Agitation and distress are commonly encountered in mechanically ventilated patients and are typically managed by the use of a sedative-hypnotic agent (e.g., propofol, midazolam) with or without an opioid analgesic.1,2 However, the significant adverse events associated with the sedatives have triggered the interest in a different approach, referred to as the analgesia-based sedation or the analgesia-first sedation. This approach involves managing pain and discomfort first, before providing sedative therapy.
Recently, a literature review was conducted by Devabhakthuni et al(3) to evaluate analgesia-based sedation in mechanically ventilated adult patients. The review included ten randomized controlled trials published in English.4-13 Nine studies compared remifentanil to other agents (morphine, fentanyl, midazolam, propofol) while one study compared morphine only to daily interruption of sedation. The sample size in the studies ranged from 20 to 205 patients and the mean duration of treatment ranged from 9 hours to 5.1 days.
The use of remifentanil, titrated to a target sedation goal before using hypnotics as rescue therapy, was associated with optimal patient comfort outcomes.9-12 Compared to sedation-based regimens, remifentanil-based analgosedation was associated with shorter extubation time (1 vs. 1.93, p=0.001), a reduction in time on ventilator by >2 days (p=0.033), a reduction in the time to extubation (21 vs. 24 hours, p<0.05), shorter ICU length of stay (46 vs. 62 hours, p<0.05), and reduced weaning time by 18.9 hours (p=0.0001). Compared to fentanyl, the use of remifentanil appeared to be as effective, but with greater incidence of pain during de-escalation with remifentanil.6 A study that compared morphine only, with no sedatives, to daily interruption of sedation, reported significantly more days without ventilation (13.8 vs. 9.6 days, p=0.019), shorter length of ICU stay (13.1 vs. 22.8 days, p=0.0316) and shorter hospital stay (34 vs. 58 days, p=0.0039) in the morphine group.13 However, patients receiving morphine had more episodes of delirium.
Despite the improved outcomes reported with analgosedation, there were several limitations noted in the studies. Seven studies were supported by the remifentanil manufacturer,4-6,9-12 only four were double blinded,5-8 and only three provided adequate allocation concealment.4,7,13 Furthermore, daily sedation interruptions were used in only one study13, the pain and sedation scales were not consistent among the studies, and the patient populations studied, dosing regimens used, and efficacy outcomes were variable, making it difficult to compare results.
The recent literature review describes a potential change in the practice of sedation, with the emphasis being on the use of analgesics initially then adding sedatives, as needed. More research is needed to confirm the results of the earlier studies, but the currently available evidence highlights the importance of opioids in the management of agitation in mechanically ventilated patients.
1. Soliman HM, Melot M, Vincent JL. Sedative and analgesic practice in the intensive care unit: the results of a European survey. Br J Anaesth 2001;87:186-92.
2. Tonner PH, Weiler N, Paris A, et al. Sedation and analgesia in the intensive care unit. Curr Opin Anaesthesiol 2003;16:113-21.
3. Devabhakthuni S, Armahizer MJ, Dasta JF, et al. Analgosedation: A paradigm shift in intensive care unit sedation practice. Ann Pharmacother 2012;46:530-40. ...