DESIGN: Harmonized data from prospective multicenter international longitudinal cohort studies SETTING:: Diverse mix of ICUs.
PATIENTS: Critically ill patients expected to be ventilated for longer than 24 hours.
INTERVENTIONS: Richmond Agitation Sedation Scale and pain were assessed every 4 hours. Delirium and mobilization were assessed daily using the Confusion Assessment Method of ICU and a standardized mobility assessment, respectively.
MEASUREMENTS AND MAIN RESULTS: Sedation intensity was assessed using a Sedation Index, calculated as the sum of negative Richmond Agitation Sedation Scale measurements divided by the total number of assessments. We used multivariable Cox proportional hazard models to adjust for relevant covariates. We performed subgroup and sensitivity analysis accounting for immortal time bias using the same variables within 120 and 168 hours. The main outcome was 180-day survival. We assessed 703 patients in 42 ICUs with a mean (SD) Acute Physiology and Chronic Health Evaluation II score of 22.2 (8.5) with 180-day mortality of 32.3% (227). The median (interquartile range) ventilation time was 4.54 days (2.47-8.43 d). Delirium occurred in 273 (38.8%) of patients. Sedation intensity, in an escalating dose-dependent relationship, independently predicted increased risk of death (hazard ratio [95% CI], 1.29 [1.15-1.46]; p < 0.001, delirium hazard ratio [95% CI], 1.25 [1.10-1.43]), p value equals to 0.001 and reduced chance of early extubation hazard ratio (95% CI) 0.80 (0.73-0.87), p value of less than 0.001. Agitation level independently predicted subsequent delirium hazard ratio [95% CI], of 1.25 (1.04-1.49), p value equals to 0.02. Delirium or mobilization episodes within 168 hours, adjusted for sedation intensity, were not associated with survival.
CONCLUSIONS: Sedation intensity independently, in an ascending relationship, predicted increased risk of death, delirium, and delayed time to extubation. These observations suggest that keeping sedation level equivalent to a Richmond Agitation Sedation Scale 0 is a clinically desirable goal.
OBJECTIVES: To present the protocol and analysis plan of a large randomised clinical trial investigating the effect of a sedation strategy, in critically ill patients who are mechanically ventilated, based on a protocol targeting light sedation using dexmedetomidine as the primary sedative, termed "early goal-directed sedation", compared with usual practice.
METHODS: This is a multinational randomised clinical trial in adult intensive care patients expected to require mechanical ventilation for longer than 24 hours. The main exclusion criteria include suspected or proven primary brain pathology or having already been intubated or sedated in an intensive care unit for longer than 12 hours. Randomisation occurs via a secured website with baseline stratification by site and suspected or proven sepsis. The primary outcome is 90-day all-cause mortality. Secondary outcomes include death, institutional dependency, cognitive function and health-related quality of life 180 days after randomisation, as well as deliriumfree, coma-free and ventilation-free days at 28 days after randomisation. A predefined subgroup analysis will also be conducted. Analyses will be on an intention-to-treat basis and in accordance with this pre-specified analysis plan.
CONCLUSION: SPICE III is an ongoing large scale clinical trial. Once completed, it will inform sedation practice in critically ill patients who are ventilated.
DESIGN: An online survey was conducted.
SETTING AND PARTICIPANTS: An online survey was distributed to intensive care doctors in sites participating in a large-scale international randomised clinical trial evaluating oxygen therapy targets in 15 countries and to additional intensive care clinicians from Canada.
MAIN OUTCOME MEASURES: Outcomes included the expressed level of support for a large pragmatic trial to evaluate minimum MAP targets in critically ill adults and stated current practice and acceptability of minimum MAP for specific scenarios.
RESULTS: The response rate to our survey for respondents who work in sites participating in the mega randomised registry trial research program was 265 out of 701 (37.8%), with an additional 56 out of 256 (21.8%) responses obtained from a direct email containing a link to the survey sent to intensive care clinicians in Canada. A total of 309 of 321 respondents (96.3%) were supportive, in principle, of conducting a very large pragmatic trial to evaluate MAP targets in intensive care unit patients receiving noradrenaline. The commonest response in all scenarios was to agree that the optimal minimum MAP target was uncertain. In all scenarios, except for active bleeding, the most common reported minimum MAP target was 65 mmHg; for patients who were actively bleeding, the most common reported target was 60 mmHg.
CONCLUSIONS: Our data suggest that intensive care clinicians are broadly supportive of a large-scale pragmatic minimum MAP targets in intensive care unit patients receiving noradrenaline.