Alternative application site of transdermal nitroglycerin and the reduction of pain on propofol injection

EDITOR: Pain associated with intravenous (i.v.) injection of propofol has an incidence rate of 24-80% [1] and is related to the release of local kininogens; bradykinin is increased twofold after propofol injection. Anti-inflammatory drugs and kallikrein inhibitors ameliorate this pain [2,3]. Nitroglycerin has vasodilating properties, is a nitric oxide generator and is used in the treatment of angina pectoris and phelebitis [4]. We compared the effects of two different doses of transdermal nitroglycerin with placebo on pain after propofol injection. After obtaining the approval of the local Ethics Committee, 150 patients (ASA II-III) who were to undergo various elective operations were enrolled in the study. All patients used transdermal nitroglycerin patches as a part of their routine treatment. Patients with allergies, Parkinson's disease, a history of chronic pain syndromes, concurrent analgesic administration and those with thin dorsal veins of the hand were excluded from the study. The patients were randomly assigned to three groups: all were premedicated with midazolam 0.06 mg kg−1 and atropine 0.01 mg kg−1 intramuscularly (i.m.). The patients underwent bilateral venous cannulation using 20-G cannulae inserted into the dorsal veins of each hand. Group 1: the patch contained no nitroglycerin; Group 2: 5 mg nitroglycerin; Group 3: 10 mg nitroglycerin. In each group, the patch was applied 2 h before induction of anaesthesia over the dorsum of the hand adjacent to the tip of the i.v. cannula. Patients were monitored very closely for ischaemia, and anaesthesia was induced 1% propofol 2 mg kg−1. Pain on injection was assessed by an anaesthesiologist who was blinded to the type of patch applied. Reactions such as reporting discomfort and pain, or withdrawal of the hand on administering the first 5 mL propofol, at a rate of 10 mg in 5 s by a mechanical syringe, were noted. Pain was evaluated according to a scale of 0 (no pain) to 3 (Table 1). Induction of anaesthesia was continued with the remaining dosage of propofol. Then the nitroglycerin tape was removed and reapplied on the chest for patients in Groups 2 and 3. In Group 1, new nitroglycerin tape was applied to the chest, but nitroglycerin was infused in case ischaemia developed. Crystalloids and additional anaesthetic drugs were infused via another cannulae on the opposite hand. Atracurium 0.5 mg kg−1 was administered for muscle relaxation, and after tracheal intubation anaesthesia was maintained with 2% sevoflurane in 50% O2 with N2O. Within the first 24 h after the operation, the injection site was checked for any complications such as pain, swelling, allergic reactions, by an anaesthesiologist who did not know which type of patch had been applied. A t-test was used for the demographic data, a χ2-test for pain scores; P < 0.05 was taken as significant. There were no significant characteristic differences between the patients in the study groups (Table 2). The distribution of pain scores is shown in Table 3. Examination of the injection sites revealed no complications.Table 1: Assessment of pain during injection of propofol.Table 2: Patient characteristics data.Table 3: Intensity of pain.Propofol has been widely used for nearly two decades, but the mechanism by which the injection of propofol causes pain is still ill understood. The lipid emulsion directly irritates the vascular endothelium, causing pain. This may be related to the release of local kininogens. It has been shown that the concentrations of bradykinin increase twofold after propofol injection. Anti-inflammatory drugs such as ketorolac and kallikrein inhibitors have a preventative effect on pain caused by propofol injection [2,3]. Nitroglycerin is frequently used in patients with ischaemic heart disease. It provides a substrate for the enzymatic production of nitric oxide. Nitric oxide causes activation of guanyl cyclase and an increase in cyclic guanine monophosphate (cGMP), which mediates the relaxation vascular smooth [4,5]. Nitric oxide is also a potent inhibitor of neutrophil adhesion to vascular endothelium. Nitric oxide donors have also been shown to protect vascular endothelium from ischaemia- and reperfusion-mediated endothelial dysfunction. Nitric oxide is also a potent inhibitor of platelet adhesion to endothelial surfaces [4]. Transdermal nitroglycerin has been used as an adjuvant analgesic in cancer pain [5]. There appear to be no reports nitroglycerin patches being used to modify the pain associated with the injection of propofol. There are two studies, with conflicting results, about the use of nitroglycerin ointment. Wilkinson and colleagues [6] studied the effect of nitroglycerin ointment on propofol injection pain in 60 patients and found it effective in decreasing pain. O'Hara and colleagues [7], in a randomized placebo-controlled study, compared lidocaine and topical nitroglycerin ointment and found that the ointment did not decrease the incidence of propofol-induced pain. Various treatments have been tried in the hope that they will reduce such pain and it is still not clear what is the best treatment. Our study has shown that patients using nitroglycerin patches as a part of their normal medication can wear the patch over the cannulated vein with the advantage that this reduces the pain following propofol injection. A. Turan B. Karamanlioğlu D. Memiş Z. Pamukçu Department of Anesthesiology and Reanimation; Trakya University Medical Faculty; Edirne, Turkey