Fever is frequently observed in patients with severe acute brain injury (SABI). Around half of these episodes will have an infectious origin and prompt antimicrobial treatment is essential. Neurogenic fever is an additional non-infectious cause of raised temperature that is common after SABI due to complex disturbances of central mechanisms of thermoregulation. Fever in these patients has been associated with both higher mortality and worse neurological outcomes.1 Targeted temperature management (TTM) is a complex intervention to maintain precise control over a patient's body temperature that can contribute part of a multi-modal approach to neuroprotection that aims to minimize secondary brain injury and improve functional outcomes.

Prior to TTM, the term ‘therapeutic hypothermia’ was used. There are multiple theoretical neuroprotective mechanisms from hypothermia which are summarized in Table 1. These positive effects appeared to be supported by two trials in out-of-hospital cardiac arrest (OOHCA) published simultaneously by the New England Journal of Medicine in 2002. These led to the widespread adoption of recommendations supporting therapeutic hypothermia in international resuscitation guidelines. However more recent evidence, including from the TTM2 and TTM23 trials, has supported a more nuanced temperature control approach; possibly due to some of the challenges in consistently implementing hypothermic temperature targets, or due to the potential adverse systemic effects of hypothermia which are summarized in Table 2.

Recent guidance in varying types of acute brain injury have therefore shifted the paradigm towards the term TTM which includes different levels of temperature control, including; prevention of fever (<37.5°C), maintenance of normothermia (36.0–37.5°C), and in some cases induction of therapeutic hypothermia (32.0–36.0°C). To avoid confusion with the TTM trials some organizations, including the European Resuscitation Council and the European Society of Intensive Care Medicine (ERC-ESICM), have adopted the term ‘temperature control’ instead of TTM, however, both terms are widely used.

Looking beyond the large randomized controlled trials (RCTs) conducted in OOHCA and traumatic brain injury (TBI), evidence for TTM in other models of SABI relies mainly on small RCTs and observational data. Although fever is associated with worse outcomes, whether treating fever leads to improvement in these outcomes remains unclear. The gap between published evidence and the need for treatment protocols is bridged by expert consensus statements.