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Oxybutynin chloride in control of post-transurethral vesical pain and spasm
OXYBUTYNIN CHLORIDE IN CONTROL OF POST-TRANSURETHRAL VESICAL PAIN AND SPASM DAVID
F. PAULSON,
M.D.
From the Department of Urology, Duke University Medical Center, Durham, North Carolina
- Oxybutynin chloride (Ditropan) and placebo were randomized in a double-blind trial to determine the effectiveness of the test agent in controlling post-transurethral pain and spasm. Oxybutynin chloride was found effective in controlling pain and spasm; no signijcant side effects were noted.
ABSTRACT
Oxybutynin chloride (Ditropan) is an anticholinergic, antispasmotic drug. It inhibits the muscarinic action of acetylcholine on smooth muscle and exerts a direct antispasmotic effect. No blocking effects occur at skeletal neuromuscular junctions or anatomic ganglia (antinicotinic effects). l-s This study was undertaken to assess the efficacy of oxybutynin chloride in relieving smooth-muscle spasm and pain following endoscopic resection and to assess the drug’s effectiveness in relieving associated symptoms.
tions were scored by an impartial study nurse who had no participation in drug assignment. In addition, a global evaluation as to efficacy was made by the investigator. Results One hundred twelve (39 infected, 73 uninfected) and 116 patients (41 infected, 75 uninfected) were randomized to receive oxybutynin chloride or placebo, respectively. Twenty-one of 112 and 18 of 116 were females.
Methods Patients undergoing endoscopic resection for management of either bladder or prostatic disease were randomly assigned to either placebo or oxybutynin chloride tablets (5 mg. orally every six hours) postoperatively for three full regardless of whether or not their days, symptoms were adequately relieved. No analgesics were given prophylactically, but morphine was administered on demand. Objective criteria for judging drug efficacy were the number of morphine injections required during the treatment period, and the observed level of restlessness with portrayed manifestations characteristic of pain and spasm. Three subjective parameters were scored with ten-point linear scales: (1) pain of diffuse or “general” nature, (2) sensations of spasm, cramps, painful tightness, as differentiated from diffuse, noncramping pain, and (3) urgency. The observa-
UROLOGY / MARCH 1978 / VOLUME XI, NUMBER 3
TABLE I.
Comparison of results in infected and noninfected patients* No. of Patients
Results OXYBUTYNIN
Responded Did Not to Respond to Treatment Treatment
CHLORIDE
Patients with infection Patients without infection PLACEBO Patients with infection Patients without infection
39
39 (100%)
73
60 (82%)
13 (18%)
41
32 (78%)
9 (22%)
7s
49 (65%)
26 (35%)
0
*Statistical significance of difference, oxybutynin chloride over placebo, in infected patients p < 0.02, and in noninfected patients p < 0.05.
237
TABLE II.
Infection Oxybutynin chloride Placebo No infection Oxybutynin chloride
Placebo
Totals Oxybutynin chloride Placebo
Results of global evaluations
18 12
13 16
6 4
0 1
0 8
37 41
16 15
31 26
12 7
8 9
5 17
72
34 27
44 42
18
8
5
109
11
10
25
115
Objecthe. When the number of patients requiring morphine were compared, a statistically significant (p < 0.05) difference favoring oxybutynin chloride was found. Among the infected patients, 23 per cent receiving the study drug required morphine in contrast to 44 per cent of the placebo patients. Although the difference between treatment groups in the noninfected patients was not statistically significant, the comparison again favored oxybutynin chloride, only 34 per cent receiving the study drug required morphine, whereas 52 per cent of those on placebo required morphine. There were no statistically significant differences found between drug groups in the other objectively evaluated parameters. Subjective. Oxybutynin chloride was more effective than placebo in relieving urgency in infected patients. After one day’s treatment with oxybutynin chloride the infected patients had a mean urgency score significantly (p < 0.001) below their pretreatment mean score and significantly (p < 0.001) below the placebo mean score. No significant difference between the treatment groups in either the infected or noninfected patients was found after the second or third days of treatment. Global evaluation. The over-all response to treatment could be completed in 224 of the 228 patients (Table I). When the results of treatment are segregated into response or no response categories, oxybutynin chloride is seen to be more effective than placebo. All 39 infected patients who were treated with the study whereas only 32 of 41 drug responded, placebo-treated infected patients responded (p
