Trial Sequential Analysis and Meta-analysis of Intranasal Ketamine Versus Intranasal Opioids for Analgesia in...

Ketamine (KT) is known to have analgesic and sedative effects. Intranasal (IN)/inhalational KT has been used in different trials involving paediatric patients for analgesic and anxiolytic function. The present meta-analysis was conducted to establish the role of IN/inhalational KT compared to that of inhalational opioids (OPs).

A systematic literature search was performed through the Cochrane Library, Pub Med and ClinicalTrials.gov databases from inception to February 2024 using the following keywords: inhalational OR IN OR nebulised' and 'ketamine' and 'analgesia'. Randomised clinical trials published in English that analysed the efficacy and safety of inhalational KT either alone or as an adjunct to the standard of care (SoC) compared to OP in paediatric patients undergoing various procedures were included in the analysis. The important outcomes included patients who were pain responders, required rescue analgesics, achieved mild-moderate sedation and experienced any adverse events (AEs), dizziness, nausea/vomiting or unpleasant taste. A trial sequential analysis (TSA) was also performed. The analysis included seven studies with 489 paediatric patients. In the KT group, a smaller number of patients were pain responders and required rescue analgesics (RR = 0.94; 95% CI = 0.78-1.13; P = .52 and RR = 0.80; 95% CI = 0.44-1.43; P = .45, respectively). Similarly, more patients in the KT group achieved mild-moderate sedation and experienced any AEs (RR = 1.44; 95% CI = 0.95-2.18; P = .09; and RR = 1.99; 95% CI = 1.47-2.69; P < .00001, respectively). A greater number of patients experienced dizziness (RR = 5.47; 95% CI = 3.12-9.58; P < .00001) and an unpleasant taste (RR = 2.91; 95% CI = 1.51-5.61; P = .001) in the KT group. In the meta-analysis, the required information size (RIS) could not be obtained.

KT had efficacy outcomes comparable to those of OP, but KT had very high adverse effects. OP seems to have better tolerability than KT. However, as the number of patients was less than the RIS, it was not possible to draw any conclusions.