A systematic review and meta-analysis of noradrenaline compared to adrenaline in the management of septic shock

Trudy D Leong^{1

2

3}, Rephaim Mpofu^{4

3}, Sumaya Dadan⁵, Karen Cohen^{2

4

3

6}, Halima Dawood^{3

7

8}, Tamara Kredo^{1

2

6

9}, Andy Parrish^{6

10

11}, Marc Blockman^{4

3

6}, P Dean Gopalan^{3

12}

Affiliations

¹ Health Systems Research Unit, South African Medical Research Council, South Africa.
² South African GRADE Network, South Africa.
³ South African Adult Hospital and Primary Healthcare Expert Review Committee of the National Essential Medicines List Committee, South Africa, 2020-2024.
⁴ Division of Clinical Pharmacology, Department of Medicine, University of Cape Town, South Africa.
⁵ Division of Epidemiology and Biostatistics, University of Cape Town, South Africa.
⁶ South African National Essential Medicines List Committee, South Africa, 2021-2025.
⁷ Centre for the AIDS Programme of Research in South Africa (CAPRISA), University of KwaZulu-Natal, South Africa.
⁸ Department of Internal Medicine, Grey's Hospital, Pietermaritzburg, South Africa.
⁹ Division of Clinical Pharmacology, Department of Medicine and Division of Epidemiology and Biostatistics, Department of Global Health, Faculty of Medicine and Health Sciences, Stellenbosch University, Stellenbosch, South Africa.
¹⁰ Department of Internal Medicine, Faculty of Health Sciences, Walter Sisulu University, Mthatha, South Africa.
¹¹ Internal Medicine, Frere and Cecilia Makiwane Hospitals, East London, South Africa.
¹² Discipline of Anaesthesiology and Critical Care, School of Clinical Medicine, University of KwaZulu Natal, South Africa.

PMID: 40677279
PMCID: PMC12269591
DOI: 10.1016/j.afjem.2025.05.005

Review

A systematic review and meta-analysis of noradrenaline compared to adrenaline in the management of septic shock

Trudy D Leong et al. Afr J Emerg Med. 2025 Sep.

. 2025 Sep;15(3):100881.

doi: 10.1016/j.afjem.2025.05.005. Epub 2025 Jun 30.

Authors

Affiliations

¹ Health Systems Research Unit, South African Medical Research Council, South Africa.
² South African GRADE Network, South Africa.
³ South African Adult Hospital and Primary Healthcare Expert Review Committee of the National Essential Medicines List Committee, South Africa, 2020-2024.
⁴ Division of Clinical Pharmacology, Department of Medicine, University of Cape Town, South Africa.
⁵ Division of Epidemiology and Biostatistics, University of Cape Town, South Africa.
⁶ South African National Essential Medicines List Committee, South Africa, 2021-2025.
⁷ Centre for the AIDS Programme of Research in South Africa (CAPRISA), University of KwaZulu-Natal, South Africa.
⁸ Department of Internal Medicine, Grey's Hospital, Pietermaritzburg, South Africa.
⁹ Division of Clinical Pharmacology, Department of Medicine and Division of Epidemiology and Biostatistics, Department of Global Health, Faculty of Medicine and Health Sciences, Stellenbosch University, Stellenbosch, South Africa.
¹⁰ Department of Internal Medicine, Faculty of Health Sciences, Walter Sisulu University, Mthatha, South Africa.
¹¹ Internal Medicine, Frere and Cecilia Makiwane Hospitals, East London, South Africa.
¹² Discipline of Anaesthesiology and Critical Care, School of Clinical Medicine, University of KwaZulu Natal, South Africa.

PMID: 40677279
PMCID: PMC12269591
DOI: 10.1016/j.afjem.2025.05.005

Abstract

Background: Septic shock is associated with significant mortality. The International Surviving Sepsis Campaign guidelines recommend noradrenaline as first-line vasopressor, whilst South African guidelines recommend adrenaline. Clinical trials show similar efficacy but suggest safety advantages for noradrenaline. We reviewed the evidence comparing noradrenaline and adrenaline in the initial management of adult patients with septic shock.

