Skip to main content
Top
Published in: Intensive Care Medicine 1/2018

01-01-2018 | Systematic Review

Pooled analysis of higher versus lower blood pressure targets for vasopressor therapy septic and vasodilatory shock

Authors: François Lamontagne, Andrew G. Day, Maureen O. Meade, Deborah J. Cook, Gordon H. Guyatt, Mathieu Hylands, Peter Radermacher, Jean-Marie Chrétien, Nicolas Beaudoin, Paul Hébert, Frédérick D’Aragon, Ferhat Meziani, Pierre Asfar

Published in: Intensive Care Medicine | Issue 1/2018

Login to get access

Abstract

Purpose

Guidelines for shock recommend mean arterial pressure (MAP) targets for vasopressor therapy of at least 65 mmHg and, until recently, suggested that patients with underlying chronic hypertension and atherosclerosis may benefit from higher targets. We conducted an individual patient-data meta-analysis of recent trials to determine if patient variables modify the effect of different MAP targets.

Methods

We searched the MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials for randomized controlled trials of higher versus lower blood pressure targets for vasopressor therapy in adult patients in shock (until November 2017). After obtaining individual patient data from both eligible trials, we used a modified version of the Cochrane Collaboration’s instrument to assess the risk of bias of included trials. The primary outcome was 28-day mortality.

Results

Included trials enrolled 894 patients. Controlling for trial and site, the OR for 28-day mortality for the higher versus lower MAP targets was 1.15 (95% CI 0.87–1.52). Treatment effect varied by duration of vasopressors before randomization (interaction p = 0.017), but not by chronic hypertension, congestive heart failure or age. Risk of death increased in higher MAP groups among patients on vasopressors > 6 h before randomization (OR 3.00, 95% CI 1.33–6.74).

