Pregnancy outcomes following gestational exposure to papaverine: An observational comparative study.

AIMS: Papaverine is indicated for abdominal pain of various aetiologies. However, data on maternal and foetal safety following gestational exposure are lacking. The aim was to examine whether first trimester exposure to papaverine is associated with increased risk for major malformation and whether gestational exposure at any stage is associated with increased risk for preterm delivery, lower birthweight, small for gestational age, caesarean section (CS), lower Apgar score and perinatal death. METHODS: A retrospective comparative study consisted of pregnant women treated with papaverine between February 2010 and October 2019 at a large tertiary center. The control group comprised of livebirth deliveries randomly selected from the institutional obstetric database. RESULTS: The study group consisted of 498 pregnancies, which resulted in 537/544 (98.7%) live births, of whom 46/537 (8.6%) were exposed during the first trimester. The control group consisted of 498 pregnancies and 514 live births. Rate of major malformations did not differ between study group (2/46, 4.3%) and control (25/315, 4.9%, P = .67). Papaverine exposure was associated with higher rate of preterm delivery (22.3 vs. 10.3%, P < .001), CS (35.9 vs. 24.1%, P < .001) and lower birth weight (3207 vs. 3246 g, P = .02). Adjustment for treatment indication demonstrated that these remained significant only when given for obstetrical/surgical aetiologies. Comparable rates were observed for the remaining outcomes. CONCLUSIONS: Short-term gestational exposure to papaverine adjusted for indication was not associated with preterm deliveries, CS, lower birthweight, small for gestational age or perinatal death. Rate of major malformations among 46 first trimester exposures was comparable to controls.

Clinical Efficacy of Intracoronary Papaverine After Nicorandil Administration for Safe and Optimal Fractional Flow Reserve Measurement.

Fractional flow reserve (FFR) is considered the standard for assessment of the physiological significance of coronary artery stenosis. Intracoronary papaverine (PAP) is the most potent vasodilator used for the achievement of maximal hyperemia. However, its use can provoke ventricular tachycardia (VT) due to excessive QT prolongation. We evaluated the clinical efficacy and safety of the administration of PAP after nicorandil (NIC), a potassium channel opener that prevents VT, for optimal FFR measurement.A total of 127 patients with 178 stenoses were enrolled. The FFR values were measured using NIC (NIC-FFR) and PAP (PAP-FFR). We administered PAP following NIC (NIC-PAP). Changes in the FFR and electrogram parameters (baseline versus NIC versus PAP) were assessed and the incidence of arrhythmias after PAP was evaluated. In addition, we analyzed another 41 patients with 51 stenoses by assessing the FFR using PAP before NIC (PAP-NIC). After propensity score matching, the electrogram parameters between 2 groups were compared.The mean PAP-FFR was significantly lower than the mean NIC-FFR (0.82 ± 0.11 versus 0.81 ± 0.11, P < 0.05). The mean baseline-QTc, NIC-QTc, and PAP-QTc values were 425 ± 37 ms1/2, 424 ± 41 ms1/2, and 483 ± 54 ms1/2, respectively. VT occurred in only 1 patient (0.6%). Although PAP induced QTc prolongation (P < 0.05), the PAP-QTc duration was significantly shorter in NIC-PAP compared to PAP-NIC (P < 0.05).The administration of PAP with NIC may induce sufficient hyperemia and prevent fatal arrhythmia through reductions in the PAP-induced QTc prolongation during FFR measurement.

Superior mesenteric artery syndrome coexists with Nutcracker syndrome in a female: a case report.

