DJ, Suter PM, et al.The prevalence of nosocomial infection in intensive care units in Europe. Results of the European Prevalence of Infection in Intensive Care (EPIC) Study. EPIC International Advisory Committee. JAMA. 1995; 274(8): 639-44.

16. Kett DH, Azoulay E, Echeverria PM, et al. Candida bloodstream infections in intensive care units: analysis of the extended prevalence of infection in intensive care unit study. Crit Care Med. 2011; 39(4): 665-70.

17. Martin GS, Mannino DM, Eaton S, et al. Epidemiology of sepsis in the United States from 1979 through 2000. N Engl J Med 2003; 348:1546–54.

18. Jain S, Khety Z. Changing antimicrobial resistance pattern of isolates from an ICU over a 2 year period. J Assoc Physicians India. 2012; 60: 278-333.

19. Barai L, Fatema K, Haq JA, et al. Bacterial profile and their antimicrobial resistance pattern in an intensive care unit of a tertiary care hospital of Dhaka. Ibrahim Med. Coll. J. 2010; 4(2): 66–9.

20. Sharma S, Kumar A. Antimicrobial management of sepsis and septic shock. Clin Chest Med 2008; 29:677–87.

21. Bochud PY, Bonten M, Marchetti O, et al. Antimicrobial therapy for patients with severe sepsis and septic shock: an evidence-based review. Crit Care Med 2004; 32(11): 495–512.

22. Garnacho-Montero J, Ortiz-Leyba C, Herrera-Melero I, et al. Mortality and morbidity attributable to inadequate empirical antimicrobial therapy in patients admitted to the ICUP with sepsis: a matched cohort study. J Antimicrob Chemother 2008; 61: 436–41.

23. National Committee for Clinical Laboratory Standards (now Clinical and Laboratory Standards Institute, CLSI).Performance standards for antimicrobial susceptibility testing; 12th information supplement (M100-S1). Villanova, PA; NCCLS: 2002.

24. Matthew EF, Patra KK, Ioannis AB. The diversity of definitions of multidrug resistant (MDR) and pandrug resistant (PDR) Acinetobacter baumannii and Pseudomonas aeruginosa. J Med Microbiol 2006; 55: 1619-29.

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Introduction:

Central venous cannulas are important portals for vascular access and for the assessment of changes in intravascular volume. Central venous cannulas permit the rapid administration of fluids, insertion of pulmonary artery catheters (PACs) or central venous O2 (ScvO2) saturation monitoring, insertion of transvenous electrodes, monitoring of central venous pressure (CVP), and for treatment of venous air embolism.1

1. Dr. Gentle Sunder Shrestha, Intensivist and Anaesthesiologist, Department of Anaesthesiology, Institute Of Medicine, Tribhuvan University Teaching Hospital, Kathmandu;

2. Dr. Sabin Koirala, Anaesthesiologist, Department of Anaesthesiology and Critical Care, Grande International Hospital, Kathmandu;

3. Dr. Arjun Gurung, Anaesthesiologist, Department of Anaesthesiology, Institute Of Medicine, Tribhuvan University Teaching Hospital, Kathmandu;

4. Dr. Prakash Chand, Medical Officer, Department of Critical Care Medicine, Alka Hospital Pvt Ltd, Jawalakhel, Lalitpur, Nepal.


Dr. Gentle Sunder ShresthaIntensivist and AnaesthesiologistMBBS, MD Anaesthesiology, FACC, EDIC, FCCPLecturer, Department of Anaesthesiology,Tribhuvan University Teaching Hospital, Institute Of Medicine,Maharajgunj, Kathmandu, NepalEmail: [email protected]

Developing nations lack the advanced blood banks and procurement of blood products in short time is not only challenging but is near impossible. However, with the advancement in health care and increase in life expectancy, sicker patients are being managed in intensive care units (ICUs). It is not uncommon for the treating physician to face a coagulopathic patient who needs urgent central venous cannulation, when there is little time to wait for blood products to correct coagulopathy.

Central vein cannulation in a critically ill patient with coagulopathy is a challenge to an anesthesiologist and intensivist due to increased risk of complications. The challenge of successfully cannulating the internal jugular vein with minimal complication is aided by the use of real time ultrasonography. G Ruesz have suggested that ultrasound guided CVC placement without routine correction of coagulation abnormalities may be safe in the ICU.2

Real time ultrasonography helps cannulation of central veins under direct visualization, thus reducing the chances of complications. Another advantage that USG cannulation offers is the visualization of vessels in hypotensive patients in whom carotid artery is difficult to palpate for landmark identification.3

Original Article

Ultrasound guided emergency cannulation of internal jugular vein in coagulopathic adult patients – a prospective observational pilot study.Gentle Sunder Shrestha1, Sabin Koirala2, Arjun Gurung3, Prakash Chand4

Abstract

Aim: This study aims to evaluate the safety of ultrasound guided emergency cannulation of internal jugular vein in coagulopathic adult patients.

Methods: Adult subjects admitted in the intensive care unit, undergoing emergency cannulation of internal jugular vein under real time ultrasonographic guidance with platelet count less than 50,000/cu mm and/or international normalized ratio (INR) more than 1.5 were enrolled. Major and minor complications during the procedure were noted.

Results: Internal jugular vein was successfully cannulated in all the patients. The mean INR of patients having minor complications (provided that platelet count > 50000) was found to be 3.07 with 95% confidence interval(CI) being 2.37-3.77. The mean platelet count of patients having minor complications (provided that the INR<1.5) was found to be 27428 with 95% CI being 19428-36000. There was a significant relationship between margin of safety and occurrence of minor complications (>7mm vs 7mm or less; p value 0.027). Number of attempts while performing internal jugular vein cannulation was associated with minor complications (mean 1.5 with CI 1.2-1.78 vs mean 1.08 with 95% CI 1.00-1.25; p value 0.023). No major complications were reported during the study regardless of platelet count, INR, margin of safety or number of attempts.

Conclusions: Emergency cannulation of internal jugular vein may be safely performed in coagulopathic adult patients under real-time ultrasound guidance when performed by an experienced physician.

Key-words: central venous cannula (CVC), coagulopathic patient, internal jugular vein, Point of care ultrasound (POCUS), venous cannulation.

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With the advent of portable and affordable ultrasound machines, the availability and the possibility to procure ultrasound machine in ICUs of even the resource limited settings is becoming more realistic. The demand for blood products is ever increasing, making timely procurement of blood products to correct coagulopathy a bigger challenge in resource limited places. We planned this prospective observational study to evaluate the safety of ultrasound guided emergency cannulation of internal jugular vein in coagulopathic adult patients when there is inadequate time for correction of coagulopathy for safe cannulation and when the demand for central venous access appears to outweigh the risk.

Subjects and Methods:

Adult subjects admitted in the intensive care unit undergoing emergency cannulation of internal jugular vein under real time ultrasonographic guidance with platelet count less than 50,000/cu mm and/or international normalized ratio (INR) more than 1.5 were enrolled in the study after obtaining a written informed consent. Patients with coagulopathy and semi-emergent indication for central venous cannulation, when there is time for correction of coagulopathy, were excluded from study.

All patients had cannulation of the internal jugular performed using the Seldinger technique. Subjects were placed in a head down position with the head turned slightly to the side opposite to that of cannulation. The skin of the anterior and lateral neck was prepared using antiseptic solution and draped. The ultrasound probe used was a 6-10 L38 MHz linear transducer SonoSite turbo unit (SonoSite®, Micromaxx, Bothwell, WA, USA). The probe was covered with a sterile sheath and sterile ultrasound gel was applied to the inside of the sheath. Each cannulation was performed by an experienced anaesthesiologist with a minimum of 3 years of experience in cannulation of central veins and a minimum of 100 ultrasound guided cannulations of internal jugular vein. Following information were recorded: indication for central venous cannulation, platelet count, prothrombin time, INR, side of internal jugular vein cannulated, mechanical ventilation status of the patient, diameter of internal jugular vein (mm), margin of safety (mm), number of attempts, approach (short / long axis) and success of cannulation.

Margin of safety was the distance between midpoint of internal jugular vein and the lateral border of carotid artery. Diameter of internal jugular vein and margin of safety were measured at the same level and in the same head position of the patient as during cannulation.

A short axis image of the internal jugular vein was obtained by placing the transducer in a transverse orientation on the patient’s neck at the level of the cricoid cartilage. The needle was inserted at 60 degrees to the vertical and advanced toward the vein employing gentle aspiration on the attached syringe. Entry to the vein was confirmed by visualizing indentation of the anterior wall of the vein followed by blood in the syringe and by visualising the tip of the needle inside the vein. Confirmation of guide wire placement was performed by scanning the vein in both short and long axis planes.

Complications if present were recorded and were categorized as major or minor. Complications like carotid puncture, carotid cannulation, pneumothorax, haemothorax, haemodynamically significant or life threatening bleeding and airway compromise attributable to bleeding were categorized as major complications. Superficial haematoma either visible or palpable and superficial oozing from cannula site were categorized as minor complications.

Results:

A total of 25 cases were enrolled in the study. Technical success was achieved in all the cases. The mean INR of patients having minor complications (provided that platelet count > 50000/cu mm) was found to be 3.07 with 95% CI of 2.37-3.77 (Table 1). The mean platelet count of patients having minor complications (provided that the INR<1.50) was found to be 27428/cu mm with 95% CI being 19428-36000/cu mm (Table 2). None of the patients had the combination of platelet count less than 50000/cu mm and INR more than 1.50. Margin of safety was found to be related to the occurrence of minor complications and the association was statistically significant (Table 3 and 4). Number of attempts for cannulation was found to be associated with the occurrence of minor complications and the association was statistically significant (Table 5 and 6). Major complications such as carotid puncture, pneumothorax, hemothorax, hemodynamically significant bleeding or airway compromise were not reported during the study regardless of platelet count, INR, safety of margin or number of attempts.

Table I: INR of patients having minor complications provided the platelet count is more than 50,000/cumm

95% Confidence Interval Lower Upper

Mean 3.07 2.37 3.77

Median 2.90 2.10 4.20

Std. Deviation 1.06 0.46 1.21

Minimum 2.10

Maximum 4.20

Range 2.10

Table II: Platelet count of patients having minor complications provided the INR is less than 1.50.

95% Confidence Interval Lower Upper

Mean 27428.57 19428.57 36000.00

Median 24000.00 15000.00 40000.00

Std. Deviation 12380.86 7181.32 14466.71

Minimum 12000.00

Maximum 40000.00

Range 28000.00


86

Discussion:

Cannulation of a large central vein is the standard clinical method for monitoring central venous pressure and is also performed for a number of additional therapeutic interventions, such as providing secure vascular access for the administration of vasoactive drugs or to initiate rapid fluid resuscitation. Frequently, the central venous location is the only site available for intravenous access.4 Due to the spectrum of usage of the central venous catheter, its requirement is increasing in medical practice. Sometimes coagulation disorders are present in patients with indication of central venous cannulation. Coagulation disorders pose a challenge as there are increased chances of complications like hemorrhage from the insertion site, hematoma formation and hemothorax. Usually, correction of coagulopathy is sought before the procedure. However, it is unclear whether fresh frozen plasma (FFP), platelet concentrate or platelet rich plasma (PRP) should be administered prior to attempted catheterization when coagulopathy is not severe. Although correction of coagulopathy may be possible, it may not be beneficial, it may be impossible to administer the corrective transfusion factor owing to lack of venous access or the condition may not be correctable by transfusion alone.5

Each year several million units of fresh-frozen plasma (FFP) are transfused all over the world. Recent data demonstrate that annual FFP usage has been steadily rising. Much of the plasma that is administered is used for the purpose of correcting coagulopathy before performing an invasive diagnostic procedure. This practice appears to be common despite the fact that most consensus guidelines do not recommend FFP for this indication when the coagulopathy is not severe. This practice exposes patients to the complications associated with transfusion of blood products and is costly. Furthermore, it promotes the use of pre-procedural laboratory testing, which also has costs and may unnecessarily delay the procedures. It can also lead to fluid overload in certain group of patients. The supposition underlying these transfusions is that even a mildly elevated INR is associated with excessive bleeding in the setting of an invasive procedure and that an intervention is needed for safety.6 In our study we came across no major complication in any of the cases with coagulopathy. Occurrence of minor complications was significant when the INR was more than 3 in patients with platelet count more than 50,000.

Table III: Relationship between margin of safety and occurrence of minor complications

Minor Complications Total

No Yes

Margin of safety (mm) ≤ 7 Number of patients 4 9 13

% within minor complications 30.8% 75.0% 52.0%

> 7 Number of patients 9 3 12


Table IV: Statistical significance between margin of safety and occurrence of minor complications

Value Asymptotic Significance (2-sided)

Pearson Chi-Square 4.891 0.027

Table V: Relationship between number of attempts and occurrence of minor complications

Minor Complications Total

No Yes

Number of attempts 1 Number of patients 12 6 18


2 Number of patients 1 6 7


Table VI: Statistical significance between number of attempts and occurrence of minor complications

Value Asymptotic Significance (2-sided)

Pearson Chi-Square 5.540 0.019


The mean platelet count of patients having minor complications (provided that the INR<1.50) was found to be 27428 (95% CI: 19428-36000). In our study we found that minor complications were significant when the platelets count was below 27,000 in presence of normal INR. Doerfler et al also had similar results. They have mentioned that central venous cannulation can be done safely by a skilled clinician even in patients with hemostasis problems and complications were encountered only when the platelet count was below 6000.7 Slichter et al suggested that attention should be focused on providing aggressive platelet therapy for active bleeding rather than transfusing platelets prophylactically. Therapeutic platelet transfusions have been documented to control bleeding, and mortality rates are not increased when comparing patients receiving therapeutic to that seen in patients receiving prophylactic platelet transfusions.8 Zeidler et al have mentioned that the risk of non-severe bleeding was increased only in patients with platelet counts below 20000, but not with platelet counts between 20000 and 49000. They have suggested pre-procedural platelet transfusions only in patients with platelet counts below 20000.9 Weigand et al have also concluded from their study that transfusion of blood products prior to CVC insertion is not necessary in most cases. A delay of CVC insertion waiting for blood products seems to be unjustified, particularly in view of complication rates.10 Another study has concluded that ultrasound guided central venous cannulation in patients with liver disease and coagulopathy is a safe and is a highly successful modality. In their study, mean INR was 2.17 ± 1.16 whereas median platelet count was 149.5 (range 12-683) × 109/L. No major vascular or non-vascular complications were recorded in their patients.11 Another study has also questioned the prophylactic plasma and platelet transfusion in the critically Ill patient. They have suggested thromboelastometry based restrictive transfusion management may reduce unnecessary plasma and platelet transfusion, and might reduce the incidence of transfusion-related adverse events and transfusion-associated hospital costs.12

Availability of compact portable ultrasound has been a boon for the anesthesiologist/intensivist facilitating bed side ultrasonography by the non-radiologist. Point of care ultrasound (POCUS) is rapid, accurate, repeatable, inexpensive, noninvasive and without the risk of radiation and thus has became an extension of the clinical examination. The use of POCUS ranges from various bedside diagnostic utility to facilitation of real time guidance for central venous cannulation.13 Some studies show that despite a strong level of evidence and recommendations for using ultrasound guidance during CVC placement and availability of USG in all the units, only half of CVC insertions were ultrasound-guided. They concluded that compliance with this recommendation needs to be improved.14 POCUS should be included in the teaching courses of residents in anesthesiology and critical care. On the basis of our study, the usual practice of pre-procedural correction of coagulopathy can be questioned. However, being a pilot study, our study has the limitation of enrolling only a small number of patients. Larger multi-centric studies need to be performed to test the validity of the findings of this small study.

To conclude, urgent central venous cannulation may be safely performed by an experienced anesthesiologist /intensivist using sonography in coagulopathic critically ill patients.

Acknowledgement:

None

Conflict of Interest:

None

References:

1. Barash PG, Cullen BF, Stoelting RK, Cahalan MK, Stock MC. Clinical anesthesia. 6th ed. Philadelphia: Lippincott Williams & Wilkins; 2009.

2. Reusz G, Langer C, Egervari G, Sarkany P, Csomos A. Safety of ultrasound-guided central venous access in critically ill patients with uncorrected coagulopathy. Critical Care 2013;17(Suppl 2):P173.

3. Agarwal A, Singh DK, Singh AP. Ultrasonography: a novel approach to central venous cannulation. Indian J Crit Care Med 2009;13:213-6.

4. Miller RD, Eriksson LI, Fliesher LA, Wiener-Kronish JP, Young WL. Miller's Anesthesia. 7th ed. Philadelphia: Churchill Livingstone; 2009

5. Mumtaz H, Williams V, Hauer-Jensen M, Rowe M, Henry-Tillman RS, Heaton K, et al. Central venous catheter placement in patients with disorders of hemostasis. Am J Surg 2000;180:503-5.

6. Segal JB, Dzik WH. Paucity of studies to support that abnormal coagulation test results predict bleeding in the setting of invasive procedures: an evidence-based review. Transfusion 2005;45:1413-25.

7. Doerfler ME, Kaufman B, Goldenberg AS. Central venous catheter placement in patients with disorders of hemostasis. Chest 1996;110:185-8.

8. Slichter SJ. Relationship between platelet count and bleeding risk in thrombocytopenic patients.Transfus Med Rev 2004;18:153-67.

