US EPA

8714293 

Journal Article 

Intravenous tramadol for postoperative pain: comparision of intermittent dose regimes with and without maintenance infusion 

Chrubasik, S; Chrubasik, J 

1997 

22 

2 SUPPL. 

56 

English 

Introduction: The cyclohexane derivative tramadol is marked by weak mu opioid receptor affinity, naloxone-reversible antinociception and low abuse potential (1-3). After single i.v. injections, the tramadol half-life of the terminal elimination phase (t 1/2Q) was found to be about 6 hours (4). The rate constant of elimination 1n2/t1/2β of 0.1 indicates that the mean hourly tramadol elimination is about 10%. Aim of the study was to compare intermittent i.v. tramadol dose regimes with and without maintenance infusion in the treatment of pain after abdominal operations. Methods: The study was approved by the Institution's Ethics Committee. 35 females (ASA I,II) scheduled for gynecological operations under general anesthesia gave written informed consent. At onset of severe postoperative pain, the patients received randomly and double-blind 150 mg tramadol i.v. before basal i.v. infusion of 15 mg tramadof/h (Group I) or saline (Group II). Subjective pain was assessed by the patients (scale 0-10) and the physician (scale 0-4) during continuous supervision over 24 h. When subjective pain exceeded 3, i.v. tramadol boluses of 100 mg were titrated to maintain analgesia. Patients with subjective pain >3 two after start of treatment were excluded from the study. Blood pressure, heart and respiratory rate, sedation scores , pulse oximetry, on-demand tramadol and side-effects were recorded at varying intervals. Blood samples were taken to determine serum tramadol by gas chromatography. For statistical analysis Repeated Measures ANOVA and KruskalWallis-Test were used. Results: 4 patients (n=1 Group I; n=3 Group II) were tramadol failures. The demographic variables, duration of surgery and intraoperative blood loss did not differ among the patients having the two tramadol dose regimes. On-demand tramadol was 150 ±29 mg (Group I) and 360 ±67 mg (Group II) (p < 0.01). Total tramadol consumption/24 h was 660 ±29 mg (Group I) and 510 ±67 mg (Group II) (p < 0.05). Subjective pain assessed by both, the patients and the physician decreased in both groups (p < 0.001) but was lower in Group I than in Group II (p < 0.05). Moderate to severe sedation lasted over 3 h (Group I) and 5 h (Group II). Sedation scores, blood pressure and respiratory rate decreased (p<0.05 - 0.001) in the course of treatment and did not differ between the groups; heart rate was unchanged, pulse oximetry in normal range. Side-effects (Group I/Group II) included nausea (9/7), emesis (5/3), dizziness (6/8), transpiration (9/9) and dry mouth (8/7). In both groups serum tramadol peaked at 15 and 60 min and decreased thereafter steadily (p < 0.01). Discussion: This study demonstrates that the maintenance infusion in addition to intermittent i.v. tramadol reduced the requirement for on-demand i.v. tramadol in the treatment of postoperative pain by 60%. Moreover, the patients receiving the tramadol maintenance infusion benefited from a better quality of postoperative analgesia. However, their total tramadol consumption was increased by 30% and associated with a higher incidence of minor side-effects. Use of the i.v. maintenance tramadol infusion did not influence fluctuation of serum tramadol by supplementary on-demand i.v. tramadol. Decreasing serum tramadol in the course of treatment indicates that tramadol overdosage may not be expected when the opiate infusion rate does not exceed the opioid elimination rate (5). The method is therefore a safe and recommended mode of intravenous analgesia in patients after abdominal operations.