BACKGROUND: Superior mesenteric artery (SMA) syndrome, also known as Wilkie's syndrome or Benign duodenal stasis, is a rare benign disease. It could threaten the life if the manifestation is severe and the treatment is inappropriate. In the patients with SMA syndrome, the third portion (transverse part) of the duodenum is compressed externally between the SMA and abdominal aorta (AA) leading to duodenal stasis and gastrointestinal obstruction. SMA syndrome may rarely combine with Nutcracker syndrome when left renal vein (LRV) was compressed between SMA and AA. CASE PRESENTATION: A 32-year-old female patient presented with complaints of gradually severe bloating, epigastric pain, left flank ache, nausea and occasional vomiting of 1 month's duration. The epigastric and left flank ache was aggravated when the patient was supine and relieved in a prone or left lateral decubitus. The abdominal bloating was associated with early satiety. The vomiting always started 40 min after meal. The patient gave a history of urine stone with drotaverine hydrochloride tablets treatment for two weeks before the gastrointestinal symptoms arising. The patient had no significant surgical history, but had a rapid weight loss of approximately 10 kg with a body mass index (BMI) from 21 kg/m2 to less than 18 kg/m2 over the last two months. An abdominal examination revealed upper abdominal tenderness and distention. The urine routine examination showed no significant abnormality. The findings of initial blood tests and other laboratory investigations were unremarkable. CONCLUSIONS: This case reports a female patient with SMA syndrome with Nutcracker syndrome predisposed by Antispasmodics. We highlight the importance of the combination therapy of long-term nutritional supporting and prokinetic agents. Rehabilitating practice after discharge is beneficial to reduce recurrence.

Efficacy and safety of fixed-dose combination of drotaverine hydrochloride (80 mg) and paracetamol (500 mg) in amelioration of abdominal pain in acute infectious gastroenteritis: A randomized controlled trial.

BACKGROUND AND AIM: This randomized controlled trial was undertaken to assess efficacy and safety of fixed-dose combination of drotaverine hydrochloride (80 mg) and paracetamol (PCM) (500 mg). This was performed by comparison of mean pain intensity difference, total pain relief at 2 h, onset of pain relief, decrease in number of pain episodes, global improvement, and adverse effects. METHODS: A randomized double-blind controlled trial for adults between 18 and 59 years of either gender with acute infectious diarrhea (≥ 3 unformed, watery, or soft stools with symptoms at least within the last 24 h preceding randomization with duration of illness not more than 72 h) with moderate-to-severe abdominal pain. Participants were treated with either a fixed-dose combination of oral drotaverine hydrochloride (80 mg) and PCM (500 mg) or oral PCM (500 mg) three times a day for 3 days. RESULTS: Of 252 (126 in each group) participants, all received at least one dose of medication. Two hundred forty-two completed the study. Mean pain intensity difference at 60 min after administration of study medication by Visual Analogue Scale (VAS) and total pain relief at 2 h using both VAS and Verbal Rating Scale showed statistically significant improvement in drotaverine hydrochloride (80 mg) and PCM (500 mg) group. The onset of pain relief was also significantly better in drotaverine hydrochloride (80 mg) and PCM (500 mg) group when using VAS. CONCLUSION: Fixed-dose combination of drotaverine hydrochloride (80 mg) and PCM (500 mg) is an effective and safe antispasmodic agent in abdominal pain associated with acute infectious gastroenteritis.

Evaluation of the risk factors for ventricular arrhythmias secondary to QT prolongation induced by papaverine injection during coronary flow reserve studies using a 4 Fr angio-catheter.

Estimation of the fractional flow reserve (FFR) is considered to be an established method by which to assess stable coronary artery stenosis. Induction of maximal coronary hyperemia is important during the FFR procedure. Papaverine has been reported to increase the risk of ventricular arrhythmia (VA). The purpose of the present study was to discover predictors of papaverine-induced VAs developing during FFR measurement. A total of 213 clinically stable patients were included in the study. FFRs were determined after intracoronary papaverine administration (12 mg into the left and 8 mg into the right coronary arteries). We compared patients in whom VA did and did not develop in terms of clinical and electrocardiogram characteristics. FFR measurements were performed on 244 lesions (133 in the left anterior descending arteries, 43 in the left circumflex arteries, and 68 in the right coronary arteries). We found that the QTc interval was prolonged in all patients after papaverine administration (average post-administration QTc interval = 569 ± 89 ms; average ΔQTc interval = 144 ± 80 ms). VA developed in three patients with significantly prolonged QT intervals (average post-administration QTc interval = 639 ± 19 ms, average ΔQTc interval = 220 ± 64 ms, p < 0.02) and transitioned from torsade de pointes to ventricular fibrillation. Bradycardia (< 50 beats/min), hypokalemia (serum K < 3.5 mEp/L), and low left ventricular function (ejection fraction (EF) < 50%) were associated with VA (bradycardia, p < 0.01; hypokalemia, p < 0.01; low left ventricular function, p < 0.01). Three-vessel disease was significantly predictive of VA (p < 0.003). In the three-vessel group, the complications of low left ventricular function, hypokalemia, and bradycardia were significantly associated with VA (p < 0.045). Three-vessel disease is a predictor of the development of VA during FFR measurement performed with the aid of papaverine, especially if accompanied by one or more of the following: low left ventricular function, hypokalemia, or bradycardia.

