Effect of Tramadol/Acetaminophen Combination Drug in Acute Pain After Spinal Surgery

Jae-Yoon Chung; Jae-Joon Lee; Hyoung-Yeon Seo; Suk-June Shon; Eun-Kyung Chung

doi:10.4184/jkss.2007.14.3.137

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Chung, Lee, Seo, Shon, and Chung: Effect of Tramadol/Acetaminophen Combination Drug in Acute Pain After Spinal Surgery

Original Article

Journal of Korean Spine Surg 2007;14(3):137-143.

Published online: 21 February 2007

DOI: https://doi.org/10.4184/jkss.2007.14.3.137

Effect of Tramadol/Acetaminophen Combination Drug in Acute Pain After Spinal Surgery

Jae-Yoon Chung, M.D., Jae-Joon Lee, M.D., Hyoung-Yeon Seo, M.D., Suk-June Shon, M.D.^#, Eun-Kyung Chung, M.D.^$

Department of Orthopedics, Chonnam National University Hospital, Gwangju, Korea

^#Department of Preventive Medicine, Chonnam National University Medical School, Gwangju, Korea

^$Department of Medical Education, Chonnam National University Medical School, Gwangju, Korea

Address reprint requests to Jae-Joon Lee, M.D. Department of Orthopedics, Chonnam National University Hospital 8 Hak-dong, Dong-gu, Gwangju 501-757, Korea Tel: 82-62-227-1640, Fax: 82-62-225-7794, E-mail: sanggunlee@lycos.co.kr

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Study Design

A single center, double-blind, randomized, placebo-controlled trial

Objectives

The aim of this study was to evaluate the efficacy and safety of Ultracet ^TM compared with a placebo in the treatment of acute pain after spinal surgery.

Summary of Literature Review

Ultracet ^TM is a combination drug of Tramadol and Acetaminophen, and the synergistic effect in pain control was demonstrated by animal experiments.

Materials and Methods

Seventy-six patients who satisfied the selection and exclusion criteria after spinal surgery were enrolled in this study. The patients measured perceptible pain relief time and meaningful pain relief time using a two stop-watch technique. The pain intensity (PI) and pain relief (PAR) were recorded at 30 minutes and then hourly over a 4 hour period, and the pain intensity difference (PID), the sum of the pain intensity difference (SPID), and the total pain relief (TOPAR) were also checked.

Results

The study and control group comprised of 56 and 20 patients, respectively. The baseline pain intensity was an average of 5.9±1.2 in the study group and 6.1±1.4 in the control group (p=0.683). The final pain intensity was 2.5±2.4 and 4.1±2.2 in the study and control group, respectively. The study group was superior to placebo (p=0.008). In addition, the study group was statistically superior in terms of the PID (p=0.025), SPID (p=0.028), and TOPAR (p=0.048), particularly over 2 hours, as well as the overall assessment (p=0.005). The median time of the meaningful pain relief time was 90 and 193 minutes in the study and control group, respectively.

Conclusions

The analgesic efficacy of Ultracet ^TM was superior to the placebo on the SPID, TOPAR, and the subjects’ overall assessments over the 4 hour observation period. These results suggest that Ultracet^TM is an effective therapeutic option for the management of acute pain after spinal surgery without serious complications.

Keywords: Spinal disease, Surgical treatment, Acute pain, Randomized double-blind test, Ultracet ^TM

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Figures and Tables%

Formula 1.

Estimation of sample size needed in a randomized trial.

Fig. 1.

The graph for mean PID scores

Fig. 2.

The graph for mean PAR scores

Fig. 3.

Overall assessments of the study medication

Table 1.

Demographic and baseline characteristics

	Ultracet (n=56)	Placebo (n=20)	Total (n=76)	p value*
Sex
Male	26 (46.4)	11 (55)	37 (48.7)
Female	30 (53.6)	9 (45)	39 (51.3)
Age (yr)
Mean (SD)	51.25 (16.93)	54.65 (13.45)	52.14 (16.07)
Median	52.50	61.00	53.50
Range	16~83	31~73	16~83
Operation				0.735
Major	34 (60.7)	13 (65.0)	47 (61.8)
Minor	22 (39.3)	7 (35.0)	29 (38.2)
Anesthesia				0.602
General	53 (94.6)	18 (90.0)	71 (93.4)
Local	3 (5.4)	2 (10.0)	5 (6.6)
Height (cm)
Mean (SD)	161.18 (11.41)	159.20 (9.29)	160.66 (10.87)
Median	163.00	159.25	160.50
Range	138~185	142~182	138~185
Weight (kg)
Mean (SD)	62.66 (9.86)	62.88 (11.61)	62.72 (10.27)
Median	60.75	62.95	62.45
Range	44~87	44~83	44~87
Systolic blood pressure
Mean (SD)	126.25 (12.29)	131.00 (11.65)	127.50 (12.23)
Median	130.00	130.00	130.00
Range	100~160	110~150	100~160
Diastolic blood pressure
Mean (SD)	79.29 (8.92)	81.50 (8.75)	79.87 (8.87)
Median	80.00	80.00	80.00
Range	60~100	70~100	60~100
Pulse rate
Mean (SD)	76.75(7.92)	76.00 (6.81)	76.55 (7.61)
Median	76.00	78.00	76.00
Range	60~104	54~84	54~104
Baseline pain intensity
Moderate	42 (75.0)	16 (80.0)	58 (76.3)
Severe	14 (25.0)	4 (20.0)	18 (23.7)

