Adrenaline vs noradrenaline: Equity, context, and the realities of best practice

“Best practice is not universal – it is contextual, constructed and contested.”

There is a widespread and established narrative that clinical protocols and practice recommendations from high-income settings instinctively represents the gold standard or reference standard worldwide. Best practice recommendations from high-income settings are assumed to be the benchmark for all, without taking into consideration the substantial contextual differences that exist elsewhere. This not only creates undue pressure and expectations on low- and middle-income countries (LMICs) to align their practices, regardless of feasibility, but also perpetuate the implied hierarchy of offering “second best” or “inferior” care. This binary framing disregards the diverse realities of health systems and challenges the very definition of best practice – what works safely and equitably within a given health system. A recent meta-analysis comparing adrenaline to noradrenaline for septic shock [1] offers a useful case study to unpack these concepts further and perhaps an opportunity to interrogate the assumption of seamless transfer of standard practices across contexts. This editorial builds on the concept of best practice and explores the tension between global standards and local realities.

Boelen et al. [2], through the World Health Organization project, “Towards Unity For Health”, highlight that in our strive to deliver services that adequately address the health needs of both individuals and communities, we need to strike a balance between achieving quality, equity, relevance and cost-effectiveness within a specific health setting. He uses a metaphor of a health compass to both illustrate the tension and complexity between these values (quality vs equity and cost-effectiveness vs relevance) and as an instrument to identify direction or in this case, balance. Health systems decisions need to emphasize all these values, not as trade-offs, but as coexisting imperatives – and best practice should therefore be understood as the point of balance where quality, equity, relevance and cost-effectiveness intersect within a specific setting.

These values are embedded and operationalised in national decision-making processes such as Essential Medicines Lists and Standard Treatment Guidelines (EML/STG). These tools translate these system-level considerations into practical and implementable policy. The World Health Organization maintains a model list of Essential Medicines as a reference for countries developing their own national lists, promoting access to essential care grounded in evidence, public health relevance and cost-effectiveness. While variations exist, the goal remains consistent – to define best practice within realities of health systems. In South Africa as an example, these processes are led by the National Essential Medicines List Committee (NEMLC) – a ministerially appointed committee - and the Essential Drugs Programme (EDP) [3] within the National Department of Health. Their structured, transparent, iterative and evidence-informed processes explicitly considers feasibility, equity and systems alignment. These mechanisms serve as the vehicles that define and deliver best practice.

Another critical limitation in transferring high-income practice recommendations to LMICs lies in the misalignment of the questions that the evidence seeks to answer. The PICO framework that recommendations are structured around often reflect clinical dilemmas, priorities and capabilities of the specific setting – with the Population, Interventions, Comparisons or especially the Outcomes often not relevant or feasible in LMICs. As an example, outcomes such as ICU length of stay or vasopressor-free days may be less meaningful in settings where access to critical care is limited and survival may be more appropriate. This further reinforces the need for each setting to critically interrogate global recommendations, and where necessary formulate their own context-specific questions and evidence processes. Best practice in LMICs may mean asking different questions altogether and building guidance from the ground up.

Noradrenaline is widely accepted as the gold standard vasopressor in septic shock and often presented in guidelines as first-line, evidence-based best practice. This recommendation is strongly supported by the Surviving Sepsis Campaign (SSC) [4] – which carries significant influence across both high- and low-resourced settings. Current practice in low- and middle-income settings does not however reflect this. An article in the same issue by Kilindimo et al. [5], demonstrates that even though septic shock is prevalent in Tanzania, noradrenaline was often unavailable and a lack of infusion pumps, insufficient monitoring equipment and training gaps were frequent barriers to administration of vasopressors. Adrenaline was much more frequently used, and providers were more familiar and comfortable with prescribing and administering adrenaline. They expressed ongoing tension between guideline ideals and actual system realities and appealed for improved access to noradrenaline. This disconnect between global guideline recommendations and real-world implementation underscores the need to evaluate medicines not only on clinical efficacy, but on whether they can be effectively integrated into the health system. A similar misalignment may exist in trauma care, where global guidelines often recommend noradrenaline as first-line, reinforcing the need to critically interrogate guidance across emergency presentations to ensure feasibility, relevance, and alignment with system capacity.

Noradrenaline is substantially more expensive than adrenaline; even though exact figures vary, estimates in South Africa are around 7 to 20 times more. Adrenaline is already included in essential supply chains for numerous other indications, including anaphylaxis, cardiopulmonary resuscitation, management of croup, asthma and symptomatic bradycardias, while noradrenaline tends to be associated with more complex procurement processes and may face supply challenges and variable availability. Despite the multiple indications, flexible dosing options and familiarity among providers, adrenaline may be more feasible for peripheral administration (in the acute phase), especially in emergency departments, making it an attractive and practical option in resource-challenged settings; noradrenaline administration requires central venous access and with that, the associated critical care infrastructure. While these system-level factors are central to defining best practice, clinical efficiency remains an important consideration. Prior to this meta-analysis, noradrenaline was thought to have an improved safety profile, even though mortality rates and clinical efficacy were comparable – despite these findings being based on studies with varying quality and bias.

The recent meta-analysis by Leong et al. [1], found adrenaline to be non-inferior to noradrenaline for adults with septic shock and recommended that adrenaline is a valid first-line option, even from an efficacy point of view. Mortality rates, time to haemodynamic stabilisation, prevalence of dysrhythmias and vasopressor free days were all similar between noradrenaline and adrenaline. These findings are consistent with previous meta-analysis, despite the strong contradictory recommendations from the SSC[4]. The evidence to support the concerns around the safety profile of adrenaline, particularly regarding splanchnic vasoconstriction and the risk of dysrhythmias, are lacking, unclear, or are of low quality. While the authors note limitations related to small sample sizes and heterogeneity in study designs, the consistency of findings across diverse settings strengthens the relevance of their conclusions. For emergency care systems in LMICs, where best practice decisions need to balance quality (efficacy and safety) and equity, relevance and cost-effectiveness, this meta-analysis represents a pivotal moment. This meta-analysis challenged the assumption of adrenaline’s inferiority and reframed adrenaline not as a fallback, but as evidence informed best practice recommendation.

The comparison between adrenaline and noradrenaline is more than a pharmacological debate - it is a reminder that best practice is not determined by evidence alone, but by the intersection of evidence with equity, cost-effectiveness, and relevance. For LMICs, especially in emergency care, the challenge is not to replicate the standards of high-income settings, but to define excellence on our own terms. This meta-analysis reinforces that contextually grounded decisions are not second-best - they are the foundation of best practice.

Declaration of competing interest

The author declares that he has no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. The author is an Associate Editor for this journal and although invited to write this editorial, was not involved in the editorial review or the decision to publish this article.