9. Zeidler K, Arn K, Senn O, Schanz U, Stussi G. Optimal preprocedural platelet transfusion threshold for central venous catheter insertions in patients with thrombocytopenia. Transfusion 2011;51:2269-76.

10. Weigand K, Encke J, Meyer FJ, Hinkel UP, Munder M, Stremmel W, et al. Low levels of prothrombin time (INR) and platelets do not increase the risk of significant bleeding when placing central venous catheters. Med Klin (Munich) 2009;104:331–5.

11. Singh SA, Sharma S, Singh A, Singh AK, Sharma U, Bhadoria AS. The safety of ultrasound guided central venous cannulation in patients with liver disease. Saudi J Anaesth 2015;9:155–60.

12. Gorlinger K, Saner FH.Prophylactic plasma and platelet transfusion in the critically ill patient:just useless and expensive or even harmful? BMC Anesthesiol 2015;15:86.

13. Abu-Zidan FM. Point-of-care ultrasound in critically ill patients: Where do we stand? J Emerg Trauma Shock 2012;5:70–1.

14. Zieleskiewicz L, Muller L, Lakhal K, Meresse Z, Arbelot C, Bertrand PM, et al. Point-of-care ultrasound in intensive care units: assessment of 1073 procedures in a multicentric, prospective, observational study. Intensive Care Med 2015;41:1638–47.

87

Discussion:

Cannulation of a large central vein is the standard clinical method for monitoring central venous pressure and is also performed for a number of additional therapeutic interventions, such as providing secure vascular access for the administration of vasoactive drugs or to initiate rapid fluid resuscitation. Frequently, the central venous location is the only site available for intravenous access.4 Due to the spectrum of usage of the central venous catheter, its requirement is increasing in medical practice. Sometimes coagulation disorders are present in patients with indication of central venous cannulation. Coagulation disorders pose a challenge as there are increased chances of complications like hemorrhage from the insertion site, hematoma formation and hemothorax. Usually, correction of coagulopathy is sought before the procedure. However, it is unclear whether fresh frozen plasma (FFP), platelet concentrate or platelet rich plasma (PRP) should be administered prior to attempted catheterization when coagulopathy is not severe. Although correction of coagulopathy may be possible, it may not be beneficial, it may be impossible to administer the corrective transfusion factor owing to lack of venous access or the condition may not be correctable by transfusion alone.5

Each year several million units of fresh-frozen plasma (FFP) are transfused all over the world. Recent data demonstrate that annual FFP usage has been steadily rising. Much of the plasma that is administered is used for the purpose of correcting coagulopathy before performing an invasive diagnostic procedure. This practice appears to be common despite the fact that most consensus guidelines do not recommend FFP for this indication when the coagulopathy is not severe. This practice exposes patients to the complications associated with transfusion of blood products and is costly. Furthermore, it promotes the use of pre-procedural laboratory testing, which also has costs and may unnecessarily delay the procedures. It can also lead to fluid overload in certain group of patients. The supposition underlying these transfusions is that even a mildly elevated INR is associated with excessive bleeding in the setting of an invasive procedure and that an intervention is needed for safety.6 In our study we came across no major complication in any of the cases with coagulopathy. Occurrence of minor complications was significant when the INR was more than 3 in patients with platelet count more than 50,000.


The mean platelet count of patients having minor complications (provided that the INR<1.50) was found to be 27428 (95% CI: 19428-36000). In our study we found that minor complications were significant when the platelets count was below 27,000 in presence of normal INR. Doerfler et al also had similar results. They have mentioned that central venous cannulation can be done safely by a skilled clinician even in patients with hemostasis problems and complications were encountered only when the platelet count was below 6000.7 Slichter et al suggested that attention should be focused on providing aggressive platelet therapy for active bleeding rather than transfusing platelets prophylactically. Therapeutic platelet transfusions have been documented to control bleeding, and mortality rates are not increased when comparing patients receiving therapeutic to that seen in patients receiving prophylactic platelet transfusions.8 Zeidler et al have mentioned that the risk of non-severe bleeding was increased only in patients with platelet counts below 20000, but not with platelet counts between 20000 and 49000. They have suggested pre-procedural platelet transfusions only in patients with platelet counts below 20000.9 Weigand et al have also concluded from their study that transfusion of blood products prior to CVC insertion is not necessary in most cases. A delay of CVC insertion waiting for blood products seems to be unjustified, particularly in view of complication rates.10 Another study has concluded that ultrasound guided central venous cannulation in patients with liver disease and coagulopathy is a safe and is a highly successful modality. In their study, mean INR was 2.17 ± 1.16 whereas median platelet count was 149.5 (range 12-683) × 109/L. No major vascular or non-vascular complications were recorded in their patients.11 Another study has also questioned the prophylactic plasma and platelet transfusion in the critically Ill patient. They have suggested thromboelastometry based restrictive transfusion management may reduce unnecessary plasma and platelet transfusion, and might reduce the incidence of transfusion-related adverse events and transfusion-associated hospital costs.12

Availability of compact portable ultrasound has been a boon for the anesthesiologist/intensivist facilitating bed side ultrasonography by the non-radiologist. Point of care ultrasound (POCUS) is rapid, accurate, repeatable, inexpensive, noninvasive and without the risk of radiation and thus has became an extension of the clinical examination. The use of POCUS ranges from various bedside diagnostic utility to facilitation of real time guidance for central venous cannulation.13 Some studies show that despite a strong level of evidence and recommendations for using ultrasound guidance during CVC placement and availability of USG in all the units, only half of CVC insertions were ultrasound-guided. They concluded that compliance with this recommendation needs to be improved.14 POCUS should be included in the teaching courses of residents in anesthesiology and critical care. On the basis of our study, the usual practice of pre-procedural correction of coagulopathy can be questioned. However, being a pilot study, our study has the limitation of enrolling only a small number of patients. Larger multi-centric studies need to be performed to test the validity of the findings of this small study.

To conclude, urgent central venous cannulation may be safely performed by an experienced anesthesiologist /intensivist using sonography in coagulopathic critically ill patients.

Acknowledgement:

None

Conflict of Interest:

None

References:

1. Barash PG, Cullen BF, Stoelting RK, Cahalan MK, Stock MC. Clinical anesthesia. 6th ed. Philadelphia: Lippincott Williams & Wilkins; 2009.

2. Reusz G, Langer C, Egervari G, Sarkany P, Csomos A. Safety of ultrasound-guided central venous access in critically ill patients with uncorrected coagulopathy. Critical Care 2013;17(Suppl 2):P173.

3. Agarwal A, Singh DK, Singh AP. Ultrasonography: a novel approach to central venous cannulation. Indian J Crit Care Med 2009;13:213-6.

4. Miller RD, Eriksson LI, Fliesher LA, Wiener-Kronish JP, Young WL. Miller's Anesthesia. 7th ed. Philadelphia: Churchill Livingstone; 2009

5. Mumtaz H, Williams V, Hauer-Jensen M, Rowe M, Henry-Tillman RS, Heaton K, et al. Central venous catheter placement in patients with disorders of hemostasis. Am J Surg 2000;180:503-5.

6. Segal JB, Dzik WH. Paucity of studies to support that abnormal coagulation test results predict bleeding in the setting of invasive procedures: an evidence-based review. Transfusion 2005;45:1413-25.

7. Doerfler ME, Kaufman B, Goldenberg AS. Central venous catheter placement in patients with disorders of hemostasis. Chest 1996;110:185-8.

8. Slichter SJ. Relationship between platelet count and bleeding risk in thrombocytopenic patients.Transfus Med Rev 2004;18:153-67.

9. Zeidler K, Arn K, Senn O, Schanz U, Stussi G. Optimal preprocedural platelet transfusion threshold for central venous catheter insertions in patients with thrombocytopenia. Transfusion 2011;51:2269-76.

10. Weigand K, Encke J, Meyer FJ, Hinkel UP, Munder M, Stremmel W, et al. Low levels of prothrombin time (INR) and platelets do not increase the risk of significant bleeding when placing central venous catheters. Med Klin (Munich) 2009;104:331–5.

11. Singh SA, Sharma S, Singh A, Singh AK, Sharma U, Bhadoria AS. The safety of ultrasound guided central venous cannulation in patients with liver disease. Saudi J Anaesth 2015;9:155–60.

12. Gorlinger K, Saner FH.Prophylactic plasma and platelet transfusion in the critically ill patient:just useless and expensive or even harmful? BMC Anesthesiol 2015;15:86.

13. Abu-Zidan FM. Point-of-care ultrasound in critically ill patients: Where do we stand? J Emerg Trauma Shock 2012;5:70–1.

14. Zieleskiewicz L, Muller L, Lakhal K, Meresse Z, Arbelot C, Bertrand PM, et al. Point-of-care ultrasound in intensive care units: assessment of 1073 procedures in a multicentric, prospective, observational study. Intensive Care Med 2015;41:1638–47.

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Introduction :

Cardiac Troponin (I or T) is highly sensitive and specific biomarker of myocardial Injury. The Joint ESC / ACCF / AHA / WHF Task Force for the third universal definition of Myocardial Infarction(MI) includes cardiac troponin as an essential component.1 Myocardial infarction is defined as detection and/or fall of cardiac troponin with at least one

1. Dr. Shihan Mahmud Redwanul Huq. MBBS, MRCP (UK). Specialist, ICU. Square Hospitals Ltd. Dhaka, Bangladesh.

2. Dr. Ahmad Mursel Anam. MBBS, MRCP (UK). Specialist, ICU. Square Hospitals Ltd. Dhaka, Bangladesh.

3. Dr. Jamia Ahmad. MBBS. RMO-ICU. Square Hospitals Ltd. Dhaka, Bangladesh.

4. Dr. Raihan Rabbani, MBBS, FCPS (Medicine), Board certified USA. Consultant, Medicine & ICU. Square Hospitals Ltd. Dhaka, Bangladesh.

5. Dr. Mirza Nazim Uddin, MBBS, MRCP. Consultant, Medicine & ICU; and Director. Square Hospitals Ltd. Dhaka, Bangladesh.

6. Dr. Mohammad Mufizul Islam Polash, MBBS, Clinical Staff. ICU. Square Hospitals Ltd. Dhaka, Bangladesh.

7. Dr. Shahzadi Sayeeda Tun Nessa, MBBS, Clinical Staff. ICU. Square Hospitals Ltd. Dhaka, Bangladesh.


Dr. Shihan Mahmud Redwanul HuqMBBS, MRCP (UK)Specialist- ICU Square Hospitals Ltd. 18/F B.U.Kazi Nuruzzaman Sarak, West PanthapathDhaka, Bangladesh.Email: [email protected]

value above the 99th percentile of the upper reference limit, together with evidence of myocardial ischaemia, with at least one of the following: (a) symptoms of ischemia (e.g. chest pain); (b) electrocardiographic evidence of ischemia; (c) imaging evidence of new loss of viable myocardium or new regional wall motion abnormality (d) Intracoronary thrombus identified by angiography or autopsy.1 However, troponin I is not specific for acute thrombotic occlusion of coronary artery. Rather, it can be elevated in myocardial injury secondary to non coronary causes (table I) including sepsis or septic shock. Serum Troponin is frequently requested in intensive care unit to exclude any cardiac component in patients who are presented with shock or arrhythmia or acute heart failure. Moreover, critically ill patients often cannot communicate classical symptoms of acute coronary syndrome like chest pain, may be due to sedation or ventilation or acute confusional state etc. Several studies show rise of troponin is very common (up to 85%) in critically ill patients,2,3 without evidence of significant coronary artery disease however, associated with worse prognosis.2-11 The aim of the present study is to detect the frequency of myocardial ischemia or non ST elevation MI on the basis of echocardiography in critically ill patients with septic shock who presented with elevated Troponin I where symptoms and electrocardiography (ECG) were not suggestive of ischemia as well as any association of raised troponin with mortality.

Original Article

Frequency of Myocardial Ischaemia and Mortality in Septic Shock with Elevated Cardiac TroponinShihan Mahmud Redwanul Huq1, Ahmad Mursel Anam2, Jamia Ahmad3, Raihan Rabbani4, Mirza Nazim Uddin5, Mohammad Mufizul Islam Polash6, Shahzadi Sayeeda Tun Nessa7

Abstract

Background & Aim: Cardiac Troponin I is a sensitive and specific biomarker of myocardial injury, however, it can be elevated in non cardiac conditions. Our aim was to detect the frequency of myocardial infarction (non ST elevation MI) on the basis of echocardiography in critically ill patients with septic shock presented with elevated Troponin I where symptoms and electrocardiography (ECG) were not suggestive of ischemia and any association with mortality.

Methods: A prospective observational study including 85 patients with septic shock in intensive care unit (ICU) of a tertiary hospital in Bangladesh, from March, 2017 to September, 2017.

Results: Out of 85 patients 72 (84.7%) had elevated Troponin I. out of 72 only 38 (52.8%) had regional wall motion abnormality and 36 (50%) had left ventricular ejection fraction below 50 %. There was significant correlation between raised troponin I and low ejection fraction (p-value .00). Elevated troponin I along with left ventricular systolic dysfunction was significantly associated with in-hospital mortality (p-value 0.026).

Conclusion: Around half of the patients with elevated Troponin I had echocardiography evidence of myocardial ischemia. To identify true frequency of myocardial infarction, optimise treatment and predict mortality, cardiac imaging in ICU should be a routine.

Key words: cardiac biomarkers, critical care, sepsis, shock, troponin.

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Table 1: Non-Ischemic causes of Troponin I elevation 12

• Pulmonary embolism

• Acute heart failure

• Tachyarrhythmias

• Acute aortic dissection

• Hypotension / Shock

• Peri-myocarditis (Septic cardiomyopathy)

• Endocarditis

• Tako-tsubo or stress cardiomyopathy

• Radiofrequency catheter ablation

• Sepsis

• ARDS

• Stroke (Infarction ,SAH)

• Renal Failure

• Strenuous exercise

• Sympathomimetic drugs

• Chemotherapy

Table II: Association between Troponin I and Echocardiography findings

Troponin I Regional wall motion abnormality (RWMA) Left ventricular Ejection Fraction (LVEF)

Absent Present Chi -square p-value (2- sided) EF<50% EF 55% or more Chi-square p-value (2-sided)

Normal 11 2 0 13

(<0.03) 6.180 0.013 11.276 0.001

Elevated 34 38 36 36

p-value<0.05 considered significant.

Table III: Comparing means of variables between survivor and non-survivor

Continuous Survivor Non-survivor p-value 95%Confidence Interval of the Difference

variable (n=45) (n=40) (2-tailed)

Mean SD Mean SD Lower Upper

Age 59.84 17.70 64.15 16.39 0.250 -11.69 3.08

Troponin I 2.62 6.85 4.45 9.05 0.293 -5.27 1.60

EF% 49 7.80 45.13 9.50 0.042 0.138 7.61

Figure 1: Various clinical entities associated with Troponin elevation 1

Methods:A prospective observational study was done in intensive care unit (ICU) of Square Hospitals Ltd., a tertiary care hospital in Bangladesh, from March, 2017 to September, 2017 and the

study included 85 adult patients diagnosed as septic shock. Patients with ECG evidence of ST elevation MI were excluded from the study. Serum Troponin I was measured at least once (cut of value used was <0.034 ng/ml). Bedside colour Doppler echocardiography was performed by expert cardiologists. Data analysis was done by SPSS IBM 22. Consents were taken from the patients or next of kin.

Results:

Out of 85 patients, 54 (63.5%) were male and 31 (36.5%) female; age was between 22 to 90 years, 52 (61.2%) were elderly (> 60yrs) . Troponin I elevated in 72 (84.7%) and normal in 13 (15.3%). Among 72 patients 38 (52.8%) had RWMA (regional wall motion abnormality). Among 72 patients 36 (50%) had left ventricular systolic dysfunction that is ejection fraction (EF ) below 50%.There was significant correlation between raised troponin I and low ejection fraction (p-value .00). Elevated troponin I along with left ventricular systolic dysfunction was significantly associated with in-hospital mortality (p-value 0.026).

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Discussion:

Sepsis is defined as a life-threatening organ dysfunction caused by a dysregulated host response to infection. Septic shock is a subset of sepsis in which profound circulatory, cellular and metabolic abnormalities are associated with a greater risk of mortality than with sepsis Alone.13 Troponin elevation is common in septic shock patients, and it was estimated that 43–85 % of patients with sepsis showed cardiac troponin I elevation 2-4,12 and associated with short and long term mortality and increased length of stay at hospital. Possible mechanisms are the following; 1) Tachycardia, hypoxemia ,hypotension, decreased perfusion pressure, anemia etc.are commonly observed in sepsis which may lead to increased oxygen demand or decreased supply causing cardiac ischemia. 2) Cytokine & endotoxin released in sepsis or septic shock causes microvascular dysfunction, myocardial depression, myocarditis. 3) Free radicals cause myocardial cell damage & Apoptosis. Moreover, 4) Left ventricular diastolic & right ventricular systolic dysfunction found in septic shock may contribute to elevated troponin level.4,15,16 In our study we found that around half of the patients with elevated Troponin I had echocardiography evidence of RWMA (regional wall motion abnormality) & left ventricular systolic dysfunction (EF% below 50%) suggestive of myocardial ischemia or non ST elevation MI. However, sepsis-induced cardiomyopathy is another possibility which is global ventricular dysfunction and typically reverses in a week.17 Advanced imaging like myocardial contrast echocardiography18 may be used to differentiate these which was not available in our ICU. Troponin rise in rest of the patients was due to non coronary causes which is often called as Troponin Leak. No patient with normal troponin I had systolic dysfunction evidenced by Echocardiography. Elevation of troponin I significantly correlates with low left ventricular ejection fraction. Raised troponin I with systolic dysfunction together is significantly associated with increased in-hospital mortality rather than elevated troponin alone. Elevated troponin in sepsis or septic shock with MODS (Multi organ dysfunction syndrome) is also associated with increased mortality.