Sinus Standstill in a Patient after Intracoronary Papaverine Administration for a Coronary Fractional Flow Reserve.

A 78-year-old woman had paroxysmal atrial fibrillation and effort angina. Two months before she was admitted for a coronary angiography, she had been feeling dizzy. A Holter 24-hour electrocardiography monitor exhibited an asymptomatic episode of 2.9 seconds of RR interval. She underwent a coronary angiography, which showed intermediate stenosis in the left descending artery. Fractional flow reserve (FFR) measurement using intracoronary papaverine administration was performed. After intracoronary papaverine (12 mg) administration, pause of 4 seconds led to polymorphic ventricular tachycardia (VT), although the VT terminated spontaneously. Premature ventricular beat occurred and led to sustained polymorphic VT. In cardiac electrophysiology study, pacing from the right atrium showed that the maximum sinus node recovery time (SRT) was 910 ms. After procainamide (10 mg/kg) administration, the maximum SRT was 16.3 seconds with some junctional escapes. After intravenous papaverine administration, there was a slight change. Intracoronary papaverine administration induced about 9-seconds pause with some junctional escapes. We conclude that intracoronary papaverine administration reveals potential sinus node dysfunction. The patient has been asymptomatic since the implantation of the pacemaker. Patients with suspicious sinus dysfunction should be careful.

Etiological factors and management in priapism patients and attitude of emergency physicians.

OBJECTIVE: To present the underlying etiological factors in patients referring with priapism, sharing how they are managed according to etiology and priapism type together with our experiences, creating awareness so that urologists and emergency physicians may play a more active role together in priapism management. MATERIALS AND METHODS: Patients referring to emergency service with priapism were examined. Penile Doppler ultrasonography (PDU) and/or corporeal aspiration and blood gas analysis were made in order to determine priapism type after anamnesis and physical examination. The most appropriate treatment option was chosen and applied on the patients considering priapism type, underlying etiological factors and priapism time. Presence of a statistical difference between etiological factors causing priapism, priapism type and applied treatment methods was calculated using Chi square (χ2) test. RESULTS: A total of 51 patients referring to emergency service with priapism attacks for 53 times were included in the evaluation. When compared to other etiological factors, number of priapism cases developing secondary to papaverine after PDU was found statistically significantly high (p < 0.001). Ischemic priapism ratio was detected statistically higher compared to other groups (p < 0.001). Aspiration and/or irrigation treatment were the most common method used for treatment at a statistically significant level (p < 0.001). All patients (100%) were hospitalized in urology service without applying any treatment in emergency service and had treatment and intervention under the control of the urologist. CONCLUSIONS: Application of non-invasive treatments in suitable priapism patients would protect patients from invasive painful interventions. We believe that emergency physicians should be more effective in priapism phase management and at least noninvasive treatment phase.

Papaverine-induced polymorphic ventricular tachycardia during coronary flow reserve study of patients with moderate coronary artery disease.

