52 in 52 – #37: POLAR trial – Hypothermia for Severe TBI

Author: Christiaan van Nispen, MD (Resident, Emergency Medicine Physician, San Antonio, TX); Brannon Inman, MD (Chief Resident, Emergency Medicine Physician, San Antonio, TX) // Reviewed by: Alex Koyfman, MD (@EMHighAK); Brit Long, MD (@long_brit)

Design: Multi-centered, single-blinded, randomized controlled trial

Population:

• Inclusion Criteria:
  • Patients aged 18-60 years
  • GCS < 9
  • Actual or imminent endotracheal intubation
• Out of Hospital Exclusion Criteria:
  • SBP < 90 mm Hg
  • Heart rate > 120 per minute
  • Pregnancy
  • Possible or suspected uncontrolled bleeding
  • GCS = 3 with unreactive pupils
  • Ability to intubate the patient without the use of medications
  • Cardiac arrest
  • Illicit drugs or alcohol ingestion suspected
  • Known use of anticoagulation
  • Penetrating injuries to the neck or torso
• In Hospital Exclusion Criteria:
  • All above out of hospital criteria, if not already identified by emergency medical services
  • Failure by EMS to transport the patient to a participating hospital
  • Patient was determined to likely need a surgery or embolization procedure for hemostasis
  • Cooling deemed to be not in patient’s best medical interest, according to the judgement of the attending physician
• Enrollment/Randomization:
  • Randomization was performed in the field by 5 emergency medical services units
  • Randomization was performed in hospital at 14 emergency departments
  • Randomization sites were spread across 6 countries
  • Total of 511 patients recruited with 466 completing primary outcome evaluation
    • Of these, 231 were enrolled out of hospital
  • Enrollment was conducted from 2010-2017, with final follow-up completed in 2018
  • There was a similarity in characteristics between the two groups

Intervention:

• Prophylactic cooling to between 33⁰C and 35⁰C was performed through patient exposure, up to 2000 mL intravenous normal saline at 4⁰C, and surface cooling wraps
• Hypothermia was maintained for at least 72 hours
• Rewarming at 72 hours if intracranial pressures (ICPs) were less than 20 mm Hg; patients remained cooled for up to 7 days if intracranial pressure was elevated

Comparator:

• Enforced normothermia, with target temperature of 37⁰C ±5⁰C
  • Use of surface cooling wraps for pyrexia and/or refractory intracranial hypertension

Outcome:

• Primary outcome: favorable neurological outcomes defined by Glasgow Outcome Scale-Extended (GOS-E) Score, 5-8 at 6 months
  • Occurred in 117 patients (48.8%) in the hypothermia group
  • Occurred in 111 patients (49.1%) in the normothermia group
• No significant differences in most secondary outcomes, including:
  • Mortality at 6 months after injury
  • Time to death
  • Time to reach target temperature
  • Days of mechanical ventilation
  • Intensive care unit length of stay
  • Hospital length of stay
  • Mean GOS-E score at 6 months
  • Unfavorable GOS-E score for survivors
• Some secondary outcomes with significant, worse outcomes in hypothermia group:
  • Pneumonia (as measured in per protocol analysis): 70.5% vs. 57.1%
  • Bradycardia: 18.8% vs. 4.2%
  • Average ventilator days (8.3 vs. 6.9)

Take Aways:

• The data do not suggest that targeted hypothermia improves neurological function, reduces death, or reduces hospital length of stay as compared to normothermia.
• Several secondary outcomes suggest a signal toward harm with hypothermia, including incidence of pneumonia, bradycardia, and more days ventilated.
• Multiple centers, strong follow-up, and rapid induction of hypothermia are strengths of the trial.
• That 19% of patients were withdrawn from the study decreases generalizability.

My take:

• This trial is consistent with other recent data which demonstrate lack of support for prophylactic hypothermia as a standard of care in traumatic brain injury.

Source Article:

Cooper DJ, Nichol AD, Bailey M, 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; 320(21):2211-2220. DOI: 10.1001/jama.2018.17075

Appendix:

Glasgow Outcome Scale – Extended

• 1: Dead
• 2: Vegetative state (only reflex responses and periods of eye opening)
• 3: Low severe disability (requires full assistance with acts of daily living)
• 4: Upper severe disability (requires partial assistance with acts of daily living)
• 5: Low moderate disability (Some disability which presents resumption of work or school, but independent)
• 6: Upper moderate disability (Some disability, but can at least partly resume work or other activities)
• 7: Low good recovery (Minor deficits that affect daily life)
• 8: Upper good recovery (Any deficits still present are not disabling)