Methods: We searched PubMed, Epistemonikos, Cochrane Library, and clinical trial registries for clinical practice guidelines, health technology assessments, and systematic reviews of randomised controlled trials (RCTs) through July 2024. We appraised these using AGREE II and AMSTAR 2 tools and assessed eligible RCTs extracted from systematic reviews with Cochrane's Risk of Bias 2.0 Tool. We estimated random-effects rate ratios (RR) and mean differences (MD) with 95 % confidence intervals and rated certainty of evidence using GRADE. Key outcomes included mortality, time to shock reversal, and adverse effects. (PROSPERO: CRD42022368373).

Results: We identified three guidelines, one systematic review, from which five RCTs were extracted. Comparing adrenaline to noradrenaline, we found little to no difference in mortality (RR 0.99, 0.83 to 1.18), time to improvement of mean arterial pressure (MD 7.17 min, -16.74 to 31.08), vasopressor-free days (MD -0.05 days, -4.07 to 3.96), or dysrhythmias (RR 0.92, 0.59 to 1.45). Change in lactate concentrations 24 h after resuscitation was lower for noradrenaline than adrenaline. The certainty of evidence was assessed as low to very low.

Conclusion: Adrenaline and noradrenaline are associated with similar outcomes in managing septic shock. The choice of vasopressor should be based on availability, patient population, and cost.

Keywords: Adrenaline; Dysrhythmias; Lactate; Mortality; Noradrenaline; Septic shock.

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Conflict of interest statement

TDL and TK were part-funded by the Research, Evidence, and Development Initiative (READ-It) project (project number 35,300,342-104). READ-It is funded by aid from the UK government; however, the views expressed do not necessarily reflect the UK government’s official policies. The research reported in this publication is the sole responsibility of the researchers and does not reflect the official views or position of SA-MRC or Stellenbosch University. Payments were not made to TDL or TK, but to their institution, SA-MRC. AP: ELIMET Trustee - Support for academic activities, public sector internal medicine staff in East London. No direct payments to self. HD: Speaker fees and conference attendance sponsorship from Sanofi-South Africa. MB: SAHPRA Pharmacovigilance and Clinical Expert Committees; South Africa National Essential List Committee; Uppsala Monitoring Centre (UMC)-technical expert. PDG: MacRoberts: Payment for expert testimonies x3; Adcock-Ingram South Africa: Support to attend World Anaesthesia Conference in Singapore (paid directly by company); MSD-South Africa: Support to attend meeting in Gauteng (paid directly by company); Pfizer-South Africa: Support to attend meeting in Cape Town (paid directly by company); MSD-South Africa: Honorarium for round table x3; Pfizer-South Africa: Honorarium for round table x1. RM, SD, and KC have no conflict of interest to declare.

Figures

Fig 1: — **Fig. 1**
Forest plots comparing A) adrenaline vs noradrenaline monotherapy or noradrenaline-dopamine derivative (dobutamine or dopexamine) combination therapy in septic shock, for the outcome: mortality; B) adrenaline vs noradrenaline monotherapy in septic shock, for the outcome: mortality; C) adrenaline vs noradrenaline+dopamine derivative in septic shock, for the outcome: mortality; D) adrenaline vs noradrenaline+dopamine derivative in septic shock, for the outcome: Time to MAP stabilisation (70 to 80 mmHg) [minutes]; E) adrenaline vs noradrenaline in septic shock, for outcome: vasopressor free days (Day 28); F) adrenaline vs noradrenaline+dobutamine combination in critically ill adults (including septic shock), on arterial lactate concentrations after 24 h; G) adrenaline vs noradrenaline+dopamine derivative in septic shock, for the outcome: Arrhythmias.

Fig 2 — **Fig. 2**
Kaplan-Meier estimates for the probability of achieving MAP, comparing adrenaline (epinephrine) vs noradrenaline (norepinephrine) in critically ill adults [7].

See this image and copyright information in PMC

References

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A systematic review and meta-analysis of noradrenaline compared to adrenaline in the management of septic shock

Affiliations

A systematic review and meta-analysis of noradrenaline compared to adrenaline in the management of septic shock

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

References

Publication types

LinkOut - more resources

Full Text Sources