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Thoracic epidural analgesia: What about the urinary bladder?
Trends in Anaesthesia and Critical Care 2 (2012) 138e144
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REVIEW
Thoracic epidural analgesia: What about the urinary bladder? Patrick Y. Wuethrich a, *, Fiona C. Burkhard b a b
University Department of Anaesthesiology and Pain Therapy, University Hospital Bern, Inselspital, CH-3010 Berne, Switzerland Department of Urology, University Hospital Bern, Switzerland
s u m m a r y Keywords: Thoracic epidural analgesia Urinary retention Bladder function
The impact of thoracic epidural analgesia (TEA) on lower urinary tract function, although a common observation in everyday clinical practice, has not been examined in depth. One factor often observed in patients with TEA is postoperative urinary retention (POUR). POUR is linked to several factors including age, gender, postoperative pain, type of surgical procedure, use of opioids and neuraxial anaesthesia/ analgesia. Its inadequate management can lead to urinary tract infections and/or bladder overdistension with long term debilitating morbidities and associated high costs. This paper discusses the effects and potential modulatory mechanisms of the TEA on lower urinary tract function. Ó 2012 Elsevier Ltd. All rights reserved.
1. Introduction In recent years, epidural analgesia has been shown to be an effective method of postoperative pain management,1 which facilitates postoperative rehabilitation,2 and reduces the 30-day mortality after surgery3 as well as being an established part of fast tract surgery protocols. Thoracic epidural analgesia (TEA) favourably benefits physiological functions such as respiration, coagulation, bowel function and hormonal stress response.4,5 Postoperative urinary retention (POUR) is one of the most common complications of epidural anaesthesia/analgesia with an incidence of up to 75% after major surgery.6 It is a common practice to place an indwelling catheter in the bladder of patients receiving epidural analgesia and to leave the catheter as long as the epidural analgesia is maintained despite a lack of evidence supporting this approach. However, transurethral catheterization is associated with significant morbidity such as patient discomfort, urethral trauma and urinary tract infections (UTI). Prolonged catheterization is the primary risk factor for catheter associated urinary tract infections (CAUTI) and is the most common site of nosocomial infections in the United States.7 CAUTI account for more than 1 million cases each year, 900,000 additional hospitalization days per year and are directly responsible for 13% of the deaths related to nosocomial infections.8 In addition, bacteriuria leads to unnecessary antimicrobial use and urinary catheters often serve as a reservoir for multidrug-resistant bacteria.9 For this reason, increasing focus is placed on limiting the duration of catheterization and
* Corresponding author. Tel.: þ41 316322483; fax: þ41 6320554. E-mail address: [email protected] (P.Y. Wuethrich). 2210-8440/$ e see front matter Ó 2012 Elsevier Ltd. All rights reserved. doi:10.1016/j.tacc.2012.02.003
finding methods to avoid unnecessary catheterization in perioperative medicine.10,11 This review article offers an overview of lower urinary tract function including anatomy and physiology of the lower urinary tract and outlines the impact of epidural analgesia on bladder function with a focus on TEA. 2. Anatomy and physiology of lower urinary tract The lower urinary tract is composed of two functional units: a reservoir (bladder) and an outlet (bladder neck, urethra and urethral sphincter). The two essential functions of the lower urinary tract are to store and periodically expel liquid waste. An average adult human empties the bladder 5e7 times a day and has a bladder capacity of about 400e500 ml. The predominant role of the bladder is to store urine at low pressure even during filling to capacity. When necessary the bladder is also dynamic and able to empty essentially any volume at any time and as often as necessary in a short time by actively contracting. Normal lower urinary tract function requires the integrity of the central and peripheral nervous systems supplied by the somatic and autonomous systems which are under both voluntary and involuntary control. 2.1. Anatomy of the lower urinary tract The bladder is a hollow smooth muscle organ, composed of the bladder body located above the ureteral orifices and the base, consisting of the trigone and the urethrovesical junction. The bladder or detrusor muscle is composed of three layers of typical smooth muscle cells, where the inner and outer layers are oriented longitudinally and the middle one circularly. This orientation is
