CASE REPORTS
after 22 days of treatment. No side effects or systemic toxicity were observed from intravenous infusion of 1.2 grams per day for 30 days by European investigators. The highest dosage used intravenously in Europe was 1.2 grams per day in divided doses. Due to the severe disseminated disease in this black patient, the intravenous dose was carried from 200 mg to 800 mg every eight hours. The dosage of 600 mg every eight hours was well tolerated. There were no immediate local or systemic side effects and no hematologic or biochemical abnormalities after a total of 68.4 grams of miconazole was given in 59 days. The serum concentration of the drug, after 400 mg intravenous miconazole, was 0.42 micrograms per ml after 21/2 hours, and 0.22 micrograms per ml after 7½/2 hours, respectively. However, no attempt was made to use the serum level of miconazole as a guide for daily dosage administration. In our mycology laboratory, the minimal fungicidal concentration of miconazole in vitro was 0.218 micrograms per ml. Despite its early investigational status and unknown potential for delayed side effects, the dramatic effectiveness of miconazole in a patient with coccidioidal osteomyelitis and disseminated abscesses and granulomata makes it worthy of further clinical trial.
Summary A fulminating case of disseminated coccidioidomycosis in a black man was refractory to amphotericin B therapy, but successfully treated with miconazole. No immediate side effect or toxicity was observed with intravenous doses of up to 1.8 grams per day. The safety and effectiveness of this drug are worthy of further clinical study. REFERENCES 1. Miller RP, Bates JH: Amphotericin B toxicity-A follow-up report of 53 patients. Ann Intern Med 71:1089-1095, Dec 1969 2. Bennett JE: Chemotherapy of systemic mycoses. N Engl J Med 290:30-32, Jan 1974 3. Godefroi EF, Heeres J, Gutesm JN, et al: The preparation and antimycotic properties of derivatives of L-phenethylimidazole. J Med Chem 12:784-791, Sep 1969 4. Brugmans JP, van Cutsem J, Heykants J, et al: Systemic antifungal pitential, safety, biotransport and transformation of miconiazole. Eur J Clin Pharmacol 5:93-99, 1972 5. Van Cutsem JM, Thienpont D: Miconazole, a broad-spectrum antimycotic agent with antibacterial activity. Chemotherapy 17: 392-404, 1972 6. Scheef W, Symoens J, Van Camp K, et al: Chemotherapy of candidiasis. Br Med J 1:78, Jan 1973 7. Daneels R, Demeyere R, Egger L, et al: Treatment of systemic candidiasis with miconazole. Med Welt 25:428-429, 1974 8. Zazgornik J, Schmidt P, Kopsa H, et al: Successful treatment of Candida albicans septicemia after kidney transplantation. Dtsch Med Wochenschr 98:15-17, 1973 9. Hoeprich PD, Goldstcin E: Miconazole therapy for coccidioidomycosis. JAMA 230:1153-1157, Nov 1974
64
JANUARY 1976 * 124 * 1
Refer to: Garfinkle SE, Chiu GW, Cohen SE, et al: Spontaneous perforation of the neurogenic urinary bladder. West J Med 124:64-66, Jan 1976
Spontaneous Perforation of the Neurogenic Urinary Bladder SYDNEY E. GARFINKLE, MD GEORGE W. CHIU, MD SHELDON E. COHEN, MD EARL F. WOLFMAN, JR., MD Davis, California
ALTHOUGH SPONTANEOUS PERFORATION of the bladder has been reported in the literature,1-4 little attention has been focused on its occurrence in patients with neurogenic bladder disturbances. Two cases of peritonitis due to spontaneous intraperitoneal perforation of the urinary bladder in neurologically handicapped patients were recently seen on the general surgical service at the University of California, Davis, Sacramento Medical Center.
