Ketamine Plus Propofol (Ketofol) Administration Before ECT for Depression: A Systematic Review for Hemodynamic Parameters and Depression Outcomes

Introduction: Ketamine, in theory, as an anesthetic prior to electroconvulsive therapy (ECT) can potentiate anti-depressant effects given that both ketamine and ECT have demonstrated benefit. However, ketamine can cause significant hemodynamic instability, which can limit its use. Propofol can help mitigate these issues, resulting in ketofol, a combination of ketamine and propofol as an anesthetic agent. In this systematic review, we see if this anesthetic cocktail proves to be effective pre-ECT for patients with depression and evaluate the hemodynamic side effects and post-ECT depression outcomes as compared to ketamine or propofol alone.

Methods: Search strategies using keywords were created to explore two databases: PubMed and Google Scholar. After removing duplicates, 71 articles were found. All abstracts and full texts were examined by 3 independent reviewers to solve discrepancies in the screening decisions. We included 15 observational articles that are not reviews which had a direct comparison of ketofol with ketamine or propofol only in regards to hemodynamic or depression outcomes.

Results: The review included 12 studies looking at the anesthetic effects of ketofol and 8 studies looking at the depressive effects of ketofol. Based on the GRADE approach, the evidence level of primary and secondary outcomes regarding anesthetic effects ranged from low (1/12 observational study) to moderate-high (11/12 randomized control trials (RCTs)) while the evidence level for depressive effects were moderate to high (8/8 RCTs). Anesthetic effects were mostly assessed using hemodynamic parameters such as systolic and diastolic blood pressure, mean arterial pressure, and heart rate. Out of the 12 studies, 4 RCTs concluded that ketofol was significantly more hemodynamic favorable compared to propofol, whereas 3 RCTs found the opposite. The remaining 4 RCTs and 1 observational study concluded that there was no statistically significant difference in hemodynamic parameters when administering ketofol. Depressive effects were assessed using validated psychometric testing. Out of the 8 studies, 2 RCTs concluded that ketofol had a greater reduction in depressive symptoms compared to propofol. The remaining 6 RCTs concluded that there was no statistically significant difference in reduction of depressive symptoms with the use of ketofol.

Conclusion: Ketofol is an anesthetic combination that is being used for a variety of procedures, including ECT. While theorized to assist with the hemodynamic changes that ketamine or propofol alone cause in opposite directions, most studies have demonstrated no significant difference between ketofol and one medication. Furthermore, most studies also show no difference in depression outcomes after ECT between ketofol and ketamine or propofol monotherapy. If a statistically significant change is seen, it is usually attributable to the ketamine portion of ketofol rather than an effect from the combination.

Funding: No Funding