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important because it determines the bladder’s shape and intraluminal pressure. During the storage phase, the muscle cells have to relax and to elongate for a long time interval for storage, whereas during the voiding phase they have to shorten in a synchronized way over a short time period to expel the urine as quickly as possible. The urethra allows urinary outflow to the exterior and prevents leakage of urine during storage by generating a higher pressure than in the bladder. In men, the urethra is divided into the bladder neck, prostatic, membranous, bulbar and penile sections, in women the urethra is shorter and has a more uniform structure.12 The urethra is composed of smooth muscle, striated muscle and a lamina propria which has a submucosa and a mucosal layer. Striated muscle structures compose the external urethral sphincter (also called intramural sphincter or rhabdosphincter) and contribute to the resting urethral pressure.12 Smooth muscle structures are found throughout the length of the urethra in women and in the membranous urethra in men. Circular and longitudinal layers are well defined, generating spontaneous myogenic tone. The circular muscle layer seems to play an important role in maintaining urethral pressure during the storage phase. In contrast the function of the longitudinal muscle layer is less clear: contraction of the muscle fibers may lead to shortening and opening of the urethra during micturition. The submucosal layer plays an important role in mediating the pressure generated by the muscle layers and keeping the lumen closed. This function is of particular importance in women, as it is advocated to contribute to urinary continence. 2.2. Neurophysiology of the lower urinary tract Motoneurons of both urethra and bladder are located in the sacral spinal cord (S2-4) in the nucleus of Onuf and reach the periphery through the pudendal nerves (Fig. 1).13 The detrusor smooth muscle is innervated by parasympathetic fibers, which reside in the sacral intermediolateral cell group and are located in S2-4. These fibers exit the spinal cord through the anterior roots, intermingle with somatic fibers forming the spinal nerves, continue in the anterior spinal rami and travel via the pelvic splanchnic nerves to ganglion cells in the pelvic plexus, the vesical plexus and the cavernous nerves. Cholinergic transmitters are the major excitatory mechanism in the human bladder, resulting in detrusor contraction via M3 and M2 muscarinic receptors. In contrast the trigone muscle is sparsely innervated by parasympathetic fibers, while sympathetic fibers are prevalent.14 Sympathetic fibers innervating the bladder and urethra originate in the intermediolateral cell column of the spinal cord (T11L2)13 and play an important role in promoting continence.15 These fibers exit the spinal cord by the anterior root and intermingle with somatic efferent fibers to form the spinal nerve. They either synapse in one of the nearby paravertebal ganglia or continue peripherally with associated somatic segmental fibers to reach the pelvic floor or pass directly through the paravertebral ganglia and exit as splanchnic nerves to synapse on prevertebral or collateral ganglia and then continue as the right and left hypogastric nerves which contribute to the pelvic plexus. The pelvic plexus consists of a dense network of pre- and postganglionic sympathetic and parasympathetic nerve fibers and ganglia, which give rise to, beside others, the vesical plexus to the bladder and urethra and the cavernous nerves to the urethral sphincter complex. Stimulation of a1-adrenoceptors in the bladder base and urethra by the postganglionic fibers of the sympathetic nervous system has an excitatory effect while b-adrenoreceptors lead to an inhibition of the detrusor muscle. These fibers may also inhibit parasympathetic
Fig. 1. Innervation of the lower urinary tract. Figure reproduced with permission, from 13 Ó (2010) Elsevier.
