Ketamine/midazolam reduces maximum intraprocedural pain by 1.4 points compared to fentanyl/midazolamKetamine and midazolam reduce pain during lung and bone biopsies

This randomized clinical trial evaluated the efficacy and safety of ketamine/midazolam compared to fentanyl/midazolam for analgesia during image-guided procedures. The study enrolled 260 participants, consisting of adults undergoing image-guided lung biopsy, bone biopsy, or abscess drainage. The study was conducted at a single academic center to compare these two distinct anesthetic protocols for procedural pain management.

The intervention group received ketamine combined with midazolam, while the comparator group received fentanyl combined with midazolam. The study aimed to determine if the ketamine-based regimen provided superior pain relief and safety profiles during these specific interventional procedures.

The primary outcome was maximum intraprocedural pain, measured on a 0 to 10 scale using the Numeric Rating Scale. Patients receiving ketamine/midazolam reported a lower maximum intraprocedural pain score, with a reduction of 1.4 points (95% CI: -2.0, -0.8; p <.001). Additionally, pain scores greater than 4 were less frequent in the ketamine/midazolam group, occurring in 2.3% of cases compared to 17% in the fentanyl/midazolam group (95% CI: 8, 21; p <.001).

Secondary outcomes included physiological parameters and patient-reported experience. Patients in the ketamine/midazolam group demonstrated higher nadir oxygen saturation, with an increase of 1.4% (95% CI: 0.6, 2.2; p =.001). Furthermore, there were fewer oxygen desaturation events below 90% in the ketamine/midazolam group, with 3 (2.3%) events compared to 13 (9.8%) in the fentanyl/midazolam group (95% CI: 1.9, 13.3; p =.02). Patient-reported experience was also improved in the ketamine/midazolam group.

Safety and tolerability findings revealed a notable difference in neuropsychiatric side effects. Hallucinations were more frequent in the ketamine/midazolam group, occurring in 15 (11.4%) patients compared to 5 (3.8%) in the fentanyl/midazolam group (95% CI: 1.3, 13.9; p =.03). However, procedure-related and sedation-related complications did not differ between the two groups. No serious adverse events were reported.

These results provide a specific comparison for procedural analgesia. While previous literature has established the role of ketamine in various contexts, such as the treatment of depressive disorders or functional neurological disorders, this trial specifically addresses the acute management of image-guided interventions. The findings suggest that ketamine/midazolam provides superior analgesia and better oxygenation compared to fentanyl/midazolam, despite the increased risk of hallucinations.

Methodological limitations include the study being conducted at a single academic center, which may limit the generalizability of the findings to broader clinical settings. The lack of reported follow-up data means the long-term effects of these interventions are not addressed. Clinical implications suggest that ketamine/midazolam may be a preferred choice for patients requiring high-quality analgesia and stable oxygenation during image-guided procedures, provided the clinician and patient are comfortable with the increased risk of hallucinations. Questions remain regarding the optimal dosing of ketamine and midazolam for these specific procedures and how these results translate across different types of image-guided interventions beyond those studied. The specific impact of the ketamine/midazolam combination on long-term recovery or post-procedural pain is also not reported.