REEVALUATING MEAN ARTERIAL PRESSURE TARGETS IN SEPSIS AND SEPTIC SHOCK: INSIGHTS FROM A SYSTEMATIC REVIEW AND META-ANALYSISREEVALUATING MEAN ARTERIAL PRESSURE TARGETS IN SEPSIS AND SEPTIC SHOCK: INSIGHTS FROM A SYSTEMATIC REVIEW AND META-ANALYSIS
DOI:
https://doi.org/10.22159/ajpcr.2025v18i1.53234Keywords:
Sepsis,, Septic shock, Mean arterial pressure, Higher mean arterial pressure, Lower mean arterial pressure, InfectionAbstract
The conflicting evidence on the clinical impact of higher versus lower mean arterial pressure (MAP) targets in sepsis and septic shock underscores the urgent need to redefine optimal MAP thresholds to improve outcomes in these critical illnesses. This systematic review and meta-analysis adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 guidelines. A data search was conducted on July 1, 2024, for randomized controlled trials and observational studies published from January 2004 to December 2023, assessing patient outcomes based on MAP goal parameters. The primary outcomes were all-cause mortality and overall adverse events. Patients with elevated MAP targets exhibited significantly higher odds of all-cause mortality (odds ratio [OR]: 1.10, 95% confidence interval [CI]: 1.00–1.22), atrial fibrillation (OR: 2.52, 95% CI: 1.25–5.07), and supraventricular arrhythmia (OR: 1.81, 95% CI: 1.07–3.04) compared to those with lower MAP targets (all p≤0.05). In contrast, higher MAP patients with chronic hypertension and sepsis had significantly lower odds of requiring renal replacement therapy (RRT) (OR: 0.77, 95% CI: 0.62–0.97; p=0.03). No significant differences were observed in overall adverse events, acute myocardial infarction, intensive care unit length of stay, major bleeding, mesenteric ischemia, RRT, 28-day survival, or ventricular tachycardia between the groups. This study highlights that targeting higher MAP in sepsis patients may elevate the risk of cardiac complications, such as atrial fibrillation and supraventricular arrhythmia, without having substantial benefits in reducing mortality or adverse events.
The conflicting evidence on the clinical impact of higher versus lower mean arterial pressure (MAP) targets in sepsis and septic shock underscores the urgent need to redefine optimal MAP thresholds to improve outcomes in these critical illnesses. This systematic review and meta-analysis adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 guidelines. A data search was conducted on July 1, 2024, for randomized controlled trials and observational studies published from January 2004 to December 2023, assessing patient outcomes based on MAP goal parameters. The primary outcomes were all-cause mortality and overall adverse events. Patients with elevated MAP targets exhibited significantly higher odds of all-cause mortality (odds ratio [OR]: 1.10, 95% confidence interval [CI]: 1.00–1.22), atrial fibrillation (OR: 2.52, 95% CI: 1.25–5.07), and supraventricular arrhythmia (OR: 1.81, 95% CI: 1.07–3.04) compared to those with lower MAP targets (all p≤0.05). In contrast, higher MAP patients with chronic hypertension and sepsis had significantly lower odds of requiring renal replacement therapy (RRT) (OR: 0.77, 95% CI: 0.62–0.97; p=0.03). No significant differences were observed in overall adverse events, acute myocardial infarction, intensive care unit length of stay, major bleeding, mesenteric ischemia, RRT, 28-day survival, or ventricular tachycardia between the groups. This study highlights that targeting higher MAP in sepsis patients may elevate the risk of cardiac complications, such as atrial fibrillation and supraventricular arrhythmia, without having substantial benefits in reducing mortality or adverse events.
