Lie Still, Sleep Becalmed: The Effects of Deep Sedation in the First 48 Hours of ICU Care
Abstract & Commentary
Lie Still, Sleep Becalmed: The Effects of Deep Sedation in the First 48 Hours of ICU Care
By Saadia R. Akhtar, MD, MSc, St. Luke's Idaho Pulmonary Associates, Boise, is Associate Editor for Critical Care Alert.
Dr. Akhtar reports no financial relationships relevant to this field of study.
Synopsis: This multicenter prospective study found that deep sedation in the first 48 hours of mechanical ventilation and ICU care is associated with delayed extubation and increased risk of hospital and 180-day mortality.
Source: Shehabi Y, et al; Sedation Practice in Intensive Care Evaluation (SPICE) Study Investigators and the ANZICS Clinical Trials Group. Early intensive care sedation predicts long-term mortality in ventilated critically ill patients. Am J Respir Crit Care Med 2012;186:724-731.
The authors note a paucity of literature on early (0-48 hours of ventilation and ICU admission) sedation practices and their impact on outcomes; thus they performed this multicenter prospective cohort study with the hypothesis that early sedation is associated with delirium, time to extubation, and hospital and 180-day mortality. Twenty-five Australian and New Zealand ICUs participated. Over a 3-month period in 2010, up to 20 patients were recruited from each study site. Inclusion criteria were age ≥ 18 years, need for mechanical ventilation and sedation for 0-24 hours at enrollment, and expected ongoing need for this support. Exclusions included neurological impairment, psychiatric illness, dementia, burns, or palliative care. Usual demographic and clinical data were recorded. Richmond Agitation Sedation Score (RASS) and a pain score were measured every 4 hours ("deep sedation" defined as RASS -3 to -5). Confusion Assessment Method for ICU (CAM) was assessed daily. Cumulative doses of sedatives, analgesics, and antipsychotics were recorded. Patients were followed to ICU discharge or death (up to 28 days), and 180-day survival data were obtained from medical records or national death registries. Standard statistical methods were applied.
The study cohort consisted of 251 patients. A total of 629 met the initial inclusion criteria; however, the majority were excluded for neurological impairment, 72 due to study staff not being available for enrollment, and 27 were discharged or died within 24 hours. The cohort had mean APACHE II score 21; median ventilator days 5.1; ICU length of stay 8.5 days; and ICU, hospital, and 180-day mortality of 16.7%, 21.1%, and 25.8%, respectively. Midazolam and propofol were used with similar frequency; fentanyl was slightly preferred to morphine. Delirium was quite common, with at least 50% of patients being CAM positive for at least 1 day. About two-thirds of these patients received haloperidol, dexmedetomidine, or diazepam for delirium or agitation; these drugs were also given to about 28% of patients without delirium or agitation. Specific sedation targets were only ordered on 25% of patients and met just 35% of the time; routine sedation holidays occurred rarely (3.1% of all study days). Most patients were maintained with deep sedation early on (76% at 4 hours into mechanical ventilation and 68% at 48 hours), but this decreased to 24% at ≥ 5 days. After adjusting for nine variables defined a priori, early deep sedation was associated with longer time to extubation (7.7 vs 2.4 days; each 4-hour measure of deep sedation delayed extubation 12.3 hours); cumulative doses of midazolam and fentanyl were predictive as well but propofol or morphine doses were not. Early deep sedation was associated with delirium at 48 hours but not later. Finally, hospital and 180-day mortality risk were increased by early deep sedation but not the choice of agent.
Commentary
Patients in the ICU often have pain, anxiety, and/or delirium for a variety of reasons. It is essential that health care providers treat these symptoms and provide comfort, and continuous infusions of sedative medications are frequently the most effective way to accomplish this. At the same time, it is clear that excessive sedation leads to increased time on mechanical ventilation and ICU length of stay.1 Shehabi et al's study further corroborates this by correlating time spent in deep sedation in the first 48 hours of ICU stay with longer time to extubation as well as higher hospital and 180-day mortality; there is an association with delirium at 48 hours as well. Although these results are not surprising, prior studies have generally addressed impact of sedation beyond the first 48 hours; the authors note this study is unique in focusing on this early time period.
It is also well-established that less sedation, achieved by using protocol-driven sedation administration and daily interruption of sedation (i.e., sedation holidays), is associated with improved outcomes without adverse psychological effects.2 Despite good evidence supporting this, implementation rates of such an approach remain quite low as noted again here. This multicenter Australasian report found no clear sedation protocols, no apparent guidelines for triggers for specific medications (implied from the description of antipsychotic use for patients without delirium or agitation), limited use of sedation targets (and when given, usually not met), and appallingly rare sedation holidays (occurring on only 3.1% of study days).
This study is interesting for three reasons. First, it describes current ICU sedation practices in Australia and New Zealand, which I suspect may not differ from practices in other developed areas of the world. Second, it adds further evidence to the literature on adverse effects of excessive sedation and the high frequency of delirium in ICU patients. Third, and perhaps most importantly, it reminds us of how difficult it can be to implement evidence and change clinical practice.
If the Australasian experience sounds familiar, then it is time to take action today because previous well-designed, randomized, controlled studies and ongoing reports like this one leave little doubt of the harm of excessive sedation and the potential benefits of changing our approach to management of sedation in the ICU.
References
- Brook AD, et al. Effect of a nursing-implemented sedation protocol on the duration of mechanical ventilation. Crit Care Med 1999;27:2609-2615.
- Girard TD, et al. Efficacy and safety of a paired sedation and ventilator weaning protocol for mechanically ventilated patients in intensive care (Awakening and Breathing Controlled trial): A randomized controlled trial. Lancet 2008;371:126-134.
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