BACKGROUND: Papaverine is useful for evaluating the functional status of a coronary artery, but it may provoke malignant ventricular arrhythmia (VA). The aim of this study was to investigate the incidence, and clinical and ECG characteristics of patients with papaverine-induced VAs. METHODS AND RESULTS: The 182 consecutive patients underwent fractional flow reserve (FFR) measurement of 277 lesions. FFR was determined after intracoronary papaverine administration by standard procedures. The clinical and ECG characteristics were compared between patients with and without ventricular tachycardia (VT: ≥3 successive premature ventricular beats (PVBs), or ventricular fibrillation (VF)). After papaverine administration, the QTc interval, QTUc interval, and T-peak to U-end interval were prolonged significantly. Single PVBs on the T-wave or U-wave type developed in 29 patients (15.9%). Polymorphic VT (torsade de pointes) occurred in 5 patients (2.8%), and of those, VF developed in 3 patients (1.7%). No clinical and baseline ECG parameters were predictors for VT or VF except for sex and administration of papaverine into the left coronary artery. Excessive prolongation of QT (or QTU), T-peak to U-end intervals and giant T-U waves were found immediately prior to the ventricular tachyarrhythmias (VTAs), which were unpredictable from the baseline data. CONCLUSIONS: Intracoronary administration of papaverine induced fatal VTAs, although the incidence is rare. Excessive prolongation of the QT (and QTU) interval appeared prior to VTAs; however, they were unpredictable.

Effects of drotaverine hydrochloride on viability of rat cultured cerebellar granulocytes.

The neurocytotoxic effect of drotaverine hydrochloride was studied in culture of rat cerebellar granulocytes. Incubation of cells with 100 and 250 µM drotaverine reduced neuronal survival to 60 and 4%, respectively.

[Application of alpha1-adrenoblockers in treatment of ureteral calculi].

The results of evaluation of the efficacy of alpha1-adrenoblockers in treatment of ureteral calculi are presented. Comparative, prospective, placebo-uncontrolled nonrandomized single-center study was performed, which included 118 patients with solitary diagnosed calculi in various parts of ureter. After the pain relief, all the patients underwent conservative therapy aimed at spontaneous discharge of concretions. The maximum duration of conservative treatment was 28 days. Ultrasound monitoring was performed every week in all patients. The control group of patients received only Drotaverinum 40 mg three times a day, and analgesics. The main group received alpha1-adrenoblocker tamsulosin at a standard dose of 0.4 mg once a day along with Drotaverinum and analgesics. The overall probability of a discharge of concrements localized in the distal ureter was significantly (P = 0.02) higher in the patients treated with alpha1-adrenoblockers. Treatment regimen in main group of patients allowed better control of pain during all periods of observation, even if the discharge of concretions was not registered. The overall probability of migration of concrements from the proximal to the distal ureter in main group of patients was 52% versus 32% in controls (P = 0.17). The frequency of adverse effects was comparable in both groups. Vertigo, postural hypotension, and weakness were significantly more frequent in the main group of patients. Univariate and multivariate analyses of the proportional hazards model have demonstrated that the administration of alpha1-adrenoblocker increased the likelihood of a discharge of concrement from the distal ureter. It is shown that the nature of the applied therapy has directly influence on the risk of an earlier discharge of concretions. Inclusion of alpha1-adrenoblockers in the treatment scheme increased the probability of discharge of concrements at 4.11 times.

Drotaverine to shorten the duration of labour in primigravidas: a randomised, double-blind, placebo-controlled trial.

Background: Drotaverine, a spasmolytic, has been found to have potential to achieve a reduction in the duration of labour and prevent prolonged labour. Objective: To compare the effects of intravenous drotaverine hydrochloride with placebo for shortening the duration of active phase of labour in primigravidas. Methods: A double-blind, placebo-controlled randomized trial of 246 primigravidas in active phase of labour at term was conducted. They were randomly (1:1 ratio) administered intravenous 2 ml (40mg) of drotaverine hydrochloride or 2 ml of Vitamin B complex as placebo. The primary outcome measure was the duration of active phase of labour. The secondary outcome measures were cervical dilatation rate, oxytocin augmentation rate, incidence of prolonged labour, labour pain scores, mode of delivery, maternal and neonatal outcomes. Results: The mean duration of active phase of labour (hour) was significantly lower in the drotaverine group compared to the control (drotaverine; 6.22 ± 2.41 vs placebo; 8.33 ± 3.56; p <0.001). Also, the cervical dilatation rate (cm/hr) was significantly faster in the drotaverine arm (drotaverine; 1.68 ± 1.02 versus placebo; 1.06 ± 0.53, p <0.001). There was a significantly higher probability of faster delivery among women who were given drotaverine (log-rank test, p < 0.001). The oxytocin augmentation rate, incidence of prolonged labour, labour pain scores, mode of delivery, maternal and neonatal outcomes were not significantly different among the groups. Conclusions: Drotaverine hydrochloride is effective in shortening the duration of active phase of labour without adverse maternal and neonatal outcomes. However, more evidence is needed to explore its role in active phase of labour among primigravid women. Trial registration number: PACTR201810902005232.

