Fig. 7.1
Survival benefit of daily interruption of sedatives paired with spontaneous breathing trials. In the Awakening and Breathing Controlled Trial, patients in the intervention group were managed with daily interruption of sedatives paired with spontaneous breathing trials and were 32 % less likely to die at any instant during the year following enrollment than patients in the control group (hazard ratio for death, 0.68; 95 % CI, 0.50–0.92; p = 0.01) (From Girard et al. [11], with permission)
7.2.3 Combining Daily Interruption of Sedatives with Targeting Light Sedation
Whereas the two aforementioned trials demonstrated the safety and efficacy of daily interruption of sedatives for mechanically ventilated ICU patients, several other trials have shown that targeting light levels of sedation yields similar benefits. Both Brook et al. [5] and Treggiari et al. [13], for example, randomized mechanically ventilated medical and surgical ICU patients to receive either deep sedation or targeted light levels of sedation and found that less time was spent on mechanical ventilation and in the ICU by patients managed with light sedation. Strom and colleagues [14] took light sedation further by randomizing ICU patients requiring mechanical ventilation to a protocol of no sedation (relying instead on morphine to treat pain and haloperidol to treat agitation) versus sedation with propofol and midazolam. Patients in the intervention group (only 18 % of whom required continuous sedation) benefited from reduced ventilator time and shorter ICU and hospital stays compared with those in the control group.
Given evidence that both daily interruption of sedatives and targeted light sedation improve outcomes in the ICU, several randomized trials were conducted to determine whether combining these two strategies would have additional benefit. An early trial by de Wit et al. [15] was stopped prematurely due to concerns that daily interruption of sedatives was harming patients with alcohol withdrawal, and another by Mehta et al. [16] was not powered to compare clinical outcomes. The third, also by Mehta and colleagues [17], was a large, multicenter, randomized controlled trial of 430 mechanically ventilated medical and surgical ICU patients. This study compared a sedation protocol combining targeted light levels of sedation with daily interruption of sedatives with targeted light sedation alone. Unlike earlier trials of daily interruption of sedatives, the trial by Mehta et al. failed to consistently implement daily sedative interruption in the intervention group, which had sedatives interrupted on only 72 % of eligible days. In fact, patients in the intervention group received significantly higher doses of sedatives (p = 0.04) and opioids (p < 0.001) than patients managed without daily interruption of sedatives. Furthermore, the sedative doses administered were consistent with those expected to cause moderate to deep levels of sedation rather than light sedation according to pharmacologic models [18], and mean sedation scores did indicate moderate sedation levels in both groups. Overall, no difference was found between groups in time to extubation or in duration of ICU and hospital stay.
7.3 Therapeutic Use
7.3.1 Safety Screens
A critical step in successful daily interruption of sedatives protocols is the daily use of a safety screen to identify circumstances during which sedatives may not be safely withdrawn. In their early trial, Kress and colleagues relied on a very simple safety screen: patients on paralytics did not undergo interruption of sedatives. Girard and coworkers subsequently expanded the safety screen to include six elements: (1) active seizures, (2) alcohol withdrawal, (3) ongoing agitation, (4) paralysis, (5) active myocardial ischemia, and (6) elevated intracranial pressure. The presence of any of these safety screen items should prompt the ICU team to refrain from interruption of sedatives at that time and rescreen later (typically the following morning).
7.3.2 Reduction of Sedative Exposure
Taken together, randomized trials of daily interruption of sedatives as well as targeted light sedation make it clear that clinical outcomes in the ICU are improved when exposure to sedatives, especially benzodiazepines, is reduced; in contrast, outcomes are unchanged by sedation protocols that do not reduce exposure to sedatives (Table 7.1). Whereas patients in these trials were primarily sedated with benzodiazepines, which were the most commonly used class of sedatives at the time the trials were performed despite their association with longer ICU length of stay and duration of mechanical ventilation [20], a recent observational study found that early deep sedation was associated with delayed extubation and higher mortality regardless of which sedatives were used [21].
Table 7.1
Benzodiazepine exposure in trials of sedation in the ICU
Trial | Control | Intervention | P | Effect of intervention |
|---|---|---|---|---|
Daily interruption of sedative trials | ||||
Kress et al. [7] | 58 mg/day | 47 mg/day | 0.05 | ↓ duration of MV ↓ ICU LOS |
Girard et al. [11] | 84 mg/day | 54 mg/day | 0.02 | ↑ ventilator-free days ↓ ICU and hospital LOS ↑ survival |
Mehta et al. [17] | 82 mg/day | 102 mg/day | 0.04 | No difference |
Targeting light levels of sedation trials | ||||
Bucknall et al. [19] | 67 mg/day | 64 mg/day | 0.49 | No difference |
Treggiari et al. [13] | 54 mg/day | 7 mg/day | NR | ↓ duration of MV ↓ ICU and hospital LOS |
Strom et al. [14] | 6 mg/day | 0 mg/day | <0.001 | ↑ ventilator-free days ↓ ICU and hospital LOS |
7.3.3 Barriers to Sedative Reduction in the ICU
Despite evidence showing that daily interruption of sedatives improves outcomes, many clinicians are still reluctant to implement sedative reduction protocols in their ICUs. Commonly cited barriers include concerns about lack of nursing acceptance, patient discomfort or respiratory compromise, and device removal or self-extubation [22]. Despite these barriers, a large number of hospitals, both community- and university-based, are reporting successful incorporation of protocols that include daily interruption of sedatives. Often, this approach to reduce sedative exposure is implemented as part of a larger set of protocols that seek to increase patient arousal, interaction, and mobility. One recent study, for example, reported that patients managed with an ABCDE program (Awakening and Breathing Coordination, Delirium Monitoring/Management, and Early Exercise/Mobility) spent more days breathing without ventilator assistance (p = 0.04) and had fewer days with delirium (p = 0.004) than did patients managed at the same institution prior to implementation of ACBDE management [23]. Furthermore, the 2013 Pain, Agitation, and Delirium Clinical Practice Guidelines from the Society of Critical Care Medicine describe an integrated approach to intensive care and advocate for sedative reduction using either daily interruption of sedation or targeted light sedation strategies [1].
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