Conclusions

Targeting higher blood pressure targets may increase mortality in patients who have been treated with vasopressors for more than 6 h. Lower blood pressure targets were not associated with patient-important adverse events in any subgroup, including chronically hypertensive patients.
Appendix
Available only for authorised users
Literature
1.
go back to reference Dellinger RP, Levy MM, Rhodes A, Annane D, Gerlach H, Opal SM, Sevransky JE, Sprung CL, Douglas IS, Jaeschke R, Osborn TM, Nunnally ME, Townsend SR, Reinhart K, Kleinpell RM, Angus DC, Deutschman CS, Machado FR, Rubenfeld GD, Webb SA, Beale RJ, Vincent JL, Moreno R, Surviving Sepsis Campaign Guidelines Committee including the Pediatric S (2013) Surviving sepsis campaign: international guidelines for management of severe sepsis and septic shock: 2012. Crit Care Med 41:580–637CrossRefPubMed Dellinger RP, Levy MM, Rhodes A, Annane D, Gerlach H, Opal SM, Sevransky JE, Sprung CL, Douglas IS, Jaeschke R, Osborn TM, Nunnally ME, Townsend SR, Reinhart K, Kleinpell RM, Angus DC, Deutschman CS, Machado FR, Rubenfeld GD, Webb SA, Beale RJ, Vincent JL, Moreno R, Surviving Sepsis Campaign Guidelines Committee including the Pediatric S (2013) Surviving sepsis campaign: international guidelines for management of severe sepsis and septic shock: 2012. Crit Care Med 41:580–637CrossRefPubMed
2.
go back to reference Cecconi M, De Backer D, Antonelli M, Beale R, Bakker J, Hofer C, Jaeschke R, Mebazaa A, Pinsky MR, Teboul JL, Vincent JL, Rhodes A (2014) Consensus on circulatory shock and hemodynamic monitoring. Task force of the European Society of Intensive Care Medicine. Intensive Care Med 40:1795–1815CrossRefPubMedPubMedCentral Cecconi M, De Backer D, Antonelli M, Beale R, Bakker J, Hofer C, Jaeschke R, Mebazaa A, Pinsky MR, Teboul JL, Vincent JL, Rhodes A (2014) Consensus on circulatory shock and hemodynamic monitoring. Task force of the European Society of Intensive Care Medicine. Intensive Care Med 40:1795–1815CrossRefPubMedPubMedCentral
3.
go back to reference Lamontagne F, Cohen D, Herridge M (2017) Understanding patient-centredness: contrasting expert versus patient perspectives on vasopressor therapy for shock. Intensive Care Med 43:1052–1054CrossRefPubMed Lamontagne F, Cohen D, Herridge M (2017) Understanding patient-centredness: contrasting expert versus patient perspectives on vasopressor therapy for shock. Intensive Care Med 43:1052–1054CrossRefPubMed
4.
go back to reference Andreis DT, Singer M (2016) Catecholamines for inflammatory shock: a Jekyll-and-Hyde conundrum. Intensive Care Med 42:1387–1397CrossRefPubMed Andreis DT, Singer M (2016) Catecholamines for inflammatory shock: a Jekyll-and-Hyde conundrum. Intensive Care Med 42:1387–1397CrossRefPubMed
5.
go back to reference Asfar P, Meziani F, Hamel JF, Grelon F, Megarbane B, Anguel N, Mira JP, Dequin PF, Gergaud S, Weiss N, Legay F, Le Tulzo Y, Conrad M, Robert R, Gonzalez F, Guitton C, Tamion F, Tonnelier JM, Guezennec P, Van Der Linden T, Vieillard-Baron A, Mariotte E, Pradel G, Lesieur O, Ricard JD, Herve F, du Cheyron D, Guerin C, Mercat A, Teboul JL, Radermacher P, Investigators S (2014) High versus low blood-pressure target in patients with septic shock. N Engl J Med 370:1583–1593CrossRefPubMed Asfar P, Meziani F, Hamel JF, Grelon F, Megarbane B, Anguel N, Mira JP, Dequin PF, Gergaud S, Weiss N, Legay F, Le Tulzo Y, Conrad M, Robert R, Gonzalez F, Guitton C, Tamion F, Tonnelier JM, Guezennec P, Van Der Linden T, Vieillard-Baron A, Mariotte E, Pradel G, Lesieur O, Ricard JD, Herve F, du Cheyron D, Guerin C, Mercat A, Teboul JL, Radermacher P, Investigators S (2014) High versus low blood-pressure target in patients with septic shock. N Engl J Med 370:1583–1593CrossRefPubMed