Conclusion:

Sepsis or septic shock may elevate serum troponin I in almost half of the critically ill patients who doesn’t have any evidence of myocardial ischemia or infarction. Therefore, to identify myocardial infarction (Non ST elevation MI), optimise treatment and predict mortality in intensive care unit, bedside echocardiography is a must. Further research is needed to differentiate non ST elevation MI in septic shock and sepsis-induced cardiomyopathy or stress cardiomyopathy by applying myocardial contrast echocardiography17,18 or simply repeating 2 D echocardiography.

References:1. Thygesen K, Alpert JS, White HD; Joint ESC/ACCF/AHA/WHF

Task Force for the Redefinition of Myocardial Infarction. Universal definition of myocardial infarction. Eur Heart J 2007; 28: 2525–38.

2. Ammann P, Fehr T, Minder EI, et al. Elevation of troponin I in sepsis and septic shock. Intensive Care Med 2001; 27: 965–9.

3. Bessiere F, Khenifer S, Dubourg J, et al. Prognostic value of troponins in sepsis: a meta-analysis. Intensive Care Med 2013; 39: 1181–9

4. Zochios V, Valchano K. Raised cardiac troponin in intensive care patients with sepsis, in the absence of angiographically documented coronary artery disease. Journal of the Intensive Care Society 2015, Vol. 16(1): 52–7.

5. Ammann P, Maggiorini M, Bertel O, et al. Troponin as a risk factor for mortality in critically ill patients without acute coronary syndromes. J Am Coll Cardiol 2003; 41: 2004–9.

6. Lim W, Qushmaq I, Devereaux PJ, et al. Elevated cardiac troponin measurements in critically ill patients. Arch Intern Med 2006; 166: 2446–54.

7. Arlati S, Brenna S, Prencipe L, et al. Myocardial necrosis in ICU patients with acute non-cardiac disease: a prospective study. Intensive Care Med 2000; 26: 31–7.

8. Altmann DR, Korte W, Maeder MT, et al. Elevated cardiac troponin I in sepsis and septic shock: no evidence for thrombus associated myocardial necrosis. PLoS One 2010; 5: e9017.

9. Vasile VC, Chai HS, Abdeldayem D, et al. Elevated cardiac troponin T levels in critically ill patients with sepsis. Am J Med 2013; 126: 1114–21.

10. Tiruvoipati R, Sultana N Lewis D. Cardiac troponin I does not independently predict mortality in critically ill patients with severe sepsis. Emerg Med Australas 2012; 24: 151–8.

11. John J, Woodward DB, Wang Y, et al. Troponin-I as a prognosticator of mortality in severe sepsis patients. J Crit Care 2010; 25: 270–5.

12. S. Agewall, E. Giannitsis, T. Jernberg et al.Troponin elevation in coronary vs. non-coronary disease.European Heart Journal (2011) 32, 404–11. doi:10.1093/eurheartj/ehq456.

13. Singer M, Deutschman CS, Seymour CW, et al.The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA. 2016; 315(8):801-10. doi:10.1001/ jama. 2016. 0287.

14. Vallabhajosyula S, Sakhuja A, Geske JB et al.Role of Admission Troponin-T and Serial Troponin-T Testing in Predicting Outcomes in Severe Sepsis and Septic shock J Am Heart Assoc 2017;6:e005930. DOI: 10.1161/JAHA.117.005930.

15. Hussain N. Elevated cardiac troponins in setting of systemic inflammatory response syndrome, sepsis, and septic shock. ISRN Cardiol 2013; 2013: 1–7.

16. Klouche K, Pommet S, Amigues L et al. Plasma brain natriuretic peptide and troponin levels in severe sepsis and septic shock: relationships with systolic myocardial dysfunction and intensive care unit mortality. J Intensive Care Med. 2014; 29:229–37.

17. Sato R,Nasu M. A review of sepsis-induced cardiomyopathy. Journal of Intensive Care (2015) 3: DOI 10.1186/ s40560 - 015 - 0112-5

18. Orde S, McLean A. Bedside myocardial perfusion assessment with contrast echocardiography. Critical Care 2016; 20:58. doi: 10.1186/ s13054-016-1215-7.

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Introduction:

Acute cholecystitis (AC) and its complications remain among most common surgical condition which require emergency hospitalization. These patients are commonly treated initially

1. Dr. Md. Ezharul Haque Ratan, MS (General Surgery), Associate Professor, Surgery, Ibrahim Medical College and BIRDEM General Hospital, Dhaka

2. Dr. Hasina Alam, FCPS (General Surgery), Registrar Surgery, Ibrahim Medical College and BIRDEM General Hospital, Dhaka

Corresponding Author :

Dr. Md. Ezharul Haque RatanAssociate Professor, SurgeryIbrahim Medical College and BIRDEM General HospitalRoom no-445, BIRDEM General HospitalShahbagh, Dhaka-1000, BangladeshEmail: [email protected]

non-operatively followed by delayed surgery six weeks or longer after acute event has subsided 1. Recently, there have been significant paradigm shifts in management of such cases to early surgery at same admission with the advantage of reduced length of stay (LOS) in hospital while complications rate remain the same 2. Moreover, conservative management is not always successful. About one fifth of the cases, who were waiting for delayed surgery, had persistent symptoms or developed another acute attack requiring intervention before planned operation 3.

Controversy persists regarding the optimal timing for intervention in AC. Some follow the policy of emergency surgery in 24-96 hours after onset of symptoms while others suggest early surgery in acute phase within 3 days after admission and still others define ‘early’ as ranging from 24 hours to 7 days from diagnosis or onset of symptoms 4,5. The Tokyo guidelines of the Japanese society of hepatobiliary pancreatic surgery suggested that emergency

Original Article

Early Laparoscopic Cholecystectomy in acute cholecystitis and its sequlae- Experience in tertiary care hospitalMd Ezharul Haque Ratan1, Hasina Alam2

Abstract

Background: Acute cholecystitis (AC) is a common surgical condition requiring emergency hospitalization. Traditionally, these patients were treated conservatively, followed by delayed surgery six weeks or longer after acute event has subsided. Recently, early emergency cholecystectomy at same admission is suggested. This has the advantage of reduced length of stay (LOS) in hospital without any significant increase in complication rate. Moreover, conservative management is not always successful. We are here, observing the feasibility of emergency cholecystectomy in practical setting.

Method: Between March 2008 and March 2017, 483 patients were admitted in a surgical unit of BIRDEM general hospital with thediagnosis of acute cholecystitis or its complications. The patients were assessed clinically with laboratory and imaging investigations. We planned early laparoscopic cholecystectomy (ELC) in all case, as soon as assessment and resuscitation were completed, irrespective of duration from symptom onset. Cases were analyzed for gender, age, operation time, volume of blood loss, conversion to open surgery, post-operative complication and length of hospital stay.

Results: A total of 483 patients with AC and its sequlae were admitted, between March 2008 and March 2017 in a single unit of a tertiary care hospital which deals most of the diabetic patients of the country. Among them 477 patients were treated with emergency or urgent laparoscopic cholecystectomy (LC). The earlier the patient presented for surgery and those who were treated with antibiotics were easier to operate. Incidence of gangrene and perforation were more among those with acalculus cholecystitis. Surgical procedures were the most difficult in those presented beyond two weeks of symptom onset. Consequently operation time was over 100 minutes and blood loss was more than 250 ml in such cases. Fortunately none required conversion to open procedure. Subhepatic drain were used in 17 cases. Subcutaneous simple tube drain in umbilical port was used in those with gangrene, perforation and transmural gall bladder wall pyogenic infection. Consequently umbilical port infection were very low (3cases, 0.6%). One patient presented with subhepatic fluid collection, 6 weeks after emergency LC. Laparotomy was done and found to have altered blood and pseudo-aneurysm of cystic artery (chronic blood loss from one of its lateral twig). Length of stay (LOS) in hospital were short (mean-1.8 days, range: 20 hours-4 days) except those with bile leak (5, 8 and 9 days respectively). None of the cases had bile duct injury or uncontrolled bleeding. There was no mortality in this series.

Conclusion: Early laparoscopic cholecystectomy (ELC)has proved to be an effective and safe day case surgical procedure for AC and their complications. It provides much benefits with low complication and conversion in experienced hands.

Key words: Laparoscopic cholecystectomy (LC), early laparoscopic cholecystectomy (ELC), delayed laparoscopic cholecystectomy (DLC), Acute cholecystitis (AC), Length of stay (LOS).

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cholecystectomy was indicated for patients with symptoms within 72 hours while that of the national institute for health and care excellence (NICE) recommended that AC should be treated within seven days of diagnosis7.

While accepting early surgery for AC, consensus is still lacking regarding technical aspects, whether open or laparoscopic cholecystectomy is to be done. 48.7% of AC are operated with the open technique considering presence of inflammation, oedema, necrosis and adhesion are unfavorable for safe dissection2. Some literature and Tokyo guideline 2013 have shown concern about supposedly higher mortality rates in emergency laparoscopic cholecystectomy (AL) in AC. According to some author, conversion rate to open procedure is also higher during LC in acute phase8, 9. On the other hand, some randomized controlled trials10-13 and meta-analysis14-16

recommended acute phase LC with the advantage of fewer complications, less operative blood loss and shorter post-operative LOS6. Gonzalez Rodrigueg FJ et al considered urgent LC 72 hours after onset of symptoms to be difficult and associated with higher risk of complications16. While some studies found no difference in conversion rate, morbidity and LOS between patients with symptoms less or more than 72 hours.

Many of our patients present late due to financial or personal constrains, delayed diagnosis, received treatmentin another hospital, ignorance and fear of operation. Delay also occurs due to failed conservative management, recurrent symptoms before planned operation or delay due to optimization of medical condition for possible safe anaesthesia .Whatever may be the cause of delay, progressive inflammation may lead to complication like gangrene and perforation of the gallbladder and pericholecystic abscess formation compelling urgent surgery. The feasibility and safety of LC for AC and its sequlae after 7 days of symptom onset in patients who were unable to receive earlier surgery are unclear. This retrospective study was aimed to observe the feasibility and safety of emergency and urgent LC in AC and its sequlae during persisting symptom in same admission.

Materials and methods

Between March 2008 and March 2017, 483 patients were admitted in a surgical unit of BIRDEM general hospital with a diagnosis of acute cholecystectomy or its complications. The patients were assessed clinically (murphy’s sign or right upper quadrant abdominal pain or tenderness or mass & fever) with laboratory tests (leukocytosis, liver & pancreatic enzymes) and imaging (ultrasound examination and computed tomography in selected cases). Diagnostic and/or therapeutic endoscopic retrograde cholangiopancreatography (ERCP) was done in those with suspected biliary tree stone or pathology. We planned laparoscopic cholecystectomy in all cases as soon as assessment and resuscitation were completed irrespective of duration from symptom onset. Surgery was delayed in seven patients for five days after antiplatelet agent has stopped or for ERCP. Six patients were excluded from this study as their surgery was due to high risk for emergency surgery (poor general, cardiac, renal function, or recent

stroke). Emergency LC was done in rest of the patients (477), by a single attending surgeon using standard four port technique. Carbon dioxide was used for peritoneal insufflation maintaining a pressure between 10 and 12 mmHg. The gallbladder was decompressed by aspirating its contents. The cystic artery and duct were skeletonized and sealed using hem-o-lock individually. Cystic duct was ligated or transfixed with 1-0 vicryl in selected cases (wide and /or fragile). Saline irrigation was done in all cases. A subhepatic tube drain was placed in those with perforated or gangrenous cholecystitis or pericholecystic abscess. Gallbladder were removed through umbilical port. Those having gangrene, perforation, transmural infection or spillage of stone were placed in ‘glove-bag’ before removal. Histopathological examination of resected gall bladder was routinely performed to confirm acute cholecystitis. Cases were analyzed for gender, age, operation time, volume of blood loss, conversion to open surgery, post-operative complication and length of hospital stay. Operation time was defined as beginning with skin incision and ending when dressing has been placed over ports.

Results

A total of 483 patients with AC and its sequlae were admitted, between March 2008 and March 2017 in a single unit of a tertiary care hospital which deals most of the diabetic patients of the country. Among them 477 patients were treated with emergency or urgent laparoscopic cholecystectomy. As most of the cases were evaluated in emergency or outpatient department, preoperative hospital stay were only few hours for resuscitation except inpatient referred cases, those required ERCP, acute pancreatitis, or anti-platelet drugs. Patients demographics are shown in Table I. the ASA scores of the patients were classified as 1E (n=81, 17%), 2E (n=181, 59%) and 3E (n=115, 24%). Table-2 shows clinical characteristics of the patients. The patient numbers underwent LC on the days after symptom onset were as follows- 23(day 0), 47 (day 1), 71 (day 2), 76 (day 3), 63 (day 4), 55 (day 5), 47 (day 6), 33 (day 7), 44 (day 8-14), 18 (day 15 and beyond). Operative findings of the patients are demonstrated in Table 3. The earlier the patient presented for surgery and those who were treated with antibiotics were easier to operate. Incidence of gangrene and perforation were more among those with acalculus cholecystitis. Among six patients with acute pancreatitis, two were in ICU for initial days of management and surgery were done one day after stepping down to ward or cabin. Surgical procedures were the most difficult in those presented beyond two weeks of symptom onset. Consequently operation time was over 100 minutes and blood loss was more than 250 ml in such cases (Table 4). Fortunately none required conversion to open procedure. Subhepatic drain were used in 17 cases, most of which were removed 2-3 days postoperatively except three, who had bile leak due to total gangrene of gall bladder and cystic duct. Bile discharge dried up in 4th, 7th and 9th post-operative day respectively. Subcutaneous simple tube drain in umbilical port was used in those with gangrene, perforation and transmural gall bladder wall pyogenic infection ; removed in first follow up on 7th post-operative day, consequently

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umbilical port infectionwere very low (3 cases, 0.6%) . One patient presented with subhepatic fluid collection, 6 weeks after emergency LC. Laparotomy was done and found to have altered blood and pseudo-aneurysm of cystic artery (chronic blood loss from one of its lateral twig). Length of stay (LOS) in hospital were short (mean-1.8 days, range: 20 hours-4 days) except those with bile leak (5, 8 and 9 days respectively). None of the cases had bile duct injury or uncontrolled bleeding. There was no mortality in this series.

Discussion

Early LC (emergency, urgent, expedited) is a feasible treatment option in patients with AC1. Gall stone related complications develop in 1-4% of patients per year such as AC. Since pre-laparoscopic era early surgery has shown advantage in terms of hospital stay and reoperation time2. Modern trend is towards an increased rate of early laparoscopic cholecystectomy (ELC) for AC. But the exact time point of ELC in AC is still a matter of debate. Tokyo Guidelines 2013 preferred to perform LC within 72 hours of symptom onset6, whereas NICE recommended LC in AC within 7 days of diagnosis7. Till now there is no published document on LC beyond 7 days of onset of AC. We have treated all of our patients (except 6 out of 483, 1.2%) who presented with AC or its sequlae irrespective of its severity, time of appearance from symptom onset and treatment received. All these cases were analyzed retrospectively for efficacy and safety of urgent LC during acute phase. We did not require any conversion during operation. Some author considered potentially serious complications and conversion rates were higher in early LC in AC17, 18. But facts are changing with time and expertise. A meta-analysis demonstrated a reduction in overall mortality rate with LC in AC performed in the same admission and so was the mortality rate2. LC in late phase of AC (4-7 days) till 2004 was reported to have higher conversion rate to open surgery while recent studies revealed equivalent hospital stay and lower conversion rate among recent studies of 3% in early phase and 8% in late phase of AC1. In one of our study including all cases of LC, we found that chronic symptom in elderly male and fibrosed contracted GB at imaging (USG or CT scan) were independent predictors of procedure conversion during LC. They concluded that ELC in late phase is superior to delayed laparoscopic cholecystectomy (DLC)6-8 weeks after AC subsided with conservative treatment. One study from UK demonstrated that a third of their patients were readmitted with recurrent symptoms often more than once while awaiting for DLC 7.

We operated most of our cases within 24 hours after admission. As expected, we found that severity of AC increases with time from its onset, thickening and hardening of GB wall leads to difficulty in handling and dissection with conventional instruments, neovascularization increased blood loss from adhesions associated GB surface. The sooner the LC is attempted, the easier and less time consuming with least bleeding- the procedure can be accomplished. Pericholecystic oedema creates an easy dissection plain especially in those who received antibiotics. These facts increased operation time but did not increase perioperative complication or hospital

stay. Meta-analysis found that bile leak rate had no relation with technique (open or laparoscopy). Severity of bleeding in AC, treated either by open or laparoscopy, was not significantly different2. It also confirmed reduced mortality, morbidity and post-operative hospital stay without increasing the operation time, reduced operative haemorrhage rates, less expensive, and resulted in better quality of life when AC was treated with ELC compared to DLC. Patience, taking time in dissection, keeping operation field as clean as possible by taking care of ‘first drop of blood’, clear identification of structures of the region before division, use of telescope with an angle (we used 450) when needed, were important tricks in successful completion of LC in complicated AC cases.