Table 2.

Study completion/withdrawal information

	Ultracet	Placebo	Total
Total subjects	56	20	76
Subjects who completed	56	20	76
No rescue analgesic (%)	49 (87.5)	15 (75.0)	64 (84.2)
Took rescue analgesic (%)	47 (12.5)	45 (25.0)	12 (15.8)
Subjects who withdrew
Adverse event	0	0	0

Table 3.

Baseline and final NRS of pain

	Ultracet	Placebo	p value*
Baseline	5.88±1.16	6.05±1.40	0.683
Final	2.54±2.41	4.10±2.20	0.008

^∗ paired t-test

Table 4.

Mean pain intensity difference (PID) scores Unit : Mean±SD

	30 min	1 hour	2 hour	3 hour	4 hour
Ultracet	0.50±0.63	0.77±0.74	0.93±0.83	1.14±0.88	1.11±0.89
Placebo	0.45±0.60	0.30±0.73	0.55±0.89	0.55±0.83	0.50±0.83

PID: -1 = pain worse than baseline, 3 = complete relief from severe baseline pain p = 0.025 by repeated measure ANOVA

Table 5.

Mean pain relief(PAR) scores Unit : Mean±SD

	30 min	1 hour	2 hour	3 hour	4 hour
Ultracet	1.20±1.10	1.77±1.27	42.18±1.38	2.41±1.49	2.36±1.51
Placebo	1.00±0.92	1.20±1.11	11.60±1.19	1.65±1.31	1.55±1.43

PAR: 0 = no relief, 4 = complete relief p = 0.062 by repeated measure ANOVA

Table 6.

Results on the primary analgesic efficacy measures Unit : Mean±SD

	Ultracet	Placebo	p value*
A. 0-4 Hours
SPID^†	3.81±2.9	51.98±3.02	0.028
TOPAR^†	8.43±5.07	45.90±4.67	0.048
B. 0-2 Hours
SPID	1.56±1.38	0.93±1.48	0.093
TOPAR	3.66±2.36	2.70±2.11	0.112
C. 2-4 Hours
SPID	2.25±1.75	1.05±1.64	0.012
TOPAR	4.77±2.94	3.20±2.69	0.030

SPID = sum of pain intensity difference, TOPAR = total pain relief

^† Scale, 0-4 hour SPID: -4 = pain worse than baseline at every evaluation, 12 = complete relief from severe baseline pain at every evaluation

^† Scale, 0-4 hour TOPAR: 0 = no relief, 16 = complete relief * repeated measure ANOVA

Table 7.

Time to onset of perceptible and meaningful pain relief

	Ultracet (N=56)	Placebo (N=20)
Onset of perceptible pain relief (minutes)
Mean± SD	59.7±71.0	67.9±88.6
Median	29.0	25.0
Range	10 - ∝*	10 - ∝
Onset of meaningful pain relief (minutes)
Mean± SD	117.5±75.7	160.8±85.0
Median	90.0	192.5
Range	24 - ∝	42 - ∝

^∗ ‘∝'means absence of perceptible or meaningful pain relief during observation period.

Table 8.

The adjusted risk ratio and their 95% confidence interval (CI) of perceptible and meaningful pain relief

	Adjusted risk ratio of perceptible pain relief*			Adjusted risk ratio of meaningful pain relief*
	Risk ratio	Lower 95% CI	Upper 95% CI	Risk ratio	Lower 95% CI	Upper 95% CI
Placebo	1.000			1.000
Ultracet	0.922	0.504	1.689	2.508	1.190	5.287

^∗ Adjusted rate ratio for time to onset of perceptible and meaningful pain relief by Cox's proportional hazard models for operation and anesthesia

Table 9.

Subjects’ overall assessments of study medication*

	Very good (5)	Good (4)	Fair (3)	Poor (2)	Very poor (1)	Mean± SD
Ultracet	24	18	2	6	6	3.86±1.37
Placebo	2	7	3	3	5	2.90±1.41

^∗ p = 0.005 by Mann-whitney U test

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