Downloads
References
Gyawali B, Ramakrishna K, Dhamoon AS. Sepsis: The evolution in definition, pathophysiology, and management. Sage Open Med. 2019;7:2050312119835043. doi: 10.1177/2050312119835043, PMID 30915218
Basodan N, Al Mehmadi AE, Al Mehmadi AE, Aldawood SM, Hawsawi A, Fatini F, et al. Septic shock: Management and outcomes. Cureus. 2022;14(12):e32158. doi: 10.7759/cureus.32158, PMID 36601152
Chatterjee S, Bhattacharya M, Todi SK. Epidemiology of adult-population sepsis in India: A single center 5 year experience. Indian J Crit Care Med. 2017;21(9):573-7. doi: 10.4103/ijccm.IJCCM_240_17, PMID 28970656
Fleischmann-Struzek C, Mellhammar L, Rose N, Cassini A, Rudd KE, Schlattmann P, et al. Incidence and mortality of hospital- and ICU-treated sepsis: Results from an updated and expanded systematic review and meta-analysis. Intensive Care Med. 2020;46(8):1552-62. doi: 10.1007/s00134-020-06151-x, PMID 32572531
Prest J, Nguyen T, Rajah T, Prest AB, Sathananthan M, Jeganathan N. Sepsis-related mortality rates and trends based on site of infection. Crit Care Explor. 2022;4(10):e0775. doi: 10.1097/CCE.0000000000000775, PMID 36248320
Leone M, Asfar P, Radermacher P, Vincent JL, Martin C. Optimizing mean arterial pressure in septic shock: A critical reappraisal of the literature. Crit Care. 2015;19(1):101. doi: 10.1186/s13054-015-0794-z, PMID 25888071 7. Dari MA, Fayaz A, Sharif S, Hernandez Galaviz S, Hernandez Galaviz E, Bataineh SM, et al. Comparison of high-normal versus low-normal mean arterial pressure at target on outcomes in sepsis or shock patients: A meta-analysis of randomized control trials. Cureus. 2024;16(1):e52258. doi: 10.7759/cureus.52258, PMID 38352092
Yoshimoto H, Fukui S, Higashio K, Endo A, Takasu A, Yamakawa K. Optimal target blood pressure in critically ill adult patients with vasodilatory shock: A systematic review and meta-analysis. Front Physiol. 2022;13:962670. doi: 10.3389/fphys.2022.962670, PMID 36051909
Rikhraj KJ, Ronsley C, Sekhon MS, Mitra AR, Griesdale DE. High-normal versus low-normal mean arterial pressure thresholds in critically ill patients: A systematic review and meta-analysis of randomized trials. Can J Anaesth. 2023;70(7):1244-54. doi: 10.1007/s12630-023-02494- 3, PMID 37268800
Sarkar S, Singh S, Rout A. Mean arterial pressure goal in critically ill patients: A meta-analysis of randomized controlled trials. J Clin Med Res. 2022;14(5):196-201. doi: 10.14740/jocmr4702, PMID 35720230
Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, et al. The PRISMA 2020 statement: An updated guideline for reporting systematic reviews. BMJ. 2021;372:n71. doi: 10.1136/bmj.n71
Cochrane. Training. Cochrane Revman (Web Version); 2024.