Reports of Cases CASE 1. A 21-year-old man sustained a fracture dislocation of the fourth and fifth cervical vertebrae in an automobile accident. The injury resulted in a spastic paralysis below the level of the sixth cervical vertebra. While the patient was in hospital, urinary drainage was instituted with an indwelling urethral catheter. Two years later the patient was readmitted for treatment of sacral decubiti and multiple bladder calculi. Cystogram disclosed a "Christmas tree" appearance of the bladder and bilateral ureteral reflux. Intravenous pyelogram showed small radiopaque calculi in the right renal pelvis. Results of cystometric examination were consistent with a spastic neurogenic bladder. A cystolithalopaxy was done. Postoperatively, the indwelling catheter was removed and From the Department of Surgery, University of California, Davis, School of Medicine. Submitted May 12, 1975. Reprint requests to! S. E. Garfinkle, MD, Department of Surgery, University of California, Davis, School of Medicine, Davis,
CA 95616.
CASE REPORTS
the patient discharged with condom catheter drainage. Eight months later the patient was readmitted with pneumonia. Following this admission, nausea, vomiting and abdominal distention occurred, and findings on roentgenograms of the abdomen were compatible with an ileus. Surgical consultation was obtained, abdominal paracentesis carried out and grossly purulent material was aspirated. Celiotomy was done and a perforation of a bladder wall abscess was found. The necrotic portion of the bladder was excised, the defect closed and a suprapubic cystostomy established. The postoperative course was complicated by an episode of septic shock and disseminated intravascular coagulation. Intermittent episodes of sepsis finally resolved following ureteroileostomy.
*vi.
4
........... e
,
?
;AC 8 04
4'
Figure 1.-Photomicrograph of bladder in area of perforation in Case 2 showing pronounced inflammatory changes.
...
£
..
Figure 2.-Cystogram (Case 2) showing extravasation of contrast from bladder into peritoneal cavity.
CASE 2. A 74-year-old woman entered the emergency department with a 24-hour history of abdominal pain and progressive obtundation. One episode of vomiting had occurred before admission. Bowel movements had been regular. The remainder of the gastrointestinal history was negative. Five years previously, cerebral thrombosis resulted in a right hemiparesis, chronic organic brain syndrome and urinary incontinence. Catheter drainage of the urinary bladder was instituted, but the catheter was repetitively removed by the patient. On admission the patient was cachectic and obtunded with a blood pressure of 80/0 mm of mercury. A supraventricular tachycardia of 170 per minute and a temperature of 38.9°C (102°F) rectally were present. Positive physical findings included (1) flexion contractures of the hips and knees, (2) a protodiastolic gallop rhythm and (3) abdominal tenderness in' the right lower quadrant with voluntary muscle guarding in both lower abdominal quadrants. Intestinal sounds were normal. Results of rectal and pelvic examinations were within normal limits. A hemoglobin determination was 14.9 grams per 100 ml, and the leukocyte count was 3,400 per cu mm with 52 percent nonsegmented neutrophils, 3 percent segmented neutrophils and toxic granulations of the neutrophils. A nonspecific intestinal gas pattern with no free intraperitoneal air was present on the abdominal roentgenogram. Electrocardiographically, a sinus tachycardia and left bundle branch block were noted to be present. Resuscitative measures were instituted with the intravenous administration of fluids, antibiotics (penicillin and garramycin) and hydrocortisone. After ten hours of treatment, pulse rate diminished to 128 per minute, blood pressure increased to 120/90 mm of mercury and central venous pressure rose from 0 to 11 cm of water. Abdominal paracentesis yielded grossly purulent material. At operation a perforated, necrotic diverticulum of the bladder wall was excised (Figure 1), the defect closed and a suprapubic cystostomy established. The patient improved and was discharged on the 21st postoperative day. One month later the patient was readmitted to the hospital, having removed the suprapubic tube 48 hours earlier. On physical examination, signs of an acute condition within the abdomen were present. Cystography (Figure 2) showed intraperitoneal extravasation of the dye from the urinary bladder. On operation, a new perforation in THE WESTERN JOURNAL OF MEDICINE
65
CASE REPORTS
the area of the previous bladder closure without disruption of the suture line was noted. The new perforation was closed and suprapubic cystostomy reestablished. The postoperative course was uncomplicated.
