Analgesia and sedation in high-risk critically ill patients: still waiting for evidence about remifentanil.

C ill patients requiring invasive vital support such as mechanical ventilation almost uniformly show anxiety, agitation and pain during their Intensive Care Unit (ICU) stay. The use of analgesic and sedative drugs is essential to improve comfort, reduce anxiety and facilitate nursing care, despite the fact that these drugs present several side effects. In the past decades, liberal doses of propofol and benzodiazepines were used to adapt patients to the harsh ICU environment through deep levels of sedation. Recently, evidence based medicine has shown that heavy sedation may increase mortality and morbidity:1 new protocols have been proposed to change this cultural approach.2 Spontaneous awakening and breathing trial,3 early mobility and physical therapy,4 analgesia-based sedation,5 the use of newer drugs with favorable pharmacokinetics 6 and the use of an enteral approach 7 are the most important recent innovations. They all share the new target of maximizing comfort and adaptation to invasive procedures while patients remain awake, interactive, and oriented.1, 8 High-risk critically ill patients are the most difficult ICU population to take care of, for which any therapeutic intervention could have a significant role in changing the outcome.9 Both inadequate and excessive analgesic use has been associated with several disadvantages: nosocomial pneumonia, delirium, long-term psychological disorder, prolonged mechanical ventilation, higher risk of tracheostomy, higher risk of requiring diagnostic imaging to clarify abnormal neurological status, and unnecessary prolonged ICU and hospital stay.10 Currently, morphine, sufentanil and fentanyl are the most commonly used analgesics in high-risk critically ill patients: the 2010 “Evidence and consensus-based German guidelines for the management of analgesia, sedation and delirium in intensive care” still suggest their use for analgesia extending beyond 72 hours. However, the duration of their effect may become unpredictable because of redistribution and accumulation with prolonged infusion, especially in patients with organ failure. In this context, the use of remifentanil for analgesiabased sedation 5 has been a significant innovation in recent years, “awakening” several intensivists to wake up their critical patients thanks to its manageability. Remifentanil is a strong selective μ-opioid receptor agonist, rapidly metabolized by nonspecific plasma and tissue esterases into inactive metabolites; it has very short context-sensitive half-life (2-3 minutes) even after prolonged infusion or in patients with organ failure. Remifentanil is easy to titrate and provides excellent analgesia: it allows higher doses administration than are normally used with traditional opioids without concerns about accumulation or delayed recovery.11 However, more than the known side effects of opiates like hypotension, bradicardia, decreased respiratory drive, delirium, nausea and vomiting, ileus, sleep disruption, itch, and urinary retention, remifentanil determined Analgesia and sedation in high-risk critically ill patients: still waiting for evidence about remifentanil