The Pre-brief
Targeted temperature management (TTM), formerly known as therapeutic hypothermia, is a bundle of interventions aimed at minimizing reperfusion injury following return of spontaneous circulation after cardiac arrest. There are 3 phases of TTM – induction of cooling, maintenance at goal temperature, and controlled rewarming to normothermia. Continuous core temperature monitoring is integral for the duration of the entire process
Shivering is the body’s compensatory and counterproductive reaction to the TTM process. The body’s shivering threshold is approximately 1°C lower than the vasoconstriction threshold. Medications can be used to widen the interthreshold range by lowering the vasoconstriction and shivering thresholds. This helps facilitate a decrease in core temperature.

No studies to date have demonstrated superiority of a particular medication regimen for shivering in TTM. 1 However, it is intuitive to use shorter acting drugs to potentially limit drug accumulation and delayed awakening which could confound a provider’s neurological assessment
There are two categories of shivering treatments:
- Medications which reduce the shivering threshold
- Medications which stop shivering

Medications which stop shivering:
PRN or continuous paralytics should only be used if patients experience refractory shivering after the above medications and high dose analgesia/sedation targeting a RASS of -3 to -5 have failed. If paralytics are used, a RASS of -5 should be targeted before initiation. Unfortunately, hypothermia decreases the clearance of paralytics and prolongs the duration of neuromuscular blockade which could mask convulsive seizures and obscure neuro assessments. Furthermore, train-of-four monitoring is not reliable during hypothermia due to alteration in peripheral response. Clinical monitoring or continuous EEG use may be necessary.
Is there a role for anti-epileptics?
Seizures following cardiac arrest are associated with increased mortality. BDZ should be considered first-line to abort seizures but should be avoided in the absence of seizure activity due to a significant increase in the development of delirium secondary to BDZ use. Phenytoin, barbiturates, valproic acid, and propofol can all be used as well but caution must be taken due to decreased clearance attributed to the process of TTM.3 Prophylactic use of anti-epileptics is not recommended.
The Debrief
- Preventing shivering is vital in achieving and maintaining a hypothermic state during TTM.
- Medications that reduce the seizure threshold should be attempted before using paralytics which stop shivering completely, due to the risks associated with paralytic use.
- If seizures occur, they should be treated promptly; however, seizure prophylaxis is not recommended.
References
- Taccone F, Picetti E, Vincent J. High Quality Targeted Temperature Management after Cardiac Arrest. Critical Care. 2020; 24:6. PMID: 31907075
- Weant K, Martin J, Humphries R, et al. Pharmacologic Options for Reducing the Shivering Response to Therapeutic Hypothermia. Pharmacotherapy. 2010; 30(8):830-841. PMID: 20653360
- Benken S. Acute Cardiac Care. ACCP/SCCM Critical Care Pharmacy Prep Course. American College of Clinical Pharmacy. 2018.
- Jain A, Gray M, Slisz, S, et al. Shivering Treatments for Targeted Temperature Management: A Review. J Neurosci Nurs. 2018 Apr; 50(2):63-67. PMID: 29278601
- Kuroda Y, Kawakita K. Targeted Temperature Management for Postcardiac Arrest Syndrome. J Neurocrit Care. 2020; 13(1):1-18.