Discussion Previous reports of spontaneous perforation of the urinary bladder have emphasized chronic infection, bladder outlet obstruction' and indwelling urethral catheters' as etiologic factors. Cystography has been recommended as a diagnostic aid.:' The mortality rate associated with spontaneous perforation has ranged from 47 to 57 percent.'' The difficulty in establishing diagnosis early, however, has not been widely appreciated, nor has the neurogenic bladder itself been emphasized as an underlying factor in spontaneous perforation. The patients in cases presented are representative of a large number of neurologically handicapped persons living today. Because of improved rehabilitation techniques, patients with neurologic deficits are living longer and presenting a previously undocumented spectrum of disease peculiar to paralyzed patients. The lack of conventional response to pain following spinal cord injury or cerebrovascular thrombosis decreases the diagnostic accuracy of a history and physical examination in acute abdominal emergencies, and the subsequent delay in diagnosis increases the morbidity and mortality rates. Infections and obstructive urinary tract complications are well documented in the long term management of patients with neurogenic bladder.78 Spontaneous perforation may also occur. In such cases, patients may present with unexplained fever or ileus. We have found that the use of diagnostic abdominal paracentesis has made earlier diagnosis of peritonitis possible in neurologically handicapped patients. Abdominal paracentesis as described by Root13 can also be used when abdominal distention is present. In such instances the paracentesis catheter is placed intraabdominally under direct
66
JANUARY 1976 *
124 *
1
vision through a small midline abdominal incision. Fluid obtained is cultured and analyzed for red and white blood cell determinations, amylase and bile. If less than 30 ml is aspirated, lavage of the peritoneal cavity with 20 ml per kg of body weight of Ringer's lactate solution (maximum of 1,000 ml) is carried out, followed by aspiration of the infused fluid. We are currently evaluating criteria for the 'diagnosis of' peritonitis when the fluid aspirated is not grossly purulent. Operative treatment of a perforated neurogenic bladder consists of excision of the necrotic bladder with primary closure of the defect and suprapubic drainage. Long-term measures to prevent perforation of such bladders include treatment of established urinary tract in'fections and prevention of urinary retention by catheter drainage, transurethral resection of the bladder neck or supravesical diversion.
Summary Two cases of spontaneous perforation of a neurogenic bladder are presented. The problem of early diagnosis in neurologically handicapped patients is discussed, abdominal paracentesis is emphasized as a diagnostic aid and the emergency operative treatment of 'perforated bladder is outlined. This diagnosis should be considered in the evaluation of an acute condition within the abdomen, a fever of unknown origin or an unexplained ileus in patients with neurologic deficits. REFERENCES 1. Bastable JRY, DeJode LR, Warren RP: Spontaneous rupture of the bladder. Br J Urol 31:78-86, 1959 2. Hammer B: Spontaneous rupture of the bladder. Br J Urol 33:289-291, Sep 1961 3. Thompson IM, Johnson EL, Riss G Jr: The acute abdomen of recognized bladder rupture. Arch-Surg 90:371-374, Mar 1965 4. Duncan HJ: Spontaneous rupture of the bladder. S Afr Med J 37:657-658, Jun 1963 5. Hughes JP, Gambee J, Edwards C: Perforation of the bladder-A complication of long-dwelling Foley catheter. J Urol 109: 237, 1973 6. Root HD, Hariser CW, McKinley CR, et al: Diagnostic peritoneal lavage. Surgery 57:633, 1965 7. Janieson RM: Surgical management of the neurogenic bladder and its complications. Br J Clin Pract 23:359-363, Sep 1969 8. Comarr AE: Present day treatment of the traumatic cord neurogenic bladder. J Urol 83:34-38, Jan 1960
after 22 days of treatment. No side effects or systemic toxicity were observed from intravenous infusion of 1.2 grams per day for 30 days by European investigators. The highest dosage used intravenously in Europe was 1.2 grams per day in divided doses. Due to the severe disseminated disease in this black patient, the intravenous dose was carried from 200 mg to 800 mg every eight hours. The dosage of 600 mg every eight hours was well tolerated. There were no immediate local or systemic side effects and no hematologic or biochemical abnormalities after a total of 68.4 grams of miconazole was given in 59 days. The serum concentration of the drug, after 400 mg intravenous miconazole, was 0.42 micrograms per ml after 21/2 hours, and 0.22 micrograms per ml after 7½/2 hours, respectively. However, no attempt was made to use the serum level of miconazole as a guide for daily dosage administration. In our mycology laboratory, the minimal fungicidal concentration of miconazole in vitro was 0.218 micrograms per ml. Despite its early investigational status and unknown potential for delayed side effects, the dramatic effectiveness of miconazole in a patient with coccidioidal osteomyelitis and disseminated abscesses and granulomata makes it worthy of further clinical trial.
