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Age related inverse dose relation of sedatives and analgesics in the intensive care unit.

ABSTRACT: Sedative and analgesic practices in intensive care units (ICUs) are frequently based on anesthesia regimes but do not take account of the important patient related factors. Pharmacologic properties of sedatives and analgesics change when used as continuous infusions in ICU compared to bolus or short-term infusions during anesthesia. In a prospective observational cohort study, we investigated the association between patient related factors and sedatives/analgesics doses in patients on mechanical ventilation (MV) and their association with cessation of sedation/analgesia. We included patients expected to receive MV for at least 24 hours and excluded those with difficulty in assessing the depth of sedation. We collected data for the first 72 hours or until extubation, whichever occurred first. Multivariate analysis of variance, multivariate regression as well as logistic regression were used. The final cohort (N = 576) was predominantly male (64%) with mean (SD) age 61.7 (15.6) years, weight 63.4 (18.2) Kg, Acute Physiology and Chronic Health Evaluation II score 28.2 (8) and 30% hospital mortality. Increasing age was associated with reduced propofol and fentanyl doses requirements, adjusted to the weight (p<0.001). Factors associated with higher propofol and fentanyl doses were vasopressor use (Relative mean difference (RMD) propofol 1.56 (95% confidence interval (CI) 1.28-1.90); fentanyl 1.48 (1.25-1.76) and central venous line placement (CVL, RMD propofol 1.64 (1.15-2.33); fentanyl 1.41 (1.03-1.91). Male gender was also associated with higher propofol dose (RMD 1.27 (1.06-1.49). Sedation cessation was less likely to occur in restrained patients (Odds Ratio, OR 0.48 (CI 0.30-0.78) or those receiving higher sedative/analgesic doses (OR propofol 0.98 (CI 0.97-0.99); fentanyl 0.99 (CI 0.98-0.997), independent of depth of sedation. In conclusion, increasing age is associated with the use of lower doses of sedative/analgesic in ICU, whereas CVL and vasopressor use were associated with higher doses.

SUBMITTER: Mukhopadhyay A

PROVIDER: S-EPMC5619735 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Age related inverse dose relation of sedatives and analgesics in the intensive care unit.

Mukhopadhyay Amartya A Tai Bee Choo BC Remani Deepa D Phua Jason J Cove Matthew Edward ME Kowitlawakul Yanika Y

PloS one 20170928 9

Sedative and analgesic practices in intensive care units (ICUs) are frequently based on anesthesia regimes but do not take account of the important patient related factors. Pharmacologic properties of sedatives and analgesics change when used as continuous infusions in ICU compared to bolus or short-term infusions during anesthesia. In a prospective observational cohort study, we investigated the association between patient related factors and sedatives/analgesics doses in patients on mechanical ...[more]

PMID: 28957364

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Project description:Critically ill intensive care unit (ICU) patients commonly develop severe muscle wasting and impaired muscle function, leading to delayed recovery, with subsequent increased morbidity and financial costs, and decrease quality of life of survivors. Acute Quadriplegic Myopathy (AQM) is one of the most common neuromuscular disorders associated with ICU-acquired muscle weakness. Although there are no available treatments for the ICU-acquired muscle weakness, it has been demonstrated that early mobilization can improve its prognosis and functional outcomes. This study aims at improving our understanding of the effects of passive mechanical loading on skeletal muscle structure and function by using a unique experimental rat ICU model allowing analyses of the temporal sequence of changes in mechanically ventilated and pharmacologically paralyzed animals at durations varying from 6 h to 14 days. Results show that passive mechanical loading alleviated the muscle wasting and the loss of force-generation associated with the ICU intervention, resulting in a doubling of the functional capacity of the loaded vs. unloaded muscles after a 2-week ICU intervention. We demonstrated that the improved maintenance of muscle structure and function is likely a consequence of a reduced oxidative stress, and a reduced loss of the molecular motor protein myosin. A complex temporal gene expression pattern, delineated by microarray analysis, was observed with loading-induced changes in transcript levels of sarcomeric proteins, muscle developmental processes, stress response, ECM/cell adhesion proteins and metabolism. Thus, the results from this study show that passive mechanical loading alleviates the severe negative consequences on muscle structure and function associated with mechanical silencing in ICU patients, strongly supporting early and intense physical therapy in immobilized ICU patients. This study aims to unravel the effects of passive mechanical loading on skeletal muscle structure and function in an experimental rat ICU model at duration varying between 6h and 14 days. A total of 23 experimental female Sprague-Dawley rats were included in this study. The experimental rats were anaesthetized, treated with the neuromuscular blocking agent (NMBA) M-NM-1-cobrotoxin, mechanically ventilated and monitored for durations varying from 6h to 4 days (n=13), from 5 to 8 days (n=4), and from 9 to 14 days (n=6). The left leg of the animal was activated for 6 hours at the shortest duration and 12 hours per day at durations 12 hours and longer throughout the experiment, using a mechanical lever arm that produced a continuous passive maximal ankle joint flexions-extensions at a speed of 13.3 cycles per minute. Muscle biopsies were obtained from gastrocnemius muscle (proximal part) immediately after euthanasia, were quickly frozen in liquid propane cooled by liquid nitrogen, and stored at -80M-BM-0C. RNA was extracted.

Dataset Information

Age related inverse dose relation of sedatives and analgesics in the intensive care unit.

Publications

Age related inverse dose relation of sedatives and analgesics in the intensive care unit.

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