Physiological assessment of renal artery stenosis: comparisons of resting with hyperemic renal pressure measurements.

OBJECTIVES: We compared resting and hyperemic pressure gradients induced by intrarenal papaverine for the assessment of renal artery stenosis (RAS). We also investigated the incidence of the QT interval prolongation and ventricular arrhythmias. BACKGROUND: In the coronary circulation, maximal hyperemia is essential in determining the significance of a stenosis. In the renal circulation, the role of maximal hyperemia for the assessment of RAS has not been established. METHODS: In 55 patients with RAS (67 RAS), resting P(d)/P(a) ratio (the ratio between distal renal pressure to the aortic pressure), renal fractional flow reserve (FFR), and resting and hyperemic systolic gradients (RSG and HSG, respectively) were measured with a pressure guidewire. In a subset of 16 patients, renal vein renin activity (RVRA) was measured. RESULTS: HSG was significantly greater than RSG (20 ± 14 mm Hg vs. 9.0 ± 13 mm Hg, respectively; P < 0.001). Renal FFR was significantly lower than baseline P(d)/P(a) ratio (0.91 ± 0.06 vs. 0.94 ± 0.06 vs. respectively; P < 0.001). RVRA increased from 50 ± 66% at rest to 122 ± 112% at hyperemia, P < 0.01. At HSG of 21 mm Hg or renal FFR of 0.90, RVRA increased markedly (120%), but RVRA increased modestly (18%) when RSG was 16 mm Hg or resting P(d)/P(a) ratio was 0.93. The corrected QT intervals at baseline vs. hyperemia were not significantly different (433 ± 26 vs. 436 ± 25 msec, respectively; P = NS); no episodes of ventricular arrhythmias were noted. CONCLUSIONS: Renin production, an index of renal ischemia, was markedly greater at hyperemia than at rest, suggesting that RAS, with either an HSG of 21 mm Hg or a renal FFR of 0.90, can be considered a hemodynamically significant stenosis. Intrarenal papaverine neither prolonged the QT interval nor induced ventricular arrhythmias and the safety of which will need to be corroborated in a large study. © 2010 Wiley-Liss, Inc.

The actual incidence of papaverine-induced priapism in patients with erectile dysfunction following penile colour Doppler ultrasonography.

Penile color Doppler sonography is a valuable method for evaluating erectile dysfunction. However, there are some concerns about the safety of this method due to the intracorporeal pharmacological injection, which may cause priapism as a complication, resulting in penile fibrosis. To evaluate the actual incidence of papaverine-induced priapism in patients with erectile dysfunction (ED) who underwent penile colour Doppler sonography and to determine the safety of this diagnostic tool, a retrospective study was conducted using the database of our institution. A total of 672 men with ED underwent penile color Doppler ultrasonography with the intracorporeal injection of 60 mg papaverine hydrochloride. The patient characteristics of priapism cases were retrospectively evaluated. Priapism in 18 of the 672 patients (2.68%) was successfully treated with blood aspiration, irrigation and injection of an alpha-agonist medication, when needed. Patients with priapism were younger compared with those without priapism; mean age 45 +/- 12.51 (20-68) versus 50.93 +/- 12.04 (17-78) (P < 0.001). Penile Doppler ultrasound is a safe procedure in evaluating erectile dysfunction. The incidence of priapism, which is the most important complication of this procedure, is low and can be managed successfully with conservative approaches.

Independent Predictive Factors for Occurrence of Ischemic Priapism after Papaverine Injection.

