An updated catecholamine-sparing strategy for managing patients with refractory septic shock, emphasising early interventions to restore perfusion while reducing the risks associated with vasopressor therapy, has been proposed by a UK specialist centre.

Refractory septic shock is a heterogeneous and inconsistently defined syndrome, typically characterised by ongoing tissue hypoperfusion and organ dysfunction despite adequate fluid resuscitation and high-dose vasopressor therapy.

A subset of patients will continue to experience persistent hypotension and organ hypoperfusion despite guideline-directed sepsis care.

In response, clinicians at a UK specialist referral centre have proposed an updated, pragmatic approach for this high-risk group.

The work drew on experiences from a Severe Respiratory and Cardiac Failure Centre that manages more than 50 cases of refractory septic shock annually and aimed to synthesise emerging evidence with real-world practice to provide practical guidance for clinicians and pharmacists treating this under-studied population.

The authors emphasised the growing concern that prolonged catecholamine escalation could lead to worse outcomes by causing tachyarrhythmias, ischaemia and metabolic issues, and advocated earlier use of catecholamine-sparing strategies.

Catecholamine-sparing strategy for refractory septic shock

The initial management approach focuses on careful preload assessment using invasive haemodynamic monitoring, serial echocardiography and dynamic bedside assessment. Buffered isotonic crystalloids are recommended as first-line fluids, with 20% albumin added if further volume expansion is required.

A continuous hydrocortisone infusion of 200 mg/day is recommended to accelerate shock resolution, consistent with the updated Surviving Sepsis Campaign guidance. Although the role of fludrocortisone remains uncertain, meta-analyses have suggested that routine use may confer a mortality benefit, and the authors used fludrocortisone 100 μg daily until shock resolution.

Early vasopressin is recommended, typically when noradrenaline reaches 0.2–0.3 µg/kg/min, with a maximum dose of 0.04 IU/min to minimise ischaemic adverse effects.

Practical measures to reduce unnecessary vasopressor exposure are highlighted, including preferential placement of femoral arterial lines to avoid underestimation of mean arterial pressure, minimised and targeted sedation to limit vasodilation, and individualised blood pressure targets.

In selected younger patients without chronic hypertension or coronary disease, mean arterial pressure targets as low as 50–55 mmHg may be acceptable, provided organ perfusion is closely monitored.

For patients with septic cardiomyopathy or low cardiac output, low-dose milrinone is preferred, with levosimendan reserved for refractory cases.

Additional supportive measures include early parenteral nutrition when enteral feeding is unsafe, routine thiamine supplementation, cautious use of sodium bicarbonate in severe acidosis, and short-term, high-dose renal replacement therapy to improve metabolic parameters and reduce vasopressor requirements.

In advanced refractory shock, rescue therapies that target alternative vasoregulatory pathways are considered. These include angiotensin II for vasoplegia; methylene blue or hydroxocobalamin to block nitric oxide pathways; low-dose epoprostenol for severe peripheral hypoperfusion; antimicrobial agents to suppress toxins in suspected toxic shock; intravenous immunoglobulin for certain hyperinflammatory phenotypes; and extracorporeal membrane oxygenation for carefully selected patients with septic cardiomyopathy.

Although some uncertainty remains, the authors said an individualised, dynamic and multimodal approach – implemented early and in combination – may therefore mitigate catecholamine toxicity and improve outcomes.

Many of the proposed interventions are low-cost and widely applicable, and the authors hope their framework will stimulate discussion and inform future research in this high-mortality condition.

Reference
Palmesino F et al. Refractory septic shock: our updated pragmatic approach. J Anesth Analg Crit Care 2026;6:21.