One of our female patient required readmission and laparotomy, 6 weeks after ERCP followed by LC for common bile duct stone and AC, due to subhepatic fluid collection. Rest of our patients recovered without any intraabdominal consequences. Cases with gangrenous and perforated cholecystitis or per-operative tear of GB with spillage of stones were common in late presented cases which were managed with copious saline irrigation, removal of stone and GB in a ‘glove-bag’ and use of a subhepatic drain, hence outcome was not affected in terms of mortality or LOS in hospital. As we assessed most of our patients before admission, LOS in hospital was much less than other series. The total expenditure of treatment was not documented but a rough overview of cost involvement assessed. Other options of management of AC using antibiotics alone or in combination with percutaneous cholecystectomy followed by DLC were associated with no difference in operative time or conversion rate, but LOS, readmission and costs were higher than ELC19. Strength of the study is that all AC cases, fit and willing to undergo ELC were included, irrespective of severity and duration of disease onset. Weakness of the study is that it is a retrospective study.

Conclusion

Emergency and urgent laparoscopic cholecystectomy in acute cholecystitis and its sequlae appears to be effective and safe at any time during persisting symptoms. It has the benefit of minimum conversion rate, morbidity, mortality and short hospital stay. Technical difficulties of the procedure are proportional to the time of surgery since onset of the symptoms. The procedure in late presenting cases are associated with longer operation time and more blood loss without influencing operative complications.

However large randomized controlled trials are needed to draw a solid conclusion and firm recommendation.

Conflict of interest

None

Funding

None

Ethical approval

Not applicable

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Table-I : Patients' Demographic

March 2008 - March 2017

Total number of patients – 477

Gender– Male – 181 (38%)

Female 296 (62%)

Mean Age- 49.9 years (22-68 years)

Table-II : Clinical characteristics

Clinical features No of patients

ASA 1E - 81(17%)

2E - 181(59%)

3E - 115 (24%)

Time from onset of symptomsto admission -8.2 (0.5-16) days

Murphy's sign/Right upper quadranttenderness or mass -396 (83%)

Tempurature (>370 C) - 267(56%)

USG/CT/MRCP findings -Enlarged distended gall bladder - 324(68%

-Wall thickness - 3.6(2-8mm)

-Pericholecystic oedema - 391((82%)

-Swollen oedematous pancreas - 6 (1.3%)

-Abdominal fluid collection - 6 (1.3%)

Leucocyte count - 13,200 (6700 - 24300)/ cmm

Table-III : Operative findings

Findings No of patients

Simple calculous acute cholecystitis -405 (84.9%)

Acute cholecystitis with dense adhesion -31 (6.5%)

Acalculous acute cholecystitis -17 (3.5%)

Gangranous cholecystitis -12 (2.5%)

Perforated cholecystitis -06 (1.3%)

Gall stone with acute pancreatitis -06 (1.3%)

Table-IV : Outcome of emergency laparoscopic cholecystectomy

Conversion to open surgery nil

Operation time 68 (35-122) minutes

Blood loss 140 (10-350) ml

Use of sub-hepatic drain 19 (4%)

Use of umbilical port drain 54(11.3%)

Complications-

Bile leakage 3(0.6%)

Sub-hepatic fluid collection 1(0.2%)

Wound infection (ports) 3(0.6%)

Length of stay in hospital 1.8days (20hours- 9 days)

Readmission for pain 1(0.2%)

References :

1. Christos S, Omar J, Rahul D, George Z, Nagy H, Emmanouil Z. Is early laparoscopic cholecystectomy for acute cholecystitis preferable to delayed surgery? Int JSurg 2012;10:250-58.

2. Federico C, Fausto C, Michele P, et al. Open versus laparoscopiccholecystectomy in acute cholecystitis. Systematic review and meta-analysis. Int J Surg2015; 18:196-204.

3. Siddiqui T, MacDonald A, Chong PS, Jenkins JT. Early versus delayed laparoscopiccholecystectomy for acute cholecystitis: a meta-analysis of randomized clinical trials. Am J Surg 2008; 195:40-7.

4. Yamashita Y, Takada T, Kawarada Y, et al. Surgical treatment of patientswith acute cholecystitis:Tokyo guidelines. J Hepatobiliary Pancreat Surg 2007;14:91-7.

5. Zhu MW, Gu XD, Xiang JB,Chen ZY. Comparison of clinical safety and outcomes of early versus delayed laparoscopic cholecystectomy for acute cholecystitis: a meta-analysis. Scientific world journal 2014;274516.

6. Shinke G, Noda T, Hatano H, Shimizu J, Hirota M, Takata A, et al. Feasibitity and safety of urgent laparoscopic cholecystectomy for acute cholecystitis after 4 days from symptom onset. J Gastrointest Surg (2015);19:1787-93.

7. Bokhari S, Walsh U, Qurashi K, Liasis L, Watfah J, Sen M, et al. Impact of dedicated emergency surgical unit on early laparoscopic cholecystectomy for acute cholecystitis. Ann R CollSurgEngL (2016);98:107-15.

8. Cheema S, Brannigan AE, Johnson S, Delaney PV. Grace PA, Timing of laparoscopic cholecystectomy in acute cholecystitis. Ir J Med Sci(2003);172:128-31.

9. Livingston EH, Rege R V. A nationwide study of conversion from laparoscopic to open cholecystectomy. Am J Surg (2004); 188:205-211.

10. Lo CM, Liu CL, Fan ST, Lai EC, Wong J. Prospective randomized study of early versus delayed laparoscopiccholecystectomy for acute cholecystitis. Ann Surg(1998);227:461-7.


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11. Laip B, Kwong KH, Leuug KL, Kwok SP, Chan AC, Chung SC, Lauv WY. Randomized trial of early versusdelayedlaparoscopic cholecystectomy for acute cholecystitis, Br J Surg (1998);85:764-7.

12. Chandler CF, Lane JS, Ferguson P, Thompson JE, Ashley SW. Prospective evaluation of early versus delayed laparoscopic cholecystectomy for treatment of acute cholecystitis. Am Surg(2000);66:896-900.

13. Lua H, Lo CY, Patil NG, Yuen WK. Early versus delayed-interval laparoscopic cholecystectomy for acutecholecystitis:A meta-analysis. SurgEndos 2006;35:553-60.

14. Shikata S, NoguchiY, Fukui T. Early versus delayed cholecystectomy for acute cholecystitis:A meta-analysis of randomized controlled trials. Surg Today 2005;35:553-60.

15. Siddidui T, MacDonald A, Chong PS, Jenkins JT. Early versus delayed laparoscopic cholecystectomy for acute cholecystitis:A meta-analysis of randomized clinical trials.Am J Surg 2008;195:40-7.

16. Gurusamy K, Samraj K, Gluud C, Wilson E, Davidson BR. Meta-analysis of randomized controlled trials on the safety and effectiveness of early versus delayed cholecystectomy for acute cholecystitis.Br J Surg 2010;97:141-50.

17. Cuschieri A, Dubbins F, Moulel J,et al. The European experience with laparoscopic cholecystectomy.Am J Surg (1991);161:385-7.

18. Kum CK, Goh PM, Isaac JR, et al. Laparoscopic cholecystectomy for acute cholecystitis. Br J Surg(1994);81(11):1651-4.

19. Feza YK, Aydincan A, Mahir K, Ali H, Yahya E, Gokhan M. Emergency cholecystectomy vs percutaneous cholecystectomy plus delayed cholecystectomy for patients with acute cholecystitis. HepatobiliaryPancreat Dis Int (2014);13:316-22.

20. Gonzalez-Rodriguez FJ, Paredes-Cotore JP, Ponton C, Rojo Y, Flores E, Luis-Calo ES, et al. Early or delayed laparoscopic cholecystectomy in acute cholecystitis? Conclusions of a controlled trial. Hepatogastroenterology(2009);56:11-16.

21. Conlon K. The gallbladder and bile ducts. In Norman SW, Christopher JK Bulstrode, Ronan O’Connell. Bailey and Love’s Short practice of surgery.26th edition. CRC Press: UK; 2013:1097-1117.

22. Danny Rosin. A comparison of laparoscopic cholecystectomy for acute cholecystitis both within and beyond 72 hours of symptom onset during the emergency admission. World J Surg (2012); 36:2659-60.

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Introduction :

Rhabdomyolysis (RM) is a clinical entity characterized by the dissolution of skeletal muscle with resultant release of intracellular enzymatic content into the bloodstream that leads to systemic complications1-3. The classic triad of presentations are limb weakness, muscle pain and dark tea colored urine. Nevertheless, more than half of the patients do not report muscular symptoms. In more severe cases malaise, fever, tachycardia, nausea, and vomiting, may occur. Therefore, elevation of serum creatine kinase (CK), usually, five to ten times above the upper limit of normal is considered as diagnostic.The term “crush syndrome” first described it, in 1941, by Bywaters and co-workers, after the bomb attack in London, which is now used to describe muscle destruction after direct trauma, injury, or compression.2,4 However, non-traumatic causes like sepsis, toxins or drugs are currently more frequently observed.5-7

1. Dr. Shihan Mahmud Redwanul Huq, MRCP (UK). Specialist, ICU,

Square Hospitals Ltd. Dhaka

2. Dr. Ahmad Mursel Anam, MRCP (UK), Specialist, ICU, Square Hospitals Ltd. Dhaka

3. Dr. Raihan Rabbani, FCPS (Medicine), Board certified in Internal Medicine, Consultant, Critical Care & Internal Medicine, Square Hospitals Ltd. Dhaka

4. Dr. Mirza Nazim Uddin, MRCP, Consultant, Critical Care & Internal Medicine, Square Hospitals Ltd. Dhaka

5. Dr. Mohammad Mufizul Islam Polash, MBBS, Clinical Staff, ICU, Square Hospitals Ltd. Dhaka

6. Dr. Shahzadi Sayeeda Tun Nessa, MBBS, Clinical Staff, ICU, Square Hospitals Ltd. Dhaka


Dr. Shihan Mahmud Redwanul HuqSpecialist, ICU, Square Hospitals Ltd.18/F,B.U. Kazi Nuruzzaman SarakWest Panthapath, Dhaka, BangladeshEmail: [email protected]

Acute kidney injury (AKI) is the most potential systemic complication of Rhabdomyolysis. Therefore, preservation of renal function with intravenous fluid therapy remains the key treatment.However,controversy remains regarding the type of fluid, volume, and time of initiation, whether to add bicarbonate or mannitol; whether or when to follow protocolized treatment etc. Management is currently based on observations from retrospective studies, case reports and case series which describe diverse and often parallel medical treatments.2,7-9

Pathophysiology:

The pathogenic pathway includes an increase in free ionized calcium in the cytoplasm (sarcoplasm). The increased cytoplasmic calcium initiates a complex network of intracellular processes, such as the activation of phospholipase A2, prolonged contraction of muscle cells, mitochondrial dysfunction, and production of reactive oxygen species, which eventually promote muscle cell damage and the release of various substances (e.g., myoglobin, creatine phosphokinase, potassium, organic acids, and other enzymes and electrolytes) into the systemic circulation, thereby leading to the clinical manifestation of Rhabdomyolysis.8

Aetiology:

The causes of Rhabdomyolysis have been classified differently by several authors. Here we broadly divide them into three categories (Table 1).McMahon et al.revealed in a large study (n=2371), the most frequently associated conditions were trauma (26%), immobilization (18%), sepsis (10%), vascular surgery (8%) and cardiac surgery (6%).10Alcohol and illicit drugs were the most common causes in another series of 475 patients.11Up to 60% had more than one etiologic factor.1, 3, 10-20

Review Article

Update on Management of Rhabdomyolysis - A ReviewShihan Mahmud Redwanul Huq1, Ahmad Mursel Anam2, Raihan Rabbani3, Mirza Nazim Uddin4, M Mufizul Islam Polash5, Shahzadi Sayeeda Tun Nessa6

Abstract

Rhabdomyolysis is a potentially life threatening syndrome of muscle injury associated with myoglobinuria,electrolyte abnormalities and often acute kidney injury (AKI).The diagnosis is confirmed by elevated creatinine kinase level as symptoms may be non-specific. The management includes prompt hydration, elimination of the causative agents and treatment and prevention of any complications. Many protocols have been practiced but there is a lack of high quality evidence to support these. The aim of this review is to summarize the published literature in last 15 years to have an overview of rhabdomyolysis and management options in both traumatic and non-traumatic causes. Intravenous fluid being the cornerstone of therapy, no controlled trial was found to compare intravenous fluid plus sodium bicarbonate/mannitol to fluid alone. Based on current literature we can conclude that bicarbonate should be administered only if necessary to correct acidosis and mannitol to maintain urine output of 300 ml/h or more despite adequate fluid resuscitation.

Key words: Rhabdomyolysis, Acute kidney injury, Myoglobinuria, Creatinine kinase, Crush syndrome.

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Table I: Causes of Rhabdomyolysis

Multiple traumaTraumatic or compression Crush Injuries eg. car crash, collapsed building Vascular or orthopaedic surgery Struggle against restrain Immobilization High voltage electric injury or BurnNon-traumatic:Exertional NonexertionalExtreme exertion AlcoholEnvironmental heat illness/Heat stroke Drugs and toxins-opioid,amphetamineSickle cell trait Infections-Sepsis, Viral, Bacterial (Legionella, Streptococcus, Salmonella, E.coli, Staphylococcus)Seizures Electrolyte abnormalities (hypokalemia, hypophosphatemia)Hyperkinetic states Metabolic /mitochondrial myopathy Near drowning/hypothermiaNeuroleptic malignant syndrome EndocrinopathiesMalignant hyperthermia Inflammatory myopathies

Table II:Complications of Rhabdomyolysis

• Acute Kidney Injury

• Hyperkalemia

• Hypocalcaemia

• Hepatic inflammation

• Cardiac arrhythmia and cardiac arrest

• Disseminated intravascular coagulation

• Compartment syndrome

Labarotory Work-up:

Serum Creatinine Kinase (CK) is the most sensitive test. CK rises 2 to 12 hours after muscle injury, peaks at 1 to 3 days, and usually declines within 3 to 5 days after muscle injury ceases. Serum and urine myoglobin areless sensitive, short half-life (2–3 hours) and rapidly cleared by renal excretionand metabolism to bilirubin. Positive urine dipstick for blood detects myoglobulinuria in absence of RBCs in urine. A metabolic panel including serum potassium, calcium, phosphorousand renal function should be obtained. The anion gap is often increased more than expected due to phosphates and organic acids released from muscle. A coagulation panel to detect disseminated intravascular coagulation (DIC). An ECG to screen any conduction abnormality or evidence of hyperkalemia (P-Rprolongation, peaked T, widened QRS).A urine drug screen should be done.2,12

Incidence & Risk Factors of AKI:

Incidence ranges from 10 and 55% 1,2,7,9,11. Patients with AKI due to Rhabdomyolysis have three to five times higher mortality than that of patients without AKI (59% versus

22%).Higher CK level indicates greater muscle injury but marginally correlates with the development of AKI or mortality. McMahon and co-workers (2013) recently validated a risk assessment score to predict AKI and mortality.Variables like age >70yrs, female sex, initial creatinine >2.2 mg/dL, initial calcium <7.5 mg /dL, Initial CPK >40000 U/L, initial phosphate >5.4 mg/dL, initial bicarbonate <19 mEq/L predict higher risk of AKI. Another recent study by Rodriguez et al proposed a risk score.CK levels >12,750 IU/L, hypoalbuminemia, metabolic acidosis, and decreased PT<82% had a 98% probability of developing AKI.10,16

Treatment:

The first step in medical intervention is usually treatment of underlying cause,if identified which includes discontinue a potentially harmful drug,control of patients temperature and treat underlying infection or sepsis etc.

IV Fluid Therapy:

Early and aggressive fluid resuscitation is the main intervention for preventing and treating AKI in both traumatic and non-traumatic causes of RM. The goal of volume repletion is to restore renal perfusion and increase the urine flow as in RM Capillary damage and fluid leakage lead to a “functional” dehydration .The evidence is largely based upon studies on traumatic RM or crush injuries but they are believed to be broadly applicable to prevent AKI in non-traumatic causes as well, given their common underlying pathogenesis.9,12,18,22

In Non-traumatic RM, initial fluid resuscitation with isotonic saline,preferably within 6 hours, at a rate of 1 to 2 Lt/hour particularly for those who are at high risk for AKI,usually if CK>5000 U/L. Most studies showed that the risk is low in CK

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below 5000U/L. However, El-Abdellati et al. (2013)25showed AKI due to RM may happen in lower CK 1000 U/L. So, sequential CK measurement is critical in tailoring therapeutic interventions.Moreover, the volume status should be carefully assessed by hemodynamic monitoring devices and fluid is titrated to maintain a urine output 200 to 300 ml/hour until CK falls below 1000 U/L.

On the other hand, in Crush injury more vigorous fluid may be necessary.Gunal et al25showed in crush injury mean volume of fluid was approximately 21 L and started within 3.7(+/- 3.3) hr had better outcome. Irajet al28 found that >6 L fluid in severe RM (>15000 CPK) and 3-6 L in moderate RM(<15000) was effective in reducing AKI in 638 patients with crush injury. Sever MS et al9suggested,isotonic saline should be given @1L/hour (10-15ml/Kg) while the victim is still under the rubble. After 2 Litres are given the rate should be decreased to 500 ml /hour to avoid volume overload. However this volume should be individualized considering age,BMI,trauma pattern, amount of presumed fluid loss or ongoing blood loss,hot climate. Then after extraction, reduce rate @0.5 L/hour for 6 hours and re-assess urine output. By this time 3 to 6 L fluid should be given. If victim is anuric adjust fluid as 0.5 to 1 L/day plus losses of previous day. Generally, up to 12 L can be given safely if urine output is 300ml/hr whereas, in elderly or heart failure 3-6 L supposed to be optimum. Here is a flow chart used for giving fluid in crush injury victims.

