Ruud Bosch

Drug-induced urinary retention: incidence, management and prevention.

Urinary retention is a condition in which impaired emptying of the bladder results in postvoidal residual urine. It is generally classified into ‘acute’ or ‘chronic’ urinary retention. Because of the complex mechanism of micturition, many drugs can interact with the micturition pathway, all via different modes of action. Although the incidence of urinary retention, in particular acute urinary retention, has been well studied in observational studies and randomized controlled trials, data on the incidence of drug-induced urinary retention are scarce. Data from observational studies suggest that up to 10% of episodes might be attributable to the use of concomitant medication. Urinary retention has been described with the use of drugs with anticholinergic activity (e.g. antipsychotic drugs, antidepressant agents and anticholinergic respiratory agents), opioids and anaesthetics, α-adrenoceptor agonists, benzodiazepines, NSAIDs, detrusor relaxants and calcium channel antagonists. Elderly patients are at higher risk for developing drug-induced urinary retention, because of existing co-morbidities such as benign prostatic hyperplasia and the use of other concomitant medication that could reinforce the impairing effect on micturition. Drug-induced urinary retention is generally treated by urinary catheterization, especially if acute, in combination with discontinuation or a reduction in dose of the causal drug. Studies have been carried out examining the effects of preventive measures for anaesthesia-related urinary retention, both during and after surgery, particularly into the effect of using opioids in combination with non-opioid analgesic drugs on the incidence of postoperative urinary retention. Although combination therapy reduces the opioid-related adverse events, the effect on urinary retention yields contradictory results. This article reviews the literature on drug-induced urinary retention and focuses on its incidence, the different classes of drugs that have been associated with it, and options for its management and prevention.

Acetylcholine as a Possible Neurotransmitter in Penile Erection

We investigated the erectile response to intracavernous injection of increasing doses of acetylcholine (0.5 to 500 micrograms.) in 10 monkeys. To differentiate between nicotinic (ganglionic) and muscarinic (parasympathetic postganglionic) effects, acetylcholine was likewise administered after 1.6 mg. trimethaphan camsylate and 0.1 mg. atropine, alone or sequentially. Erections were induced by cavernous nerve stimulation before and after atropine. Acetylcholine induced a dose-dependent, triphasic erectile response: a first tumescence phase followed by contraction and a subsequent second phase of tumescence. Atropine reduced but did not abolish the erectile response to acetylcholine: attainment of maximal intracavernous pressure after neurostimulation was both delayed and reduced (mean 25 cm. H2O). Only after combined nicotinic and muscarinic blockade was the erectile response to acetylcholine completely abolished. Histologic staining for acetylcholinesterase in five additional monkeys that had not received acetylcholine showed dense staining within the cavernous erectile tissue and around the cavernous arteries. Our data suggest that acetylcholine is a possible neurotransmitter for penile erection in monkeys.

A possible role for calcitonin-gene-related peptide in the regulation of the smooth muscle tone of the bladder and penis.

We investigated the effect of calcitonin-gene-related peptide (CGRP) on bladder contractions and penile erection in 12 dogs. In a system in which the arteries were tied bilaterally to ensure delivery of high drug levels to the bladder, arterial injections of CGRP significantly reduced the peak intravesical pressure of bladder contractions induced by pelvic nerve stimulation or arterial injection of carbachol. When given intravenously, CGRP had no effect on bladder contractions consequent to neural stimulation. Intravesical instillation of CGRP, however, reduced the bladder contractions significantly. Histologic staining showed CGRP-immunoreactive nerve fibers within the smooth muscle layers of the bladder wall. Intracavernous CGRP increased cavernous arterial flow and induced cavernous smooth muscle relaxation and venous outflow occlusion. Muscarinic blockade had no effect on the canine intracavernous pressure response to intracavernous injection of CGRP. Histologic staining for CGRP-immunoreactivity showed nerve-fiber-like staining within the cavernous arterial wall, the nerves running near the cavernous arteries, and the cavernous smooth muscles. Our results suggest a possible role for CGRP in the regulation of the smooth muscle tone of the bladder and penis.

Local and systemic effects of chronic intracavernous injection of papaverine, prostaglandin E1, and saline in primates

To compare the local and systemic effects of chronic intracavernous injection of papaverine, prostaglandin E1, and saline on erectile tissue, eight pigtail monkeys underwent 75 injections over a nine-month period. Monkeys were divided into three groups; each group received papaverine (10 mg.), prostaglandin E1 (20 micrograms.), or saline (one ml.). The erectile response was closely observed for two hours after each injection to monitor the onset, degree, and duration of erection. Liver function tests were performed every three months to detect early systemic metabolic changes. After sacrifice, the simian penises were perfused in situ and examined histologically with both light and electron microscopy. Papaverine resulted in an initially strong erectile response, but this was maintained throughout the length of the study in only two monkeys. In contrast, prostaglandin E1 resulted in tumescence that was maintained in all monkeys over the nine-month period. In addition, the papaverine group had elevated liver enzymes and significant histologic changes with loss of normal architecture on both light and electron microscopy. The other two groups showed only minimal histologic changes or none.

