The STEPCARE-trial is designed with three major arms of interventions; targeted temperature management (TTM), mean arterial pressure (MAP) and sedation.
In contrast to the current recommendation to use light sedation for almost all mechanically ventilated patients, deep sedation was introduced for cardiac arrest patients as an essential part of the targeted temperature management (TTM) regimen to counteract undesirable physiological effects and discomfort from induced sub-normal temperatures and to facilitate the cooling process. Based on physiological reasoning and animal data, sedation has also been proposed as a potentially brain protective and seizure prophylactic intervention in itself.
In cardiac arrest patients with hypoxic-ischemic encephalopathy and potentially impaired autoregulation of cerebral blood flow it is unclear whether the potential benefits of sedation outweigh the detrimental effects. For mechanically ventilated patients, sedation can increase comfort, improve ventilator synchrony, and avoid adverse effects of agitation. Sedation may also have beneficial effects on the function of the glymphatic system through inducing non-REM-sleep. The glymphatic system is believed to eliminate toxic breakdown products from the brain such as Beta-amyloid and tau-protein from damaged neurons, thereby preventing aggregation which is a central neurodegenerative mechanism in Alzheimer’s disease. However, while sedation may be beneficial it may also increase the risk of adverse effects like pneumonia, circulatory compromise, delirium, delayed awakening and mobilization, and prolonged ICU stay, which all may negatively affect outcome. In addition, sedation interferes with neurological prognostication as it confounds clinical neurologic examination and may alter EEG-patterns.
Approximately one third of cardiac arrest patients have epileptic seizures and sedative drugs are potent antiepileptic agents commonly used for treating refractory status epilepticus. Seizures may cause metabolic stress which could further aggravate the hypoxic injury. Propofol, the most commonly used sedative drug in cardiac arrest protocols effectively suppresses clinical seizures.
Minimizing sedation through daily interruptions of sedative infusions or using a protocol targeting light sedation resulted in fewer days of mechanical ventilation and fewer days in the ICU. A strategy of non-sedation has been compared with light sedation in general ICU patients with two trials finding conflicting results.
In the context of these conflicting arguments for and against deep sedation in the first days following cardiac arrest, there is substantial uncertainty as to optimal clinical practice.