Figure 1: Flow chart -Fluid therapy in Crush Injury

Adapted from Sever MS et al. 20129

Bicarbonate:The rationale of using sodium bicarbonate is that raising urine pH above 6.5 may prevent heme-protein precipitation with Tamm-Horsfallprotein, intratubular pigment cast formation and uric acid precipitation;correct metabolic acidosis and reduce hyperkalemia. Generally, administer a bicarbonate infusion who have severe RM CK>5000 U/L or a rising trend or crush injuries provided following conditions are met; Hypocalcemia is not present, arterial pH is less than 7.5 and serum bicarbonate is less 30 eq/L. The infusion should be isotonic that is 130 mEq NaHCO3 (150 ml) of 8.4% mixed with 1L of 5% Dextrose or sterile water (or in our country where 7.5% NaHCO3 is available it should be approximately 175 ml NaHCO3 mixed with 825 ml 5% dextrose) at the rate

of 200 ml /hour to achieve urine pH>6.5. Monitor arterial pH and serum calcium every 2 hourly. Bicarbonate infusion should be discontinued If urine pH does not rise above 6.5 after 3-4 hours or arterial pH exceeds 7.5 or serum bicarbonate exceeds 30mEq/Lor symptomatic hypocalcemia (tetany, seizure, arrythmias) develops.1,2,7,9,12

There is some variation in bicarbonate/fluid regimen in traumatic RM where usually more fluid is needed and it may be difficult to prepare this solution while victim is under rubble. Usually, 1 to 2 Lt of isotonic saline alternating with 1 Lt of half isotonic saline plus 50 mEq of sodium bicarbonate is started after extrication. Generally a total of 200-300 mEq of bicarbonate is given on the first day as long as the patient is not alkalemic.Mannitol: Thought to be protective by causing dieresis which minimizes intratubularheme pigment deposition and cast formation, and/or by acting as a free radical scavenger. However, due to lack of strong evidences it is not routinely used except in crush injuries where CK is usually very high (>30000U/L). In Crush related AKI if urinary flow is >20 ml/hr, 50 ml of 20% mannitol (1-2 gm/Kg) [Total 120 gm] given at a rate of 5 gm/hr may be added to each Litre of fluid. Its reasonable to give a test dose of 20% 60 ml mannitol over 5 minitues. If no significant increase in output by 30-50 ml/hr above baseline after test dose or desired diuresis 200-300 ml/hr is not achieved or osmolar gap >55 mosml/Kg; mannitol should be not be continued since there is risk of hyperosmolarity, hyperkalemia and volume overload.1,2,7,12

Loop diuretics:No impact on outcome of AKI. But judicious use may be justified in case of volume overload and compartment syndrome. 12

RM Protocol:Various treatment protocols are used which includes fluids with bicarbonate or mannitol, particularly for trauma-induced rhabdomyolysis. However, none of them were proved to be superior to others in any randomised control trial. We support the treatment flow chart (below) suggested by Neto EC et al27 in their review article “Up To Date in Rhabdomyolysis: Cocepts and Protocol Evaluation”.

Rhabdomyolysis Treatment Flow Chart27

Clinic support & periodic evaluation Correct electrolytes abnormality and complications

Failure in treatment Hyperkalemia pH<7.1 Sign of uremia Oligo-anuria

Metabolic acidosis Or

Urine pH<6.5

Urine flow rate >20 and <300 ml/h

Bicarbonate 20% Mannitol @ 1-2 gm/Kg Dialysis

Early 0.9% saline 1-2 L/hr Urine Debit 200-300 ml/hr

Up to CK <1000 U/L

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Renal Replacement Therapy:

Petejova et al32 in critical review of Acute kidney injury due to rhabdomyolysis and renal replacement therapy, recommend Intermittent hemodialysis or CRRT in KIDGO Stage 2 or 3 AKI due to rhabdomyolysis for renal or metabolic indications;not for preventive elimination of myoglobin.As myoglobin has a molecular mass of 17 kDawhich is poorly removed from circulation using conventional extracorporeal techniques. They suggest isotonic fluid with forced alkaline diuresis for stage 1 AKI.2,32

Treatment of electrolyte abnormalities:

Reinstatement of the biochemical equilibrium during rhabdomyolysis should be undertaken with care in order to avoid adverse effects of treatment. Hyperkalemia is the only electrolyte abnormality that requires rapid correction in order to reduce the risk of cardiac dysrhythmias. Administration of calcium chloride/ gluconate for hypocalcemia should be avoided since calcium supplementation may increase muscle injury 1,2,7,9,12.

Correction of hyperphosphatemia requires careful monitoring

of both phosphorus and calcium levels since increased levels of phosphorus may promote calcium deposition in necrotic muscle tissue 1,2,7,8,9,12.

Outcome:

Outcomes from rhabdomyolysis vary considerably with the type of patient population, cause and comorbidities. The mortality of patients with rhabdomyolysis and AKI is higher than in patients with no renal failure.Mortality ranges from 1.7% to 46%. The variability is likely due to causes,coexisting conditions and improved treatment over time.12

Conclusion:

After this review of medical literature, it was observed that there is a consensus about the use of early hydration as the main form of preservation of renal function during the management of rhabdomyolysis. Despite existing conflicts in the literature, most revisions suggest the use of mannitol and sodium bicarbonate only if there is an adequate indication and should be considered as supportive therapy. Finally, prospective well-designed trials in rhabdomyolysis are sorely needed for more definite guidance on treatment plan.

Table III: Key points of a few important current Literatures7,22-31

Study Regimen Outcome Comments

(AKI, RRT, Mortality)

Brown et al. (2004) Inf.0.45% Normal saline Not preventive in CK >5000 to 30,000 U/L Did notRetrospective 2083 with bicarbonate May be beneficial in very high support protocolPatients with plusmannitol. CK>30,000 U/Ltrauma

Shapiro et al. (2012) Early aggressive fluid (either normal saline or ringers lactate) as well as early Did not supportReview article Hemodialysis can prevent incidence of AKI protocol

Altintepe et al. (2007) Used protocol Target Urine PH>6.5 FavoursCase series Reduced AKI(Crush injury=9)

Cho etal. (2007) Bicarbonate to Keep No incidence of AKI FavoursProspective Urine PH>6.5Non-traumatic n=28

Scharman et al. Emphasize early Fluid (<6 h)at a rate to maintain U/O 300 ml /hr or more. No evidence of(2013) Sodium bicarbonate only if necessary to correct systemic acidosis and superiority of Review mannitol only to maintain urine output of 300 mL/h or more despite adequate bicarbonate / mannitol fluid administration. over fluid therapy alone.

Sever MS, Vanholder Emphasize early isotonic saline fluid. SupportsR and the workgroup Sodium bicarbonate added to half isotonic saline may be protective until(2012) symptomatic alkalosis,hycalcemia or volume overload develops.Recommendations No consensus supports mannitol, although a test dose may be tried to assess response.

Nielsen et al. Oregon Health & Science CK<10000 U/L Favours protocol (2017) University (1992) RM protocol No protocol=ARD 24% in high CK (>10000)10 year RS N=77 Used when CK>10,000U/L CK>10000 U/LCrush symdrome Protocol = 26% ARD No protocol=70% ARD

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References:1. Bosch X, Poch E, Grau JM. Rhabdomyolysis and acute kidney

injury. N Engl J Med. 2009;361(1):62–72.

2. Chavez LO, Leon M, Varon J.Beyond muscle destruction: a systematic review ofrhabdomyolysis for clinical practice. Critical Care2016;20:135.

3. Huerta-Alardin AL, Varon J, Marik PE. Bench-to-bedside review: rhabdomyolysis—an overview for clinicians. Crit Care 2005;9(2):158–69.

4. Bywaters E, Beall D. Crush injuries with impairment of renal function. Br MedJ. 1941;1:427–32.

5. Cervellin G, Comelli I, Benatti M, et al. Non-traumatic rhabdomyolysis: Background, laboratory features, and acute clinical management.ClinBiochem 2017 Aug; 50(12):656-62.

6. Efstratiadis G, Voulgaridou A, Nikiforou D, et al. Rhabdomyolysis updated.Hippokratia 2007 Jul;11(3):129-37.

7. Scharman EJ, Troutman WG. Prevention of kidney injury following rhabdomyolysis: a systematic review. Ann Pharmacother 2013;47(1):90–105.

8. Chatzizisis YS, Misirli G, Hatzitolios AI, et al. The syndromeof rhabdomyolysis: complications and treatment.Eur J Intern Med 2008 Dec;19(8):568-74.

9. Sever MS, Vanholder R, Ashkenazi L, etal.Recommendation for the management of crush victims in mass disasters. Nephrol Dial Transplant. 2012;27 (Suppl 1):i1–i67.

10. McMahon GM, Zeng X, Sushrut S, et al. Prediction Score for Kidney Failure or Mortality in Rhabdomyolysis. JAMA Intern Med. 2013 Oct 28; 173(19): 1821–28.

11. Melli G, Chaudhry V, Cornblath DR. Rhabdomyolysis: an evaluation of 475 hospitalized patients.Medicine (Baltimore). 2005 Nov;84 (6):377-85.

12. Zimmerman JL, Shen MC.Rhabdomyolysis.Chest 2013 Sep;144(3):1058-65. doi: 10.1378/chest.12-2016.

13. Chakravartty S, Sarma DR, Patel AG. Rhabdomyolysis in bariatric surgery: a systematic review.ObesSurg 2013;23(8):1333–40.

14. Iwere RB, Hewitt J. Myopathy in older people receiving statin therapy: asystematic review and meta-analysis. Br J ClinPharmacol 2015;80(3):363–71.

15. Oshima Y. Characteristics of drugs-associated rhabdomyolysis: analysis of 8,610 cases reported to the U.S. Food and Drug administration. Intern Med. 2011;50(8):845–53.

16. Rodríguez E, Soler MJ, Rap O, et al..Risk Factors for AcuteKidney Injury in Severe Rhabdomyolysis.PLoS One 2013; 8(12): e82992.

17. Blanco JR, Zabalza M, Salcedo J, et al. Rhabdomyolysis of infectious and noninfectious causes.South Med J. 2002 May;95(5):542-4.

18. Khan FY, Sayed H. Rhabdomyolysis associated with Mycoplasma pneumoniae pneumonia. Hong Kong Med J 2012 Jun;18(3):247-9.

19. Sertogullarindan B, Ozbay MB, Ertem FU, et al. Rhabdomyolysis associated with Mycoplasma pneumoniae infection. Pol Arch Med Wewn. 2013;123(1-2):66-7.

20. Patel C, Delmas T, White H, et al. Mycoplasma-Induced Rhabdomyolysis. Chest 2017;152 (Suppl):A305.

21. de Meijer AR, Fikkers BG, de Keijzer MH, et al. Serum creatine kinase as predictor of clinical course in rhabdomyolysis a 5-year intensive care survey. Intensive Care Med 2003;29(7):1121–25.

22. Altintepe L, Guney I, Tonbul Z, et al. Early and intensive fluid replacement prevents acute renal failure in the crush cases associated with spontaneous collapse of an apartment in Konya. Ren Fail. 2007;29(6):737–41.

23. Cho YS, Lim H, Kim SH. Comparison of lactated Ringer’s solution and 0.9 % saline in the treatment of rhabdomyoysis induced by doxylamine intoxication. Emerg Med J 2007;24:276–280.

24. El-Abdellati E, Eyselbergs M, Sirimsi H, et al. An observational study on rhabdomyolysis in the intensive care unit.Exploring its risk factors and main complication: acute kidney injury.Ann Intensive Care 2013;3:8. doi:10.1186/2110-5820-3-8.

25. Gunal AI, Celiker H, Dogukan A, et al. Early and vigorous fluid resuscitation prevents acute renal failure in the crush victims of catastrophic earthquakes. J Am SocNephrol 2004;15:18

26. Zutt R, van der Kooi AJ, Linthorst GE, et al. Rhabdomyolysis: review of the literature. NeuromusculDisord. 2014;24(8):651–9.

27. Neto EC, Hosoume K, Leitão L, et al. UpTo Date in Rhabdomyolysis: Concepts and Protocol Evaluation.International Journal of Scientific and Research 2014;4:1-7.

28. Iraj N, Saeed S, Mostafa H, et al. Prophylactic fluid therapy in crushed victims of Bam earthquake. Am J Emerg Med. 2011;29:738–42.

29. Brown CV, Rhee P, Chan L, et al. Preventing renal failure in patients with rhabdomyolysis: do bicarbonate and mannitol make a difference? J Trauma2004;56:1191-1196.

30. Nielsen JS, Sally M, Mullins RJ, et al. Bicarbonate and mannitol treatment for traumatic rhabdomyolysis revisited.Am JSurg 2017; 213:73-79.

31. Shapiro ML, Baldea A, Luchette FA.Rhabdomyolysis in the Intensive Care Unit. J Intensive Care Med2012;27:335-342.

32. Petejova N, Martinek A. Acute kidney injury due to rhabdomyolysis and renal replacement therapy: a critical review. Crit Care 2014;18(3):224.

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Introduction

With an estimated incidence of 0.02 to 3.23%,1 neuroleptic malignant syndrome (NMS) is a relatively uncommon but potentially fatal idiosyncratic reaction having a relatively high fatality rate of about 10%.2 It is characterized by the development of hyperthermia, muscular rigidity, autonomic dysfunction, and altered consciousness, either on exposure to antipsychotic3 and some other psychotropic medications4 or due to an abrupt withdrawal of anti-parkinsonism drugs.5 It is essentially a diagnosis of exclusion, and treatment is mainly supportive along with the instant withdrawal of the causative neuroleptic agents and starting of dopaminergic drugs. NMS presents a clinical challenge and a high index of suspicion is necessary to diagnose a case as the patient outcome depends on its early recognition and prompt implementation of appropriate management. This article reports, a case of a 38-year-old female patient with schizoaffective disorder who presented with typical features of NMS after initiation of risperidone (an atypical antipsychotic drug).

Case summary:

A 38-year-old housewife, mother of one child, was admitted to the intensive care unit (ICU) of Bangladesh Medical Hospital on September 2016, with the history of high grade continued fever for 4 days, rigidity of all four limbs and altered level of consciousness for 1 day. According to her husband, two days prior to hospital admission she was also

1. Dr. Rajib Ahsan Sumon; DA, MBBS, Junior Consultant, Department of Intensive Care Unit, Bangladesh Medical College & Hospital, Dhanmondi, Dhaka

2. Dr. Eshita Majumder; MBBS, Resident Medical Officer, Department of Endocrinology, BIRDEM General Hospital, Shahbag, Dhaka.


Dr. Eshita Majumder; MBBSResident Medical Officer, Department of EndocrinologyBIRDEM General Hospital, Shahbag, Dhaka.Email: [email protected]

showing unusual behavior, altered sleep pattern and resting tremor. She had no history of trauma, drug abuse or recent traveling to home and abroad. Her previous medical history revealed, she was a diagnosed case of schizoaffective disorder for last 2 years and was on tablet Quetiapine (100 mg thrice daily), Escitalopram (10 mg daily), with questionable adherence to treatment. As her psychotic symptoms were not responding well, 11 days prior to this hospital admission tablet risperidone 2 mg was started and gradually increased to 4 mg/day. She had no other documented organic co-morbidity.

On admission, a thorough physical examination demonstrated, the patient was disoriented with Glasgow coma score 8/15 (E3M4V1); temperature 102o F and was tachycardic (110 beats/min) with blood pressure 90/60 mm of Hg. Increased spasticity and tremulousness in all extremities were present. Other systemic examinations were unremarkable. Routine laboratory investigations showed Haemoglobin 11.5 gm/dL, leukocyte 6,000/mm3, platelets 3,00,000/mm3; serum creatine phosphokinase (CPK) was 2,388 U/L, but her level of blood urea nitrogen, serum creatinine, serum electrolytes, serum transaminases and blood gases were all within normal limit. The finding of the MRI of brain and chest X-ray were unremarkable. A provisional diagnosis of NMS was made. All antipsychotic drugs were withheld instantaneously. To rule out the possibility of central nervous system (CNS) infection, lumbar puncture was done and the CSF studies were found normal. Blood, urine, and sputum cultures showed no growth in 48 hours. Supportive cares including adequate hydration were maintained to prevent acute kidney injury (AKI); to lower body temperature tepid sponging with ice water and acetaminophen were used as required. Tablet Bromocriptine was started at a dose of 2.5 mg thrice daily and increased to 15mg/day. On the 5th day, patient’s temperature was subsided, her level of consciousness and muscle rigidity improved. On the 8th day, she was shifted to ward. After normalization of her CPK level, the dose of bromocriptine was slowly tapered and withdrawn subsequently. On the 13th day, she was discharged from hospital without further complication. On subsequent follow-up, in order to control her ongoing psychotic

Case Report

Neuroleptic Malignant Syndrome – A medical emergency in a psychiatry patientRajib Ahsan Sumon1, Eshita Majumder2

Abstract

Neuroleptic malignant syndrome (NMS) is a rare idiosyncratic reaction to antipsychotic drugs. Here, we are reporting, a 38 years old female schizoaffective patient, presented with fever, muscle rigidity and altered sensorium who had started tablet risperidone(an atypical antipsychotic drug) 11 days prior to hospital admission. After initial sepsis work up and neuroimaging, infective causes and acute cerebrovascular incidents were ruled out and a presumptive diagnosis of NMS was made. Immediate discontinuation of suspected causative agent, along with the provision of supportive care leads to complete resolution of all the symptoms in our patient.

