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Title: Sedation Intensity in the First 48 Hours of Mechanical Ventilation and 180-Day Mortality: A Multinational Prospective Longitudinal Cohort Study.
Austin Authors: Shehabi, Yahya;Bellomo, Rinaldo ;Kadiman, Suhaini;Ti, Lian Kah;Howe, Belinda;Reade, Michael C;Khoo, Tien Meng;Alias, Anita;Wong, Yu-Lin;Mukhopadhyay, Amartya;McArthur, Colin;Seppelt, Ian;Webb, Steven A;Green, Maja;Bailey, Michael J
Affiliation: Critical Care and Perioperative Services, Monash University and Monash Health, Melbourne, Victoria, Australia
Clinical School, University New South Wales, Sydney, NSW, Australia
Faculty of Medicine, University of Melbourne, Melbourne, Victoria, Australia
Faculty of Medicine, Australian New Zealand Intensive Care Research Centre, Monash University, Melbourne, Victoria, Australia
Intensive Care Unit, Austin Health, Heidelberg, Victoria, Australia
Department of Anaesthesiology and Intensive Care, National Heart Institute, Kuala Lumpur, Malaysia
Yong Loo Lin School of Medicine, National University of Singapore, National University Hospital, Singapore
Australian New Zealand Intensive Care Research Centre, School of Public Health and Preventive Medicine, Monash University, Melbourne, Victoria, Australia
University of Queensland, Royal Brisbane and Women's Hospital, Herston, QLD, Australia
Department of Anesthesiology and Intensive Care, Hospital Queen Elizabeth, Sabah, Malaysia
Department of Anaesthesia and Intensive Care, Hospital Melaka - Jalan Mufti Hj Khalil, Melaka, Malaysia
Department of Anaesthesia, Tan Tock Seng Hospital, Singapore
Department of Critical Care Medicine, University of Auckland, Auckland City Hospital, Auckland, New Zealand
Department of Intensive Care Medicine, University of Sydney, Sydney Medical School, Nepean, NSW, Australia
Department of Intensive Care, St John of God Hospital, Subiaco, Perth, WA, Australia
Issue Date: Jun-2018
Publication information: Critical Care Medicine 2018; 46(6): 850-859
Abstract: In the absence of a universal definition of light or deep sedation, the level of sedation that conveys favorable outcomes is unknown. We quantified the relationship between escalating intensity of sedation in the first 48 hours of mechanical ventilation and 180-day survival, time to extubation, and delirium. Harmonized data from prospective multicenter international longitudinal cohort studies SETTING:: Diverse mix of ICUs. Critically ill patients expected to be ventilated for longer than 24 hours. 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. 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. 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.
DOI: 10.1097/CCM.0000000000003071
ORCID: 0000-0002-1650-8939
PubMed URL: 29498938
Type: Journal Article
Appears in Collections:Journal articles

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