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

<div><p>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.</p></div

Factors associated with cessation of sedation and analgesia.

<p>Factors associated with cessation of sedation and analgesia.</p

Adjusted mean total dose of propofol according to age groups.

<p>Adjusted mean total dose of propofol according to age groups.</p

Flowchart showing patient inclusion in the study.

<p>Flowchart showing patient inclusion in the study.</p

Details of medications.

<p>Details of medications.</p

Multivariate association between total propofol and total fentanyl dose adjusted to weight and significant risk factors.

<p>Multivariate association between total propofol and total fentanyl dose adjusted to weight and significant risk factors.</p

Univariate association between total propofol and fentanyl dose adjusted to weight and individual risk factors.

<p>Univariate association between total propofol and fentanyl dose adjusted to weight and individual risk factors.</p

Adjusted mean total dose of fentanyl according to age groups.

<p>Adjusted mean total dose of fentanyl according to age groups.</p

Demographics, procedures and outcomes.

<p>Demographics, procedures and outcomes.</p

The Synergistic Effect of Functional Status and Comorbidity Burden on Mortality: A 16-Year Survival Analysis

<div><p>Objectives</p><p>The relationship between disability and comorbidity on mortality is widely perceived as additive in clinical models of frailty.</p><p>Design</p><p>National data were retrospectively extracted from medical records of community hospital.</p><p>Data Sources</p><p>There were of 12,804 acutely-disabled patients admitted for inpatient rehabilitation in Singapore rehabilitation community hospitals from 1996 through 2005 were followed up for death till 31 December 2011.</p><p>Outcome Measure</p><p>Cox proportional-hazards regression to assess the interaction of comorbidity and disability at discharge on all-cause mortality.</p><p>Results</p><p>During a median follow-up of 10.9 years, there were 8,565 deaths (66.9%). The mean age was 73.0 (standard deviation: 11.5) years. Independent risk factors of mortality were higher comorbidity (p<0.001), severity of disability at discharge (p<0.001), being widowed (adjusted hazard ratio [aHR]: 1.38, 95% confidence interval [CI]:1.25–1.53), low socioeconomic status (aHR:1.40, 95%CI:1.29–1.53), discharge to nursing home (aHR:1.14, 95%CI:1.05–1.22) and re-admission into acute care (aHR:1.54, 95%CI:1.45–1.65). In the main effects model, those with high comorbidity had an aHR = 2.41 (95%CI:2.13–2.72) whereas those with total disability had an aHR = 2.28 (95%CI:2.12–2.46). In the interaction model, synergistic interaction existed between comorbidity and disability (p<0.001) where those with high comorbidity and total disability had much higher aHR = 6.57 (95%CI:5.15–8.37).</p><p>Conclusions</p><p>Patients with greater comorbidity and disability at discharge, discharge to nursing home or re-admission into acute care, lower socioeconomic status and being widowed had higher mortality risk. Our results identified predictive variables of mortality that map well onto the frailty cascade model. Increasing comorbidity and disability interacted synergistically to increase mortality risk.</p></div