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REGIONAL ANESTHESIA

Tramadol, an Alternative to Morphine for Treating Posttraumatic Pain in the Prehospital Situation

Emergency Department and Department of Anesthesiology, CHR de la Citadelle, Liege, Belgium

Address correspondence and reprint requests to Vergnion Michel, Service des Urgences, Bd du 12ème de Ligne, 4000 Liège, Belgium. Address e-mail to michel.vergnion{at}chrcitadelle.be

Abstract

In this randomized, double-blinded, parallel-group study, we compared the efficacy of tramadol and morphine administered IV for the management of pain in trauma patients in the prehospital situation. One-hundred-five patients were randomly allocated to receive tramadol (Group T) or morphine (Group M). The initial dose was 100 mg tramadol in Group T and 5 mg morphine (body weight 70 kg) or 10 mg morphine (body weight >70 kg) in Group M; this could be increased to 200 mg in Group T and 15 or 20 mg in Group M if necessary. Pain intensity was assessed with four-point verbal rating scales. Sedation, physiologic data, and adverse events were also recorded. Analgesia was similar in both groups; the 95% confidence interval for the difference between the decrease in pain intensity observed with tramadol or morphine was -0.26 to 0.30, which was within the predefined equivalence range (-0.50 to 0.50). Neither sedation scores nor physiologic data differed between groups. Tramadol is an acceptable alternative to morphine in the prehospital trauma setting.

Implications: We demonstrated an equivalent efficacy and safety of IV tramadol and morphine in the management of pain in the prehospital trauma setting. Because tramadol is not a narcotic drug, its use would allow emergency medical systems to avoid the inconvenience of transporting controlled substances.

In traumatic injuries, pain relief at the scene of the accident and during the transfer to hospital is a primary therapeutic objective. This has led to continuing research to provide drugs with rapid onset and durable analgesic action without untoward side effects. In addition to adequate potency, the ideal analgesic must not alter vital functions, hide complications, or cause delay in therapeutic decision making (1).

Tramadol (Contramal^®; Searle, Brussels, Belgium), has only weak opioid agonist properties and enhances monoaminergic spinal inhibition of pain (2). In patients with moderate to severe postoperative pain, it is one tenth as potent as morphine (on a weight basis) when given IV (3). The onset of its action after parenteral administration is in the range of minutes. The maximum effect is reached after 15–30 min, and the duration of its effect is 3–6 h (4,5). In comparison with other opioids, respiratory depression has rarely been observed after its use in equianalgesic doses. Cardiovascular side effects are minor (6,7). Tramadol has minimal central actions, although dizziness, nausea, sedation, dry mouth, and sweating are adverse effects (8,9). Furthermore, tramadol is categorized as a nonnarcotic drug in many countries and can therefore be easily carried in ambulances or mobile intensive care units.

Because tramadol has a favorable efficacy and safety profile, this study was conducted to evaluate its use in the prehospital situation in trauma patients with significant posttraumatic musculoskeletal pain and to compare it with the reference analgesic morphine.

Methods

Patients with posttraumatic musculoskeletal pain requiring rapid analgesia with opioids were enrolled in this study at the site of the accident and were followed until their arrival at an emergency department for at least 40 min.

Patients with severe head injury, multiple trauma, or a Glasgow Coma Scale score <12 were excluded. Other exclusion criteria were age <18 yr, weight >100 kg, alcohol intoxication, a recent history of drug abuse, pregnancy, and known contraindications to tramadol or morphine. Patients who had already received an opioid analgesic (either self-administered or by an another physician in attendance) were also excluded.

This single-center, randomized, double-blinded, parallel-group study was organized in full observance of the European Good Clinical Practice guidelines and the current version of the declaration of Helsinki. The Institutional Ethics Committee gave its approval, and all patients provided oral informed consent in the presence of a witness.

Eligible patients were randomly allocated to receive either tramadol or morphine IV. Patients in the tramadol group (Group T) received an initial dose of 100 mg tramadol, and patients in the morphine group (Group M), 5 mg morphine (body weight 70 kg) or 10 mg morphine (body weight >70 kg). If pain relief was considered to be inadequate (no difference recorded in pain score) after 10 min, a further dose of 50 mg tramadol or 5 mg morphine was administered every 5 min to a maximum of 200 mg in Group T and 15 mg (body weight 70 kg) or 20 mg (weight >70 kg) in Group M. To preserve blinding of the emergency physician administering the study medication, 50-mL infusion sets with morphine (5 mg morphine in 50 mL in the first set [set A, body weight 70 kg], 10 mg in the first set [set B, body weight >70 kg], 5 mg morphine in 50 mL in the second and third sets) or tramadol (100 mg tramadol in 50 mL in the two first sets, A and B, 50 mg tramadol in 50 mL in the second and the third sets) were prepared each day by the hospital pharmacy according to a computer-generated random assignment schedule and coded in a manner suitable for randomized treatment allocation.

