Impact of age on PUAL as an indicator of opioid effect in adult subjects

Figures

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  Fig. 1. A Pupillary unrest (PUAL) values (mean ± 95% confidence interval) over time during the 10-minute remifentanil infusion and 25-minute recovery period are shown, in older and younger age groups. B Estimated remifentanil effect site concentrations (CEREMI, mean ± 95% CI, ng/mL) during the 10-minute infusion and 25-minute recovery are shown. The age-dependent lower rate of modeled drug clearance from the central compartment, in the context of a non-age-adjusted infusion scheme, explains the higher estimated drug concentration observed in the older subjects (5.71 ± 0.46 vs. 4.91 ± 0.69 ng/mL, p = 0.0025)

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  Fig. 2. A Cumulative proportion of subjects reaching SpO2 < 90% as a function of PUAL, stratified by age group. Only participants experiencing desaturation (n = 28) are included. No significant difference was observed in the distribution of PUAL at desaturation between age groups (Wilcoxon rank-sum test, exact p = 0.9900). B Kaplan Meier survival curve showing the cumulative proportion of participants without oxyhemoglobin desaturation (SpO2 ≥ 90%) as a function of time, in older and younger age groups. The time-to-event did not differ statistically by age group, occurring at median (95% CI) 6.2 [3.8, 8.3] minutes vs. 6.2 [5.1, 9.3] minutes in the younger subjects (log-rank χ2 = 0.01, P = 0.9201). Number at risk indicates the number of participants at each time point who had not yet experienced desaturation. C Kaplan-Meier curves showing the cumulative proportion of participants without oxyhemoglobin desaturation (SpO2 ≥ 90%) as a function of estimated remifentanil effect-site concentration (CEREMI), with subjects stratified by age group. Desaturation events occurred at median (95% CI) CEREMI = 3.7 (2.7, 5.2) in older subjects versus 3.2 (2.4, 3.8) lower CEREMI levels in the younger…

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  Fig. 3. A PUAL (pupillary unrest) distinguished between high-risk opioid exposure defined as CEREMI (estimated remifentanil effect site concentration) ≥ 2.0 ng/mL versus low-moderate-risk opioid exposure versus CEREMI (estimated remifentanil effect site concentration) < 2.0 ng/mL with excellent discrimination (AUROC = 0.9833 [0.8935, 0.9995] in older subjects and 0.9549 [0.8998, 0.9889] in younger subjects), difference by age group not statistically significant (χ2 = 1.02, P = 0.3129). B: PUAL (pupillary unrest) distinguished between high-toxic opioid exposure (time window 5.0–12.5 min post start of the remifentanil infusion) versus low-moderate opioid exposure (time window 0–2.5 min post start of remifentanil infusion) with excellent discrimination (AUROC = 0.9700 [0.8847, 0.9959] in older subjects and 0.9432 [0.8918, 0.9946] in younger subjects), difference by age group not statistically significant (χ2 = 0.70, P = 0.4020)