Summary A fulminating case of disseminated coccidioidomycosis in a black man was refractory to amphotericin B therapy, but successfully treated with miconazole. No immediate side effect or toxicity was observed with intravenous doses of up to 1.8 grams per day. The safety and effectiveness of this drug are worthy of further clinical study. REFERENCES 1. Miller RP, Bates JH: Amphotericin B toxicity-A follow-up report of 53 patients. Ann Intern Med 71:1089-1095, Dec 1969 2. Bennett JE: Chemotherapy of systemic mycoses. N Engl J Med 290:30-32, Jan 1974 3. Godefroi EF, Heeres J, Gutesm JN, et al: The preparation and antimycotic properties of derivatives of L-phenethylimidazole. J Med Chem 12:784-791, Sep 1969 4. Brugmans JP, van Cutsem J, Heykants J, et al: Systemic antifungal pitential, safety, biotransport and transformation of miconiazole. Eur J Clin Pharmacol 5:93-99, 1972 5. Van Cutsem JM, Thienpont D: Miconazole, a broad-spectrum antimycotic agent with antibacterial activity. Chemotherapy 17: 392-404, 1972 6. Scheef W, Symoens J, Van Camp K, et al: Chemotherapy of candidiasis. Br Med J 1:78, Jan 1973 7. Daneels R, Demeyere R, Egger L, et al: Treatment of systemic candidiasis with miconazole. Med Welt 25:428-429, 1974 8. Zazgornik J, Schmidt P, Kopsa H, et al: Successful treatment of Candida albicans septicemia after kidney transplantation. Dtsch Med Wochenschr 98:15-17, 1973 9. Hoeprich PD, Goldstcin E: Miconazole therapy for coccidioidomycosis. JAMA 230:1153-1157, Nov 1974
64
JANUARY 1976 * 124 * 1
Refer to: Garfinkle SE, Chiu GW, Cohen SE, et al: Spontaneous perforation of the neurogenic urinary bladder. West J Med 124:64-66, Jan 1976
Spontaneous Perforation of the Neurogenic Urinary Bladder SYDNEY E. GARFINKLE, MD GEORGE W. CHIU, MD SHELDON E. COHEN, MD EARL F. WOLFMAN, JR., MD Davis, California
ALTHOUGH SPONTANEOUS PERFORATION of the bladder has been reported in the literature,1-4 little attention has been focused on its occurrence in patients with neurogenic bladder disturbances. Two cases of peritonitis due to spontaneous intraperitoneal perforation of the urinary bladder in neurologically handicapped patients were recently seen on the general surgical service at the University of California, Davis, Sacramento Medical Center.