238
Ineffective Total
Good
Scoring
Fair
Slight
Excellent
74
< 0.01). Among the noninfected patients, 60 of 73 patients (82 per cent) responded to oxybutynin chloride, whereas only 49 of 75 (65 per cent) responded to placebo treatment (p < 0.05) (Table II). No adverse reactions to oxybutynin chloride were identified. Comment Oxybutynin chloride, in double-blind study to evaluate for control of bladder pain and spasm after transurethral resection of the prostate or bladder (for malignancy), was more effective than placebo in (1) reducing the need for morphine analgesia, (2) reducing the sensation of urgency, and (3) improving the patient’s clinical status so that the investigator noted a beneficial response. The high level of placebo response reinforces the necessity for inclusion of nontreatment arms in trials to evaluate pharmaceutical control of pain. Oxybutynin chloride appears an acceptable alternative to methantheline (Banthine) or belladonna-opium for control of postresection pain and spasm. Durham, North Carolina 27710 References 1. Fredericks CM, Anderson GF, and Kreulen DL: A study of the antichohnergic and antispasmodic activity of oxybutynin (Ditropan) on rabbit detrusor, Invest. Ural. 12: 317 (1975). 2. Diokno AC, and Lapides J: Oxybutynin: a new drug with analgesic and antichohnergic properties, J. Urol. 168: 307 (1972). 3. Lish PM, Labudde JA, Peters EL, and Robbins SI: Oxybutynin - a musculotropic antispasmodic drug with moderate anticholinergic action, Arch. Int. Pharmacodyn. 156: 467 (1965). 4. La Vallina FV: The use of a new antispasmodic and anticholinergic compound in some painful disorders of the genitourinary tract, Med. Rev. Mex. 45: 455 (1965). 5. de 10s Cobos JA: Antispasmodic activity of oxybutynin in infants, ibid. 45: 556 (1965).
UROLOGY
/
MARCH 1978
/
VOLUME
XI, NUMBER
3
F. PAULSON,
M.D.
From the Department of Urology, Duke University Medical Center, Durham, North Carolina
- Oxybutynin chloride (Ditropan) and placebo were randomized in a double-blind trial to determine the effectiveness of the test agent in controlling post-transurethral pain and spasm. Oxybutynin chloride was found effective in controlling pain and spasm; no signijcant side effects were noted.
ABSTRACT
Oxybutynin chloride (Ditropan) is an anticholinergic, antispasmotic drug. It inhibits the muscarinic action of acetylcholine on smooth muscle and exerts a direct antispasmotic effect. No blocking effects occur at skeletal neuromuscular junctions or anatomic ganglia (antinicotinic effects). l-s This study was undertaken to assess the efficacy of oxybutynin chloride in relieving smooth-muscle spasm and pain following endoscopic resection and to assess the drug’s effectiveness in relieving associated symptoms.
tions were scored by an impartial study nurse who had no participation in drug assignment. In addition, a global evaluation as to efficacy was made by the investigator. Results One hundred twelve (39 infected, 73 uninfected) and 116 patients (41 infected, 75 uninfected) were randomized to receive oxybutynin chloride or placebo, respectively. Twenty-one of 112 and 18 of 116 were females.
Methods Patients undergoing endoscopic resection for management of either bladder or prostatic disease were randomly assigned to either placebo or oxybutynin chloride tablets (5 mg. orally every six hours) postoperatively for three full regardless of whether or not their days, symptoms were adequately relieved. No analgesics were given prophylactically, but morphine was administered on demand. Objective criteria for judging drug efficacy were the number of morphine injections required during the treatment period, and the observed level of restlessness with portrayed manifestations characteristic of pain and spasm. Three subjective parameters were scored with ten-point linear scales: (1) pain of diffuse or “general” nature, (2) sensations of spasm, cramps, painful tightness, as differentiated from diffuse, noncramping pain, and (3) urgency. The observa-
UROLOGY / MARCH 1978 / VOLUME XI, NUMBER 3
TABLE I.
