Unlocking the Optimal Analgesic Potential: A Systematic Review and Meta-Analysis Comparing Intravenous, Oral, and Rectal Paracetamol in Equivalent Doses

Paracetamol (acetaminophen) is an extensively used analgesic for acute and chronic pain management. Currently, paracetamol is manufactured for oral, rectal, and intravenous (IV) use. Research has shown varied results on the analgesic properties of IV paracetamol compared to oral and rectal paracetamol; however, research on the same doses of paracetamol is limited. Therefore, this review was constructed to explore the analgesic properties of IV paracetamol compared with oral and rectal paracetamol administered in equivalent doses. A broad and thorough literature search was performed on five electronic databases, including PubMed, ScienceDirect, Medline, Scopus, and Google Scholar. Statistical analysis of all outcomes in our review was then performed using the Review Manager software. Outcomes were categorized as primary (pain relief and time to request rescue analgesia) and secondary (adverse events after analgesia). An extensive quality appraisal was also done using the Review Manager software’s Cochrane risk of bias tool. The literature survey yielded 2,945 articles, of which 12 were used for review and analysis. The pooled analysis for patients undergoing surgical procedures showed that IV paracetamol had statistically similar postoperative pain scores at two (mean difference (MD) = -0.14; 95% confidence interval (CI) -0.58-0.29; p = 0.51), 24 (MD = 0.09; 95% CI = -0.02-0.21; p = 0.12), and 48 (MD = 0.04; 95% CI = -0.08-0.16; p = 0.52) hours as oral paracetamol. Similarly, the data on time to rescue analgesia showed no considerable difference between the IV and oral paracetamol groups (MD = -1.58; 95% CI = -5.51-2.35; p = 0.43). On the other hand, the pooled analysis for patients presenting non-surgical acute pain showed no significant difference in the mean pain scores between patients treated with IV and oral paracetamol (MD = -0.35; 95% CI = -2.19-1.48; p = 0.71). Furthermore, a subgroup analysis of analgesia-related adverse events showed that the incidences of vomiting/nausea and pruritus did not differ between patients receiving IV and oral paracetamol (odds ratio (OR) = 0.71; 95% CI = 0.45-1.11; p = 0.13 and OR = 0.48; 95% CI = 0.18-1.29; p = 0.05, respectively). A review of information from two trials comparing equal doses of IV and rectal paracetamol suggested that the postoperative pain scores were statistically similar between the groups. IV paracetamol is not superior to oral or rectal paracetamol administered in equal doses. Therefore, we cannot recommend or refute IV paracetamol as the first-line analgesia for acute and postoperative pain.