May 2007

Dr CHAN Chin Pang Ian

Intensive Care Unit, United Christian Hospital



Severe sepsis triggers a series of mediator release leading to multiple organ injuries. Management of sepsis is multifactorial comprising source control, adequate antimicrobial therapy, early resuscitation of perfusion abnormalities, tight glycemic control and minimization of iatrogenic ventilator-induced lung injury.  Yet the morbidity and mortality associated with severe sepsis remains substantial.  Mediator removal by extracorporeal blood purification has been recently introduced into clinical practice with promising preliminary results.


With the introduction of newer and more sophisticated haemofiltration system, higher ultrafiltration rate (UF) (4L-6L/hour) is feasible.  Regarding the dose of CRRT, Ronco and coworkers demonstrated survival benefits, particularly in the subgroup suffering from sepsis, with higher UF (i.e. 35ml/kg/hr or 45ml/kg/hour as compared to 20ml/kg/hr).  Role of high-volume haemofiltration (HVHF) (UF > 35ml/kg/hour) in severe sepsis attracted clinicians’ attention.  They further proposed “Pulse” high-volume haemofiltration (PHVHF): i.e. the application of HVHF for 6–8 hours per day, followed by conventional continuous venovenous haemofiltration (CVVH) for treatment of severe sepsis complicated with acute renal failure.



This is a retrospective single-arm case review study conducted in United Christian Hospital, Hong Kong.  Patients with severe sepsis and associated acute renal failure who had undergone PHVHF were reviewed.  The effect on physiological responses, biochemical parameters, inotrope and vasopressor requirement, clinical outcomes and side effects were analyzed by studying the clinical records between 30th September, 2005 and 30th September, 2006 retrieved from the Clinical Management System (CMS) and Clinical Data and Reporting System (CDARS).



Eighteen patients with severe sepsis and underwent daily PHVHF (12 males and 6 females; mean APACHE II score 28.3, mean SAPS II score 56.6) were identified.  Haemodynamics and respiratory rate were improved after PHVHF, i.e. heart rate (P<0.001), MAP (P=0.016), DBP (P=0.013) and RR (P=0.001).  Predicted mortality rates were 61.6% (based on APACHE II score) and 57% (based on SAPS II score) respectively, and the observed 28-day mortality rate was 27.8%. Hypokalaemia and mild hypothermia were the main side effects associated with PHVHF.



PHVHF is a potential adjuvant treatment modality for management of severe sepsis with acute renal failure.  Retrospective analysis showed improvement in blood pressure, respiratory rate and survival benefits when compared to predictions based on severity scoring systems. Hypokalaemia and mild hypothermia are the major side effects.  However, current evidence base of application of PHVHF in clinical practice is not adequate.  Further large-scale, properly design clinical trials to establish the benefits and side effects of PHVHF are required.





Bone RC, Balk RA, Cerra FB: Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. The ACCP/SCCM Consensus Conference Committee. American College of Chest Physicians/Society of Critical Care Medicine. Chest 1992; 101: 1644-1655


Martin GS, Mannino DM, Eaton S: The epidemiology of sepsis in the United States from 1979 through 2000. N Engl J Med 2003 Apr 17; 348(16): 1546-54


Michael R Filbin, MD, et al: Shock, Septic. Emedicine 2006 Fev 23


Chalfin DB, Holbein ME, Fein AM, Carlon GC. Cost-effectiveness of monoclonal antibodies to gram-negative endotoxin in the treatment of gram-negative sepsis in ICU patients. JAMA 1993;269:249-254.


Angus DC, Linde-Zwirble WT, Lidicker J, Clermont G, Carcillo J, Pinsky MR. Epidemiology of severe sepsis in the United States: analysis of incidence, outcome, and associated costs of care. Crit Care Med 2001;29:1303-1310.


Bernard GR, Vincent JL, Laterre PF, et al. Efficacy and safety of recombinant human activated protein C for severe sepsis. N Engl J Med 2001;344:699-709.