Keywords: Neuroleptic Malignant Syndrome (NMS), Antipsychotic drug, Risperidone

pathognomonic sign or gold standard investigation for NMS and timely initiation of management is critical for favorable outcome; when there is a dilemma about etiology, it is prudent to withhold all neuroleptic drugs in a psychotic patient until rigorous investigations reveal a conclusive diagnosis.

References:1. Pelonero AL, Levenson JL, Pandurangi AK. Neuroleptic malignant

syndrome: a review Psychiatr Serv. 1998 Sep; 49(9):1163-72.

2. Shalev A, Hermesh H, Munitz H. Mortality from neuroleptic malignant syndrome.J Clin Psychiatry 1989 Jan; 50(1):18-25.

3. Nielsen RE, Wallenstein Jensen SO, Nielsen J. Neuroleptic malignant syndrome-an 11-year longitudinal case-control study. Can J Psychiatry 2012; 57:512-8.

4. Haddad PM. Neuroleptic malignant syndrome may be caused by other drugs.BMJ 1994; 308:200–1.

5. Keyser DL, Rodnitzky RL. Neuroleptic malignant syndrome in Parkinson's disease after withdrawal or alteration of dopaminergic therapy. Arch Intern Med. 1991 Apr; 151(4):794-6.

6. Delay J, Pichot P, Lemperiere T, et al: Un neuroleptique majeur non phenothiazine et non reserpine, l'haloperidol, dans le traitement des psychoses [Haloperidol, a nonphenothiazine, nonreserpine neuroleptic for the treatment of psychosis]. Ann Medi-Psychol 1960; 118:145-52.

7. Lazarus A, Mann SC, Caroff SN. The Neuroleptic Malignant Syndrome and Related Conditions. Washington, DC, American Psychiatric Press, 1989.

8. Hasan S, Buckley P. Novel antipsychotics and the neuroleptic malignant syndrome: a review and critique. Am J Psychiatr 1998; 155:1113-6.

9. Trollor JN, Chen X, Chitty K, et al. Comparison of neuroleptic malignant syndrome induced by first- and second-generation antipsychotics.Br J Psychiatry. 2012 Jul; 201(1):52-6.

10. Keck PE Jr, Pope HG Jr, Cohen BM, et al. Risk factors for neuroleptic malignant syndrome. A case-control study, Arch Gen Psychiatry 1989 Oct; 46(10):914-8.

11. Seitz DP, Gill SS. Neuroleptic malignant syndrome complicating antipsychotic treatment of delirium or agitation in medical and surgical patients: case reports and a review of the literature. Psychosomatics. 2009 Jan-Feb; 50(1):8-15.

12. Shalev A, Hermesh H, Munitz H.The role of external heat load in triggering the neuroleptic malignant syndrome. Am J Psychiatry. 1988 Jan; 145(1):110-1.

13. Trollor JN, Sachdev PS. Electroconvulsive treatment of neuroleptic malignant syndrome: a review and report of cases.Aust N Z J Psychiatry. 1999 Oct; 33(5):650-9

14. Brantley E, Cohn J, Babu K. Case files of the program in medical toxicology at brown university: amantadine withdrawal and the neuroleptic malignant syndrome. J Med Toxicol. 2009; 5:92-8

15. Mann SC, Caroff SN, Fricchione G, et al. Central dopamine hypoactivity and the pathogenesis of the neuroleptic malignant syndrome. Psychiatr Ann 2000; 30:363–74

16. Lurdes Tse, Alasdair M. Barr, Vanessa Scarapicchia, et al. Neuroleptic Malignant Syndrome: A Review from a Clinically Oriented Perspective. Curr Neuropharmacol. 2015 May; 13(3): 395–406.

17. Brian D. Berman. Neuroleptic Malignant Syndrome:A Review for Neurohospitalists. Neurohospitalist 2011 Jan; 1(1): 41–7.

18. Adnet P, Lestavel P, Krivosic-Horber R. Neuroleptic malignant syndrome. Br J Anaesth 2000; 85(1):129-35. Bond WS.

19. Detection and management of the neuroleptic malignant syndrome. Clin Pharm. 1984 May-Jun; 3(3):302-7.

20. Caroff SN, Mann SC. Neuroleptic malignant syndrome. Psychopharmacol Bull. 1988; 24(1):25-9.

21. Schatzberg AF, Nemeroff CB. Textbook of Psychopharmacology. 2nd ed. Washington, DC: American Psychiatric Press; 1998.

22. Geethan J. Chandran, John R. Mikler, and David L. Keegan Neuroleptic malignant syndrome: case report and discussion. Can. Med. Assoc. J. 2003 Sep 2; 169(5): 439–42.

23. Davis JM, Caroff SN, Mann SC: Treatment of neuroleptic malignant syndrome. Psychiatr Ann 2000; 30:325–31.

24. J.R. Strawn, P.E. Keck, S.N. Caroff. Neuroleptic malignant syndrome,Am J Psychiatry 2007; 164:870–6.

25. Caroff, Stanley N. ; Mann, Stephan C.; Keck, Paul E. Jr ; et al. Residual Catatonic State Following Neuroleptic Malignant Syndrome. Journal of Clinical Psychopharmacology 2000 Apr; 20(2): 257-9.

26. Pope HG Jr, Aizley HG, Keck PE Jr, et al. Neuroleptic malignant syndrome: long-term follow-up of 20 cases. J Clin Psychiatry 1991; 52:208–12.

symptoms, tablet olanzapine was prescribed, starting at a dose of 2.5 mg daily and gradually increased up to 10 mg daily. For preventing extrapyramidal side-effects, tablet procyclidine hydrochloride was also given. With these treatments, her depressive and psychotic symptoms improved considerably without any notable adverse effects, till date.

Discussion:

In 1960 Delay and colleagues, a group of French clinicians, first described an akinetic hypertonic syndrome in a group of patients using haloperidol;6 they named it "syndrome malin des neuroleptiques", from which the term ‘neuroleptic malignant syndrome’ is derived.7 Since then numerous case reports of this syndrome have been published from different countries and the incidence rate was estimated from 0.2 to 3.23%.1,7 It was identified in the literature that, in a susceptible individual, both typical and atypical antipsychotic drugs, at any dose, can induce symptoms of NMS.8,9 But, initiation of a new neuroleptic, the rapid increase in dosage, use of high potency or long-acting intramuscular depot formulation, all raise the possibility of developing NMS. Other suspected risk factors are dehydration, iron deficiency, hyperthyroidism, malnutrition, alcoholism, male gender, younger age, increased ambient temperature, previous episode of NMS, concomitant use of other psychoactive substances (especially lithium), and presence of structural or functional brain disorders such as encephalitis, tumor, delirium, or dementia.10-13 Sudden withdrawal of dopaminergic drugs in a Parkinson disease patient may also provoke NMS.5,14 In our patient, risperidone, a potent antipsychotic drug was started and the dose was also increased rapidly in a view to controlling her schizophrenic symptoms, all these seem to trigger her to develop NMS.

The exact pathophysiology of neuroleptic malignant syndrome is still not well elucidated; among several theories, the most enduring one is excessive blockage of D2 dopamine receptor within the nigrostriatal, hypothalamic, and mesolimbic/cortical pathways, leading to a marked and sudden reduction in central dopaminergic activity, plays a pivotal role in this condition.15,16 Another group of experts advocate that, increase release of calcium from the sarcoplasmic reticulum of muscle fibers with antipsychotic usage, may be responsible for exaggerated muscle contraction, rigidity and break down.17

Although the clinical presentation of NMS is often heterogeneous, the cardinal manifestations are high-grade fever, generalized rigidity, altered level of consciousness (from confusion to coma) and autonomic instability in the form of blood pressure fluctuation, tachycardia, tachypnoea, profuse sweating, flushing, excessive salivation and urinary incontinence.17-19 Infrequently observed features are dysphagia, tremor, chorea, tonic-clonic seizure, mutism, trismus, oculogyric crisis, positive babinski’s sign and opisthotonus. The symptoms may develop within one to thirty days after exposure to antipsychotic medications but typically appear within two weeks.20 Due to rhabdomyolysis, creatine phosphokinase (CPK) is characteristically found elevated and

threatens to cause acute kidney injury. Mild leukocytosis and increased serum transaminases levels are commonly reported. Unfortunately, none of these are either specific for the syndrome or universally present in all cases. So, a number of other fatal conditions presenting with similar clinical scenario must be excluded. Apart from central nervous system infection, septicaemia, acute intoxication and cerebrovascular accidents, the important neuropsychiatric differential diagnoses are serotonin syndrome, malignant hyperthermia, and lethal catatonia. Careful history taking, especially drug history and detailed physical examinations are helpful to distinguish between these life-threatening conditions. However, laboratory investigations such as CSF studies, blood, and urine culture, toxicology screening and neuroimaging are essential in the evaluation of other etiologies.

Neuroleptic malignant syndrome is a medical emergency; if the diagnosis is delayed the case fatality could be as high as 30%.21 Widespread awareness among clinicians regarding the syndrome has thankfully reduced the rate near to 10% in recent years.2 As antipsychotic drugs are strongly protein-bound, they cannot be removed by dialysis, so early discontinuation of offending agents along with the provision of supportive therapy is the crucial strategy in the management of suspected NMS. To prevent dehydration and AKI from myoglobinuria, vigorous fluid resuscitation is mandatory. Antipyretics are less effective in lowering body temperature in NMS, manual cooling with ice water and cold blankets are usually employed. Correction of hypoxaemia, electrolyte imbalance and acidosis and maintenance of nutrition is necessary. Fulminant cases may require intensive care monitoring and ventilatory support. Although data supporting the efficacy of adjunctive pharmacotherapy is insufficient, several drugs are being administered empirically to alleviate acute symptoms. Bromocriptine, amantadine, and other dopaminergic drugs; dantrolene a muscle relaxant, and benzodiazepines are frequently tried alone or in combination in different case studies.22-24 In refractory cases, electroconvulsive therapy may be beneficial to hasten recovery. If appropriate interventions are not taken immediately, disease course may prolong with serious complications like DIC, renal failure, aspiration pneumonia, sepsis, deep vein thrombosis, pulmonary embolism, acute respiratory distress syndrome, arrhythmia, cardiorespiratory failure;1,24 and surviving patients may have life-long morbidity secondary to cognitive impairment, cerebellar neuronal degeneration, residual catatonia or parkinsonism.25,26

After complete resolution of an episode (within 2-14 days) of NMS, because of compelling indication, it is often required to restart antipsychotic drugs. But it should preferably be done at least after two weeks, with an alternative low potency agent at a low dose and titrated gradually with great caution as recurrent cases are reported in literatures.17,26

Conclusion:

Although majority of cases of neuroleptic malignant syndrome follow an indolent course, lack of clinical vigilance may lead to life-threatening complications As there are no

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Introduction:

Angiodysplasia is the most common vascular lesion of the gastrointestinal tract, and this condition may be asymptomatic, or it may cause gastrointestinal (GI) bleeding.1

The vessel walls are thin, with little or no smooth muscle, and the vessels are ectatic and thin. It is a degenerative lesion of previously healthy blood vessels found most commonly in the cecum and proximal ascending colon but bleeding from proximal intestinal angiodysplasias, and nasal bleeding is also reported.2,3 After diverticulosis, it is the second leading cause of lower GI bleeding in patients older than 60 years. An association between colonic angiodysplasia and aortic stenosis was described by Dr. Edward C. Heyde in 1958.4 It is caused by the induction of Von Willebrand disease type IIA (vWD-2A) by a depletion of Von Willebrand factor (vWF) in blood flowing through the narrowed valvular stenosis. The existence of this syndrome was debated for a considerable period of time when finally it was shown that the gastrointestinal bleeding did actually resolve after aortic valve replacement in many such patients, thereby giving a definite credence to the existence of this syndrome.2,5 The multiple blood transfusions. We describe a case of Heyde’s

1. Dr. Deepankar Kumar Basak, MBBS, FCPS (Medicine), Specialist-Gastroenterology, Square Hospitals Ltd, Dhaka

2. Dr. Richmond Ronald Gomes, MBBS, FCPS (Medicine), Assistant Professor, Internal Medicine, Ad-din Women’s Medical College & Hospital, Dhaka

3. Prof. Dr. Md.Samsul Arfin, MBBS, FCPS (Medicine), Consultant, Gasroenterology, Square Hospitals Limited, Dhaka


Dr. Deepankar Kumar BasakMBBS, FCPS (Medicine)Specialist-GastroenterologySquare Hospital Ltd, [email protected]

bleeding could be severe and the patient usually requires syndrome with multiple angiodysplastic lesions throughout the colon, mostly at the distal part and discuss the various challenges in the diagnosis and treatment of such patients.

Case report

Mrs. Chaina Chakraborty, 71 year old pleasant lady, known to have multiple myeloma (MULTIPLE MYELOMA-IgG Kappa Myeloma and Beta2 Microglobulin-4.2) chronic liver disease (HCV related) with Esophageal Varices (grade 2), duodenal ulcer and aortic stenosis with IHD was admitted to SHL gastroenterology department through ER with the complaints of passage of black tarry stool for last five days and generalized weakness for same duration. She had previous history of hospital admission for several times in the last three months with these same complaints and received 8-10 units of blood and blood products over that period. Now her hemoglobin 5 gm/dl, Haematocrit 20.9%, TC 10.5 K/uL, Platelets 40K/uL, PT, aPTT was normal. Echocardiogram shows narrow LVOT with Dynamic subvalvular Aortic Stenosis Gr 78/28mmHg with no AR. Endoscopy shows grade 2 esophageal varix but no active bleeding from varix. Colonoscopy shows angiodysplastic lesions through the colon with hamorrhoids. Bleeding occur most probably from angiodysplastic lesions but we don’t see any active bleeding from any angiodysplasia. Initially patient was managed with blood transfusion with fresh frozen plasma and also platelet aphaeresis.

Fig 1:- Angioplastic lesion in colon

Case Report

Heyde’s syndrome: Rare cause of GI bleedingDeepankar Kumar Basak1, Richmond Ronald Gomes2, Md. Samsul Arfin3

Abstract

Bleeding from gastrointestinal tract is very common and important problem in clinical practice. Sometimes it is very difficult to locate and treat gastrointestinal bleeding. Here we discuss Heyde’s syndrome, an important cause of gastrointestinal bleeding in an elderly female patient who is also suffering from HCV related decompensated CLD with multiple myeloma. Heyde's syndrome is now known to be gastrointestinal bleeding from angiodysplastic lesions due to acquired vWD-2A secondary to aortic stenosis, and the diagnosis is made by confirming the presence of those three things. For this, a wide range of investigations and treatment modalities are now available. Aortic valve replacement is claimed to minimize or even stop the bleeding in such patients. But still there are a few reports showing gastrointestinal bleeding after aortic valve replacement. Old age and co-morbidities may create a hindrance in valve replacement or resection surgery. Some newer treatment options like hormonal and thalidomide therapy look promising but they have inadequate evidence behind them. Here, we discuss this clinical problem, strategies and evidence, areas of uncertainty, available guidelines, and our conclusions about Heyde’s syndrome.

Key words: Heyde’s syndrome, gastrointestinal angiodysplasias, gastrointestinal bleeding.

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Our patient is an elderly lady with multiple co-morbidities. She was treated by thalidomide for multiple myeloma that was controlled. Two times EVL was done for HCV related decompensated CLD with feature of hypersplenism with low platelet count. Her past history of multiple episodes of life-threatening blood loss makes it necessary to do something to prevent gastrointestinal blood loss. The options available are angiographic intervention, endoscopic intervention, intestinal resection, aortic valve replacement, and estrogen-progesterone therapy/thalidomide therapy. The patient herself along with her relatives were unwilling for any major surgical intervention due to her advanced age and the multiple co morbidities that she had, further compromising the likely outcome after the surgery. There was a high chance of more angiodysplastic lesion in small gut which is not approachable on colonoscopy and there was no capsule endoscope in our country.

Angiographic intervention is also not preferable as there is a possibility of existence of multiple unnoticed angiodysplasias, possibility of gut infarction after angiography, and the deranged renal function of the patient would be a contraindication for angiography. All these problems make it difficult to choose the best and acceptable solution for this patient like aortic valve replacement.

Fig 2:-Argon plasma coagulation (APC)

Fig 3:- Endoscopic variceal ligation (EVL)

We do argon plasma coagulation (APC) of angiodysplastic lesion in colon as far as possible in 2 sessions with injection of octreotide. In this measure she was recovered well and there was no bleeding at least 1 year follow-up. After that again melaena started on/off. She was also treated by desmopressin nasal spray with cap.danazol to increase vWF with inj octreotide. This measure decreases her incidence of melaena. We offer her to do aortic valvae replacement for further management but she was not interested.

