Critically evaluate the role of induced hypothermia in the management of traumatic brain injury.
Induced hypothermia refers to the use of techniques to intentionally lower the core body temperature below a physiological level (i.e. <36 degrees), in this case, in a patient with a traumatic brain injury.
• Reduction in metabolic rate
• Reduction in oedema
• Modification of the inflammatory response
Therapeutic (for the management of elevated intracranial pressure)
• Reduction in core body temperature is associated with a reduction in cerebral metabolic
rate and reduction in cerebral blood flow
• Will be associated with a reduction in intracranial pressure
• Noted cerebral protective effect in animal models and in case reports of survival with good
neurological recovery in hypoxic ischaemic encephalopathy in patients with severe
• Known that hyperthermia is associated with worse neurological outcomes
• Requires sedation and neuromuscular blockade with the attendant adverse effects
• Lower temperature predisposes to infective complications, in particular pneumonia
• Cardiac dysrhythmias
• Overshoot can expose patients to adverse effects of more severe hypothermia
o Diuresis and electrolyte disturbance
o Immune suppression
• Adverse effects of cooling devices (loss of skin integrity) and monitoring devices
• Cost of prolonged ICU stay and increased requirement for intervention and monitoring
• Initial studies and meta-analysis showed promising results with regards to improved
• Subsequent studies are less positive
Cochrane Systematic Review 2009
No evidence of benefit.
Significant benefit shown in low quality trials with tendency to over-estimate the treatment effect
• Nine class I and II studies, and 3 Class III studies summarised in BTF.
• Since then two paediatric studies and a Japanese study have been published
Brain Trauma Foundation (2016):
“Level II B: Early (within 2.5 hours), short-term (48 hours post-injury) prophylactic hypothermia is not recommended to improve outcomes in patients with diffuse injury”.
Elevated ICP management:
• EUROTHERM-3235 study
o Induced hypothermia has an effect on reducing intracranial pressure, but the effect on
outcome is variable
o Little clinical evidence on the effect on other important aspects of cerebral physiology
e.g. cerebral blood flow or cellular metabolism
• It is important to avoid hyperthermia
• Routine use of induced hypothermia in all TBI patients is not warranted
• Careful reduction in core body temperature may help control ICP in selected severe TBI
patients who may otherwise be at risk of a decompressive craniectomy.
• Await results of high-quality RCTs
Arguments against the use of hypothermia in TBI
Evidence for and against hypothermia in TBI
If the college examiners had any investment in the process of writing these answers, they'd probably have offered their trainees some references beyond "two paediatric studies and a Japanese study". At least one of the "two paediatric studies" is Hutchison et al (2008), who concluded that prophylactic hypothermia "does not improve the neurologic outcome and may increase mortality". The other paediatric trial may be Li et al (2009), which came to totally opposite conclusions ( "moderate hypothermia provided neuronal protection for children with severe TBI, and maintaining the intracranial temperature at 34.5°C for 72 h was safe"). Looking at the list of trials undergoing meta-analysis in Lewis et al (2017), the "Japanese study" is probably Hifumi et al (2016), whose B-HYPO trial did not find any significant difference in mortality or neurological outcome among 135 adult patients.
Sedzimir, C. B. "Therapeutic Hypothermia in Cases of Head Injury*." Journal of neurosurgery 16.4 (1959): 407-414.
Rosomoff, Hubert L. "Experimental Brain Injury During Hypothermia*." Journal of neurosurgery 16.2 (1959): 177-187.
Lundberg, Nils, Kai C. Nielsen, and Eric Nilsson. "Deep Hypothermia in Intracranial Surgery*." Journal of neurosurgery 13.3 (1956): 235-247.
Jennett, B., et al. "Treatment for severe head injury." Journal of Neurology, Neurosurgery & Psychiatry 43.4 (1980): 289-295.
Drake, C. G., and T. A. Jory. "Hypothermia in the treatment of critical head injury." Canadian Medical Association journal 87.17 (1962): 887.
Marion, Donald W., et al. "Treatment of traumatic brain injury with moderate hypothermia." New England Journal of Medicine 336.8 (1997): 540-546.
Fay, T. "Observations on generalized refrigeration in cases of severe cerebral trauma." Assoc Res Nerv Ment Dis Proc. Vol. 24. 1945.
Polderman, Kees H. "Mechanisms of action, physiological effects, and complications of hypothermia." Critical care medicine 37.7 (2009): S186-S202.
Xu, Lijun, et al. "Mild hypothermia reduces apoptosis of mouse neurons in vitro early in the cascade." Journal of Cerebral Blood Flow & Metabolism 22.1 (2002): 21-28.
Globus, Mordecai Y‐T., et al. "Detection of free radical activity during transient global ischemia and recirculation: effects of intraischemic brain temperature modulation." Journal of neurochemistry 65.3 (1995): 1250-1256.
Busto, Raul, et al. "Effect of mild hypothermia on ischemia-induced release of neurotransmitters and free fatty acids in rat brain." Stroke 20.7 (1989): 904-910.
Siesjö, Bo K., et al. "Calcium, Excitotoxins, and Neuronal Death in the Brain." Annals of the New York Academy of Sciences 568.1 (1989): 234-251.
Fischer, Silvia, et al. "Hypothermia abolishes hypoxia-induced hyperpermeability in brain microvessel endothelial cells." Molecular brain research 74.1 (1999): 135-144.
Schmutzhard, Erich, et al. "Therapeutic hypothermia: The rationale." Critical Care 16.2 (2012): 1.
Andrews, Peter JD, et al. "Hypothermia for intracranial hypertension after traumatic brain injury." New England Journal of Medicine 373.25 (2015): 2403-2412.
Cooper, D. James, et al. "Effect of early sustained prophylactic hypothermia on neurologic outcomes among patients with severe traumatic brain injury: the POLAR randomized clinical trial." JAMA (2018) Published online October 24, 2018. doi:10.1001/jama.2018.17075
Hutchison, James S., et al. "Hypothermia therapy after traumatic brain injury in children." New England Journal of Medicine 358.23 (2008): 2447-2456.
Hifumi, Toru, et al. "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." Journal of neurotrauma 33.11 (2016): 1047-1053.
Li, Hao, et al. "Protective effect of moderate hypothermia on severe traumatic brain injury in children." Journal of neurotrauma 26.11 (2009): 1905-1909.