6.
go back to reference Lamontagne F, Meade MO, Hebert PC, Asfar P, Lauzier F, Seely AJE, Day AG, Mehta S, Muscedere J, Bagshaw SM, Ferguson ND, Cook DJ, Kanji S, Turgeon AF, Herridge MS, Subramanian S, Lacroix J, Adhikari NKJ, Scales DC, Fox-Robichaud A, Skrobik Y, Whitlock RP, Green RS, Koo KKY, Tanguay T, Magder S, Heyland DK, Canadian Critical Care Trials G (2016) Higher versus lower blood pressure targets for vasopressor therapy in shock: a multicentre pilot randomized controlled trial. Intensive Care Med 42:542–550CrossRefPubMed Lamontagne F, Meade MO, Hebert PC, Asfar P, Lauzier F, Seely AJE, Day AG, Mehta S, Muscedere J, Bagshaw SM, Ferguson ND, Cook DJ, Kanji S, Turgeon AF, Herridge MS, Subramanian S, Lacroix J, Adhikari NKJ, Scales DC, Fox-Robichaud A, Skrobik Y, Whitlock RP, Green RS, Koo KKY, Tanguay T, Magder S, Heyland DK, Canadian Critical Care Trials G (2016) Higher versus lower blood pressure targets for vasopressor therapy in shock: a multicentre pilot randomized controlled trial. Intensive Care Med 42:542–550CrossRefPubMed
7.
go back to reference Hylands M, Moller MH, Asfar P, Toma A, Frenette AJ, Beaudoin N, Belley-Cote E, D’Aragon F, Laake JH, Siemieniuk RA, Charbonney E, Lauzier F, Kwong J, Rochwerg B, Vandvik PO, Guyatt G, Lamontagne F (2017) A systematic review of vasopressor blood pressure targets in critically ill adults with hypotension. Can J Anaesth 64:703–715CrossRefPubMed Hylands M, Moller MH, Asfar P, Toma A, Frenette AJ, Beaudoin N, Belley-Cote E, D’Aragon F, Laake JH, Siemieniuk RA, Charbonney E, Lauzier F, Kwong J, Rochwerg B, Vandvik PO, Guyatt G, Lamontagne F (2017) A systematic review of vasopressor blood pressure targets in critically ill adults with hypotension. Can J Anaesth 64:703–715CrossRefPubMed
8.
go back to reference Brown SM, Lanspa MJ, Jones JP, Kuttler KG, Li Y, Carlson R, Miller RR 3rd, Hirshberg EL, Grissom CK, Morris AH (2013) Survival after shock requiring high-dose vasopressor therapy. Chest 143:664–671CrossRefPubMed Brown SM, Lanspa MJ, Jones JP, Kuttler KG, Li Y, Carlson R, Miller RR 3rd, Hirshberg EL, Grissom CK, Morris AH (2013) Survival after shock requiring high-dose vasopressor therapy. Chest 143:664–671CrossRefPubMed
9.
go back to reference Briel M, Meade M, Mercat A, Brower RG, Talmor D, Walter SD, Slutsky AS, Pullenayegum E, Zhou Q, Cook D, Brochard L, Richard JC, Lamontagne F, Bhatnagar N, Stewart TE, Guyatt G (2010) Higher vs lower positive end-expiratory pressure in patients with acute lung injury and acute respiratory distress syndrome: systematic review and meta-analysis. JAMA 303:865–873CrossRefPubMed Briel M, Meade M, Mercat A, Brower RG, Talmor D, Walter SD, Slutsky AS, Pullenayegum E, Zhou Q, Cook D, Brochard L, Richard JC, Lamontagne F, Bhatnagar N, Stewart TE, Guyatt G (2010) Higher vs lower positive end-expiratory pressure in patients with acute lung injury and acute respiratory distress syndrome: systematic review and meta-analysis. JAMA 303:865–873CrossRefPubMed
10.
go back to reference Heyland DK, Muscedere J, Drover J, Jiang X, Day AG, Canadian Critical Care Trials G (2011) Persistent organ dysfunction plus death: a novel, composite outcome measure for critical care trials. Crit Care 15:R98CrossRefPubMedPubMedCentral Heyland DK, Muscedere J, Drover J, Jiang X, Day AG, Canadian Critical Care Trials G (2011) Persistent organ dysfunction plus death: a novel, composite outcome measure for critical care trials. Crit Care 15:R98CrossRefPubMedPubMedCentral
12.