Patients were asked to assess the intensity of their pain by using a descriptive verbal rating scale (none = 0, mild = 1, moderate = 2, severe = 3) both before and 40 min after initial administration of the study drug. Sedation was also assessed by the emergency physician with a four-point rating scale (fully awake = 0, drowsy = 1, asleep but easily aroused = 2, deeply asleep = 3) before and 40 min after treatment. At the end of the study, 40 min after the administration, overall patient and investigator satisfaction (very satisfied = 5, satisfied = 4, no opinion = 3, dissatisfied = 2, very dissatisfied = 1) were recorded.

Safety evaluation included monitoring of blood pressure, heart rate, respiratory rate, oxygen saturation by pulse oximetry, Glasgow Coma Scale score, and recording of nausea, vomiting, and other adverse events.

The analgesic effects were compared by using an equivalence test: a 95% confidence interval for the difference between the decrease in pain intensity observed with tramadol and that with morphine was calculated. Equivalence was present if this interval decreased within the equivalence area, defined as -0.5 to 0.5. The sedative effects were also compared for equivalence. Values are provided as mean ± SD. A two-tailed Wilcoxon’s test was used for statistical comparison of treatment groups, except for binary variables, for which a two-tailed Fisher’s exact test was applied.

Results

A total of 105 patients with severe pain resulting from musculoskeletal trauma participated in the study, but four patients were excluded for protocol violation. Before randomization, three patients assessed their pain as mild. They remained in the protocol because, in the opinion of the emergency physician in attendance, their pain required rapid relief and was of sufficient intensity to warrant use of an opioid analgesic. Thus, the efficacy and tolerance analyses are based on 53 patients in Group T and 48 patients in Group M.

There was no significant difference between the treatment groups with regard to baseline demographic characteristics, vital signs, severity of pain, or sedation scores (Table 1). On entry in the study, severe pain was reported by 49% of patients in Group T and by 56% of patients in Group M (Table 1). Three patients in Group T and four patients in the Group M were drowsy before study administration of medication.

View larger version (15K): [in this window] [in a new window]   Figure 1. Severity of pain before and 40 min after the first administration of study medication in 101 patients with postraumatic pain in a prehospital situation.

A mean increase of sedation score of 0.14 was noted over the study period in both treatment groups. At the final assessment, 82% of patients experienced no change, whereas two patients who were drowsy at baseline (one in each treatment group) were fully awake. Among patients who were fully awake at baseline, eight in Group T and seven in Group M were drowsy. Changes in sedation scores were similar in both groups; the 95% interval for the difference between the mean changes in sedation score of the two treatment groups was -0.17 to 0.10, which was included within the predefined equivalence range (-0.5 to 0.5).

The time course of monitored vital signs over the study period was similar in both treatment groups; the differences observed were not statistically significant. Concerning the Glasgow Coma Scale score, a statistically significant difference was observed between treatment groups (P = 0.01). Six patients in Group M experienced a decrease of one point in comparison with no patients in Group T, but this difference was not clinically relevant because it always referred to spontaneous closing of the eyes.

When comparing the incidence of adverse events, nausea and vomiting were reported with a similar frequency. Nine patients (17%) treated with tramadol and seven patients (15%) treated with morphine experienced at least one episode of nausea, probably related to use of the study medication (P = 0.79). Three patients in Group T experienced at least one episode of vomiting, whereas no patient in Group M vomited (P = 0.24).

An antiemetic treatment was administered to six patients (11%) treated with tramadol and three patients (6%) treated with morphine. No serious adverse events were reported. At hospital arrival, one patient treated with tramadol reported dizziness.

In the global assessment of efficacy and tolerance, 40 patients (76%) in Group T and 32 patients (67%) in Group M were satisfied or very satisfied (P = 0.38), in agreement with the investigator’s assessment (Table 2). The results showed no differences between the two treatment groups.

Obtaining high-quality analgesia in trauma patients is an important treatment objective not only for psychological, but also for physiologic reasons. It is generally agreed that acute pain results in activation of the sympathetic nervous system, which may adversely affect cardiac and respiratory functions (10). Analgesic techniques are also necessary to facilitate the extrication of trapped patients (11).

Tramadol is safe for the management of acute pain, including postoperative pain, pain associated with labor, and acute myocardial infarction. Its safety has not yet been studied in trauma patients in the prehospital situation, in comparison with a reference opioid (12–14).

The results of this study show that analgesia with tramadol is as rapid and effective as analgesia with morphine; the incidence of side effects, principally nausea and vomiting, was similar and of little clinical relevance if we consider that transport by ambulance itself often induces nausea and vomiting.

The minor levels of sedation never affected clinical and neurological evaluation on hospital arrival, and the stability of vital signs was compatible with optimal medical management of these patients. Other side effects were negligible. Patient and investigator assessments confirmed these observations.

At the doses used in the study, we demonstrated an equivalent efficacy and safety of IV tramadol and morphine in the management of acute pain in trauma patients in the prehospital situation. Because tramadol is not a narcotic drug, it can be easily introduced into the emergency therapeutic protocols of emergency medical systems in many countries.

References

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This Article Abstract Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (8) Citing Articles via Google Scholar Google Scholar Articles by Vergnion, M. Articles by Magotteaux, V. Search for Related Content PubMed PubMed Citation Articles by Vergnion, M. Articles by Magotteaux, V. Related Collections Trauma Pharmacology