ganglia of the bladder via a2-adrenoceptors or facilitate bladder parasympathetic ganglia via a1-adrenoceptors. It appears that inhibition and facilitation occur at different firing frequencies thus allowing the same mechanism to facilitate emptying and storage. During the filling phase, noradrenaline activates the b-adrenergic inhibitory receptors in the detrusor muscle to contribute to bladder relaxation as well as the a-adrenergic excitatory receptors in the urethra and the bladder neck14 which contribute to the outlet closure. Most afferent fibers from the lower urinary tract enter the sacral spinal cord through the pelvic nerve at segments L1-S2. These afferents consist firstly of myelinated Ad fibers, which are stimulated by passive distension and active contraction of the bladder, giving information on the state of filling. They seem to be low threshold mechanoreceptors with activation by pressure ranging from 5 to 15 cm H2O. Secondly, afferent unmyelinated C fibers are also present and respond to chemical irritation of the bladder mucosa (cold) and may become mechanosensitive. These fibers are normally inactive. 2.3. Storage phase In more than 90% of the time the bladder is in the storage phase. Afferent information on bladder filling is conveyed through afferent visceral fibers of the sympathetic and parasympathetic nervous system to the neurons in the lumbar and sacral spinal cord and then to the periaqueductal grey (PAG). The PAG has a coordinating function. During the filling phase it maintains input to an area of the ventral pons (lateral region) which results in an increase in urethral closing pressure and relaxation of the detrusor muscle to
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maintain continence and an intravesical pressure lower than 10 cm H2O. During the filling phase, parasympathetic innervation of the detrusor is inhibited and both urethral sphincters are activated, an urethral reflex known as the guarding reflex.14 Adrenergic inhibitory modulation in the bladder is effective during storage through b-adrenergic receptors and excitation of the bladder base and urethra via a-adrenoreceptors. Some inputs from the lateral pons (“pontine storage centre”) contribute to sphincter reflexes and involuntary sphincter control (Fig. 1). Three different normal sensations during the filling phase have been described and applied during cystometry: first sensation of filling (at a mean of 40% of the bladder capacity), first desire to void (60% of the total bladder capacity) and strong desire to void. Sensation dysfunction may cause urgency or high micturition frequency including nocturia. Sensations related to the desire to void are transmitted by the pelvic nerves and the sensation of imminent micturition through the pudendal nerves. 2.4. Voiding phase Voiding is initiated by relaxation of the pelvic floor and urinary sphincter. Voiding is associated with activation of the prefrontal cortex, the hypothalamus and the PAG before reaching the pontine micturition centre (PMC). For micturition the PAG activates a region of the dorsomedial pontine tegmentum, the PMC. This in turn activates descending pathways to excite parasympathetic neurons in the sacral spinal cord leading to a detrusor contraction while simultaneously stimulating inhibitory neurons which relax the urethral sphincter. 3. Clinical assessment of lower urinary tract function The first step starts with the assessment of the patient’s history and risk factors of lower urinary tract symptoms (LUTS). Various questionnaires with scoring systems, have been developed to screen and track the symptoms of LUTS.16 The International Prostate Symptom Score (IPSS) has gained wide acceptance. Conventional urodynamic studies including mictiography, uroflowmetry, pressure flow and cystometry allow a direct assessment of lower urinary tract function by measuring all relevant physiological bladder parameters of the storage and voiding phase. They usually involve artificial filling of the bladder. Postvoid residuals can be easily measured with bedside ultrasound or bladder scan. 3.1. International prostate symptom score (IPSS) The IPSS, created by the American Urological Association in 1992, is a questionnaire consisting of 8 questions covering frequency, nocturia, weak urinary stream, hesitancy, intermittence, incomplete emptying, urgency and quality of life, which is