Annane D, Aegerter P, Jars-Guincestre MC, Guidet B. Current epidemiology of septic shock: the CUB-Rea Network. Am J Respir Crit Care Med 2003;168:165-172.


Schrier RW, Wang W. Acute renal failure and sepsis. N Engl J Med 2004;351:159-169.


Rivers E, Nguyen B, Havstad S, et al. Early goal-directed therapy in the treatment of severe sepsis and septic shock. N Engl J Med 2001;345:1368-1377.


Ibrahim EH, Sherman G, Ward S, Fraser VJ, Kollef MH. The influence of inadequate antimicrobial treatment of bloodstream infections on patient outcomes in the ICU setting. Chest 2000;118:146-155.


Leibovici L, Shraga I, Drucker M, Konigsberger H, Samra Z, Pitlik SD. The benefit of appropriate empirical antibiotic treatment in patients with bloodstream infection. J Intern Med 1998;244:379-386.


The Acute Respiratory Distress Syndrome Network. Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. N Engl J Med 2000;342:1301-1308.


Bernard GR, Vincent JL, Laterre PF, et al. Efficacy and safety of recombinant human activated protein C for severe sepsis. N Engl J Med 2001;344:699-709.


Bernard GR, Margolis BD, Shanies HM, et al. Extended Evaluation of Recombinant Human Activated Protein C United States Trial (ENHANCE US): a single-arm, phase 3B, multicenter study of drotrecogin alfa (activated) in severe sepsis. Chest 2004;125:2206-2216.


Abraham E, Laterre PF, Garg R, et al. Drotrecogin alfa (activated) for adults with severe sepsis and a low risk of death. N Engl J Med 2005;353:1332-1341.


Annane D, Sebille V, Charpentier C, et al. Effect of treatment with low doses of hydrocortisone and fludrocortisone on mortality in patients with septic shock. JAMA 2002;288:862-871.


Marik PE, Zaloga GP. Adrenal insufficiency during septic shock. Crit Care Med 2003;31:141-145.




Van den Berghe G, Wouters P, Weekers F, et al. Intensive insulin therapy in critically ill patients. N Engl J Med 2001;345:1359-1367.


Van den Berghe G, Wilmer A, Hermans G, et al. Intensive insulin therapy in the medical ICU. N Engl J Med 2006;354:449-461.


Hotchkiss RS, Karl IE. The pathophysiology and treatment of sepsis. N Engl J Med 2003;348:138-150.


Claudio Ronco, Paola Inguaggiato, Vincenzo D’Intini, Luise Cole, Rinaldo Bellomo, Sonya Poulin, Valeria Bordoni1, Carlo Crepaldi, Fiorella Gastaldon, Alessandra Brendolan, Pisitkun Trairak, Tiranathanagul Khajohn. The role of extracorporeal therapies in sepsis. J NEPHROL 2003;16(suppl.7): S34-S41.


James A. Russell, M.D. Management of Sepsis. N Engl J Med Vol. 355:1699-1713 October 19, 2006 Number 16.


Study protocol: The DOse REsponse Multicentre International collaborative initiative (DO-RE-MI). Ronco et al. Critical Care 2005, 9:R396-R406.


Criteria for Acute Renal Failure in Hospitalized Patients. Crit Care Med. 2006;34(7):1913-1917. Bellomo, Ronco, et al.


Grootendorst AF, van Bommel EF, van der Hoven B, van Leengoed LA, van Osta AL: High volume hemofiltration improves right ventricular function in endotoxin-induced shock in the pig. Intensive Care Med 1992, 18:235-240.


Grootendorst AF, van Bommel EF, van Leengoed LA, Nabuurs M, Bouman CS, Groeneveld AB: High volume hemofiltration improves hemodynamics and survival of pigs exposed to gut ischemia and reperfusion. Shock 1994, 2:72-78.


Bellomo R, Kellum JA, Gandhi CR, Pinsky MR, Ondulik B: The effect of intensive plasma water exchange by hemofiltration on hemodynamics and soluble mediators in canine endotoxemia. Am J Respir Crit Care Med 2000, 161:1429-1436.


