Sedation, Temperature and Pressure After Cardiac Arrest and Resuscitation- STEPCARE Trial

Sedation strategy: deep continuous sedation target for at least 36h • For patients randomized to continuous sedation a continuous infusion of a short-acting usual care sedative agent (eg. propofol) should be started at randomization and continue for 36hrs. • Short-acting drugs by continuous infusion (eg. propofol) are preferred to benzodiazepines (by either continuous infusion or bolus dosing). • Medical records will be reviewed by research staff to monitor adherence to the intervention. Sedation strategy: light sedation target with early wakening. • In patients randomized to minimal sedation sedative agents shall not be used unless needed for usual clinical care. • If sedatives are required, short-acting drugs by continuous infusion (eg. propofol) are preferred to benzodiazepines (by either continuous infusion or bolus dosing). Weaning from sedatives should be performed as early as possible, ideally within 6 hours of randomization if not at the time of ICU admission. • Medical records will be reviewed by research staff to monitor adherence to the intervention. Temperature strategy: fever management (<37.5°C) using standard care cooling devices • Temperature will preferentially be recorded via a bladder thermometer. If the patient is oliguric, or if a bladder recording is not available then core temperature will be assessed by an esophageal or intravascular probe. • Standard cooling devices include endovascular cooling devices with closed loop systems (heat exchange pads attached to the body surface or with heat exchange catheters introduced in a central vein) and surface cooling devices with closed loop systems ( cold fluid or cold air is circulated through blankets or pads that are wrapped around the patient). • The duration of the intervention is for up to 72 hours post-cardiac arrest. • ICU nurses will administer the intervention. • Medical records will be reviewed by research staff to monitor adherence to the intervention. Temperature strategy: fever management primarily with medications (no standard care cooling devices) • Temperature will preferentially be recorded via a bladder thermometer. If the patient is oliguric, or if a bladder recording is not available then core temperature will be assessed by an esophageal or intravascular probe. • Fever management in this group should not differ from other critically ill patients in the ICU. No specific temperature target will be set. Antipyretics and non-pharmacological cooling measures may be used on the same indications as for any ICU patient. • The duration of the intervention is for up to 72 hours post-cardiac arrest. • Medical records will be reviewed by research staff to monitor adherence to the intervention. Blood pressure strategy: A Mean Arterial Pressure target of >85mmHg • The means of achieving the targeted MAP will be up to the treating clinician according to local protocols, usually intravenous fluid boluses and vasoactive/inotropic therapies. The most common vasoactive and inotropic drugs used in intensive care units include noradrenaline, adrenaline, phenylephrine, vasopressin, milrinone, dobutamine, dopamine and levosimendan. The dose of the vasoactive and inotropic drugs is dependent on patient weight. • Participants allocated to a MAP target of at least 85 mmHg will have their vasopressor infusions increased until a MAP of at least 85 mmHg is achieved for the first 72 hours after randomization. After the 72-hour intervention period, the MAP target is decided by the treating clinician. • Blood pressure monitoring will occur at the following timepoints after randomization into the study: 0, 2, 4, 6, 8, 12, 14, 16, 18, 20, 22, 24, 28, 32, 36, 40, 48, 56, 72 hours. • Medical records will be reviewed by research staff to monitor adherence to the intervention. Blood pressure strategy: A Mean Arterial Pressure target of >65mmHg • The means of achieving the targeted MAP will be up to the treating clinician according to local protocols, usually intravenous fluid boluses and vasoactive/inotropic therapies. The most common vasoactive and inotropic drugs used in intensive care units include noradrenaline, adrenaline, phenylephrine, vasopressin, milrinone, dobutamine, dopamine and levosimendan. The dose of the vasoactive and inotropic drugs is dependent on patient weight. • Participants allocated to a MAP target of at least 65 mmHg will have their vasopressor infusions increased until a MAP of at least 65 mmHg is achieved for the first 72 hours after randomization. After the 72-hour intervention period, the MAP target is decided by the treating clinician. • Blood pressure monitoring will occur at the following timepoints after randomization into the study: 0, 2, 4, 6, 8, 12, 14, 16, 18, 20, 22, 24, 28, 32, 36, 40, 48, 56, 72 hours. • Medical records will be reviewed by research staff to monitor adherence to the intervention. Intervention Arms All patients will be randomized to three allocation groups, and each strategy will be studied separately regarding safety and reporting of results. Sedation, temperature device and high MAP -continuous deep sedation for 36 hours, fever management with a feedback-controlled device if temperature above 37.7°C and a mean arterial pressure target of >85mmHg. Sedation, no temperature device and high MAP -continuous deep sedation for 36 hours, fever management without a feedback-controlled device and a mean arterial pressure target of >85mmHg. Sedation, temperature device and low MAP -continuous deep sedation for 36 hours, fever management with a feedback-controlled device if temperature above 37.7°C and a mean arterial pressure target of >65mmHg. Sedation, no temperature device and low MAP -continuous deep sedation for 36 hours, fever management without a feedback-controlled device and a mean arterial pressure target of >65mmHg. Minimal sedation, temperature device and high MAP -minimal sedation (and early extubation if possible), fever management with a feedback-controlled device if temperature above 37.7°C and a mean arterial pressure target of >85mmHg. Minimal sedation, no temperature device and high MAP -minimal sedation (and early extubation if possible), fever management without a feedback-controlled device and a mean arterial pressure target of >65mmHg. Minimal sedation, temperature device and low MAP -minimal sedation (and early extubation if possible), fever management with a feedback-controlled device if temperature above 37.7°C and a mean arterial pressure target of >65mmHg.