Percutaneous Nephrolithotomy: Factors Associated with Fever After the First Postoperative Day and Systemic Inflammatory Response Syndrome

OBJECTIVE Fever after the first postoperative day (POD1) after percutaneous nephrolithotomy (PCNL) is most likely caused by an infection that increases hospital stay and healthcare costs. The aim of this study was to find factors associated with fever after POD1 and systemic inflammatory response syndrome (SIRS). PATIENTS AND METHODS Ninety patients underwent 117 PCNLs. Patient characteristics, stone burden, and pre- and postoperative treatments were analyzed for association with fever (temperature >or=38 degrees C) and SIRS using univariate analysis. RESULTS In 35% of the patients with fever (temperature >or=38 degrees C), fever was present after POD1. Twelve patients developed signs of SIRS (11.2%). In univariate analysis, significant association was observed between fever after POD1 and previous ipsilateral PCNL (p = 0.022, odds ratio OR = 3.1), and between SIRS and paraplegia (p = 0.005, OR = 10.7) and caliceal stones (p = 0.03, OR = 4.8). CONCLUSIONS Previous ipsilateral PCNL increases the risk of fever after POD1. Paraplegic patients are at risk for developing SIRS after PCNL.

Penile detumescence: characterization of three phases.

In 22 dogs in which erection was induced by cavernous nerve stimulation, we analyzed the intracavernous pressure changes during detumescence without and with acute clamping of the aorta or electrostimulation of the lumbar sympathetic chains. Additionally, the degree of venous outflow obstruction was assessed by saline perfusion of the cavernous body during aortic occlusion. Detumescence had three distinct phases: an initial phase exhibiting a small pressure increase; a second phase showing a slow pressure decrease; and a third phase in which a fast decrease occurred. The first phase was abolished by aortic clamping, whereas the other phases were not significantly affected. Sympathetic stimulation abolished or prevented the second phase. Perfusion of the cavernous body during the second phase resulted in a pressure rise to off-scale values; however, when initiated during the terminal phase or in the nonstimulated penis, the pressure increase was slight. Our study indicates that the arterial flow rate influences the duration of the first phase of detumescence and that venous drainage is completely restored in the third phase. Furthermore, sympathetic stimulation causes an almost immediate full restoration of venous drainage, as cavernous perfusion initiated with an intracavernous pressure about twice as high as without sympathetic stimulation failed to increase pressure to off-scale values.

CALCITONIN GENE-RELATED PEPTIDE: POSSIBLY NEUROTRANSMITTER CONTRIBUTES TO PENILE ERECTION IN MONKEYS

The distribution of calcitonin gene-related peptide (CGRP) immunoreactivity in the cavernous tissue and the erectile response to intracavernous injection of CGRP was investigated in 7 monkeys. Intracavernous CGRP increased cavernous arterial flow and induced cavernous smooth muscle relaxation and venous outflow occlusion. Intracavernous injection of CGRP antibody did not significantly change the erectile response to cavernous nerve stimulation. Histologic staining for CGRP immunoreactivity showed nerve fiber-like staining within the cavernous arterial wall and the cavernous smooth muscles. These data suggest that CGRP may contribute to penile erection in monkeys.

The Effect of Venous Incompetence and Arterial Insufficiency on Erectile Function: An Animal Model

We designed an animal model to elucidate the effect of venous leakage and arterial insufficiency on erectile function. In 10 dogs, electrodes were implanted around the cavernous nerves for electroerection and blood flow in the internal pudendal artery was recorded. Venous leakage was mimicked by inserting needles of varying gauges (30 to 16G) into the corpus cavernosum and the erectile response to neurostimulation was recorded before and after the creation of the leak. The relationship between the size and the amount of the venous leakage, the changes in the intracavernous pressure (peak and drop), and the changes in the peak and maintenance arterial blood flow were documented. Arterial blood flow was then reduced by 25 and 50 per cent by means of a screw clamp on the terminal aorta. The erectile response to neurostimulation was again determined, with the same electrical parameters, first with reduced blood flow alone, then in combination with leakage of varying size. Our results showed that minor cavernous vein leakage in the presence of normal arterial flow and a healthy sinusoidal system had a minimal effect on erectile function owing to a compensatory increase in penile blood flow. However, when reduction of arterial blood flow was superimposed on venous leakage, even of a minor degree, the erectile response to neurostimulation was markedly impaired.

Quantification of changes in detrusor function and pressure-flow parameters after radical prostatectomy: Relation to postoperative continence status and the impact of intensity of pelvic floor muscle exercises†‡

We aim to quantify changes in detrusor function and pressure‐flow parameters after radical retropubic prostatectomy (RRP) and to determine the impact of the level of intensity of pelvic floor muscle exercises (PFME) on these changes. We also tried to identify preoperative urodynamic factors, predictive of postoperative continence status.

The sympathetic role as an antagonist of erection

SummaryThe effects of the lumbar and pelvic sympathetic system on penile erection were studied in a canine model. Erection was induced by cavernous nerve stimulation and detumescence by sympathetic trunk stimulation. Erection induced by cavernous nerve stimulation normally subsides slowly. After discontinuation of electrical stimulation the intracavernous pressure drops within a mean of 291 s to 50% and after a mean of 372 s to 10% of the highest level. However, stimulation of the sympathetic trunk at the level of L4-S1 applied directly after discontinuation of cavernous nerve stimulation accelerated this drop of intracavernous pressure significantly: to 50% after a mean of 19 s and to 10% after a mean of 36 s. If stimulation of the sympathetic trunk was initiated 20 s before cavernous nerve stimulation, the pressure rise was aborted completely. Neurostimulation of the hypogastric nerves alone or in combination with cavernous nerve stimulation did not change the intracavernous pressure. These results were not altered after neurotomy of the pudendal or hypogastric nerves. The main pathway of the fibers from the sympathetic trunk to the penis seems to run via the pelvic plexus. The stimulation voltage and frequency to induce erection or detumescence were equivalent. Our results suggest that an elevated central sympathetic tone may be one of the causes of psychogenic impotence.