PURPOSE: To analyze the predictive factors causing ischemic priapism following penile doppler ultrasonography (PDU) with intracavernosal papaverine injection   Materials and methods: Medical records of 467 patients who underwent PDU examination following intracavernosal papaverine injection for erectile dysfunction (ED) between 2009 and 2017 were retrospectively reviewed. Patients with hematological disease anamnesis, patients taking phosphodiesterase-5 inhibitor, patients with intracavernosal injection therapy anamnesis and patients who underwent PDU with other intracavernosal vasodilator drugs other than papaverine were excluded from the study. The remaining 268 patients were divided into two groups as priapism (38 patients) and non-priapism (230 patients). The groups were compared in terms of demographic data, American Society of Anesthesiologists (ASA) score, comorbidities, international index of erectile dysfunction (IIEF) score and PDU results. The significant parameters were analyzed with binary logistic regression analysis. The receiver operating analysis was used to obtain cut-off, sensitivity and specificity values for the independent predictive factors.    Results: The age, ASA score, diabetes mellitus, IIEF score, duration of ED, peak arterial and peak end diastolic venous flow values in the 20th minute were significantly different in the two groups (p<0.001). Binary logistic regression analysis found age, duration of erectile dysfunction, IIEF score, peak arterial flow and venous flow rate in the 20th minute were predictive variables for the occurrence of priapism.   Conclusions: Young patients, patients with good IIEF score, patients with ED for a short time, and patients with normal peak arterial and venous flows are more prone to developing post-papaverine ischemic priapism.

Confirmation of maximal hyperemia by the incremental dose of intracoronary papaverine.

We investigated the effect of the papaverine dose increment method to confirm maximal hyperemia for fractional flow reserve (FFR) measurements. We evaluated 115 consecutive patients involving 200 lesions. FFR was measured after intracoronary papaverine injection into the left (12 mg) and right (8 mg) coronary arteries as standard doses. Except for 2 patients who had ventricular tachyarrythmia (VTA), we administered a higher papaverine dose (2 mg added to the standard dose). We compared the FFR values after using different papaverine doses. VTA incidence and electrocardiogram parameters were compared according to the papaverine doses used. The QTU interval and corrected QTU were significantly prolonged after using a higher dose compared with a standard dose. VTA occurred in one patient (0.9%) at the higher dose. There was no significant difference with a strong correlation between the FFR values in the 2 doses (r = 0.963, P < 0.001). Maximal hyperemia was achieved in most patients at the standard papaverine dose. However, 19 lesions changed ischemic diagnosis at the higher dose (12 lesions changed from ischemia negative to positive, and 7 lesions changed from positive to negative). Therefore, to confirm the appropriate ischemia diagnosis for borderline FFR values, it may be favorable to perform another FFR measurement at an incremental papaverine dose.

Predictive factors of regional toxicity and serum creatine phosphokinase levels after isolated limb infusion for melanoma: a multi-institutional analysis.

BACKGROUND: Isolated limb infusion (ILI) is a minimally invasive technique delivering regional chemotherapy to treat in-transit extremity melanoma. Determining perioperative factors that could predict toxicity is important to optimize strategies to improve clinical outcomes after regional chemotherapy in melanoma. METHODS: Perioperative factors from 171 ILI patients performed at eight centers from 2001 to 2008 were reviewed. The Wieberdink limb toxicity scale and creatine phosphokinase (CK) levels were used to measure toxicity. Logistic regression analysis was used to estimate the association between toxicity and perioperative parameters. RESULTS: Mild (grades I-II) and severe (grades >or=III) limb toxicity developed in 68% and 32% of patients, respectively. Melphalan adjusted for ideal body weight (aIBW) and papaverine were used in 47% and 63% of patients, respectively. Median peak CK for all patients was 563 U/l, and median peak occurred at postoperative day 4. On univariate analysis, papaverine and high CK levels (>563 U/l) were significantly associated with higher toxicity. On the contrary, aIBW was significantly associated with a lower risk of severe toxicity. Perfusate blood gas at 30 min [pH, PaO(2), and base excess (BE) ], limb temperature, and ischemia time were not predictive of limb toxicity. On multivariate analysis, severe toxicity was associated with female sex (P = 0.01), papaverine (P = 0.01), and high peak CK levels (P < 0.01). Independent predictors of high CK levels included younger age, unadjusted melphalan dose, and low PaO(2) at 30 min. CONCLUSIONS: ILI can be performed with an acceptable morbidity. Papaverine use, female gender, and high peak CK were associated with higher limb toxicity. CK levels can be diminished significantly with aIBW.

