ARTICLE REVIEW

Haloperidol has been used as the “standard care” for management of delirium in the ICU setting. The authors of this recent study hypothesised that dexmedetomidine might be more effective and safer than haloperidol in nonintubated and agitated patients and aimed to evaluate the effectiveness, safety and cost of dexmedetomidine for the treatment of delirium in this population(1).

The study included 132 patients between the age 18-95 with hyperactive/agitated delirium as evaluated by the CAM-ICU and IDSC scores. All patients received IV bolus doses of haloperidol 0.5-1 mg every 10-15 minutes until control of delirium or until a maximum dose of 30 mg reached. Patients who responded to Haloperidol (86 patients, 65.2%) continued an infusion dose of 0.5-1mg/hr. Those who did not respond to initial blouses of haloperidol (46 patients, 34.8%;)  also received the infusion dose of haloperidol plus dexmedetomidine infusion at a dose of 0.2-0.7ug/kg/min and then haloperidol was tapered. Group comparison was performed once all patients reached the same level of arousal (RAAS 0).

Results showed that dexmedetomidine achieved a higher percentage of time in satisfactory sedation levels than did haloperidol (92.7% vs 59.3%; p = 0.0001). Addition of the dexmedetomidine rescue infusion promptly controlled the level of sedation in all haloperidol-refractory patients. Dexmedetomidine achieved greater stability in its sedative effect and RASS levels compared to the more fluctuating profile of haloperidol.

The authors defined  haloperidol ”failure” in 2 main aspects. Firstly, haloperidol did not control agitation in 46 patients (34.7%) who were then assigned to the addition of dexmedetomodine. Secondly, ten patients on haloperidol were oversedated and two patients had prolonged QTc intervals. This gave an overall failure rate of 43% of haloperidol. Contrarily, dexmedetomidine was able to control all the agitated haloperidol refractory patients without oversedation or QTc disturbances.The incidence of bradycardia was higher with dexdmedetomidine, but this was statistically insignificant. Patients treated with haloperidol required longer recovery times and ICU stay than patients in the dexmedetomidine group, causing an incremental cost of $4,370 per patient.

The main concern with this study is that it used a nonrandomised intervention design, which is less consistent and is subject to greater observation biases. A second limitation is that only patients with agitated (hyperactive) delirium were studied and other forms of delirium were not taken into account. A third limitation regarding cost analysis might be bias against haloperidol attributable to the delay in discharge due to complications other than oversedation such as gastrointestinal bleeding or nosocomial infections.

Take home messages

• Dexmedetomidine achieved a higher percentage of time in satisfactory sedation levels than did haloperidol and showed greater stability in the levels of sedation during the 72 hour period studied.
• Haloperidol failed to control agitated delirium in 34.8% and all patients who had dexmedetomidine added were adequately sedated.
• Incidence of oversedation and QT prolongation was higher with haloperidol and incidence of bradycardia was higher with dexmedetomidine.
• By reducing recovery times and length of ICU stay dexmedetomidine achieved lower cost per patient.

Article review was submistted by ESICM Journal Review Club member Mohamed Ghonemi.

References

1. Carrasco G, Baeza N, Cabré L, Portillo E, Gimeno G, Manzanedo D, Calizaya M. Dexmedetomidine for the Treatment of Hyperactive Delirium Refractory to Haloperidol in Nonintubated ICU Patients: A Nonrandomised Controlled Trial. Crit Care Med 2016 Feb 29. Epub 2016 Feb 29.

2.Riker RR, Picard JT, Fraser GL: Prospective evaluation of the Sedation- Agitation Scale for adult critically ill patients. Crit Care Med  1999; 27:1325–1329

3. Ely EW, Shintani A, Truman B, et al: Delirium as a predictor of mortality in mechanically ventilated patients in the intensive care unit. JAMA 2004; 291:1753–1762

4. Bergeron N, Dubois MJ, Dumont M, et al: Intensive Care Delirium Screening Checklist: Evaluation of a new screening tool. Intensive Care Med 2001; 27:859–864