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Three Part Question

[In Adults with acute pain] IS [Oral paracetamol as effective at reducing pain] [compared to IV paracetamol]

Clinical Scenario

A patient you are treating is suffering with acute, moderate to severe pain. The patient does not have any reasons why they cannot take oral paracetamol. You wonder if the intravenous (IV) presentation is superior to its oral counterpart at reducing pain and wonder what route of administration is best for treating your patients pain.

Search Strategy

PubMed and Google Scholar access from the internet - ("Intravenous paracetamol" " oral paracetamol") ("Intravenous paracetamol" vs "oral paracetamol") ("Intravenous paracetamol") ("Intravenous paracetamol" verses "oral paracetamol")

Search Outcome

309 papers initially found, out of these 4 were relevant to the three part question.

Relevant Paper(s)

Author, date and country	Patient group	Study type (level of evidence)	Outcomes	Key results	Study Weaknesses
Stagg K. 2021 UK	2456 patients over the age of 18, undergoing any surgery.	A systemic review - CEMB 3a	The paper compares the effectiveness of intravenous paracetamol with oral paracetamol at reducing pain	The paper rejects the null hypothesis P=0.003 with an overall pain deduction of 0.5 in the IV group. Oral paracetamol has been shown to be much more cost effective	Potential high risk of bias at recruitment. Inconsistencies of quantities of paracetamol given across the studies. Oral paracetamol was given Pre-operation (oral potentially has a lower plasma content at recovery, leading to reported higher pain score in the oral group) IV was given either before or during the surgery.
Charlton K, et al 2020 UK	80 ambulance care records of adults with acute pain.	Case Series - CEBM 4	The paper compares intravenous paracetamol with oral paracetamol in a pre-hospital setting	This paper saw a mean difference (1.21) in the reducing of pain in the intravenous group and rejects the null hypothesis p=0.0013	Clinical bias reporting of pain score in IV use Placebo effected of IV as pain score is subjective. The paper is a retrospective design. A double-blinded RCT would have been superior.
Furyk J, et al 2017 Australia	87 participants in the emergency department setting in moderate to severe pain, with a visual analogue scale (VAS) >40 post initial opioid.	Double-blinded individual RCT - CEBM 1b	Comparing oral paracetamol with intravenous paracetamol to see which is superior at reducing pain	The paper accepts the null hypothesis p=0.79. Table 2 shows at 180-240 minuets post IV paracetamol there is a reduction in pain score of 11.1mm, compered to oral paracetamol group of 2mm. this is the largest reduction seen. This could suggest, IV paracetamol has a pain reduction benefit seen between post 180 minutes. At 240 minutes the difference between the two groups is 13.4 which is the biggest pain difference by 65%.	Selection bias from initial recruitment. Sample size estimator states should be 44 per group however 40 for oral and 47 for IV. Paper does not mention if all participants received the same opioid.
Ibrahim T, et al 2023 United Arab Emirates	1538 participants presenting with either acute or post-operative pain	Meta-Analysis CEBM 1a	The Meta-Analysis compared the effectives of intravenous with oral paracetamol (Study compared rectal presentations however the IV and oral paracetamol was easily separated)	At 12-48 hours the study sees no statistical difference between the two groups and accepts the null hypothesis. at 0-4 hours there seems to be a reducing in pain by 1 point compared to that of oral p=0.03. The overall conclusion of the study is there is no significant statistical difference between the two groups.	Does not state primary study setting, sample size calculations not completed, not all primary studies are blinded, some studies lack Strick treatment arms meaning some patients received both IV and oral presentations, no mention of what pain scores were used.

Comment(s)

There have not been many studies completed that compare intravenous paracetamol with its oral counterpart, especially for patients in acute pain. Two of the studies I looked at reject the null hypothesis with a p value of 0.0013 and 0.003. One paper shows a lower pain score in the IV group at 0-4 hours p=0.03 which suggests a faster therapeutic benefit. The final paper accepts the null hypothesis p=0.79, however shows a greater pain reduction of 13.4mm (VAS) in the IV group at 180-240 minutes, this could suggest IV paracetamol maintains a higher plasma concentration and its comparative benefit is seen in the 3-4 hours post administration.

Clinical Bottom Line

Further robust studies need to be completed such as double-blinded RCTs. It seems that IV paracetamol may have its benefits at reducing pain over its oral equivalent, however these overall benefits appear to be marginable. IV paracetamol may have a faster onset time and may provide therapeutic advantage for a longer duration, especially from three hours onwards. The use of either IV or oral paracetamol should be a clinical decision based on a holistic approach to the patient’s presentation and needs.

References

1. Stagg K, et al Intravenous versus oral paracetamol for postoperative analgesia: A systematic review Journal of Perioperative Practice 2021, 373-378
2. Charlton K, et al Intravenous versus oral paracetamol in a UK ambulance service: a case control study British Paramedic Journal 1-6
3. Furyk J, et al Intravenous versus oral paracetamol for acute pain in adults in the emergency department setting: a prospective, double-blind, double-dummy, randomised controlled trial Emergency Medicine Journal 2017, 163-168
4. Ibrahim T, et al Unlocking the Optimal Analgesic Potential: A Systematic Review and Meta-Analysis Comparing Intravenous, Oral, and Rectal Paracetamol in Equivalent Doses Cureus 2023, 0-13