POINT COUNTERPOINT Should Dexmedetomidine Replace Benzodiazepines as the Preferred Sedative, as Suggested by New Guidelines from the Society for Critical Care Medicine*? THE “PRO” SIDE

Over the past decade, most Canadian intensive care units (ICUs) have adopted locally developed standardized protocols for delivery of analgesics and sedatives to patients who are undergoing mechanical ventilation to alleviate pain, anxiety, and agitation. Although I do acknowledge the benefits of protocol-ized care, not all patients have the same needs with respect to sedation and analgesia, so one of the consequences of this " checkbox " approach is oversedation caused by unnecessary drug exposure in many patients. 1 This year, the American College of Critical Care Medicine published clinical practice guidelines for the management of pain, agitation, and delirium in adult patients in the ICU. 2 These guidelines, which update the decade-old previous guidelines, recommend lighter levels of sedation for these patients (grade +1B [strong recommendation, supported by moderate evidence, favouring the intervention]) and avoidance of benzodiazepines (grade +2B [weak recommendation , supported by moderate evidence, favouring the intervention]). However, if benzodiazepines are removed from the pharmacological arsenal, only narcotics, propofol, and dexmedetomidine remain in terms of drugs that have anxiolytic or sedative properties and that are predictably titratable. Purposely avoiding the terms " never " and " always " , I would agree that the utility of benzodiazepines in the ICU is waning as questions about their safety and comparative efficacy begin to accumulate. Oversedation is not a new observation in the ICU and is most commonly associated with continuous infusions of benzodiazepines. Prolonged and deep sedation, although necessary for some patients, has been associated with increased mortality at 6 months and significant morbidity, including prolonged ICU stays, prolonged duration of mechanical ventilation, and increased resource utilization, as well as delirium and psychologic morbidity, in ICU survivors. 2,3 The new guidelines recommend several strategies to minimize unnecessary exposure to sedatives and opioids (e.g., nurse-driven titration algorithms, analgesia-first sedation, lighter sedation targets, and daily interruptions in sedation), but these recommendations focus on the delivery of sedation and analgesia, not necessarily the agents that are used to achieve these effects. 2 The problem is that pharmacotherapeutic choices are scarce. Traditionally, the options for pain control with supportive evidence have been limited primarily to opioids, whereas the options for controlling agitation and anxiety have been limited to benzodiazepines and propofol. Opioids provide moderate sedation in addition to analgesia, but either they have active metabolites that can accumulate (e.g., morphine, hydromorphone) or they are extremely lipophilic (e.g., fentanyl). Benzodiazepines have active metabolites …