Methods
Adult patients expected to need mechanical ventilation for more than 24 hours were randomly assigned, in a single center, either to daily interruption of continuous sedative and opioid infusion or to intermittent sedation. In both cases, our goal was to maintain a Sedation Agitation Scale (SAS) level of 3 or 4; that is patients should be calm, easily arousable or awakened with verbal stimuli or gentle shaking. Primary outcome was ventilator-free days in 28 days. Secondary outcomes were ICU and hospital mortality, incidence of delirium, nurse workload, self-extubation and psychological distress six months after ICU discharge.
Results
A total of 60 patients were included. There were no differences in the ventilator-free days in 28 days between daily interruption and intermittent sedation (median: 24 versus 25 days, P = 0.160). There were also no differences in ICU mortality (40 versus 23.3%, P = 0.165), hospital mortality (43.3 versus 30%, P = 0.284), incidence of delirium (30 versus 40%, P = 0.472), self-extubation (3.3 versus 6.7%, P = 0.514), and psychological stress six months after ICU discharge. Also, the nurse workload was not diPatients in the intermittent sedation group would be kept without continuous infusion of sedatives if the intubation had been performed in the ICU, or would have their infusion interrupted after randomization if they had been admitted already intubated from emergency department, surgical room, wards or another ICU. Patients would be kept without sedatives infusion until they awoke. After patients were awake, if they were calm and collaborative (SAS of 4), they would be kept without infusion of sedatives. If the patient was uncomfortable or agitated (SAS greater then or equal to 5), the physician (attending or resident) would be consulted, and possible causes of discomfort would be investigated in a standardized method (pain, patient-ventilator asynchrony, thirst, hunger, and position on the bed, all of them using a poster which included figures expressing these uncomfortable sensations) and treated. Pain was treated with boluses of fentanyl (50 to 150 μg). If the pain recrudesced in less than two hours or there was a persistent pain stimulus (for example, surgical scar, drains) a continuous infusion of fentanyl would be initiated and titrated by the attending nurse using numeric pain scale (which measures pain from 0 = no pain, to 10 = the worst pain ever experienced) aiming a value less than or equal to 4. If agitation had no visible cause and pain was already empirically treated with a bolus of fentanyl, then delirium would be suspected and haloperidol administrated (bolus of 2.5 or 5 mg). After 15 minutes, if the patient was still uncomfortable or agitated, a continuous infusion of midazolam or propofol would be initiated to achieve a SAS of 3 to 4. The choice between midazolam and propofol was at the discretion of the attending physician. Sedative dosing would be titrated every two hours thereafter or sooner if the patient was agitated (that is, SAS greater than or equal to 5). Interruption of sedatives infusions would then be performed during the next shift (morning, afternoon or night) in order to try to keep the patient without sedation again.fferent between groups, but it was reduced on day 5 compared to day 1 in both groups (Nurse Activity Score (NAS) in the intermittent sedation group was 54 on day 1 versus 39 on day 5, P less than 0.001; NAS in daily interruption group was 53 on day 1 versus 38 on day 5, P less than 0.001). Fentanyl and midazolam total dosages per patient were higher in the daily interruption group. The tidal volume was higher in the intermittent sedation group during the first five days of ICU stay.
Conclusions
There was no difference in the number of ventilator-free days in 28 days between both groups. Intermittent sedation was associated with lower sedative and opioid doses.
Prior research cited in the paper yielded similar results. In looking at the accumulating experience it appears that the less sedation given the better. No sedation at all may be best for those patients who can tolerate it.
The protocol for the prn sedative group is noteworthy. Again, from the paper:
Patients in the intermittent sedation group would be kept without continuous infusion of sedatives if the intubation had been performed in the ICU, or would have their infusion interrupted after randomization if they had been admitted already intubated from emergency department, surgical room, wards or another ICU. Patients would be kept without sedatives infusion until they awoke. After patients were awake, if they were calm and collaborative (SAS of 4), they would be kept without infusion of sedatives. If the patient was uncomfortable or agitated (SAS greater then or equal to 5), the physician (attending or resident) would be consulted, and possible causes of discomfort would be investigated in a standardized method (pain, patient-ventilator asynchrony, thirst, hunger, and position on the bed, all of them using a poster which included figures expressing these uncomfortable sensations) and treated. Pain was treated with boluses of fentanyl (50 to 150 μg). If the pain recrudesced in less than two hours or there was a persistent pain stimulus (for example, surgical scar, drains) a continuous infusion of fentanyl would be initiated and titrated by the attending nurse using numeric pain scale (which measures pain from 0 = no pain, to 10 = the worst pain ever experienced) aiming a value less than or equal to 4. If agitation had no visible cause and pain was already empirically treated with a bolus of fentanyl, then delirium would be suspected and haloperidol administrated (bolus of 2.5 or 5 mg). After 15 minutes, if the patient was still uncomfortable or agitated, a continuous infusion of midazolam or propofol would be initiated to achieve a SAS of 3 to 4. The choice between midazolam and propofol was at the discretion of the attending physician. Sedative dosing would be titrated every two hours thereafter or sooner if the patient was agitated (that is, SAS greater than or equal to 5). Interruption of sedatives infusions would then be performed during the next shift (morning, afternoon or night) in order to try to keep the patient without sedation again.
As illustrated above prn sedation requires a systematic, not a knee-jerk, approach to the patient involving pain control and a series of assessments for the causes of agitation, followed by bolus haloperidol before resorting to benzodiazepines or propofol.
The caveat is that this approach is not likely suitable for patients with ARDS who require low tidal volume ventilation and sometimes prone positioning and neuromuscular blockade, modalities which require continuous sedation.
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