Prolonged Mild Therapeutic Hypothermia versus Fever Control with Tight Hemodynamic Monitoring and Slow Rewarming in Patients with Severe Traumatic Brain Injury: A Randomized Controlled Trial

Abstract

Although mild therapeutic hypothermia is an effective neuroprotective strategy for cardiac arrest/resuscitated patients, and asphyxic newborns, recent randomized controlled trials (RCTs) have equally shown good neurological outcome between targeted temperature management at 33 °C versus 36 °C, and have not shown consistent benefits in patients with traumatic brain injury (TBI). We aimed to determine the effect of therapeutic hypothermia, while avoiding some limitations of earlier studies, which included patient selection based on Glasgow coma scale (GCS), delayed initiation of cooling, short duration of cooling, inter-center variation in patient care, and relatively rapid rewarming. We conducted a multicenter RCT in patients with severe TBI (GCS 4-8). Patients were randomly assigned (2:1 allocation ratio) to either therapeutic hypothermia (32-34 °C, n = 98) or fever control (35.5-37 °C, n = 50). Patients with therapeutic hypothermia were cooled as soon as possible for ≥ 72 h and rewarmed at a rate of <1 °C/day. All patients received tight hemodynamic monitoring under intensive neurological care. The Glasgow Outcome Scale was assessed at 6 months by physicians who were blinded to the treatment allocation. The overall rates of poor neurological outcomes were 53% and 48% in the therapeutic hypothermia and fever control groups, respectively. There were no significant differences in the likelihood of poor neurological outcome (relative risk [RR] 1.24, 95% confidence interval [CI] 0.62-2.48, p = 0.597) or mortality (RR 1.82, 95% CI 0.82-4.03, p = 0.180) between the two groups. We concluded that tight hemodynamic management and slow rewarming, together with prolonged therapeutic hypothermia (32-34 °C) for severe TBI, did not improve the neurological outcomes or risk of mortality compared with strict temperature control (35.5-37 °C).

Hypothermia for severe traumatic brain injury in adults: Recent lessons from randomized controlled trials

“…There were no significant differences in neurologic outcome (the primary outcome of interest) or mortality (secondary outcome) between groups, even though the trial was relatively underpowered. [13] The other trial, EuroTherm3235, was an international multicenter RCT which also failed to identify a benefit for treatment of severe TBI with hypothermia. In this study, patients were enrolled up to 10 days after TBI who had developed intracranial hypertension and had failed basic, conventional (“Stage 1”) attempts to control ICP.…”

Physical methods for the treatment of fever in critically ill patients: a randomized controlled trial

“…In contrast to the antipyretic medication which inhibits fever development by reducing the hypothalamic set point, physical methods reduce the body temperature by increasing the temperature gradient between the body and the environment, promoting heat loss by conduction and convection mechanisms (2) . Thus, the adverse effects observed in using physical methods include shivering, vasoconstriction, vasospasm of the coronary arteries and rebound hypothermia, which should also be the focus of attention of the nursing team (4,17) . Studies comparing the application of warm compresses and prescribing a warm bath for children to help in reducing the body temperature of those with fever, either alone or combined with antipyretic versus only antipyretic administration (5) can be found in the literature.…”

Fever Control Management Is Preferable to Mild Therapeutic Hypothermia in Traumatic Brain Injury Patients with Abbreviated Injury Scale 3–4: A Multi-Center, Randomized Controlled Trial

“…One hundred fifty patients were randomly assigned (2:1 allocation ratio) to either the MTH group (32°C-34°C) or the fever control group (35.5°C-37°C) and intention-to-treat analyses were performed. 9 After enrollment, informed consent could not be obtained for 2 patients, 7 patients had unstable vital signs before temperature management, and neurological outcomes could not be assessed at 6 months in 6 patients. Therefore, per-protocol analyses were performed in 135 patients (88 treated with MTH and 47 with fever control).…”

“…16 Treatment was performed as described in our original article. 9 Briefly, cooling was initiated within 2 h after onset of TBI. Cooling blankets, rapid cold fluid infusion (up to 1000 mL saline, human plasma products, or dextrose-free plasma expanders), and/or cold gastric lavage were used during the induction phase in both groups.…”

“…9 The Abbreviated Injury Scale (AIS) is an anatomical, consensus derived, global severity scoring system that classifies each injury by body region according to its relative importance on a 6-point ordinal scale (1 = minor, 2 = moderate, 3 = serious, 4 = severe, 5 = critical, and 6 = maximum [currently untreatable]). 10 The head AIS measures and describes TBI severity based on a combination of symptoms, such as loss of consciousness, physical and neurological examination findings, mechanism (blunt or penetrating), and radiographic findings (computed tomography [CT] findings).…”