Targeted Temperature Management (TTM) results in an approximate 5% decrease in metabolic rate for every 1°C drop in core body temperature, theoretically reducing lactate, excitatory neurotransmitters, inflammatory processes, and free radical production.
Shivering is a potential complication that can arise in patients undergoing targeted temperature management (TTM). It can have adverse effects by increasing the metabolic rate, leading to higher lactate production, and triggering the release of excitatory neurotransmitters. These physiological changes have the potential to counteract the intended benefits of TTM [1-10].
Medications such as acetaminophen, buspirone, magnesium, opioids, dexmedetomidine, propofol, and neuromuscular blockers are agents in our toolbox to treat and prevent shivering. It is unclear the precise mechanism of action of these medications in their modulation of shivering but literature in antitheology use for post operative shivering led to the exploration of their use in the critical ill individual undergoing TTM.
Acetaminophen is thought to act as an antipyretic through its inhibition of prostaglandin synthesis resulting in a reduction of the hypothalamic set point. Buspirones activity on 5-HT1A receptors are thought to lead to a reduction in shivering threshold through the modulation of serotonin. Both of these agents can be scheduled to allow for a multimodal approach to shivering prevention with limited safety profile to be concerned of.
Magnesium use results in vasodilation and increases the comfort of cooling while decreasing the time to goal temperature but its use can be limited due to hypotension in the post cardiac arrest period.
Opioid activity on both µ- and K- receptor activity resulting in fentanyl and meperidine being appropriate analgesia agents. Though caution is warranted due to meperidine’s hepatic metabolism and safety profile that results in neurological manifestations and reduction in the seizure threshold.
Sedation options include dexmedetomidine and propofol. With dexmedetomidine allowing for sedation while in addition to thermoregulation having demonstrated a reduction in shivering threshold by 2.4°C.
The final tool in our pharmacological toolbox is neuromuscular blocking agents which is the fastest method to achieve shivering management but is associated with prolonged time on mechanical ventilation, prolonged ICU length of stay, and increased mortality.
Protocolized Approach to Shivering Management
By combining various interventions, the study aimed to optimize patient care and enhance the success of TTM. The findings from the observational study provide valuable insights into the management of shivering during TTM and can guide future research and clinical practices in improving patient comfort and outcomes. The study's results contribute to the understanding of adjunctive strategies and multimodal approaches in reducing shivering and minimizing the reliance on deep sedation and paralysis during targeted temperature management.al use of paralytics (8.9% of TTM days), emphasizing the importance of a multimodal approach to address shivering .
Huynh et al. conducted a retrospective pre-post-trial in 2022 to investigate the impact of scheduled medications and protocol implementation on shivering management in patients undergoing therapeutic hypothermia at a target temperature of 33°C. The study aimed to assess whether the intervention could effectively maintain a lack of shivering and reduce the need for paralytics. The results showed that the implementation of a protocol led to a significant reduction in shivering incidence (57% of patients pre-intervention compared to 39% post-intervention) and a decrease in the use of paralytics (19% pre-intervention versus 6% post-intervention) .
It is important to note that a limitation of this study was the presence of noncompliance and variability in adhering to the outlined protocol. Despite this variation, the findings still demonstrated a reduction in the incidence of shivering while also reducing the administration of propofol, midazolam, and paralytics. The study highlights the potential benefits of scheduled medications and protocol implementation in effectively managing shivering during therapeutic hypothermia, ultimately improving patient care and reducing the need for certain medications and interventions.
A multimodal approach to the management of shivering has been shown to reduce the incidence of shivering. As clinical practice shifts the goal of TTM to normothermia shivering management may be able to change as well. A multimodal approach without deep sedation may be utilized to prevent and treat shivering and clinicians can utilize patient specific sedation goals rather than deeply sedating solely for the purpose of TTM.
Weant KA, Martin JE, Humphries RL, Cook AM. Pharmacologic options for reducing the shivering response to therapeutic hypothermia. Pharmacotherapy. 2010;30(8):830-841. doi:10.1592/phco.30.8.830
Madden LK, Hill M, May TL, et al. The Implementation of Targeted Temperature Management: An Evidence-Based Guideline from the Neurocritical Care Society. Neurocrit Care. 2017;27(3):468-487. doi:10.1007/s12028-017-0469-5
Choi HA, Ko SB, Presciutti M, et al. Prevention of shivering during therapeutic temperature modulation: the Columbia anti-shivering protocol. Neurocrit Care. 2011;14(3):389-394. doi:10.1007/s12028-010-9474-7
Kasner SE, Wein T, Piriyawat P, et al. Acetaminophen for Altering Body Temperature in Acute Stroke. Stroke. 2002;33(1):130-135. doi:10.1161/hs0102.101477
Zweifler RM, Voorhees ME, Mahmood MA, Parnell M. Magnesium sulfate increases the rate of hypothermia via surface cooling and improves comfort. Stroke. 2004;35(10):2331-2334. doi:10.1161/01.STR.0000141161.63181.f1
Kurz A, Ikeda T, Sessler DI, et al. Meperidine Decreases the Shivering Threshold Twice as Much as the Vasoconstriction Threshold. Anesthesiology. 1997;86(5):1046-1054. doi:10.1097/00000542-199705000-00007
Talke P, Tayefeh F, Sessler DI, Jeffrey R, Noursalehi M, Richardson C. Dexmedetomidine Does Not Alter the Sweating Threshold, But Comparably and Linearly Decreases the Vasoconstriction and Shivering Thresholds. Anesthesiology. 1997;87(4):835-841. doi:10.1097/00000542-199710000-00017
Matsukawa T, Sessler DI, Sessler AM, et al. Heat flow and distribution during induction of general anesthesia. Anesthesiology. 1995;82(3):662-673. doi:10.1097/00000542-199503000-00008
Rodríguez-Blanco J, Rodríguez-Yanez T, Rodríguez-Blanco JD, et al. Neuromuscular blocking agents in the intensive care unit. J Int Med Res. 2022;50(9):03000605221128148. doi:10.1177/03000605221128148
Huynh C, Lui J, Behbahani V, Thompson Quan A, Morris A, Baumgartner L. Pre Versus Post Implementation of a Pharmacologic Antishivering Protocol During Targeted Temperature Management Following Cardiac Arrest. Neurocrit Care. 2022;36(2):511-518. doi:10.1007/s12028-021