Comparison of results in infected and noninfected patients* No. of Patients
Results OXYBUTYNIN
Responded Did Not to Respond to Treatment Treatment
CHLORIDE
Patients with infection Patients without infection PLACEBO Patients with infection Patients without infection
39
39 (100%)
73
60 (82%)
13 (18%)
41
32 (78%)
9 (22%)
7s
49 (65%)
26 (35%)
0
*Statistical significance of difference, oxybutynin chloride over placebo, in infected patients p < 0.02, and in noninfected patients p < 0.05.
237
TABLE II.
Infection Oxybutynin chloride Placebo No infection Oxybutynin chloride
Placebo
Totals Oxybutynin chloride Placebo
Results of global evaluations
18 12
13 16
6 4
0 1
0 8
37 41
16 15
31 26
12 7
8 9
5 17
72
34 27
44 42
18
8
5
109
11
10
25
115
Objecthe. When the number of patients requiring morphine were compared, a statistically significant (p < 0.05) difference favoring oxybutynin chloride was found. Among the infected patients, 23 per cent receiving the study drug required morphine in contrast to 44 per cent of the placebo patients. Although the difference between treatment groups in the noninfected patients was not statistically significant, the comparison again favored oxybutynin chloride, only 34 per cent receiving the study drug required morphine, whereas 52 per cent of those on placebo required morphine. There were no statistically significant differences found between drug groups in the other objectively evaluated parameters. Subjective. Oxybutynin chloride was more effective than placebo in relieving urgency in infected patients. After one day’s treatment with oxybutynin chloride the infected patients had a mean urgency score significantly (p < 0.001) below their pretreatment mean score and significantly (p < 0.001) below the placebo mean score. No significant difference between the treatment groups in either the infected or noninfected patients was found after the second or third days of treatment. Global evaluation. The over-all response to treatment could be completed in 224 of the 228 patients (Table I). When the results of treatment are segregated into response or no response categories, oxybutynin chloride is seen to be more effective than placebo. All 39 infected patients who were treated with the study whereas only 32 of 41 drug responded, placebo-treated infected patients responded (p
238
Ineffective Total
Good
Scoring
Fair
Slight
Excellent
74
< 0.01). Among the noninfected patients, 60 of 73 patients (82 per cent) responded to oxybutynin chloride, whereas only 49 of 75 (65 per cent) responded to placebo treatment (p < 0.05) (Table II). No adverse reactions to oxybutynin chloride were identified. Comment Oxybutynin chloride, in double-blind study to evaluate for control of bladder pain and spasm after transurethral resection of the prostate or bladder (for malignancy), was more effective than placebo in (1) reducing the need for morphine analgesia, (2) reducing the sensation of urgency, and (3) improving the patient’s clinical status so that the investigator noted a beneficial response. The high level of placebo response reinforces the necessity for inclusion of nontreatment arms in trials to evaluate pharmaceutical control of pain. Oxybutynin chloride appears an acceptable alternative to methantheline (Banthine) or belladonna-opium for control of postresection pain and spasm. Durham, North Carolina 27710 References 1. Fredericks CM, Anderson GF, and Kreulen DL: A study of the antichohnergic and antispasmodic activity of oxybutynin (Ditropan) on rabbit detrusor, Invest. Ural. 12: 317 (1975). 2. Diokno AC, and Lapides J: Oxybutynin: a new drug with analgesic and antichohnergic properties, J. Urol. 168: 307 (1972). 3. Lish PM, Labudde JA, Peters EL, and Robbins SI: Oxybutynin - a musculotropic antispasmodic drug with moderate anticholinergic action, Arch. Int. Pharmacodyn. 156: 467 (1965). 4. La Vallina FV: The use of a new antispasmodic and anticholinergic compound in some painful disorders of the genitourinary tract, Med. Rev. Mex. 45: 455 (1965). 5. de 10s Cobos JA: Antispasmodic activity of oxybutynin in infants, ibid. 45: 556 (1965).
UROLOGY
/
MARCH 1978
/
VOLUME
XI, NUMBER
3