Association of propofol induction dose and severe pre-incision hypotension among surgical patients over age 65

Abstract

Study objective: We aimed to study the association between propofol induction dose (mg/kg) and pre-incision severe hypotension (Mean Arterial Pressure (MAP) ≤ 55 mmHg) among patients ≥65 years of age.

Design: Retrospective Observational.

Setting: 40 centers participating in the Multicenter Perioperative Outcomes Group consortium.

Patients: Patients ≥65 years of age undergoing non-cardiac, non-vascular surgery who received propofol for general anesthetic induction prior to endotracheal intubation between January 2014 and December 2018.

Interventions: None.

Measurements: The primary exposure was total propofol induction dose in mg/kg, and the primary outcome was occurrence of severe hypotension (MAP≤55 mmHg) prior to surgical incision, stratified by non-invasive vs. invasive blood pressure monitoring type.

Main results: Among 320,585 total patients, 22.6% experienced the outcome of pre-incision severe hypotension (MAP≤55 mmHg). When stratified by blood pressure monitoring type, 20.7% with non-invasive blood pressure measurements, and 35.0% with invasive blood pressure measurements had the outcome. After controlling for a variety of patient and procedural factors, there was a significant independent association between propofol induction dose and pre-incision hypotension (Non-invasive blood pressure cohort odds ratio (OR) 1.10; 95% confidence interval (CI) 1.07 to 1.13; p < 0.001; and Invasive blood pressure cohort OR 1.15; 95%CI 1.10 to 1.21; adjusted p < 0.001). The association was robust to alternative definitions of the outcome, including less severe hypotension (MAP≤65 mmHg) and blood pressure drop from baseline as a continuous measure. Although no threshold safe induction dose was identified at which hypotension was avoided, an analysis of propofol dose greater or less than 1.5 mg/kg (i.e. the maximum FDA-defined typical induction dose) demonstrated that doses in excess of the FDAs threshold were positively associated with odds of severe hypotension (Non-invasive cohort: OR 1.05; 95% CI 1.02 to 1.08; p < 0.001; Invasive cohort: OR 1.11; 95%CI 1.05 to 1.17; adjusted p < 0.001).

Conclusions: In a multicenter cohort of geriatric surgical patients receiving propofol for general anesthetic induction and endotracheal intubation, severe pre-incision hypotension (MAP ≤55 mmHg) that has previously been associated with postoperative morbidity was common. The dose of propofol used was significantly associated with increased odds of this outcome after controlling for a number of clinically relevant factors. Future studies that are designed to test different approaches to anesthesia induction for reducing severe post induction pre-incision hypotension are warranted.

Keywords: Geriatrics; Hypotension; Induction; Propofol.

Fig. 1.

Consort diagram showing derivation of final cohort.

Fig. 2.

unadjusted, univariate relationship between propofol dose and lowest MAP within both the non-invasive and invasive cohorts.

Fig. 3.

Quantile Regression Results showing the association of propofol dose as proportion of FDA maximum (y-axis) with pre-incision drop in blood pressure stratified across three quantiles of blood pressure drop (x-axis). The dotted horizontal line labeled “OLS” represents the Beta co-efficient calculated based on ordinary least squares regression across the entire cohort. The three circle and whiskers show the Beta coefficient (95%CI) plotted for each of three quantiles.

Fig. 4.

Forest plot of primary association stratified by surgery type, inclusive of surgeries with sufficient N for model convergence.