Disruption of the blood-brain barrier by intra-arterial administration of papaverine: a technical note.

INTRODUCTION: Various endovascular techniques can be used to treat cerebral vasospasm after aneurysmal subarachnoid haemorrhage (SAH) including intra-arterial administration of vasodilator drugs such as papaverine or nicardipine and balloon dilatation of the affected vessel segment. Papaverine is known to have side effects, and we report a possible new one. MATERIALS AND METHODS: After the treatment of cerebral vasospasm in a SAH patient by intra-arterial administration of papaverine into the left posterior cerebral artery, severe mesencephalic extravasation of blood and contrast media was detected. RESULTS: After reviewing the literature, the authors conclude that interruption of the blood-brain barrier by papaverine most likely combined with a secondary hyperperfusion phenomena, and perhaps a direct toxic effect on brain tissue was the mechanism of this major complication. CONCLUSION: In treating vasospasm in areas with a high density of perforating arteries, especially in the posterior circulation, papaverine should be used cautiously because a safe regimen has yet to be established. In this situation, alternative agents such as calcium channel blockers could be considered, but evidence-based data are still missing.

Adverse effects of topical papaverine on auditory nerve function.

BACKGROUND: Papaverine hydrochloride is a direct-acting vasodilator used to manage vasospasm during various neurosurgical operations. Transient cranial nerve dysfunction has been described in a few cases with topical papaverine. This study supports previous reports and provides neurophysiological evidence of an adverse effect on the auditory nerve. METHODS: We conducted a retrospective review of 70 consecutive microvascular decompression operations and studied those patients who received topical papaverine for vasospasm. Topical papaverine was used as a direct therapeutic action to manage vasospasm in a total of 11 patients. The timing of papaverine application and ongoing operative events was reviewed relative to changes in neurophysiological recordings. Brainstem auditory evoked potentials (BAEPs) were routinely used to monitor cochlear nerve function during these operations. FINDINGS: A temporal relationship was found between topical papaverine and BAEP changes leading to complete waveform loss. The average temporal delay between papaverine and the onset of an adverse BAEP change was 5 min. In 10 of 11 patients, BAEP waves II/III-V completely disappeared within 2 to 25 min after papaverine. Eight of these 10 patients had complete loss of BAEP waveforms within 10 min. One patient showed no recovery of later waves and a delayed profound sensorineural hearing loss. The average recovery time of BAEP waveforms to pre-papaverine baseline values was 39 min. CONCLUSIONS: Topical papaverine for the treatment of vasospasm was associated with the onset of a transient disturbance in neurophysiological function of the ascending auditory brainstem pathway. The complete disappearance of BAEP waveforms with a consistent temporal delay suggests a possible adverse effect on the proximal eighth nerve. Recommendations to avoid potential cranial nerve deficits from papaverine are provided.

Drotaverine hydrochloride versus hyoscine-N-butylbromide in augmentation of labor.

OBJECTIVES: To study and compare the efficacy and side effects of drotaverine hydrochloride and hyoscine-N-butylbromide in the augmentation of labor. METHODS: A prospective randomized trial of 150 women in active labor included 50 women given drotaverine (group 1), 50 women given hyoscine-N-butylbromide (group 2), and 50 women given no medication (group 3). Duration of labor, rate of cervical dilation, mode of delivery, side effects, and neonatal outcome were compared among the groups. RESULTS: The mean duration of the active phase of labor was 4.48+/-2.26 h, 3.9+/-2.42 h, and 3.6+/-2.07 h in groups 1, 2, and 3, respectively. The mean rate of cervical dilation was 2.6 cm/h, 2.4 cm/h, and 2.5 cm/h, respectively. The differences were not statistically significant. There was no difference in the duration of the second and third stages of labor. No adverse maternal or fetal outcomes were noted. CONCLUSION: Drotaverine hydrochloride and hyoscine-N-butylbromide do not have a role in augmentation of labor.