used to screen for LUTS (Table 1). Originally thought to be used for tracking the symptoms of the benign prostatic hyperplasia, the IPSS is a clinically sensible, reliable, valid and responsive questionnaire for daily clinical practice as well as research17 and can be used for both sexes.18 An IPSS score greater than 7 is considered to indicate relevant LUTS. 3.2. Urodynamic techniques: pressure flow and filling cystometry Urodynamic investigations assess parameters of both storage and voiding phases, voided volume, postvoid residual and pelvic electromyographic activity. Gold standard of the urodynamic investigation is filling cystometry with a pressure flow study which is a method by which the pressureevolume relation of the bladder is
assessed to determine detrusor activity (maximum detrusor pressure, detrusor pressure at maximum flow rate, maximum flow rate), bladder sensation (bladder volume at first desire to void, bladder volume at strong desire to void), maximum cystometric capacity and bladder compliance which are not possible with uroflowmetry or cystometry alone. Briefly, after placement of a transurethral dual channel catheter and a rectal balloon catheter, the bladder is filled with Ringer’s lactate solution at a speed of 25e50 ml/min and storage and voiding phases parameters are then recorded. Urethral pressure measurements, maximum urethral closure pressure at rest and functional profile length at rest, are determined to assess urethral function. In this specific procedure, a dual sensor catheter is pulled through the urethra at a slow but continuous rate according to the standardization of urethral pressure measurement report.19 The resulting curve illustrates the function of the urethra from the bladder neck to the meatus urethrae. One of the most relevant values resulting from the urethral pressure measurement is the maximum urethral closure pressure at rest, which is around 100 30 cm H2O and decreases with age. Terminology, assessment of the urodynamic parameters and units have been standardized by the International Continence Society (ICS).20 3.3. Urinary retention 3.3.1. Definition Urinary retention is the inability to completely empty the bladder and can be acute or chronic. There is no consensus on what is to be considered a pathological postvoid residual. The retention of more than 300 ml can be considered chronic however some investigators have defined postvoid residual between 100 and 500 ml.21,22 A postvoid residual of less than 50 ml indicates adequate bladder emptying. It is clear that the larger the postvoid residual is linked to the higher risk of cystitis.23 3.3.2. Risk factors The reported incidence of POUR ranges from 5 to 75%.6 Overall, there are various risk factors for POUR (Table 2).6 Advancing age strongly contributes to the incidence of acute urinary retention: patients in their 50s have an incidence of 0.5e0.7/1000 person-years whereas patients in their 70s have an incidence of 4e9/1000 personyears. Aging decreases the muscle to collagen ratio and M3 muscarinic receptor density, resulting in reduced autonomous activity of the bladder through altered excitation-contraction mechanisms of the muscle cells.24 In addition to aging, males have a two-fold increased risk of POUR because of bladder outlet obstruction. More than 50% of men aged gt; 50 years have LUTS, mainly due to prostatic hyperplasia, the symptoms of which can be assessed by the IPSS. A history of urinary retention before surgery increases the risk of POUR.21 Men with an IPSS greater than 7 are at increased risk of POUR with an RR of 3.2 (95% CI 1.9e5.4).25 The amount of intraoperative fluid received and a bladder volume of more than 270 ml on entry to the post anaesthesia care unit were independent predictive factors for POUR.26 Even after adjusting for age, IPSS, and peak urinary flow the RR remains 5 fold higher for patients in their 70s.27 Some types of surgery have a higher risk of POUR: for example in anorectal surgery the incidence of POUR is near 16%,28 whereas in patient undergoing arthroplastic surgery the incidence varies between 11 and 84%.6 4. Epidural anaesthesia/analgesia The incidence of POUR during epidural analgesia varies widely, depending on the type of surgery, the level insertion of the epidural
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Table 1 International prostate symptom score (IPSS) questionnaire.
