Propofol and clevidipine are both formulated as lipid emulsion preparations and are frequently used concurrently in the intensive care unit for sedation and blood pressure control, respectively. Concern exists that coadministration of two lipid emulsions could increase the risk of hypertriglyceridemia and thereby contribute to acute pancreatitis. This multicenter retrospective analysis aimed to quantify the frequency of triglyceride elevation above 400 mg/dL and the incidence of pancreatitis after initiation of concurrent continuous infusions of propofol and clevidipine, and to identify patient-level risk factors for hypertriglyceridemia.
The study included adult patients (age ≥ 18 years) from multiple sites who received overlapping continuous infusions of propofol and clevidipine for at least 6 hours. The primary outcome was the frequency of triglyceride levels greater than 400 mg/dL and the occurrence of acute pancreatitis after initiation of the combined infusions. Secondary analyses evaluated risk factors for hypertriglyceridemia while both infusions were ongoing until both were discontinued. Univariable and multivariable logistic regression models were used to assess associations between baseline characteristics and the development of hypertriglyceridemia among patients with available triglyceride measurements. For pancreatitis cases, the Naranjo Scale was applied to assess the likelihood that the event was related to propofol or clevidipine infusions.
A total of 1,226 patients met inclusion criteria. The median duration of infusion overlap was 12.4 hours with an interquartile range of 8.3 to 22.7 hours. The mean age of the cohort was 59.6 years (SD 14.9), and 59.4% of patients were male.
Assuming that patients without a triglyceride measurement did not have hypertriglyceridemia, 7.7% of the entire cohort (95% CI 6.3% to 9.3%) developed triglyceride concentrations above 400 mg/dL after initiation of concurrent propofol and clevidipine infusions. Regarding pancreatitis, 26 patients (2.1% of the cohort) received a diagnosis of pancreatitis after starting the lipid infusions. Of those 26 cases, 12 were considered possibly infusion-related and 1 was considered likely infusion-related prior to Naranjo scale calculation; after Naranjo scoring, all 13 adjudicated cases were categorized as possibly related to the infusions.
Multivariable logistic regression performed among patients with available triglyceride data identified two independent risk factors for developing hypertriglyceridemia while receiving concurrent lipid infusions:
These associations were reported after controlling for other variables included in the model; the source reports these variables specifically as statistically significant predictors in the adjusted analysis.
Twenty-six patients received a clinical diagnosis of pancreatitis after the start of propofol and clevidipine infusions, representing 2.1% of the cohort. The investigators evaluated the temporal relationship and applied the Naranjo Scale to attribute causality; all 13 cases that underwent Naranjo assessment were judged to be possibly related to either propofol or clevidipine. The source specifies that 12 of the 26 initial pancreatitis cases were identified as possibly infusion-related and one as likely infusion-related before formal Naranjo scoring; after scoring, all 13 adjudicated cases were possibly related. No additional quantification of severity, outcomes, or management of pancreatitis cases beyond these categorizations was reported in the abstract.
Multiple figures in the full text illustrate cohort selection and temporal and dose–response relationships. The CONSORT-style diagram displays patient inclusion. A histogram and boxplot show the time from initiation of concurrent propofol–clevidipine administration to the occurrence of hypertriglyceridemia among affected patients (n = 94). Incidence curves depict daily percentages of pancreatitis cases following initiation of the combination and cases attributed to infusions, with 95% confidence intervals. A scatter plot examines the relationship between increasing doses of propofol and clevidipine and serum triglyceride concentrations; the triglyceride cutoff of 400 mg/dL is indicated and a linear fit is plotted. These graphical data support the reported incidence figures and the temporal distribution of events.
In this large multicenter retrospective cohort, the frequency of hypertriglyceridemia (triglycerides >400 mg/dL) and acute pancreatitis after starting concurrent continuous infusions of propofol and clevidipine was low. The study identified prior pancreatitis within 5 years and baseline statin therapy as independent risk factors for triglyceride elevation among patients with measured triglyceride values. The investigators conclude that, while rates of triglyceride elevation and pancreatitis were low, further comparative studies are needed to clarify the incremental pancreatitis risk attributable to adding clevidipine to propofol infusions versus propofol alone.
As a retrospective analysis the study is subject to limitations inherent to observational designs; the abstract notes that the primary analyses assumed that patients without triglyceride measurements did not have hypertriglyceridemia, which may underestimate incidence. The abstract does not report additional details such as specific dosing thresholds, timing of laboratory monitoring for all patients, or severity and outcomes of pancreatitis beyond adjudication. The authors recommend further comparative and prospective studies to better define risk and to guide monitoring strategies when lipid emulsions are coadministered in critically ill patients.