High-volume versus standard-volume haemofiltration for septic shock patients with acute kidney injury (IVOIRE study): a multicentre randomized controlled trial
[en] PURPOSE : Septic shock is a leading cause of death among critically ill patients, in particular when complicated by acute kidney injury (AKI). Small experimental and human clinical studies have suggested that high-volume haemofiltration (HVHF) may improve haemodynamic profile and mortality. We sought to determine the impact of HVHF on 28-day mortality in critically ill patients with septic shock and AKI.
METHODS:
This was a prospective, randomized, open, multicentre clinical trial conducted at 18 intensive care units in France, Belgium and the Netherlands. A total of 140 critically ill patients with septic shock and AKI for less than 24 h were enrolled from October 2005 through March 2010. Patients were randomized to either HVHF at 70 mL/kg/h or standard-volume haemofiltration (SVHF) at 35 mL/kg/h, for a 96-h period.
RESULTS:
Primary endpoint was 28-day mortality. The trial was stopped prematurely after enrolment of 140 patients because of slow patient accrual and resources no longer being available. A total of 137 patients were analysed (two withdrew consent, one was excluded); 66 patients in the HVHF group and 71 in the SVHF group. Mortality at 28 days was lower than expected but not different between groups (HVHF 37.9 % vs. SVHF 40.8 %, log-rank test p = 0.94). There were no statistically significant differences in any of the secondary endpoints between treatment groups.
CONCLUSIONS:
In the IVOIRE trial, there was no evidence that HVHF at 70 mL/kg/h, when compared with contemporary SVHF at 35 mL/kg/h, leads to a reduction of 28-day mortality or contributes to early improvements in haemodynamic profile or organ function. HVHF, as applied in this trial, cannot be recommended for treatment of septic shock complicated by AKI.
Disciplines :
Anesthesia & intensive care
Author, co-author :
JOANNES-BOYAU, Olivier; CENTRE HOSPITALIER UNIVERSITAIRE de Bordeaux, France > Service d'Anesthésie-Réanimation 2
PEREZ, Paul; CHU BORDEAUX > Unité de Soutien Méthodologique à la Recherche Clinique et Epidémiologique
BAGSHAW, Sean; UNIVERSITY OF ALBERTA - Edmonton (Canada) > Faculty of Medicine and Dentistery > Division of Critical Care Medicine
GRAND, Hubert; HOPITAL R. BOULIN - Libourne (France) > POLE EPURS > Réanimation Polyvalente
CANIVET, Jean-Luc ; Centre Hospitalier Universitaire de Liège - CHU > Soins Intensifs Généraux
DEWITTE, Antoine; CENTRE HOSPITALIER UNIVERSITAIRE de Bordeaux, France > Service d'Anesthésie-Réanimation 2
FLAMENS, Claire; HOPITAL CARDIOVASCULAIRE ET PNEUMOLOGIE LOUIS PRADEL de Lyon, France > Service d'Anesthésie-Réanimation
PUJOL, Wilfried; CLINIQUE BORDEAUX NORD AQUITAINE de Bordeaux, France > Service de Réanimation
GRANDOULIER, Anne-Sophie; CHU de Bordeaux, France > Pôle de Santé Publique et CIC-EC7 > Unité de Soutien Méthodologique à la Recherche Clinique et Epidémiologique (USMR)
FLEUREAU, Catherine; CENTRE HOSPITALIER de Bordeaux, France > Service d'Anesthésie-Réanimation 2
High-volume versus standard-volume haemofiltration for septic shock patients with acute kidney injury (IVOIRE study): a multicentre randomized controlled trial
