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LETTER
Year : 2012  |  Volume : 58  |  Issue : 4  |  Page : 330-331

Titrated dose of drotrecogin alpha for liver transplant recipient


Department of Anaesthesiology, Institute of Liver and Biliary Sciences, Vasant Kunj, New Delhi, India

Date of Web Publication4-Jan-2013

Correspondence Address:
C K Pandey
Department of Anaesthesiology, Institute of Liver and Biliary Sciences, Vasant Kunj, New Delhi
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0022-3859.105487

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How to cite this article:
Saluja V, Pandey V, Pandey C K, Singhal A. Titrated dose of drotrecogin alpha for liver transplant recipient. J Postgrad Med 2012;58:330-1

How to cite this URL:
Saluja V, Pandey V, Pandey C K, Singhal A. Titrated dose of drotrecogin alpha for liver transplant recipient. J Postgrad Med [serial online] 2012 [cited 2020 Apr 3];58:330-1. Available from: http://www.jpgmonline.com/text.asp?2012/58/4/330/105487


Sir,

Infectious complications are the commonest cause of re-hospitalization and death in the first year of liver transplantation. [1] These patients are prone to develop sepsis and septic shock due to immunosuppressants resulting into high morbidity and mortality. Drotrecogin alpha has been found effective in management of severe sepsis. [2] However, the use of Drotrecogin alpha in severe sepsis in liver transplant recipients is based on case series without clinical trial.

A 36-year-old male with alcohol-related end stage liver disease underwent orthotopic liver transplant. Anesthesia and surgery were uneventful. On post-operative day 21, patient developed microbiologically documented infection, satisfying systemic inflammatory response syndrome (SIRS) criteria (heart rate >130/min, respiratory rate 38-40/min, total leukocyte counts 13400 cells/mm 3 ). He required endotracheal intubation and ventilatory support. His endotracheal aspirates were positive for cytomegalovirus (CMV) infection. His X-ray chest demonstrated bilateral infiltrates. He developed hypotension and required vasopressor. Despite escalating multi-organ support, deterioration in his clinical condition continued. His blood samples were also positive for cytomegalovirus (CMV) infection. In view of deteriorating clinical condition, all immunosuppressants were stopped and drotrecogin alpha was started in a dose of 24 μg/kg/hr, but after 12 hours of infusion, he developed fresh nasogastric bleed and the infusion was discontinued. It was re-started after 5 hours in the dose of 20 μg/kg/hr and continued till the next day and was increased to 24 μg/kg/hr and continued till completion of therapy. He developed minor ooze orally due to accidental pulling out of nasogastric tube, but infusion was continued. He demonstrated favorable recovery (gradual decrease in vasopressor, ventilatory assistance and leukocyte count) and was extubated successfully 10 days later.

Efficacy of drotrecogin alpha has been demonstrated in liver transplant recipients for management of severe sepsis. The suggested mechanisms of action are by its anticoagulant, anti-inflammatory and profibrinolytic action, which interrupt the inflammatory cascade triggered by a septic insult. Drotrecogin alpha promotes anticoagulation by the inhibition of factors V and VIII, anti-inflammatory response is created through indirect tumor necrosis factor-alpha inhibition, and fibrinolysis is via inhibition of plasminogen activator inhibitor. [2],[3]

Role of drotrecogin alpha in liver transplant recipients have been demonstrated in case reports. Browne et al.[3] demonstrated the successful use drotrecogin alpha after 93 days of liver transplantation in a dose of 24 μg/kg/hr for treatment of pneumococcal septic shock. Similarly, Feltracco [4] et al. administered drotrecogin alpha 15 days following liver transplant for acute septic shock due to nosocomial acquired pneumonia in a dose of 24 μg/kg/hr along with conventional aggressive treatment and effectively reverted the life-threatening vasoplegia.

Low dose of drotrecogin alpha (18 μg/kg/hr) has been used by Shang Wang et al. [5] in a septic patient with intestinal obstruction. Because their patient could not tolerate the 24 μg/ kg/hr dose, 18 μg/kg/hr drotrecogin alpha was administered and that patient showed a favorable recovery. We did modify the dose of drotrecogin alpha from 24 to 20 μg/kg/hr when our patient had evidence of nasogastric bleed, but subsequently we increased the dose to 24 μg/kg/hr without any adverse effects.

Based on our experience of this case, we suggest titration of drotrecogin alpha in the dose range of 20-24 μg/kg/hr. This dose range allows completion of drotrecogin alpha therapy with favorable outcome and without an increased risk of bleeding. However, recently completed Prowess Shock study demonstrated that use of drotrecogin alpha could not reduce 28 days all cause mortality to statistically significant primary end point in patients with septic shock. [6] This led to recent withdrawal of drug from the market by the

manufacturer.

 
 :: References Top

1.Kalil AC, Dakroub H, Freifeld AG. Sepsis and solid organ transplantation. Curr Drug Targets 2007;8:533-41.  Back to cited text no. 1
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2.Browne E, Cressey DM, Agarwal K, Cosgrove JF. The use of drotrecogin alfa (activated) in a patient with recent orthotopic liver transplant. Anaesthesia 2007;62:282-5.  Back to cited text no. 2
[PUBMED]    
3.Toussaint S, Gerlach H. Activated protein C for sepsis. N Engl J Med 2009;361:2646-52.  Back to cited text no. 3
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4.Feltracco P, Bortolato A, Rizzi S, Barbieri S, Furnari M, Serra E, et al. Activated recombinant protein C in septic shock early after liver transplantation: A case report. Transplant Proc 2008;40:2070-2.  Back to cited text no. 4
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5.Wang S, Dabovic K, Spector RS. Low-dose, off-label drotrecogin alfa (xigris) in severe sepsis. P T 2008;33:469-76.  Back to cited text no. 5
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6.Ranieri VM, Thompson BT, Finfer S, Barie PS, Dhainaut JF, Douglas IS, et al. Unblinding plan of PROWESS-SHOCK trial. Intensive Care Med 2011;37:1384-5.  Back to cited text no. 6
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Online since 12th February '04
2004 - Journal of Postgraduate Medicine
Official Publication of the Staff Society of the Seth GS Medical College and KEM Hospital, Mumbai, India
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