Discussion

Angiodysplasia is the most common vascular lesion of the gastrointestinal tract, and this condition may be asymptomatic, or it may cause gastrointestinal (GI) bleeding.1

Seventy-seven percent of angiodysplasias are located in the

cecum and ascending colon, 15% are located in the jejunum and ileum, and the remainder is distributed throughout the alimentary tract. Nasal bleeding is also reported.2,3 These lesions typically are nonpalpable and small (< 5 mm). Angiodysplasia may account for approximately 6% of cases of lower GI bleeding. It may be observed incidentally at colonoscopy in as many as 0.8% of patients older than 50 years. The prevalence for upper GI lesions is approximately 1-2%.Clinical presentation in patients with angiodysplasia is usually characterized by maroon-colored stool, melena, or hematochezia. Bleeding is usually low grade, but it can be massive in approximately 15% of patients. In 20-25% of bleeding episodes, only tarry stools are passed. Iron deficiency anemia and stools that are intermittently positive for occult blood can be the only manifestations of angiodysplasia in 10-15% of patients. Bleeding stops spontaneously in greater than 90% of cases but is often recurrent. An association between colonic angiodysplasia and aortic stenosis was described by Dr. Edward C. Heyde in 1958.4

The exact mechanism of development of angiodysplasia is not known, but chronic venous obstruction may play a role.6,7 Increased expression of angiogenic factors, like basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF), is also believed to play a role in the pathogenesis of colonic angiodysplasia.8 In Heyde’s syndrome, it seems that bleeding occurs from pre-existing angiodysplasias in the gut. This bleeding is due to an acquired haematological defect caused by aortic stenosis.5,9 Age-related senile tissue changes may predispose to angiodysplasia and the link between the angiodysplasia and aortic stenosis is controversial.10,11,12 Various studies have described the acquired von Willebrand factor deficiency as being a reason for bleeding in Heyde’s syndrome.5, 13 The hematological defect is identified as deficiency of high molecular weight (HMW) multimers of von Willebrand factor (vWF).14The high shearing force caused by blood jet in aortic stenosis uncoils the HMW multimers of vWF exposing the vWF cleavage site for ADAMST13. This leads to selective loss of HMW multimers of vWF due to increased proteolysis. Acquired vWF deficiency state is thus created (von Willebrand syndrome type 2A). There is evidence showing normalisation of HMW multimers of VWF after aortic valve replacement surgery.5 Heydes syndrome consists of a triad of aortic stenosis, acquired vWF deficiency and anaemia due to bleeding angiodysplasia or idiopathic bleeding. The main challenge is localization of bleeding source in these patients. The bleeding source could be hidden and out of reach for conventional endoscopies.Wireless capsule endoscopy is a useful invention that helps us to visualise the small intestine. It also guides us about the route for enteroscope insertion. It is a painless and noninvasive procedure. The disadvantages of capsule endoscopy include the inability to detect all the lesions, especially in presence of active bleeding, and the inability to intervene. The double balloon and single balloon endoscopies are described to be useful to overcome these disadvantages of capsule endoscopy.14, 15 It is claimed that double balloon and single

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balloon endoscopies can visualise most of the small bowel and thus enable diagnostic manoeuvres and therapeutic techniques like achieving haemostasis, performing polypectomies, stricture dilatation, and stenting. This technique produces superior quality images than capsule endoscopy. However, the cost and availability of these techniques could limit their use in developing countries. Therapeutic options for Heyde’s syndrome include aortic valve replacement, surgery, angiographic intervention, double or single balloon endoscopy, Argon plasma coagulation (APC) and medical therapy including hormonal and thalidomide therapy, octreotide.5 It is claimed that aortic valve replacement reduces or even stops gastrointestinal blood loss5. Cessation of bleeding after aortic valve replacement was found to be associated with improved levels of HMW multimers of vWF after replacement. This finding strengthened the hypothesis of acquired vWF deficiency in Heyde’s syndrome. However, advanced age and co-morbidities can make this an unsuitable choice in some patients. A few case reports describe massive gastrointestinal bleeding after aortic valve replacement. Thus aortic valve replacement might not be the ideal treatment in every patient of Heyde’s syndrome. Surgery and endoscopic therapy specially argon plasma coagulation are not useful in patients with diffuse angiodysplasia. Aortic stenosis and associated cardiac diseases often make patients of Heyde‘s syndrome unfit for surgery. Though double balloon endoscopy is mentioned to be able to visualise the small intestine and intervene, their cost and availability may limit their use. Angiographic intervention like embolisation of A-V malformation can lead to arterial occlusion and gangrene. It is also difficult to locate and embolise all the lesions in diffuse angiodysplasias. A few case reports, one uncontrolled trial, and recently a small double-blind, placebo-controlled, cross-over trial indicate that oestrogen-progesterone therapy may be effective in controlling severe recurrent bleeding from gastrointestinal vascular malformations. Octreotide and estroprogestative treatments are the best evaluated drugs; however, no appropriate comparison on cost-effectiveness and tolerance has been performed. Submucosal injection of a saline epinephrine solution followed by the application of APC has been reported.New endoscopic techniques such as the Olympus EVIS LUCERA variable indices of hemoglobin chart function have been developed to assess completeness of vascular mucosal ablation. Super selective embolization of visceral arterial branches is central to the management of patients with lower GI bleeding, including bleeding from colonic angiodysplasia. Partial or complete gastrectomy for management of gastric angiodysplasia has been reported to be followed by bleeding in as many as 50% of patients. Rebleeding was attributed to other angiodysplastic lesions.Right hemicolectomy for angiodysplasia is second-line therapy after endoscopic ablation, if repeated endoscopic coagulation has failed, if endoscopic therapies are not available, and for life-threatening hemorrhage.

The mortality rate associated with surgical resection ranges from 10% to 50%. This is based on the view that surgery carries a much higher risk in elderly patients, who often have multiple coexisting medical problems, including coronary artery disease, coagulopathy, and renal and pulmonary dysfunction.

In a study by Meyer et al, right hemicolectomy resulted in 63% of the subjects remaining free of intestinal bleeding (mean follow-up, 3.6 y), and 37% had some degree of recurrent bleeding.24

The Heyde’s syndrome is supposed to be one of the aquired von Willebrand factor deficiency states. The recommended guidelines for the diagnosis and management involve detection of vW factor levels, detection of antibodies against the same, and treatment with desmopressin or factor viii/vWF. These diagnostic modalities are not readily available across our country and are costly, e.g., in Bangladesh, assessment of vW factor levels may cost more than hormonal therapy for a month. There are no recommended guidelines for the management and treatment of Heyde’s syndrome. One should seek help from guidelines for management of occult gastrointestinal blood loss. Also, there should be a consideration for cardiovascular issues and hematological issues of the patient. Various treatment options are available for Heyde’s syndrome but most of them have inadequate evidence behind them. As of now, there is no universally accepted unified treatment protocol available. Recurrence of acute hemorrhage from GI angiodysplasia after hospital discharge occurred in 30% of patients after a mean follow-up (33±40 mo). In a multivariate analysis, earlier history of bleeding with a high bleeding rate, over anticoagulation, and the presence of multiple lesions were predictive factors of recurrence. Surprisingly endoscopic APC therapy was not associated with lower rates of recurrent bleeding.

Conclusions and recommendations

Potentially life-threatening nature, age and co-morbidities, and poorly understood pathophysiology make Heyde’s syndrome a tough illness to treat. High index of suspicion should be kept in mind while treating aortic stenosis and gastrointestinal hemorrhage in elderly patients. Involvement of a gastroenterologist and a hematologist in treatment of such patients helps in resolving various issues pertaining to their respective fields. An aggressive attempt should be made to visualize the bleeding source. Capsule endoscopy and double balloon endoscopy may be very useful in diagnosis and treatment. Though aortic valve replacement is thought to be corrective in most of the cases, it might not be practical in all the cases. In spite of lack of strong evidence and the possibility of side-effects, hormonal therapy could prove to be an effective treatment modality in such patients. Incidentally, our patient has done well after inj. octreotide & hormonal therapy with Argon plasma coagulation and her hemoglobin has been raised.

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References

1. Regula J, Wronska E, Pachlewski J. Vascular lesions of the gastrointestinal tract. Best Pract Res Clin Gastroenterol 2008. 22(2):313-28.

2. Warkentin TE, Moore JC. Heyde’s syndrome: From controversy to mainstream. Schattauer 2010.

3. Schodel J, Obergfell A, Maass AH. Severe aortic valve stenosis and nose bleed. International Journal of Cardiology 2007; 120 (2): 21

4. Heyde EC. Gastrointestinal bleeding in aortic stenosis. N Engl J Med 1958. 259:196.

5. King RM, Pluth JR, Guiliani ER. The association of unexplained gastrointestinal bleeding with calcific aortic stenosis. Ann ThoracSurg 1987; 44: 514-6.

6. Clouse RE. Vascular lesions: ectasias, tumors, and malformations. Yamada T, Alpers DH, Laine L, Owyang C, Powell DW, eds. Textbook of Gastroenterology. 3rd ed. Philadelphia, Pa: JB Lippincott 1999. Vol 2: 2564-78.

7. Ming SC, Goldman H. Vascular abnormalities of the gastrointestinal tract. Ming SC, Goldman H, eds. Pathology of the Gastrointestinal Tract. 2nd ed. Baltimore, Md: Williams & Wilkins Company 1998. 272-4.

8. Junquera F, Saperas E, de Torres I, et al. Increased expression of angiogenic factors in human colonic angiodysplasia. Am J Gastroenterol 1999 Apr. 94(4):1070-

9. Mishra PK et al. Intestinal angiodysplasia and aortic valve stenosis: lets not close the book on this association. European Journal of Cardiothoracic Surgery 2009; 35: 628-34.

10. Saxena R, Sharma P. Gastrointestinal Angiodysplasia and Acquired von Willebrand Syndrome: A Review of an Enigmatic Association. Journal of Coagulation Disorders 2009.

11. Bhutani MS, Gupta SC, Markert RJ et al. A prospective controlled evaluation of endoscopic detection of angiodysplasia and its association with aortic valve disease. Gastrointest Endosc 1995; 42: 398-402.

12. Greenstein RJ, McElhinney AJ, Reuben D et al. Colonic vascular ectasias and aortic stenosis: coincidence or causal relationship? Am J Surg 1986; 151: 347-51.

13. Massyn MW, Khan SA. Heyde syndrome: a common diagnosis in older patients with severe aortic stenosis. Age and Ageing 2009; 38: 267-70.

14. Hui YT et al. Heyde’s syndrome: diagnosis and management by the novel single-balloon enteroscopy. Hong Kong Med J 2009; 15: 301-3.

15. Yamamoto H, Sekine Y, Sato Y et al. Total enteroscopy with a nonsurgical steerable double-balloon method. Gastrointest Endosc 2001; 53: 216-20.

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INTRODUCTION

A psychotic episode that occurred for the first time without prior history is defined as ‘First episode psychosis’1. In the case described the psychotic episode occurred after taking dialysis. Acute psychotic reactions though less common, do occur in chronic renal failure patients.

CASE REPORT

Mrs X, a 50 year old married lady hailing from Comilla came to BIRDEM General Hospital to take dialysis on outdoor basis in the Department of Nephrology. During dialysis the patient became uncooperative, restless and violent and repeatedly refused dialysis. She tried to pull out the cannula and dialysis could not be carried out. Therefore the patient was referred to the department of Psychiatry. On history taking it was revealed that the patient was diagnosed as a case of End Stage Renal Disease (ESRD) 1 year back. Eventually she was advised dialysis which she refused. The patient’s husband convinced her to take dialysis. But the patient could not cope with the stress of the dialysis procedure and manifested hostile behaviour especially towards her husband. She was given injectable haloperidol and procyclidine stat which calmed her down. She completed the dialysis and went home. Next week she was admitted for her abnormal behaviour. She could not recognize her husband and she addressed him as a ‘stranger’. She had decreased appetite and disturbed sleep. She had difficulty falling asleep and was not refreshed after waking up. She could recognize her children and other family members and also could tell the place she was in and was oriented with her environment. On Mental

1. Dr. Umme Salma Talukder, Assistant Professor, Department of Psychiatry, Ibrahim Medical College and BIRDEM General Hospital, Dhaka, Bangladesh.


Dr. Umme Salma TalukderAssistant Professor Dept. of PsychiatryIbrahim Medical College and BIRDEM General Hospital Shahbagh, Dhaka, Bangladesh. Email: [email protected]

State Examination the patient complained that her husband was a ‘bad person’ because he forced her to receive dialysis and take medication and food regularly. The patient was dysphorictearful, felt helpless and had similar features resembling reaction to chronic stress. She was given tablet Escitalopram 10mg and Tablet Clonazepam 0.5mg and discharged. After 2 months she was again forced to get hospitalised. She developed muscular rigidity and pain in the hips. She had violent verbal behaviour rebuking her children and everybody around her then eventually her speech decreased and became mute. She could not sit up in her bed and became bed ridden. She stopped taking food and drink and needed NG tube feeding. Even if she was coaxed to open her mouth and a little bit of water was forced in, she would throw them out and keep her teeth tightly clenched. She also had incontinence, refused to communicate in any way and kept her eyes closed. She was reported to be obsessive and adamant regarding her premorbid personality. She was prescribed Injection Fluphenazine deaconate 25mg and Haloperidol 5mg 1 ampoule stat and Haloperidol 5mg 1 tablet thrice daily and Tablet Quetiapine 25mg 1 tablet at night orally. She improved with antipsychotics. Within 3 days the patient started taking food and drinks orally and opened her eyes to communicate moderately. By that time the duration of mental illness was 4 months therefore the diagnosis of schizophreniform disorder was made. The patient did not have any family history of mental illness or any prior treatment of mental illness before taking dialysis. Significant biochemical values were Serum Creatinine 4.1mg/dl, Serum Urea 41 HbA1c 5.8 Anti HCV and Anti HBsAg were negative and ECG showed sinus rhythm.

DISCUSSION

According to researches abroad 9% of all dialysis patients are hospitalised with mental disorder2. Renal failure and chronic stress is a precipitating factor for mental disorder including psychosis. Stress can be psychological and physical. Physical stress takes the form of chronic physical illness like diabetes, hypertension, dialysis, malignancy & SLE etc3-4.

Hospitalization with mental disorders is 1.5 to 3 times higher for renal failure patients compared with other chronically ill patients. Depression, Anxiety, drug abuse, especially

Case Report

First Episode Psychosis following ESRD in a 50 year old lady: A Case Report Umme Salma Talukder1

Abstract

A psychotic episode that occurred for the first time without prior history is defined as ‘First episode psychosis’.In the case described the psychotic episode occurred after taking dialysis. Hospitalization with mental disorders is 1.5 to 3 times higher for renal failure patients .Acute psychotic reactions though less common, do occur in chronic renal failure patients undergoing dialysis.

Key words: First episode psychosis, acute schizophrenic episode, organic brain syndrome, End Stage Renal Disease (ESRD).

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alcoholism, suicide, Personality Disorders and other psychotic disorders are the common comorbidities found in patients going through dialysis. Common organic causes are dementia and Delirium1-5. Among the Psychotic disorders hypomania and Schizophrenia are found1-8. In Japan the prevalence of mental disorder in dialysis patients is 10.6%5. Symptoms vary from a classic organic brain syndrome with symptoms such as confusion, disorientation, and memory loss to syndromes resembling an acute schizophrenic episode ,but usually without a classic “thought disorder” for example delusion ,thought broadcasting, and ambivalence, autism or the like, or psychotic depression with symptoms such as depression or ideas of reference. These signs and symptoms can occur in the absence of biochemical abnormalities6 and respond to antipsychotic treatments.

In the patient described, there was a first onset psychotic episode just after she started receiving dialysis. There was no such history before or any family history of mental illness. Schizophrenia is a constellation of symptoms and signs with varied presentations. This patient was verbally abusive with paranoid behaviour especially towards her husband who imposed treatment on her. She refused medication, food and even drink due to her undue suspiciousness and the irrational fear of being hurt by unknown enemies manifested by her teeth clenching and non – cooperation with doctors and nurses. Then she became mute non – communicative with muscular rigidity and stiffness mainly cogwheel. She was also immobile and incontinent, giving a characteristic scenario of Schizophrenia spectrum disorder which includes the following delusion, hallucination, disorganised speech and disorganized behaviour, including negative symptoms. There was also functional impairment. The biochemical reports excluded acute brain syndrome, electrolyte imbalance or uraemia. Therefore the first episode of psychosis was precipitated by a chronic medical illness like ESRD.

Acute psychotic reactions though less common, do occur in chronic renal failure patients undergoing dialysis. Such cases necessitate intensive and immediate medical and psychiatric intervention9-12.

References : 1. Diagnostic and Statistical manual of mental disorders 5thed

(DSM5).Arlington,VA, American Psychiatric Association, 2013.page 51-2.

2. Kimmel PL, Thamer M, Richard C M, Ray N F. Psychiatric Illness in Patients with End-stage Renal disease Sep 1998; 105 (3): 214-21.

3. Hampton T, Lea AT. Mental Health May Play a Role in Dialysis Patients’ Survival. Clin Jr Am Soc Neph. Cited 2015 Mar 30.Available from Newsonline.

4. Chilcot J, Wellsted D, Da Silva-Gane M, Farrington K. Depression on Dialysis . Renal Unit: Lister Hospital Stevenage, and University of Hertfordshire, Hatfield, UK.2008;108(4):108-256.