Publication date :
September 2013
Journal title :
Intensive Care Medicine
ISSN :
0342-4642
eISSN :
1432-1238
Publisher :
Springer Verlag, New York, United States - New York
Angus, D.C., Linde-Zwirble, W.T., Lidicker, J., Epidemiology of severe sepsis in the United States: Analysis of incidence, outcome, and associated costs of care (2001) Crit Care Med, 29, pp. 1303-1310. , 11445675 10.1097/00003246-200107000-00002 1:STN:280: DC%2BD3Mvgs12gtg%3D%3D
Bagshaw, S.M., Uchino, S., Bellomo, R., Septic acute kidney injury in critically ill patients: Clinical characteristics and outcomes (2007) Clin J Am Soc Nephrol, 2, pp. 431-439. , 17699448 10.2215/CJN.03681106
Bernard, G.R., Vincent, J.L., Laterre, P.F., Efficacy and safety of recombinant human activated protein C for severe sepsis (2001) N Engl J Med, 344, pp. 699-709. , 11236773 10.1056/NEJM200103083441001 1:CAS:528:DC%2BD3MXitFamt7s%3D
Opal, S.M., Laterre, P.-F., Francois, B., Effect of eritoran, an antagonist of MD2-TLR4, on mortality in patients with severe sepsis: The ACCESS randomized trial (2013) JAMA J Am Med Assoc, 309, pp. 1154-1162. , 10.1001/jama.2013.2194 1:CAS:528:DC%2BC3sXltlyqt7o%3D
Finfer, S., Chittock, D.R., Su, S.-S., Intensive versus conventional glucose control in critically ill patients (2009) N Engl J Med, 360, pp. 1283-1297. , 19318384 10.1056/NEJMoa0810625
Hoffmann, J.N., Hartl, W.H., Deppisch, R., Effect of hemofiltration on hemodynamics and systemic concentrations of anaphylatoxins and cytokines in human sepsis (1996) Intensive Care Med, 22, pp. 1360-1367. , 8986487 10.1007/BF01709552 1:STN:280:DyaK2s7jvF2itA%3D%3D
Heering, P., Morgera, S., Schmitz, F.J., Cytokine removal and cardiovascular hemodynamics in septic patients with continuous venovenous hemofiltration (1997) Intensive Care Med, 23, pp. 288-296. , 9083231 10.1007/s001340050330 1:STN:280:DyaK2s3js1Ggtw%3D%3D
Bellomo, R., Tipping, P., Boyce, N., Continuous veno-venous hemofiltration with dialysis removes cytokines from the circulation of septic patients (1993) Crit Care Med, 21, pp. 522-526. , 8472571 10.1097/00003246-199304000-00011 1:STN:280:DyaK3s3jtV2gsg%3D%3D
Honore, P.M., Joannes-Boyau, O., High volume hemofiltration (HVHF) in sepsis: A comprehensive review of rationale, clinical applicability, potential indications and recommendations for future research (2004) Int J Artif Organs, 27, pp. 1077-1082. , 15645619 1:STN:280:DC%2BD2M%2FhvFemtg%3D%3D
Rimmelé, T., Kellum, J.A., High-volume hemofiltration in the intensive care unit: A blood purification therapy (2012) Anesthesiology, 116, pp. 1377-1387. , 22534247 10.1097/ALN.0b013e318256f0c0
Rogiers, P., Zhang, H., Smail, N., Continuous venovenous hemofiltration improves cardiac performance by mechanisms other than tumor necrosis factor-alpha attenuation during endotoxic shock (1999) Crit Care Med, 27, pp. 1848-1855. , 10507609 10.1097/00003246-199909000-00024 1:STN:280:DyaK1MvjsFCnsQ%3D%3D
Yekebas, E.F., Eisenberger, C.F., Ohnesorge, H., Attenuation of sepsis-related immunoparalysis by continuous veno-venous hemofiltration in experimental porcine pancreatitis (2001) Crit Care Med, 29, pp. 1423-1430. , 11445702 10.1097/00003246-200107000-00021 1:STN:280: DC%2BD3MvhtVyqsg%3D%3D