George A, Stead TS, Ganti L. What’s the risk: Differentiating risk ratios, odds ratios, and hazard ratios? Cureus. 2020;12(8):e10047. doi: 10.7759/cureus.10047, PMID 32983737
Dettori JR, Norvell DC, Chapman JR. Fixed-effect vs random-effects models for meta-analysis: 3 points to consider. Glob Spine J. 2022;12(7):1624-6. doi: 10.1177/21925682221110527, PMID 35723546
Mounier N, Kutalik Z. Bias correction for inverse variance weighting Mendelian randomization. Genet Epidemiol. 2023;47(4):314-31. doi: 10.1002/gepi.22522, PMID 37036286
Serdar CC, Cihan M, Yücel D, Serdar MA. Sample size, power and effect size revisited: simplified and practical approaches in pre-clinical, clinical and laboratory studies. Biochem Med. 2021;31(1):010502. doi: 10.11613/BM.2021.010502, PMID 33380887
Ali Z, Bhaskar SB. Basic statistical tools in research and data analysis. Indian J Anaesth. 2016;60(9):662-9. doi: 10.4103/0019-5049.190623, PMID 27729694
Ariel de Lima D, Helito CP, De Lima LL, Clazzer R, Gonçalves RK, De Camargo OP. How to perform a meta-analysis: A practical step-by-step guide using R software and RStudio. Acta Ortop Bras. 2022;30(3):e248775. doi: 10.1590/1413-785220223003e248775, PMID 35694025
Emmert-Streib F, Thorlund K, Imberger G, Johnston BC, Walsh M, Awad T, et al. Evolution of heterogeneity (I2) estimates and their 95% confidence intervals in large meta-analyses. PLoS One. 2012;7(7):e39471. doi: 10.1371/journal.pone.0039471
Kwak S. Are only p-values less than 0.05 significant? A p-value greater than 0.05 Is also significant! J Lipid Atheroscler. 2023;12(2):89-95. doi: 10.12997/jla.2023.12.2.89, PMID 37265851
Sterne JA, Hernán MA, Reeves BC, Savović J, Berkman ND, Viswanathan M, et al. Robins-I: A tool for assessing risk of bias in non-randomised studies of interventions. BMJ. 2016;355:i4919. doi: 10.1136/bmj.i4919, PMID 27733354
Sterne JA, Savović J, Page MJ, Elbers RG, Blencowe NS, Boutron I, et al. RoB 2: A revised tool for assessing risk of bias in randomised trials. BMJ. 2019;366:l4898. doi: 10.1136/bmj.l4898, PMID 31462531
Maiwall R, Rao Pasupuleti SS, Hidam AK, Kumar A, Tevethia HV, Vijayaraghavan R, et al. A randomised-controlled trial (TARGET-C) of high vs. low target mean arterial pressure in patients with cirrhosis and septic shock. J Hepatol. 2023;79(2):349-61. doi: 10.1016/j. jhep.2023.04.006, PMID 37088310
Lamontagne F, Meade MO, Hébert PC, Asfar P, Lauzier F, Seely AJ, et al. Higher versus lower blood pressure targets for vasopressor therapy in shock: A multicentre pilot randomized controlled trial. Intensive Care Med. 2016;42(4):542-50. doi: 10.1007/s00134-016- 4237-3, PMID 26891677
Asfar P, Meziani F, Hamel JF, Grelon F, Megarbane B, Anguel N, et al. High versus low blood-pressure target in patients with septic shock. N Engl J Med. 2014;370(17):1583-93. doi: 10.1056/NEJMoa1312173, PMID 24635770
Lamontagne F, Richards-Belle A, Thomas K, Harrison DA, Sadique MZ, Grieve RD, et al. Effect of reduced exposure to vasopressors on 90-day mortality in older critically ill patients with vasodilatory hypotension: A randomized clinical trial. JAMA. 2020;323(10):938-49. doi: 10.1001/ jama.2020.0930, PMID 32049269
Wieruszewski PM, Bellomo R, Busse LW, Ham KR, Zarbock A, Khanna AK, et al. Initiating angiotensin II at lower vasopressor doses in vasodilatory shock: An exploratory post-hoc analysis of the ATHOS-3 clinical trial. Crit Care. 2023;27(1):175. doi: 10.1186/s13054-023- 04446-1, PMID 37147690
Gallyas F, Lamontagne F, Cook DJ, Meade MO, Seely A, Day AG, et al. Vasopressor use for severe hypotension-a multicentre prospective observational study. PLoS One. 2017;12(1):e0167840.
