Author's Names: Morgan Keller, PharmD; Susan Smith, PharmD, BCCCP, FCCM, FCCP; Madison Wiklund, PharmD Candidate 2027; Marlie Windgate, PharmD Candidate 2027; John Carr, PharmD, BCPS, BCCCP
Background:
Anesthetics such as propofol and midazolam can contribute to fluid retention and reduce diuretic responsiveness in the perioperative setting. It is unclear whether this same effect occurs in critically ill patients, and if alternative sedatives could mitigate such a risk. The goal of this study is to determine whether the use of dexmedetomidine, propofol, or midazolam is correlated with a difference in the incidence of fluid overload and diuretic resistance in critically ill patients who are mechanically ventilated in the intensive care unit.
Methods:
This investigation is a single center, retrospective, observational cohort study evaluating mechanically ventilated patients for differences in fluid balance and diuretic use while receiving propofol, midazolam, or dexmedetomidine during mechanical ventilation. Patients were grouped by primary sedative agent and data pertaining to baseline demographics, illness severity, and comorbidities were collected. Patients were excluded for pregnancy, acute/severe neurologic disorder, simultaneous use of multiple sedatives, Child-Pugh class C liver failure, dialysis or continuous renal replacement therapy at the time of initiating sedative, and/or patients who underwent surgery or procedure with sedation during the study period or within 72 hours prior. The primary outcome of fluid balance is measured as net fluid balance 72 hours after sedation initiation. Daily fluid input and output, diuretic dosing, hemodynamic parameters (mean arterial pressure, blood pressure, and heart rate), and electrolyte laboratory values were collected from patient electronic medical records. Statistical analysis was performed by multivariable regression to adjust for potential confounders, including chronic kidney disease and home diuretic use.
Results:
Twenty patients were enrolled in this study, including 8 receiving midazolam, 11 receiving propofol, and 1 receiving dexmedetomidine. Baseline characteristics were similar across age, baseline creatinine, peak creatinine, creatinine clearance, and Glasgow coma score. The primary outcome of this study is net fluid balance at 72 hours, and showed no statistically significant difference between groups (midazolam 2212.3 mL [1084.7-7601], propofol 3286 mL [1266-11032], and dexmedetomidine 8915 mL; p=0.475). Secondary outcomes including furosemide diuresis equivalents, urine output, ventilator free days at day 14, ICU length of stay, and vasopressor requirements at day 14 showed no difference across sedative groups. Additionally in multivariable analyses, no significant differences were observed between midazolam, propofol, and dexmedetomidine in SOFA scores, CrCl, and total furosemide diuresis equivalents.
Conclusions:
In this study of mechanically ventilated intensive care unit patients, there were no significant differences in fluid balance at 72 hours in patients receiving midazolam, propofol, or dexmedetomidine. Secondary outcomes including ventilator free days, ICU length of stay, and vasopressor requirements were also similar across the three sedation groups. Potential limitation factors include feasibility and exclusion criteria of multiple simultaneous sedatives and dialysis, considering the acuity of the patient population studied. Future directions should target a larger study group with less stringent exclusion factors to confirm this finding.
