Rationale:

• Membrane receptors and their responses become progressively less sensitive as the core temperature falls.
• Hypothermia alters the profiles of drug distribution, metabolism, and elimination.
• Rewarming may unintentionally increase drug concentrations, producing drug toxicity.
• During hypothermia, the concentration of drug in the blood is affected by decreased elimination and increased protein binding.
• During rewarming, the free-drug concentration may markedly increase because of the shift from the bound to the unbound form, thereby producing toxic levels.

Evidence:

• Studies show that excessive drug manipulation of hypothermic patients should be avoided. Drug levels may rise to toxic levels upon rewarming because of decreased metabolism, decreased elimination, increased availability with rewarming, and possible hepatic dysfunction with rewarming. For these reasons, intravenous drugs are often withheld until the patient's core temperature is >30°C (86°F) (166; 167; 168; 169).

Comments:

• The decreased response to cardioactive drugs is related to the severity of hypothermia.
• Initiation of drug therapy depends on the acuity of the situation, the severity of hypothermia, and the risk for cardiovascular depression.