Hall LG, Oyen LJ, Taner CB, Cullinane DC, Baird TK, Cha SS, et al. Fixed‐dose vasopressin compared with titrated dopamine and norepinephrine as initial vasopressor therapy for septic shock. Pharmacotherapy. 2004;24(8):1002-12. doi: 10.1592/ phco.24.11.1002.36139, PMID 15338849
Legrand M, Dupuis C, Simon C, Gayat E, Mateo J, Lukaszewicz AC, et al. Association between systemic hemodynamics and septic acute kidney injury in critically ill patients: A retrospective observational study. Crit Care. 2013;17(6):R278. doi: 10.1186/cc13133, PMID 24289206
Wong BT, Chan MJ, Glassford NJ, Mårtensson J, Bion V, Chai SY, et al. Mean arterial pressure and mean perfusion pressure deficit in septic acute kidney injury. J Crit Care. 2015;30(5):975-81. doi: 10.1016/j.jcrc.2015.05.003, PMID 26015150
Nakamura K, Nakano H, Ikechi D, Mochizuki M, Takahashi Y, Koyama Y, et al. The vasopressin loading for refractory septic shock (VALOR) study: A prospective observational study. Crit Care. 2023;27(1):294. doi: 10.1186/s13054-023-04583-7, PMID 37480126
Zhao L, Fan Y, Wang Z, Wei Z, Zhang Y, Li Y, et al. The blood pressure targets in sepsis patients with acute kidney injury: An observational cohort study of multiple ICUs. Front Immunol. 2022;13:1060612. doi: 10.3389/fimmu.2022.1060612, PMID 36591259
Kim JH, Kim YK, Oh DK, Jeon K, Ko RE, Suh GY, et al. Hypotension at the time of sepsis recognition is not associated with increased mortality in sepsis patients with normal lactate levels. Shock. 2023;59(3):360-7. doi: 10.1097/SHK.0000000000002067, PMID 36562261
Collet M, Huot B, Barthélémy R, Damoisel C, Payen D, Mebazaa A, et al. Influence of systemic hemodynamics on microcirculation during sepsis. J Crit Care. 2019;52:213-8. doi: 10.1016/j.jcrc.2019.05.002, PMID 31102939
Wang L, Yang H, Cheng Y, Fu X, Yao H, Jin X, et al. Mean arterial pressure/norepinephrine equivalent dose index as an early measure of initiation time for enteral nutrition in patients with shock: A prospective observational study. Nutrition. 2022;96:111586. doi: 10.1016/j. nut.2021.111586, PMID 35123283
Liang FM, Yang T, Dong L, Hui JJ, Yan J. The predictive value of dynamic arterial elastance in arterial pressure response after norepinephrine dosage reduction in patients with septic shock. Zhonghua Nei Ke Za Zhi. 2017;56(5):344-8. doi: 10.3760/cma.j.is sn.0578-1426.2017.05.008, PMID 28460504
Albanèse J, Leone M, Garnier F, Bourgoin A, Antonini F, Martin C. Renal effects of norepinephrine in septic and nonseptic patients. Chest. 2004;126(2):534-9. doi: 10.1378/chest.126.2.534, PMID 15302741
Zhong X, Li H, Chen Q, Hao P, Chen T, Mai H, et al. Association between different MAP levels and 30-day mortality in sepsis patients: A propensity-score-matched, retrospective cohort study. BMC Anesthesiol. 2023;23(1):116. doi: 10.1186/s12871-023-02047-7, PMID 37024806
Boerma EC, Ince C. The role of vasoactive agents in the resuscitation of microvascular perfusion and tissue oxygenation in critically ill patients. Intensive Care Med. 2010;36(12):2004-18. doi: 10.1007/s00134-010- 1970-x, PMID 20811874
Mouncey PR, Osborn TM, Power GS, Harrison DA, Sadique MZ, Grieve RD, et al. Trial of early, goal-directed resuscitation for septic shock. N Engl J Med. 2015;372(14):1301-11. doi: 10.1056/ NEJMoa1500896, PMID 25776532
Published
How to Cite
Issue
Section
Copyright (c) 2025 MADHU A YADAV yadav, REKHA A ASSADI, G H MIDHUN KUMAR, NEHA K KUDUMULA
This work is licensed under a Creative Commons Attribution 4.0 International License.
The publication is licensed under CC By and is open access. Copyright is with author and allowed to retain publishing rights without restrictions.