Clinical Trials In Hypothermia And Cardiac Arrest

The process of induced hypothermia as a therapy for acute brain injury was first described in the 1940s with the therapeutic cooling of patients (33). Several reports followed with the use of induced hypothermia during cardiac surgery in the 1950s (34) and 1960s (35). In the 1980s, researchers in Pittsburgh (36,37) and Miami (38,39) approached induced hypothermia for brain injury after CA in a more systematic manner, leading to extensive preclinical studies that showed functional and survival benefit of hypothermia in rodent (40,41) and canine models (42,43). Based on these findings, pilot hypothermia studies in human were undertaken and showed encouraging results of improved clinical outcomes (44,45 ).

The mechanism by which hypothermia leads to improved survival and functional recovery is not precisely understood. Numerous mechanisms have been suggested (38), including the effect of hypothermia on (i) cerebral blood flow and metabolism that retards the initial rate of ATP depletion (46,47), (ii) reduction of excitotoxic neurotransmitter release (48 ), (iii) alteration of intracellular messenger and mediator activity (49), (iv) blood-brain barrier breakdown (50 ), (v) reduction of inflammatory response (51), and (vi) alteration in gene expression and protein synthesis (52,53). Recent studies found that hypothermia-induced neuroprotection in a rodent model ameliorates cell death of hippocampal CA1 neurons via the ischemia-induced down-regulation of the AMPA-receptor subunit GluR2 (54). Neuroprotection was noted as early as two days after ischemia, with normalization of GluR2 mRNA levels in hypothermia-treated animals within one week (54). Although the brain was the primary beneficiary of hypothermia

Table 1 Checklist for Initiation of Hypothermia After Cardiac Arrest Assessment

Initial patient assessment prior to beginning cooling

  • Assess medical therapy. (Vasopressor and vasodilators might affect heat transfer, increase potential for skin injury, and contribute to adverse hemodynamic response.)
  • Obtain core (rectal or bladder) temperature
  • Obtain vitals and hemodynamic values
  • Monitor cardiac rhythm
  • Assess baseline electrolytes, glucose, ABG, coagulation labs, lactate, and CPK with MB fractions
  • Assess baseline neurologic examination
  • Assess ventilatory function
  • Assess bowel sounds, abdomen, and GI function
  • Assess skin integrity. (External cooling devices might exacerbate skin injury, especially if the patient has preexisting conditions, such as diabetes, and/or the patient is on vasopressors.)

Ongoing assessment

  • Full assessment q 4 hr
  • Temperature check q 1 hr
  • Vitals every 15 min x 4, then every 1 hr
  • Hemodynamics evaluation by pulmonary artery catheter protocol
  • Assess for signs of shivering
  • Cardiac rhythm every 4 hr
  • If shivering occurs and no pulse oximetry available, draw ABGs every 1 hr until shivering ceases
  • Maintain normal blood glucose. Use insulin as necessary Interventions (cooling process)
  • Initiate ICU sedation. (Midazolam infusion is agent of choice.)
  • Vecuronium IV for signs of shivering
  • Adjust cooling/warming based on established clinical target (32-34°C from 24 hr) and on method and device used for cooling/warming

Interventions (rewarming process)

  • Once patient is maintained at target temperature for 24 hr, remove cooling blanket; may add warm blankets, and remove wet/damp clothing or bed linens
  • Passive rewarming to normal temperature over 8 hr (not faster than 0.5°C/hr)

Abbreviations: ICU, intensive care unit; IV, intravenous; ABG, arterial blood gas; CPK, creatine phosphokinase; MB, myocardial isoenzyme (** such as in CPK-MB or creatine phosphokinase—myocardial isoenzyme); GI, gastrointestinal. Source: Modified from Johns Hopkins Hospital - CCU Nursing Protocol, 2002.

therapy, other organ systems could have also benefited from this treatment, a consequence that might play an important role in reducing extracerebral injury and help to promote overall survival (Table 1).

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