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Anesth Analg 2005;100:1858
© 2005 International Anesthesia Research Society
doi: 10.1213/01.ANE.0000151482.91599.CC


LETTER TO THE EDITOR

Propofol-Induced Injection Pain: Comparison of a Modified Propofol Emulsion and Standard Propofol with Premixed Lidocaine

Wolfgang H. Maleck, MD, Swen N. Piper, MD, and Kerstin D. Röhm, MD

Department of Anesthesiology, Spital Grenchen, CH-2540 Grenchen, Switzerland, wolfgang_maleck{at}hotmail.com (Maleck) Department of Anesthesiology and Critical Care, Klinikum Ludwigshafen, Ludwigshafen, Germany (Piper, Röhm)

To the Editor:

We have read the article by Adam et al. on propofol-induced injection pain with great interest (1). The authors have shown that plain Propofol-LipuroTM (B. Braun Melsungen AG, Melsungen, Germany), albeit in previous studies superior to DisoprivanTM (in many countries DiprivanTM; Astra Zeneca GmbH, Wedel, Germany) with respect to injection pain, is less effective than DisoprivanTM premixed with lidocaine (1 mg lidocaine per 10 mg of propofol).

We would like to point out that two other randomized controlled trials published within the 12 mo preceeding the publication of the article by Adam et al.— thus probably too late to be cited—and one other randomized controlled trial published after the study of Adam et al. provide further evidence on this topic. The first two studies used a four-armed study design comparing DisoprivanTM with and without lidocaine versus Propofol-LipuroTM with and without lidocaine; in both studies lidocaine was not mixed with the propofol solutions, but was pre-injected, and both studies were published in German (2,3).

In the study of Röhm et al. (2), 40 mg of lidocaine were preinjected 60 s before propofol without using a tourniquet. In this study, although the incidence and severity of injection pain with Propofol-LipuroTM was slightly (but not significantly) less than with DisoprivanTM, the preinjection of lidocaine significantly reduced injection pain for both propofol formulations (P < 0.001). Furthermore, DisoprivanTM with lidocaine was superior to Propofol-LipuroTM without lidocaine, just as in the study of Adam et al., although the difference just reached significance (P < 0.05). This "borderline" significance probably stems from our smaller group size (50 patients per group, as opposed to 110 patients per group in the study of Adam et al.).

Kunitz et al. (3) used a similar study design, except for the use of a tourniquet before injection of lidocaine (also 40 mg) until the injection of propofol (also after 60 s). This study, which had only 20 patients per group, found no difference between DisoprivanTM with lidocaine versus Propofol-LipuroTM without lidocaine. With both DisoprivanTM and Propofol-LipuroTM, there was a trend towards less injection pain when preinjecting lidocaine.

Most recently, an abstract has been published comparing Propofol-LipuroTM without lidocaine versus Propofol-FreseniusTM (Fresenius Kabi GmbH, Bad Homburg, Germany) preceded by 40 mg of lidocaine using the tourniquet technique (4). In this study, Propofol-FreseniusTM with lidocaine was superior to Propofol-LipuroTM without lidocaine concerning spontaneous expression of pain (P < 0.01). However, this study is not directly comparable to those studies testing Propofol-LipuroTM against DisoprivanTM, as it is unknown whether the incidence of pain after Propofol-FreseniusTM is similar to that of DisoprivanTM.

Based on the results of these four studies (1–4) and previous work in this field, mostly cited by Adam et al., plus two randomized controlled trials in German language not cited by her group (5–6), we might conclude the following:

a) Propofol-LipuroTM offers some advantage over DisoprivanTM concerning injection pain.

b) This advantage might probably be smaller than what was previously suggested (5–7).

c) Further measures, e.g., preinjecting or mixing lidocaine, preinjecting opioids, or use of large veins at forearm or even antecubital fossa (8) seem indicated with Propofol-LipuroTM, too.

d) Further investigations in the field of propofol-induced injection pain should focus on such combined strategies.

e) It would be worthwhile to compare other "new" propofol formulations—such as the one by Fresenius—against both DisoprivanTM and Propofol-LipuroTM.

Note Added in Proof: When reading the page proofs of this letter we noticed an important error made by us. Adam et al. (1) did NOT use Disoprivan (Diprivan) but Propofol-Fresenius instead, similar to Schaub et al. (4). We apologize for this mistake. It does, however, not change our conclusions a–e. Likewise, some newer publications available from www.ncbi.nlm.nih.gov/pubmed with the search item "propofol AND pain AND (lipuro OR mct OR braun)" on March 25th, 2005 do not change our conclusions a–e either.

References

  1. Adam S, van Bommel J, Pelka M, et al. Propofol-induced injection pain: Comparison of a modified propofol emulsion to standard propofol with premixed lidocaine. Anesth Analg 2004;99:1076–9.[Abstract/Free Full Text]
  2. Röhm KD, Piper SN, Schöllhorn TAH, et al. Injektionsschmerz unter Propofol-MCT/LCT und Propofol-LCT: Vergleich einer Prophylaxe mit Lidocain. Anästhesiol Intensivmed Notfallmed Schmerzther 2003;38:643–7.[Medline]
  3. Kunitz O, Lösing R, Schulz-Stübner S, et al. Propofol-LCT versus Propofol-MCT/LCT mit oder ohne Lidocain: Vergleichende Untersuchung zum Injektionsschmerz. Anästhesiol Intensivmed Notfallmed Schmerzther 2004;39:10–4.[Medline]
  4. Schaub E, Kern C, Landau R. Pain on injection: a double-blind comparison of propofol with lidocaine pretreatment versus propofol formulated with long- and medium-chain triglycerides. Anesth Analg 2004;99:1699–1702.[Abstract/Free Full Text]
  5. Larsen R, Beerhalter U, Erdkönig R, Larsen B. Injektionsschmerz durch Propofol-MCT/LCT bei Kindern. Anaesthesist 2001;50:676–8.[Medline]
  6. Larsen B, Beerhalter U, Biedler A, et al. Weniger Injektionsschmerz durch Propofol-MCT/LCT. Anaesthesist 2001;50:842–5.[Web of Science][Medline]
  7. Rau J, Roizen M, Doenicke AW, et al. Propofol in an emulsion of long- and medium-chain triglycerides: The effect on pain. Anesth Analg 2001;93:382–4.[Abstract/Free Full Text]
  8. Bachmann-Mennenga B, Ohlmer A, Heesen M. Incidence of pain after intravenous injection of a medium-/long-chain triglyceride emulsion of propofol. Arzneimittelforschung 2003;53:621–6[Medline]




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Lippincott, Williams & Wilkins Anesthesia & Analgesia® is published for the International Anesthesia Research Society® by Lippincott Williams & Wilkins and Stanford University Libraries' HighWire Press®. Copyright 2005 by the International Anesthesia Research Society. Online ISSN: 1526-7598   Print ISSN: 0003-2999 HighWire Press