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Prevention of pain on injection of propofol: systematic review and meta-analysis

BMJ 2011; 342 doi: (Published 15 March 2011) Cite this as: BMJ 2011;342:d1110
  1. Leena Jalota, visiting research fellow1,
  2. Vicki Kalira, medical student12,
  3. Elizabeth George, staff research associate1,
  4. Yung-Ying Shi, staff research associate1,
  5. Cyrill Hornuss, research fellow1,
  6. Oliver Radke, attending physician13,
  7. Nathan L Pace, professor14,
  8. Christian C Apfel, associate professor1
  9. On behalf of the Perioperative Clinical Research Core
  1. 1Department of Anesthesia and Perioperative Care, University of California at San Francisco, San Francisco 94115, CA, USA
  2. 2West Virginia School of Medicine, Morgantown, WV, USA
  3. 3Department of Anaesthesia and Critical Care Medicine, University Hospital Carl Gustav Dresden at the TU Dresden, Dresden, Germany
  4. 4Department of Anaesthesiology, University of Utah, Salt Lake City, UT, USA
  1. Correspondence to: C C Apfel apfelc{at} or apfel{at}
  • Accepted 17 January 2011


Objective To systematically determine the most efficacious approach for preventing pain on injection of propofol.

Design Systematic review and meta-analysis.

Data sources PubMed, Embase, Cochrane Library,, and hand searching from the reference lists of identified papers.

Study selection Randomised controlled trials comparing drug and non-drug interventions with placebo or another intervention to alleviate pain on injection of propofol in adults.

Results Data were analysed from 177 randomised controlled trials totalling 25 260 adults. The overall risk of pain from propofol injection alone was about 60%. Using an antecubital vein instead of a hand vein was the most effective single intervention (relative risk 0.14, 95% confidence interval 0.07 to 0.30). Pretreatment using lidocaine (lignocaine) in conjunction with venous occlusion was similarly effective (0.29, 0.22 to 0.38). Other effective interventions were a lidocaine-propofol admixture (0.40, 0.33 to 0.48); pretreatment with lidocaine (0.47, 0.40 to 0.56), opioids (0.49, 0.41 to 0.59), ketamine (0.52, 0.46 to 0.57), or non-steroidal anti-inflammatory drugs (0.67, 0.49 to 0.91); and propofol emulsions containing medium and long chain triglycerides (0.75, 0.67 to 0.84). Statistical testing of indirect comparisons showed that use of the antecubital vein and pretreatment using lidocaine along with venous occlusion to be more efficacious than the other interventions.

Conclusions The two most efficacious interventions to reduce pain on injection of propofol were use of the antecubital vein, or pretreatment using lidocaine in conjunction with venous occlusion when the hand vein was chosen. Under the assumption of independent efficacy a third practical alternative could be pretreatment of the hand vein with lidocaine or ketamine and use of a propofol emulsion containing medium and long chain triglycerides. Although not the most effective intervention on its own, a small dose of opioids before induction halved the risk of pain from the injection and thus can generally be recommended unless contraindicated.


  • We thank Wolfgang Viechtbauer (School for Public Health and Primary Care, Maastricht University, the Netherlands) for the syntax of arguments used in the R package metafor; David Moher (Ottawa Hospital Research Institute, University of Ottawa) for proving critical input for the study; and Sakura Kinjo (University of California San Francisco) for translating the Japanese manuscripts. RevMan 5.0 (Review Manager, Cochrane Collaboration, UK) statistical package was used in this systematic review for analysis. Additionally, the R packages metafor and meta were used (R Development Core Team (2010). R: A language and environment for statistical computing. R Foundation for Statistical Computing).

  • Contributors: VK, LJ, YYS, OR, and CCA wrote the study protocol. LJ and VK collected and collated the data. CCA and NLP provided statistical expertise. CCA, LJ, and NLP analysed and interpreted the data. LJ, YYS, EG, CH, CCA, and NLP drafted the article. LJ, EG, YYS, CH, CCA, OR, and NLP critically revised the article for important intellectual content. LJ, EG, YYS, CH, CCA, and NLP provided administrative, technical, or logistic support. All authors approved the final article, had full access to all the data (including statistical reports and tables), and can take responsibility for the integrity of the data and the accuracy of the data analysis. CCA, LJ, and NLP are the guarantors.

  • Funding: This study was funded by the Perioperative Clinical Research Core, University of California, San Francisco.

  • Competing interests: All authors have completed the Unified Competing Interest form at and declare that LJ, VK, EG, YYS, CH, OR, and CCA have support from the Perioperative Clinical Research Core, Department of Anaesthesia and Perioperative Care, University of California, San Francisco, CA for the submitted work; LJ, VK, EG, YYS, CH, NLP, OR, and CCA have no relationships that might have an interest in the submitted work in the previous 3 years; their spouses, partners, or children have no financial relationships that may be relevant to the submitted work; and LJ, VK, EG, YYS, OR, and CCA have no non-financial interests; and NLP is an unpaid statistical editor for a Cochrane Collaborative Review Group.

  • Ethical approval: Not required.

  • Data sharing: The technical appendix, statistical code, and dataset are available from the corresponding author at apfelc{at}

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