Reports of Cases CASE 1. A 21-year-old man sustained a fracture dislocation of the fourth and fifth cervical vertebrae in an automobile accident. The injury resulted in a spastic paralysis below the level of the sixth cervical vertebra. While the patient was in hospital, urinary drainage was instituted with an indwelling urethral catheter. Two years later the patient was readmitted for treatment of sacral decubiti and multiple bladder calculi. Cystogram disclosed a "Christmas tree" appearance of the bladder and bilateral ureteral reflux. Intravenous pyelogram showed small radiopaque calculi in the right renal pelvis. Results of cystometric examination were consistent with a spastic neurogenic bladder. A cystolithalopaxy was done. Postoperatively, the indwelling catheter was removed and From the Department of Surgery, University of California, Davis, School of Medicine. Submitted May 12, 1975. Reprint requests to! S. E. Garfinkle, MD, Department of Surgery, University of California, Davis, School of Medicine, Davis,
CA 95616.
CASE REPORTS
the patient discharged with condom catheter drainage. Eight months later the patient was readmitted with pneumonia. Following this admission, nausea, vomiting and abdominal distention occurred, and findings on roentgenograms of the abdomen were compatible with an ileus. Surgical consultation was obtained, abdominal paracentesis carried out and grossly purulent material was aspirated. Celiotomy was done and a perforation of a bladder wall abscess was found. The necrotic portion of the bladder was excised, the defect closed and a suprapubic cystostomy established. The postoperative course was complicated by an episode of septic shock and disseminated intravascular coagulation. Intermittent episodes of sepsis finally resolved following ureteroileostomy.
*vi.
4
........... e
,
?
;AC 8 04
4'
Figure 1.-Photomicrograph of bladder in area of perforation in Case 2 showing pronounced inflammatory changes.
...
£
..
Figure 2.-Cystogram (Case 2) showing extravasation of contrast from bladder into peritoneal cavity.
CASE 2. A 74-year-old woman entered the emergency department with a 24-hour history of abdominal pain and progressive obtundation. One episode of vomiting had occurred before admission. Bowel movements had been regular. The remainder of the gastrointestinal history was negative. Five years previously, cerebral thrombosis resulted in a right hemiparesis, chronic organic brain syndrome and urinary incontinence. Catheter drainage of the urinary bladder was instituted, but the catheter was repetitively removed by the patient. On admission the patient was cachectic and obtunded with a blood pressure of 80/0 mm of mercury. A supraventricular tachycardia of 170 per minute and a temperature of 38.9°C (102°F) rectally were present. Positive physical findings included (1) flexion contractures of the hips and knees, (2) a protodiastolic gallop rhythm and (3) abdominal tenderness in' the right lower quadrant with voluntary muscle guarding in both lower abdominal quadrants. Intestinal sounds were normal. Results of rectal and pelvic examinations were within normal limits. A hemoglobin determination was 14.9 grams per 100 ml, and the leukocyte count was 3,400 per cu mm with 52 percent nonsegmented neutrophils, 3 percent segmented neutrophils and toxic granulations of the neutrophils. A nonspecific intestinal gas pattern with no free intraperitoneal air was present on the abdominal roentgenogram. Electrocardiographically, a sinus tachycardia and left bundle branch block were noted to be present. Resuscitative measures were instituted with the intravenous administration of fluids, antibiotics (penicillin and garramycin) and hydrocortisone. After ten hours of treatment, pulse rate diminished to 128 per minute, blood pressure increased to 120/90 mm of mercury and central venous pressure rose from 0 to 11 cm of water. Abdominal paracentesis yielded grossly purulent material. At operation a perforated, necrotic diverticulum of the bladder wall was excised (Figure 1), the defect closed and a suprapubic cystostomy established. The patient improved and was discharged on the 21st postoperative day. One month later the patient was readmitted to the hospital, having removed the suprapubic tube 48 hours earlier. On physical examination, signs of an acute condition within the abdomen were present. Cystography (Figure 2) showed intraperitoneal extravasation of the dye from the urinary bladder. On operation, a new perforation in THE WESTERN JOURNAL OF MEDICINE
65
CASE REPORTS
the area of the previous bladder closure without disruption of the suture line was noted. The new perforation was closed and suprapubic cystostomy reestablished. The postoperative course was uncomplicated.