5. Paul L Kimmel. Psychosocial factors in dialysis patients. Kid Int; 2001 (59):1599-1613.

6. Glick ID, Goldfield MD, Kovnat PJ. Recognition and management of psychosis associated with haemodialysis. Calif Med Nov 1973; 119:56-9.

6. Abram HS, Moore GL, Westervelt FB. Suicidal Behaviour in Chronic Dialysis Patients. American J Psy 1971 Mar; 127( 9):1199-1204.

7. Schmidt RJ, Holley JL. Psychiatric illness in dialysis patients. Available from www.uptodate.com/store.

8. Cooper AJ. Hypomanic psychosis precipitated by hemodialysis. Comp Psychiatry .1967; 8:168174.

9. Gupta M, Annadatha S. Treating Bipolar Disorder in Patients with Renal Failure having Haemodialysis. Clin Pract and Epi Mental Health. 2008; 4:21.

10. Cukor D, Cohen SD, Peterson RA, Kimmel PL. Psychosocial aspect of chronic disease: ESRD as a paradigmatic Illness. Jr Am Soc of Neph Nov 2007; 12 (18):3042-55.

12. Wright R, Sand S, Livingston G. Psychological stress during hemodialysis for chronic renal failure. Ann Int Med.1966; 64: 611-27.

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Introduction:

Heparin Induced Thrombocytopenia (HIT) is defined as a pro-thrombotic adverse effect of heparin therapy.1 There are two types of HIT described. Type I is a non-immune, mediated asymptomatic, transient drop in platelet count that occurs in some heparin treated patients. It is typically characterized by a lesser fall in platelet count within the first two days after heparin initiation and often returns to normal with continued heparin administration2. The more serious form is Type II (HIT-II) is an immune-mediated disorder characterized by the formation of antibodies against heparin-platelet factor 4 complexes. The frequency of HIT varies from 0.5% to 5%, depending on the patient population studied.3 A meta-analysis noted an incidence of 2.6 percent.4

It usually develops 5-14 days after exposure to heparin, but HIT might occur sooner in individuals with previous recent heparin exposure (within the past 100 days), or rarely can occur up to 2 weeks after heparin is discontinued in patients with high titers of platelet-activating IgG antibodies.5

Case report:

A 59-year-old lady, a known patient of End Stage Renal Disease (ESRD), Diabetes Mellitus and hypertension was started on maintenance haemodialysis through a tunneled jugular venous catheter. Her CBC was checked routinely after 9 days which showed platelet count 287,000/mm3.

1. Dr. M.A. Wahab Khan, MBBS, MD (Nephrology), Consultant, Nephrology, Square hospital Limited

2. Dr. Tasnova Mahin, MBBS, MRCP, Specialist, Nephrology, Square hospital Limited


Dr. Tasnova MahinSpecialist, NephrologySquare Hospital LimitedE-mail: [email protected]: +77-9841248584

After about 2 weeks, she was admitted in hospital for accelerated hypertension with hypertensive heart failure and hypoglycemia for which I/V drugs were given through peripheral cannula in right thumb. She was discharged after 1 day but on the next day she developed pain and swelling at the cannula site which was spreading through the whole right upper limb. She was then treated conservatively with oral antibiotics as a case of cellulitis. Her CBC at that time showed Hb- 11.9gm/dl, TC- 11,900/mm3 and platelet- 31,000/mm3. This thrombocytopenia was presumed to be induced by infection. As she developed dysfunction of her tunneled venous catheter as well she was again admitted for further evaluation.

After admission, a haemodialysis catheter was inserted in right femoral vein. Doppler study of right upper limb showed extensive DVT involving right subclavian, brachiocephalic and internal jugular vein. Blood reports showed raised FDP and D-dimer, but PT and APTT were within normal limit. CBC showed Hb-10.4 gm/dl, Total WBC-18,000/mm3 and platelet- 21,000/mm3. Tunneled jugular catheter was promptly removed and low molecular weight heparin was started according to the advice of hematologist. But as the patient developed DVT of right upper limb and platelet count was not improving despite control of infection HIT was suspected and she was started on heparin free haemodialysis.

Femoral catheter was removed from the right side and a new one was inserted on left side. Patient was initially started on rivaroxaban for DVT due to poor availability of other recommended anticoagulants used in HIT in our country but later fondaparinux was started. Citrate block was given in hemodialysis catheter. Patient’s platelet count started rising and after it became 168,000/mm3 oral warfarin was started. HIT was diagnosed due to high degree of clinical suspicion according to 4T scoring system. As anti PF4/heparin antibody assay was not available in our country the patient went abroad for further evaluation where the antibody was found positive.

Case Report

Heparin Induced Thrombocytopenia in a Patient Requiring Haemodialysis - A Case ReportM.A. Wahab Khan1, Tasnova Mahin2

Abstract

Heparin has remained the most commonly used anticoagulant for patients undergoing hemodialysis. It is usually safe to use but can have severe adverse effects in some cases. Heparin-induced thrombocytopenia (HIT) is a life-threatening complication of exposure to heparin. Here we present a case of a 59-year-old lady with End Stage Renal Disease who underwent maintenance haemodialysis through a tunneled jugular venous catheter. In about two weeks, she developed thrombocytopenia and deep vein thrombosis in right upper limb. She was diagnosed as a case of acute HIT and heparin free haemodialysis was started along with alternate anticoagulation for DVT. Heparin induced thrombocytopenia is a rare but life threatening clinical condition which should be suspected and treated early in all patients requiring heparin therapy.

Key words: HIT, Haemodialys, Thrombocytopenia.

12. Boon DM, Van Vliet HH, Zietse R, et al. The Presence of Antibodies Against a PF4-Heparin Complex in Patients on Haemodialysis. Thromb Haemost 1996;76:480.

13. O’shea SI, Sands JJ, Nudo SA, et al. Frequency of Anti - Heparin - Platelet Factor 4 Antibodies in Hemodialysis Patients and Correlation with Recurrent Vascular Access Thrombosis. Am J Hematol 2002;69:72–3.

14. Luzzatto G et al. Platelet Count, Anti-Heparin/Platelet Factor 4 Antibodies and Tissue Factor Pathway Inhibitor Plasma Antigen Level in Chronic Dialysis. Thromb Res 1998;89:115–22.

15. Yamamoto S et al. Heparin - Induced Thrombocytopenia in Hemodialysis Patients. Am J Kidney Dis 1996;28:82–5.

16. Matsuo T et al. Frequency of Anti - Heparin - PF4 Complex Antibodies (HiT Antibodies) in Uremic Patients on Chronic Intermittent Hemodialysis. Pathophysiol Haemost Thromb 2006;35:445–50.

17. Yu A, Jacobson SH, Bygdén A, et al. The Presence of Heparin-Platelet Factor 4 Antibodies as a Marker of Hypercoagulability During Hemodialysis. Clin Chem Lab Med 2002; 40: 21–6.

18. Nakamoto H et al. Role of Platelet Factor 4-Heparin Complex Antibody (HiT Antibody) in the Pathogenesis of Thrombotic Episodes in Patients on Hemodialysis. Hemodial Int;2005;9 (Suppl. 1): s2-s7.

19. Lim JH, Kang KP, Lee S, et al. Recurrent Heparin-Induced Thrombocytopenia due to Heparin Rinsing before Priming the Machine in a Hemodialysis Patient: A Case Report. Hemodial Int 2017;2:30-3.

20. Koon MC, Chi YC, Ka FC. Heparin-Induced Thrombocytopenia due to Heparin Lock in a Hemodialysis Patient: A Case Report. Hemodialysis Int 2014;18(2):555-8.

21. Seculini Patiño CE, Pascualini MF, Tabares AH. Successful Treatment with Fondaparinux in Heparin-Induced Thrombocytopenia and Thrombosis. Medicina (B Aires). 2015; 75(5):307-10.

22. Warkentin TE, Greinacher A. Heparin-Induced Thrombocytopenia: Recognition, Treatment, and Prevention. Chest 2004; 126: 311S–337S.

23. Preachel M, Walenga J. The laboratory Diagnosis and Clinical Management of Patients with Heparin-Induced Thrombocytopenia: An Update. Semin Thromb Hemost 2008; 34: 86–96.

Discussion:

The presence of HIT antibody in patients undergoing hemodialysis has been reported in at least 15 studies involving 3,818 patients from 8 countries and ranges from 0% to 17.4%.6 HIT should be suspected in any patient who develops thrombocytopenia during or shortly after heparin therapy. HIT is a clinico-pathologic diagnosis: laboratory findings must be interpreted together with clinical information. The British Hemostasis and Thrombosis Task Force recommended use of the 4T criteria, as described by Warkentin et al., for estimating pretest HIT probability.7 The diagnosis of HIT requires laboratory confirmation. Functional tests measure platelet activation in the presence of patient serum and heparin. These tests, which include the 14C-serotonin release assay and the platelet aggregation assay, rely on the capability of HIT antibody to activate platelets. The 14C-serotonin release assay remains the gold standard among functional tests. It has very high sensitivity (88–94%) and specificity but is performed in only a small number of reference laboratories.7 The ELISA immunoassay is very sensitive (90–98%) but has low specificity (50–93%),8 which results in the frequent detection of HIT antibody in the absence of clinical disease.

The risk of HIT complications in the haemodialysis population remains unclear. Several studies have reported no clinical sequelae despite positive antibody tests.9-13 Other studies have reported HIT complications in patients on haemodialysis, primarily thrombocytopenia, frequent clotting of the extra corporeal circuit14-16 or an increase in the number of failed arteriovenous fistulae.17 Lim JH et al. presented a case of an 80-year-old woman with a recent diagnosis of chronic renal failure who developed acute HIT (platelet count nadir, 15 × 109 /L) on day 7 of haemodialysis performed with routine heparin anticoagulation, who despite subsequent heparin-free hemodialysis (with argatroban and warfarin) developed recurrent HIT (complicated by acute cerebral infarction) on day 11 that was attributed to "rinsing" of the circuit with heparin-containing saline performed pre-dialysis as per routine. After stopping heparin rinsing, the platelet count recovered completely, without further thrombotic or other sequelae.18 Koon Ming Chan et al. reported a case of 58-year-old woman with acute kidney injury because of obstructive uropathy who developed HIT after heparin-free hemodialysis. She was found to have severe thrombocytopenia with deep vein thrombosis of left lower limb and arterial thrombosis of the right anterior and middle cerebral arteries. The heparin-platelet factor 4 antibody was positive. Heparin lock solution in the hemodialysis catheter was believed to be the cause of HIT in this patient.19

Results of HIT-antibody testing might not be immediately available and treatment should not be delayed pending laboratory confirmation in patients judged to be at high risk of HIT on the basis of clinical findings. Sufficient evidence exists to support the use of three non-heparin based agents in patients with Hit: the direct thrombin inhibitors, lepirudin and argatroban, and the factor Xa inhibitor, danaparoid.6 Seculini Patino CE et al. reported a case of a 73 years old woman with

HIT associated with arterial and venous thrombosis that was successfully treated with fondaparinux, with normalization of the platelet count and without progression of thrombosis.20 If warfarin treatment is indicated for an underlying medical condition or HIT-associated deep vein thrombosis (DVT), it must be delayed until adequate alternative anticoagulation has been provided and platelet counts have recovered substantially(to at least 100,000/mm3 or preferably 150,000/mm3). Warfarin should be started at the expected maintenance dose (maximum 5 mg) and not at a loading dose. Parenteral anticoagulation should be overlapped with warfarin for minimum of 5 days until a target international normalised ratio (INR) range has been achieved for at least 2 days.21

Conclusion:

Mortality in individuals with HIT and thrombosis may be as high as 30%.22 Early diagnosis and treatment is imperative.

References:

1. Warkentin TE. Heparin-Induced Thrombocytopenia: Pathogenesis and Management. Br J Haematol 2003;121(4):535-55.

2. Warkentin TE, Greinacher A, Koster A, et al. Treatment and Prevention of Heparin-Induced Thrombocytopenia: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest 2008;133(6 Suppl):340S-380S.

3. Jang IK, Hursting MJ. When Heparins Promote Thrombosis: Review of Heparin-Induced Thrombocytopenia. Circulation 2005; 111(20): 2671-83.

4. Martel N, Lee J, Wells PS. Risk for Heparin-Induced Thrombocytopenia with Unfractionated and Low - Molecular - Weight Heparin Thromboprophylaxis: a Meta-Analysis. Blood 2005;106(8):2710-5.

5. Warkentin, TE, Kelton JG. Delayed Onset Heparin-Induced Thrombocytopenia and Thrombosis. Ann Intern Med 2001; 135: 502–6.

6. Syed S, Reilly RF. Heparin-Induced Thrombocytopenia: a Renal Perspective. Nat Rev Nephrol 2009;5:501-11.

7. Warkentin TE, Aird WC, Rand JH. Platelet Endothelial Interactions: Sepsis, HiT and Antiphospholipid Syndrome. Hematology Am Soc Hematol Educ Program 2003;1:497–519.

8. Greinacher A et al. Laboratory Diagnosis of Heparin-Associated Thrombocytopenia and Comparison of Platelet Aggregation Test, Heparin Induced Platelet Activation Test, and Platelet Factor 4/Heparin Enzyme-Linked Immunosorbent Assay. Transfusion 1994;34:381–85.

9. Alberio L. Heparin-Induced Thrombocytopenia: Some Working Hypotheses on Pathogenesis, Diagnostic Strategies and Treatment. Curr Opin Hematol 2008; 15: 456–64.

10. Greinacher A, Zinn wizemann S, Birk UW. Heparin-Induced Antibodies as a Risk Factor for Thromboembolism and Haemorrhage in Patients Undergoing Chronic Haemodialysis. Lancet 1996;348:764.

11. Sitter T, Spannagl M, Banas B, et al. Prevalence of Heparin-Induced PF4-Heparin Antibodies in Haemodialysis Patients. Nephron 1998; 79:245–6.

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In mid-September of 2016, a 45-year-old gentleman got admitted in our Intensive Care Unit (ICU) with shock, due to dengue haemorrhagic fever (DHF), diagnosed clinically and evidenced by positive dengue NS1 antigen and anti-dengue antibodies (IgM and IgG). We managed him with intravenous fluid as per WHO guideline1 and necessary blood products. From day 7 of his illness (day 2 following admission), his clinical condition, as well as, haemogram started to improve. However, on the day-8 of his illness, he developed gradual abdominal distension. The abdomen was non-tender on palpation, with no organomegaly. Bowel sound was present. An abdominal radiograph (figure) revealed dilated colon. Supportive management and close monitoring was continued until his symptoms alleviated on day 11. He was discharged home on day-13 of his illness (day-8 following admission) with a diagnosis of Dengue Haemorrhagic Fever complicated with acute colonic pseudo-obstruction (Ogilvie’s Syndrome).Ogilvie’s syndrome (OS), first reported by Sir Heneage Ogilvie in 1948, is a clinical condition that shows symptoms, signs, and radiographic appearance of acute large-bowel obstruction, without evidence of a mechanical cause.2,3

1. Dr. Ahmad Mursel Anam, MRCP(UK), Specialist, Intensive Care Unit, Square Hospitals Ltd., 18/F, BU Qazi Nuruzzaman Sarak (West Panthapath), Dhaka 1205, Bangladesh.

2. Dr. Dipesh Kumar Barua, MBBS, Clinical Staff, Intensive Care Unit, Square Hospitals Ltd., 18/F, BU Qazi Nuruzzaman Sarak (West Panthapath), Dhaka 1205, Bangladesh.


Ahmad Mursel Anam, MRCP(UK)Specialist, Intensive Care UnitSquare Hospitals Ltd.18/F, BU Qazi Nuruzzaman Sarak (West Panthapath)Dhaka 1205, Bangladesh.Email: [email protected]

Various factors, including infections, metabolic, pharmacological, or traumatic, can alter the autonomic regulation of colonic function, causing colonic atony, and pseudo-obstruction.2 The exact cause of OS in DHF is not completely understood, but possibly associated with post-viral dysautonomia. Hyponatraemia in DHF might also be a cause for the acute intestinal pseudo-obstruction.4 Nausea, vomiting, abdominal distension, and pain are common symptoms at presentation. The abdomen is tympanic, and bowel sounds are typically present on examination. The most severe complication is caecal perforation, when the distension is >9 cm radiographically. Supportive management is usually the mainstay of therapy.2,3 OS is probably under-recognized and under-reported, most likely due to lack of awareness and spontaneous resolution in many cases.

Figure: Plain abdominal radiograph showing dilated colon.

Clinical Image

Ogilvie’s SyndromeAhmad Mursel Anam1, Dipesh Kumar Barua2

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References1. World Health Organization. Comprehensive Guidelines for

Prevention and Control of Dengue and Dengue Haemorrhagic Fever. Revised and Expanded Edition. New Delhi: World Health Organization, Regional Office for South-East Asia, 2011.

2. Saunders MD, Kimmey MB. Ogilvie’s Syndrome. In: McDonald JWD, Burroughs AK, Feagan BG, eds. Evidence-based Gastroenterology and Hepatology, 2nd edn. London: BMJ Books; 2005:303–9.

3. Maloney N, Vargas HD. Acute intestinal pseudo-obstruction (Ogilvie’s syndrome). Clin Colon Rectal Surg 2005; 18: 96–101.

4. Anam AM, Rabbani R. Ogilvie’s Syndrome in Severe Dengue. Lancet 2013; 381:698.

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volume 5, number 2, september 2017 - critical care medicine · 9/3/2018 · dr. madiha hashmi,...

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