go back to reference Bassler D, Briel M, Montori VM, Lane M, Glasziou P, Zhou Q, Heels-Ansdell D, Walter SD, Guyatt GH, Group S-S, Flynn DN, Elamin MB, Murad MH, Abu Elnour NO, Lampropulos JF, Sood A, Mullan RJ, Erwin PJ, Bankhead CR, Perera R, Ruiz Culebro C, You JJ, Mulla SM, Kaur J, Nerenberg KA, Schunemann H, Cook DJ, Lutz K, Ribic CM, Vale N, Malaga G, Akl EA, Ferreira-Gonzalez I, Alonso-Coello P, Urrutia G, Kunz R, Bucher HC, Nordmann AJ, Raatz H, da Silva SA, Tuche F, Strahm B, Djulbegovic B, Adhikari NK, Mills EJ, Gwadry-Sridhar F, Kirpalani H, Soares HP, Karanicolas PJ, Burns KE, Vandvik PO, Coto-Yglesias F, Chrispim PP, Ramsay T (2010) Stopping randomized trials early for benefit and estimation of treatment effects: systematic review and meta-regression analysis. JAMA 303:1180–1187CrossRefPubMed Bassler D, Briel M, Montori VM, Lane M, Glasziou P, Zhou Q, Heels-Ansdell D, Walter SD, Guyatt GH, Group S-S, Flynn DN, Elamin MB, Murad MH, Abu Elnour NO, Lampropulos JF, Sood A, Mullan RJ, Erwin PJ, Bankhead CR, Perera R, Ruiz Culebro C, You JJ, Mulla SM, Kaur J, Nerenberg KA, Schunemann H, Cook DJ, Lutz K, Ribic CM, Vale N, Malaga G, Akl EA, Ferreira-Gonzalez I, Alonso-Coello P, Urrutia G, Kunz R, Bucher HC, Nordmann AJ, Raatz H, da Silva SA, Tuche F, Strahm B, Djulbegovic B, Adhikari NK, Mills EJ, Gwadry-Sridhar F, Kirpalani H, Soares HP, Karanicolas PJ, Burns KE, Vandvik PO, Coto-Yglesias F, Chrispim PP, Ramsay T (2010) Stopping randomized trials early for benefit and estimation of treatment effects: systematic review and meta-regression analysis. JAMA 303:1180–1187CrossRefPubMed
13.
go back to reference Harrell FE (2001) Regression modeling strategies: with application to linear models, logistic regression and survival analysis. Springer, New YorkCrossRef Harrell FE (2001) Regression modeling strategies: with application to linear models, logistic regression and survival analysis. Springer, New YorkCrossRef
14.
go back to reference van Buuren S (2007) Multiple imputation of discrete and continuous data by fully conditional specification. Stat Methods Med Res 16:219–242CrossRefPubMed van Buuren S (2007) Multiple imputation of discrete and continuous data by fully conditional specification. Stat Methods Med Res 16:219–242CrossRefPubMed
15.
go back to reference Sun X, Ioannidis JP, Agoritsas T, Alba AC, Guyatt G (2014) How to use a subgroup analysis: users’ guide to the medical literature. JAMA 311:405–411CrossRefPubMed Sun X, Ioannidis JP, Agoritsas T, Alba AC, Guyatt G (2014) How to use a subgroup analysis: users’ guide to the medical literature. JAMA 311:405–411CrossRefPubMed
16.
go back to reference Walsh M, Srinathan SK, McAuley DF, Mrkobrada M, Levine O, Ribic C, Molnar AO, Dattani ND, Burke A, Guyatt G, Thabane L, Walter SD, Pogue J, Devereaux PJ (2014) The statistical significance of randomized controlled trial results is frequently fragile: a case for a Fragility Index. J Clin Epidemiol 67:622–628CrossRefPubMed Walsh M, Srinathan SK, McAuley DF, Mrkobrada M, Levine O, Ribic C, Molnar AO, Dattani ND, Burke A, Guyatt G, Thabane L, Walter SD, Pogue J, Devereaux PJ (2014) The statistical significance of randomized controlled trial results is frequently fragile: a case for a Fragility Index. J Clin Epidemiol 67:622–628CrossRefPubMed
Metadata
Title
Pooled analysis of higher versus lower blood pressure targets for vasopressor therapy septic and vasodilatory shock
Authors
François Lamontagne
Andrew G. Day
Maureen O. Meade
Deborah J. Cook
Gordon H. Guyatt
Mathieu Hylands
Peter Radermacher
Jean-Marie Chrétien
Nicolas Beaudoin
Paul Hébert
Frédérick D’Aragon
Ferhat Meziani
Pierre Asfar
Publication date
01-01-2018
Publisher
Springer Berlin Heidelberg
Published in
Intensive Care Medicine / Issue 1/2018
Print ISSN: 0342-4642
Electronic ISSN: 1432-1238
DOI
https://doi.org/10.1007/s00134-017-5016-5

Other articles of this Issue 1/2018

Intensive Care Medicine 1/2018 Go to the issue