Wang, H., Zhang, Z.H., Yan, X.W., Amelioration of hemodynamics and oxygen metabolism by continuous venovenous hemofiltration in experimental porcine pancreatitis (2005) World J Gastroenterol, 11, pp. 127-131. , 15609411
Rimmelé, T., Assadi, A., Cattenoz, M., High-volume haemofiltration with a new haemofiltration membrane having enhanced adsorption properties in septic pigs (2009) Nephrol Dial Transplant, 24, pp. 421-427. , 18799607 10.1093/ndt/gfn518
Bellomo, R., Kellum, J.A., Gandhi, C.R., The effect of intensive plasma water exchange by hemofiltration on hemodynamics and soluble mediators in canine endotoxemia (2000) Am J Respir Crit Care Med, 161, pp. 1429-1436. , 10806135 10.1164/ajrccm.161.5.9809127 1:STN:280:DC%2BD3c3mvVSntA%3D%3D
Honore, P.M., Jamez, J., Wauthier, M., Prospective evaluation of short-term, high-volume isovolemic hemofiltration on the hemodynamic course and outcome in patients with intractable circulatory failure resulting from septic shock (2000) Crit Care Med, 28, pp. 3581-3587. , 11098957 10.1097/00003246-200011000-00001 1:STN:280: DC%2BD3M%2Flt1Gjsw%3D%3D
Joannes-Boyau, O., Rapaport, S., Bazin, R., Impact of high volume hemofiltration on hemodynamic disturbance and outcome during septic shock (2004) ASAIO J, 50, pp. 102-109. , 14763500 10.1097/01.MAT.0000104846.27116.EA
Cornejo, R., Downey, P., Castro, R., High-volume hemofiltration as salvage therapy in severe hyperdynamic septic shock (2006) Intensive Care Med, 32, pp. 713-722. , 16550372 10.1007/s00134-006-0118-5 1:CAS:528:DC%2BD1cXhtVyjsbvJ
Cole, L., Bellomo, R., Hart, G., A phase II randomized, controlled trial of continuous hemofiltration in sepsis (2002) Crit Care Med, 30, pp. 100-106. , 11902250 10.1097/00003246-200201000-00016 1:CAS:528:DC%2BD38XhtVylurw%3D
Cole, L., Bellomo, R., Journois, D., High-volume haemofiltration in human septic shock (2001) Intensive Care Med, 27, pp. 978-986. , 11497156 10.1007/s001340100963 1:STN:280:DC%2BD3MvltFWlsw%3D%3D
Ratanarat, R., Brendolan, A., Piccinni, P., Pulse high-volume haemofiltration for treatment of severe sepsis: Effects on hemodynamics and survival (2005) Crit Care, 9, pp. 294-R302. , 16137340 10.1186/cc3529
Boussekey, N., Chiche, A., Faure, K., A pilot randomized study comparing high and low volume hemofiltration on vasopressor use in septic shock (2008) Intensive Care Med, 34, pp. 1646-1653. , 18542921 10.1007/s00134-008-1127-3 1:CAS:528:DC%2BD1cXhtFKis7jP
Uchino, S., Bellomo, R., Morimatsu, H., Continuous renal replacement therapy: A worldwide practice survey. The beginning and ending supportive therapy for the kidney (B.E.S.T. kidney) investigators (2007) Intensive Care Med, 33, pp. 1563-1570. , 17594074 10.1007/s00134-007-0754-4
Vesconi, S., Cruz, D.N., Fumagalli, R., Delivered dose of renal replacement therapy and mortality in critically ill patients with acute kidney injury (2009) Crit Care, 13, p. 57. , 19368724 10.1186/cc7784
Lee, K., Lee, S.R., Mun, C.H., Min, B.G., Pulse push/pull hemodialysis: In vitro study on new dialysis modality with higher convective efficiency (2008) Artif Organs, 32, pp. 406-411. , 18471170 10.1111/j.1525-1594.2008.00561.x