Ronco C, Bellomo R, Homel P, Brendolan A, Dan M, Piccinni P, La Greca G: Effects of different doses in continuous venovenous haemofiltration on outcomes of acute renal failure: a prospective randomised trial. Lancet 2000, 356:26-30.


Cole L, Bellomo R, Journois D, Davenport P, Baldwin I, Tipping P: High-volume haemofiltration in human septic shock. Intensive Care Med 2001, 27:978-986.


High-volume hemofiltration as salvage therapy in severe hyperdynamic septic shock. Intensive Care Med. 2006 May;32(5):713-22. Cornejo R et al.


Pulse high-volume haemofiltration for treatment of severe sepsis: effects on hemodynamics and survival- Critical Care 2005, 9:R294-R302 Claudio Ronco et al.


Patrick Murray et al. Renal Replacement Therapy for Acute Renal Failure. Am. J. Respir. Crit. Care Med.Vol 162, No. 3, Sept 2000, 777-781.


Rinaldo Bellomo, Claudio Ronco and John A Kellum. Pro/con clinical debate: Is high-volume hemofiltration beneficial in the treatment of septic shock? Critical Care 2002, 6:18-21.


Bouman, Catherine S. C. MD; Oudemans-van Straaten, Heleen M. MD, PhD; Tijssen, Jan G. P. MD, PhD; Zandstra, Durk F. MD, PhD; Kesecioglu, Jozef MD, PhD. Effects of early high-volume continuous venovenous hemofiltration on survival and recovery of renal function in intensive care patients with acute renal failure: A prospective, randomized trial. Critical Care Medicine. 30(10):2205-2211, October 2002.




Acute Dialysis Quality Initiative, 3rd International Consensus Conference, Workgroup 1, Definition & Nomenclature.


Ramesh Venkataraman, Sanjay Subramanian and John A Kellum. Clinical review: Extracorporeal blood purification in severe sepsis. Critical Care 2003, 7:139-145.


CSC Bouman., in collaboration with the committee nephrology and intensive care of the NVIC. Academisch Medisch Centrum, Amsterdam. Continuous renal replacement therapy in the ICU: Indications, modes, timing and treatment dose.


Ronco, Claudio. Recent evolution of renal replacement therapy in the critically ill patient Critical Care 2006 10:123.


Robert W. Schrier, M.D., and Wei Wang, M.D. Acute Renal Failure and Sepsis. N Engl J Med 2004;351:159-169.


Handbook of Internal Medicine. 2nd Edition 1999. Hospital Authority.


James Li et al. Hypothermia. 22nd September, 2005.


© Emory University. The Robert W. Woodruff Health Sciences Center. 2007. Atlanta, Georgia. SMR Analysis Version 4.11.19 at


R. Phillip Dellinger. Cardiovascular management of septic shock. Crit Care Med 2003 vol. 31, No. 3.


Bhaevsh M. Patel et al. Beneficial effects of short-term vasopressin infusion during severe septic shock. Anaesthesiology 2002; 96:576-82.


Kellum et al. Convection of diffusion in continuous renal replacement therapy for sepsis. Current Opinion in Critical Care. 6(6):426-430, December 2000.


R. Phillip Dellinger et al. Surviving Sepsis Campaign guidelines for management of severe sepsis and septic shock. Crit Care Med 2004 Vol. 32 No. 3


Daniel S Soper. Free Statistical Calculators.


Rinaldo Bellomo, Claudio Ronco, John A Kellum, et al. Acute renal failure – definition, outcome measures, animal models, fluid therapy and information technology needs: the Second International Consensus Conference of the Acute Dialysis Quality Initiative (ADQI) Group. Critical Care 2004, 8:R204-R212.


Paganini EP et al. Risk modelling in acute renal failure requiring dialysis: the introduction of new model. Clin Nephrol 1996; 46: 206-11.