Known pregnancies and repetitive cardiac arrests are considered relative contraindications for therapeutic hypothermia. The benefits of TH for the mother may exceed the known risks (demise) for the fetus, but this remains controversial. Also, initiating TH while performing CPR during cardiac arrest is currently being studied. Intra-arrest TH initiation seems to be improving patient outcomes, which could suggest the need to initiate cooling during repeat arrests down the road. Currently, though, this research remains unpublished.
The generally accepted list of TH exclusion criteria includes:4
- Initial temperature less than 32°C;
- Patient responding to commands following ROSC;
- Cardiac arrest due to trauma/head injury;
- Major surgery within past two weeks;
- Known systemic infection;
- Comatose prior to cardiac arrest;
- Persistent hypotension (MAP less than 60 mmHg) despite vasoactive drugs for 30 mins.;
- Persistent hypoxemia (SaO2 less than 85%).
The Pharmacology Behind Therapeutic Hypothermia
It is important to remember that all the sedatives, analgesics and neuromuscular blocking agents given during TH will have altered pharmacodynamics.
Therapeutic hypothermia is expected to cause a delay in drug metabolism and elimination and may also modify drug response, potency and efficacy.7
Additionally, the length of cardiac arrest and pre-arrest health of the patient both impact hepatic and renal function. The functional level of the liver and kidneys directly impacts drug metabolism and elimination. As a result it is very difficult to anticipate how drugs will impact post-cardiac arrest patients, particularly once cooling is initiated.7
Using this knowledge, pharmacology is important during TH, as patients must be kept sedated. The goal is to keep a patient deeply sedated, which means unarousable and unresponsive to any tactile or verbal stimuli.4 Sedatives also provide amnesic effects so that patients ideally have no recollection of the cooling period. In addition to sedation, pain management following cardiac arrest is important, as CPR may result in rib fractures or other injuries.
Analgesia—A review of 68 intensive care units found that 26% did not administer analgesics to patients receiving therapeutic hypothermia.7 Current standards, however, stress the importance of administering analgesics prior to sedatives and especially prior to any neuromuscular blocking agents.
Fentanyl is a commonly administered and effective analgesic during TH. However, keep in mind that fentanyl clearance decreases by up to 3.7 times from normal when core body temperatures are decreased.7 Morphine metabolism results in many metabolites that are prone to accumulation during hypothermia, renal dysfunction and hepatic dysfunction. This makes the effects of morphine difficult to predict, which means it’s a poor analgesic for hypothermic patients.
Sedatives—Midazolam infusions typically begin at 2–5mg/hr, but can be increased to as high as 0.3mg/kg/hr, with the maximum dose determined based on the patient’s weight. Midazolam metabolism is likely altered, as hepatic dysfunction is common.7 In addition, the metabolites—byproducts of metabolized midazolam—can build up when renal dysfunction exists. Another disadvantage to midazolam is that its ability to consistently sedate the patient becomes lost if it is not administered at regular intervals. Thus, when utilizing midazolam, ensure a constant dosing regimen (e.g., every 20 minutes).
Diprivan (propofol) is a better choice because its metabolites do not accumulate with hepatic or renal dysfunction.7 However, it does have a low therapeutic window, and its potential for toxicity increases during hypothermia. Diprivan also has the additional benefit of lowering the shivering threshold. While not typically used in prehospital care, it is often used during critical care interfacility transport, and EMS systems implementing TH protocols may want to discuss the use of Diprivan with their medical director.
The pharmacokinetic profiles of ketamine and lorazepam make both drugs inappropriate for the sedation of patients receiving therapeutic hypothermia.7
Neuromuscular blocking agents—When aggressive sedation fails to control shivering, the use of neuromuscular blocking agents is indicated. A serious downside to NMBAs is that they mask seizure activity, which can be present following cardiac arrest, particularly if there is an anoxic brain injury. Seizures exacerbate the brain injury and are associated with worsened outcomes.7