Churchwell, M.D., Pasko, D.A., Btaiche, I.F., Trace element removal during in vitro and in vivo continuous haemodialysis (2007) Nephrol Dial Transplant, 22, pp. 2970-2977. , 17556411 10.1093/ndt/gfm352 1:CAS:528:DC%2BD2sXhtFWhur7M
Bouman, C.S., Van Kan, H.J., Koopmans, R.P., Discrepancies between observed and predicted continuous venovenous hemofiltration removal of antimicrobial agents in critically ill patients and the effects on dosing (2006) Intensive Care Med, 32, pp. 2013-2019. , 17043848 10.1007/s00134-006-0397-x
Klouche, K., Cavadore, P., Portales, P., Continuous veno-venous hemofiltration improves hemodynamics in septic shock with acute renal failure without modifying TNFalpha and IL6 plasma concentrations (2002) J Nephrol, 15, pp. 150-157. , 12018631
Kellum, J.A., Venkataraman, R., Blood purification in sepsis: An idea whose time has come? (2002) Crit Care Med, 30, pp. 1387-1388. , 12072702 10.1097/00003246-200206000-00047
Joannes-Boyau, O., Honore, P.M., Boer, W., Hemofiltration: The case for removal of sepsis mediators from where they do harm (2006) Crit Care Med, 34, pp. 2244-2246. , 16883194 10.1097/01.CCM.0000227650.77064.5F
Levy, M.M., Fink, M.P., Marshall, J.C., 2001 SCCM/ESICM/ACCP/ATS/SIS International Sepsis Definitions Conference (2003) Crit Care Med, 31, pp. 1250-1256. , 12682500 10.1097/01.CCM.0000050454.01978.3B
Bellomo, R., Ronco, C., Kellum, J.A., 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 (2004) Crit Care, 8, pp. 204-R212. , 15312219 10.1186/cc2872
Pottecher, T., Calvat, S., Dupont, H., Haemodynamic management of severe sepsis: Recommendations of the French Intensive Care Societies (SFAR/SRLF) Consensus Conference, 13 October 2005, Paris, France (2006) Crit Care, 10, p. 311. , 16941754 10.1186/cc4965
Vincent, J.L., Moreno, R., Takala, J., The SOFA (Sepsis-Related Organ Failure Assessment) score to describe organ dysfunction/failure. On behalf of the Working Group on Sepsis-Related Problems of the European Society of Intensive Care Medicine (1996) Intensive Care Med, 22, pp. 707-710. , 8844239 10.1007/BF01709751 1:STN:280:DyaK2s%2FgtFantQ%3D%3D
Le Gall, J.R., Lemeshow, S., Saulnier, F., A new Simplified Acute Physiology Score (SAPS II) based on a European/North American multicenter study (1993) JAMA, 270, pp. 2957-2963. , 8254858 10.1001/jama.1993.03510240069035
Shore, S., Nelson, D.P., Pearl, J.M., Usefulness of corticosteroid therapy in decreasing epinephrine requirements in critically ill infants with congenital heart disease (2001) Am J Cardiol, 88, pp. 591-594. , 11524081 10.1016/S0002-9149(01)01751-9 1:CAS:528:DC%2BD3MXmt1Klu7s%3D
Wernovsky, G., Wypij, D., Jonas, R.A., Postoperative course and hemodynamic profile after the arterial switch operation in neonates and infants. A comparison of low-flow cardiopulmonary bypass and circulatory arrest (1995) Circulation, 92, pp. 2226-2235. , 7554206 10.1161/01.CIR.92.8.2226 1:STN:280:DyaK28%2FhslejsA%3D%3D
Zuppa, A.F., Nadkarni, V., Davis, L., The effect of a thyroid hormone infusion on vasopressor support in critically ill children with cessation of neurologic function (2004) Crit Care Med, 32, pp. 2318-2322. , 15640648 1:CAS:528:DC%2BD2cXpsl2jtr0%3D