Discussion Previous reports of spontaneous perforation of the urinary bladder have emphasized chronic infection, bladder outlet obstruction' and indwelling urethral catheters' as etiologic factors. Cystography has been recommended as a diagnostic aid.:' The mortality rate associated with spontaneous perforation has ranged from 47 to 57 percent.'' The difficulty in establishing diagnosis early, however, has not been widely appreciated, nor has the neurogenic bladder itself been emphasized as an underlying factor in spontaneous perforation. The patients in cases presented are representative of a large number of neurologically handicapped persons living today. Because of improved rehabilitation techniques, patients with neurologic deficits are living longer and presenting a previously undocumented spectrum of disease peculiar to paralyzed patients. The lack of conventional response to pain following spinal cord injury or cerebrovascular thrombosis decreases the diagnostic accuracy of a history and physical examination in acute abdominal emergencies, and the subsequent delay in diagnosis increases the morbidity and mortality rates. Infections and obstructive urinary tract complications are well documented in the long term management of patients with neurogenic bladder.78 Spontaneous perforation may also occur. In such cases, patients may present with unexplained fever or ileus. We have found that the use of diagnostic abdominal paracentesis has made earlier diagnosis of peritonitis possible in neurologically handicapped patients. Abdominal paracentesis as described by Root13 can also be used when abdominal distention is present. In such instances the paracentesis catheter is placed intraabdominally under direct
66
JANUARY 1976 *
124 *
1
vision through a small midline abdominal incision. Fluid obtained is cultured and analyzed for red and white blood cell determinations, amylase and bile. If less than 30 ml is aspirated, lavage of the peritoneal cavity with 20 ml per kg of body weight of Ringer's lactate solution (maximum of 1,000 ml) is carried out, followed by aspiration of the infused fluid. We are currently evaluating criteria for the 'diagnosis of' peritonitis when the fluid aspirated is not grossly purulent. Operative treatment of a perforated neurogenic bladder consists of excision of the necrotic bladder with primary closure of the defect and suprapubic drainage. Long-term measures to prevent perforation of such bladders include treatment of established urinary tract in'fections and prevention of urinary retention by catheter drainage, transurethral resection of the bladder neck or supravesical diversion.
Summary Two cases of spontaneous perforation of a neurogenic bladder are presented. The problem of early diagnosis in neurologically handicapped patients is discussed, abdominal paracentesis is emphasized as a diagnostic aid and the emergency operative treatment of 'perforated bladder is outlined. This diagnosis should be considered in the evaluation of an acute condition within the abdomen, a fever of unknown origin or an unexplained ileus in patients with neurologic deficits. REFERENCES 1. Bastable JRY, DeJode LR, Warren RP: Spontaneous rupture of the bladder. Br J Urol 31:78-86, 1959 2. Hammer B: Spontaneous rupture of the bladder. Br J Urol 33:289-291, Sep 1961 3. Thompson IM, Johnson EL, Riss G Jr: The acute abdomen of recognized bladder rupture. Arch-Surg 90:371-374, Mar 1965 4. Duncan HJ: Spontaneous rupture of the bladder. S Afr Med J 37:657-658, Jun 1963 5. Hughes JP, Gambee J, Edwards C: Perforation of the bladder-A complication of long-dwelling Foley catheter. J Urol 109: 237, 1973 6. Root HD, Hariser CW, McKinley CR, et al: Diagnostic peritoneal lavage. Surgery 57:633, 1965 7. Janieson RM: Surgical management of the neurogenic bladder and its complications. Br J Clin Pract 23:359-363, Sep 1969 8. Comarr AE: Present day treatment of the traumatic cord neurogenic bladder. J Urol 83:34-38, Jan 1960
