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-Lipuro™ (B. Braun Melsungen AG, Melsungen, Germany), albeit in previous studies superior to Disoprivan™ (in many countries Diprivan™; Astra Zeneca GmbH, Wedel, Germany) with respect to injection pain, is less effective than Disoprivan™ 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 Disoprivan™ with and without lidocaine versus Propofol-Lipuro™ 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-Lipuro™ was slightly (but not significantly) less than with Disoprivan™, the preinjection of lidocaine significantly reduced injection pain for both propofol formulations (P < 0.001). Furthermore, Disoprivan™ with lidocaine was superior to Propofol-Lipuro™ 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 Disoprivan™ with lidocaine versus Propofol-Lipuro™ without lidocaine. With both Disoprivan™ and Propofol-Lipuro™, there was a trend towards less injection pain when preinjecting lidocaine.
Most recently, an abstract has been published comparing Propofol-Lipuro™ without lidocaine versus Propofol-Fresenius™ (Fresenius Kabi GmbH, Bad Homburg, Germany) preceded by 40 mg of lidocaine using the tourniquet technique (4). In this study, Propofol-Fresenius™ with lidocaine was superior to Propofol-Lipuro™ without lidocaine concerning spontaneous expression of pain (P < 0.01). However, this study is not directly comparable to those studies testing Propofol-Lipuro™ against Disoprivan™, as it is unknown whether the incidence of pain after Propofol-Fresenius™ is similar to that of Disoprivan™.
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-Lipuro™ offers some advantage over Disoprivan™ 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-Lipuro™, 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 Disoprivan™ and Propofol-Lipuro™.
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.
Wolfgang H. Maleck, MD
Department of Anesthesiology
Spital Grenchen, CH-2540 Grenchen, Switzerland
Swen N. Piper, MD
Kerstin D. Röhm, MD
Department of Anesthesiology and Critical Care
Klinikum Ludwigshafen, Ludwigshafen, Germany
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.
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.
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.
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.
5. Larsen R, Beerhalter U, Erdkönig R, Larsen B. Injektionsschmerz durch Propofol-MCT/LCT bei Kindern. Anaesthesist 2001;50:676–8.
6. Larsen B, Beerhalter U, Biedler A, et al. Weniger Injektionsschmerz durch Propofol-MCT/LCT. Anaesthesist 2001;50:842–5.
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.
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