Tsujimoto, H., Ono, S., Hiraki, S., Hemoperfusion with polymyxin B-immobilized fibers reduced the number of CD16+ CD14+ monocytes in patients with septic shock (2004) J Endotoxin Res, 10, pp. 229-237. , 15373966 1:CAS:528:DC%2BD2cXhtVyitrvI
Cruz, D.N., Antonelli, M., Fumagalli, R., Early use of polymyxin B hemoperfusion in abdominal septic shock: The EUPHAS randomized controlled trial (2009) JAMA, 301, pp. 2445-2452. , 19531784 10.1001/jama.2009.856 1:CAS:528:DC%2BD1MXnsFaqsLY%3D
Parrillo, J.E., Pathogenetic mechanisms of septic shock (1993) N Engl J Med, 328, pp. 1471-1477. , 8479467 10.1056/NEJM199305203282008 1:STN:280:DyaK3s3ktFagtg%3D%3D
Metnitz, P.G., Krenn, C.G., Steltzer, H., Effect of acute renal failure requiring renal replacement therapy on outcome in critically ill patients (2002) Crit Care Med, 30, pp. 2051-2058. , 12352040 10.1097/00003246-200209000-00016
Schrier, R.W., Wang, W., Acute renal failure and sepsis (2004) N Engl J Med, 351, pp. 159-169. , 15247356 10.1056/NEJMra032401 1:CAS:528:DC%2BD2cXls1elsbk%3D
Hernandez, A.V., Eijkemans, M.J., Steyerberg, E.W., Randomized controlled trials with time-to-event outcomes: How much does prespecified covariate adjustment increase power? (2006) Ann Epidemiol, 16, pp. 41-48. , 16275011 10.1016/j.annepidem.2005.09.007
Zhang, P., Yang, Y., Lv, R., Effect of the intensity of continuous renal replacement therapy in patients with sepsis and acute kidney injury: A single-center randomized clinical trial (2012) Nephrol Dial Transpl, 27, pp. 967-973. , 10.1093/ndt/gfr486 1:CAS:528:DC%2BC38XnsFGnsbc%3D
Ronco, C., Bellomo, R., Homel, P., Effects of different doses in continuous veno-venous haemofiltration on outcomes of acute renal failure: A prospective randomised trial (2000) Lancet, 356, pp. 26-30. , 10892761 10.1016/S0140-6736(00)02430-2 1:STN:280:DC%2BD3czovVejsw%3D%3D
Bellomo, R., Cass, A., Cole, L., Intensity of continuous renal-replacement therapy in critically ill patients (2009) N Engl J Med, 361, pp. 1627-1638. , 19846848 10.1056/NEJMoa0902413
Palevsky, P.M., Zhang, J.H., O'Connor, T.Z., Intensity of renal support in critically ill patients with acute kidney injury (2008) N Engl J Med, 359, pp. 7-20. , 18492867 10.1056/NEJMoa0802639 1:CAS:528:DC%2BD1cXotFSisr0%3D
Bellomo, R., Lipcsey, M., Calzavacca, P., Early acid-base and blood pressure effects of continuous renal replacement therapy intensity in patients with metabolic acidosis (2013) Intensive Care Med, 39, pp. 429-436. , 23306586 10.1007/s00134-012-2800-0
Demirjian, S., Teo, B.W., Guzman, J.A., Hypophosphatemia during continuous hemodialysis is associated with prolonged respiratory failure in patients with acute kidney injury (2011) Nephrol Dial Transpl, 26, pp. 3508-3514. , 10.1093/ndt/gfr075 1:CAS:528:DC%2BC3MXhtlyqtrjP
Roberts, D.M., Roberts, J.A., Roberts, M.S., Variability of antibiotic concentrations in critically ill patients receiving continuous renal replacement therapy: A multicentre pharmacokinetic study (2012) Crit Care Med, 40, pp. 1523-1528. , 22511133 10.1097/CCM.0b013e318241e553 1:CAS:528:DC%2BC38XlvVSjsbs%3D
Payen, D., Mateo, J., Cavaillon, J.M., Impact of continuous venovenous hemofiltration on organ failure during the early phase of severe sepsis: A randomized controlled trial (2009) Crit Care Med, 37, pp. 803-810. , 19237881 10.1097/CCM.0b013e3181962316