catheter (lumbar more than thoracic), the epidural mixture and the infusion rate.6 Under the influence of epidural analgesia bladder sensitivity is reduced and the urge to void depressed, which can result in acute urinary retention and bladder overdistension. Bladder overdistension is a serious adverse effect of POUR with an incidence of between 20 and 40%.29,30 Overfilling of the bladder can induce stretch related damage to the detrusor muscle as increased intravesical pressure leads to a decreased blood flow. Partial ischaemia and hypoxia with oxidative DNA damage and lipid peroxydation following reperfusion injury after catheterization can lead to the irreversible urinary tract dysfunction. In animal models, administration of free radical scavengers like mannitol and edaravone has been shown to reduce bladder dysfunction after acute urinary retention.31e34 Impaired bladder emptying and increased postvoid residuals are associated with UTIs.23,35 4.1. Lumbar epidural anaesthesia/analgesia There are few studies of the urodynamic effects of various anaesthetic agents on lower urinary tract function,36e42 and the
majority pertain to lumbar epidural anaesthesia. The use of lumbar epidural analgesia during labourlabor and delivery has frequently been implicated as a causative factor for postpartum urinary retention; however micturition is impaired during labourlabor per se. Greater postvoid residuals and a higher incidence of catheterization (83%) in parturients with epidural analgesia strongly suggested that lumbar epidural analgesia influences lower urinary tract function during labourlabor.41 In contrast, Howell et al. could not find a difference in the incidence of urinary retention in parturients randomised with (52%) or without (56%) lumbar epidural analgesia.43 Evron et al. found an overall incidence of urinary retention of 21e53% with lumbar epidural analgesia in labouring women or after caesarean sections.44,45 CAUTI is a dreaded complication after orthopaedic surgery which increases the risk for infection of the prosthetic joints. Lumbar epidural analgesia (ropivacaine 0.75%) following total knee replacement was associated with a higher rate of urinary retention and need for catheterization than when a peripheral nerve blockade was applied.46 The risk of prosthetic infection due to postoperative bacteriuria is increased by a factor of 3e6 in male
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Table 2 Overall risk factors for POUR. Age >50 yrs Internationale prostate symptome score >7 Gender: male > female Decreased bladder contractility: 1. Motor neuron injury (cauda equina, radiculopathy, neuropathy) 2. Rapidbladder overdistension 3. Anticholinergica 4. Medications with anticholinergic properties (antipsychotic drugs, antidepressants) 5. Calcium channel antagonists 6. Antiarrhythmics 7. Beta-blockers 8. Constipation Decreased afferent function: 1. Motor neuron injury (cauda equina, radiculopathy, neuropathy) 2. Systemic analgesics (morphine) Outlet obstruction: 1. Prostatic hypertrophy 2. Pelvic organ prolapse 3. Urethral stricture 4. Detrusor sphincter dyssynergia 5. Adrenergic agonist Type of surgery (anorectal surgery, inguinal repair, pelvic surgery) Prolonged surgery Spinal anaesthesia (long acting drugs, high dose of local anaesthetics, m-receptor agonists) Epidural anaesthesia (lumbar > thoracic) Hypnotics/Sedative (thiopental, benzodiazepines ketamine, halogenics)
patients with risk for POUR.6 For the same type of surgery, a metaanalysis reported a combined Odds ratio of 0.07 (95% CI: 0.02e0.27, p < 0.001) for POUR with epidural analgesia.47 A direct relationship between the incidence of POUR and the concentration of epidural bupivacaine could be detected in patients undergoing limb surgery.48 However these studies did not focus on the mechanistic impact of the epidurally administered drugs on lower urinary tract function, and urodynamic analysis were lacking. The composition of the epidural solution may also influence bladder function. Lipophilic opioids such as sufentanil and fentanyl have a higher systemic uptake than hydrophilic morphine, which remains available longer in the lumbar region and diffuses into the intrathecal space. The sustained presence of morphine in combination with its affinity to m-receptors in the spinal cord lead to decreased parasympathetic firing in the sacral region and decreased afferent inputs from the bladder to the spinal cord, which may explain the more pronounced effect of morphine on bladder function. The effect of opioids in patient-controlled epidural analgesia on urinary retention rate is ambiguous.44,49 The addition of opioids to the epidural mixture seems to increase the risk of POUR, depending on the pharmacokinetics and the receptor affinities of the different opioids. In a recently published study, Liang et al. found that the cadence of POUR was higher in parturients receiving an epidural morphine bolus (33%) than in patients receiving patient-controlled epidural analgesia with ropivacaine-fentanyl (15%) after elective cesarean delivery.49 However, intramuscular administration of pethidin was associated with an incidence of POUR of 17%.49 In patients undergoing a gastric bypass epidurally administrated morphine again was associated with more POUR than sufentanil.50 4.2. Thoracic epidural analgesia Because epidural analgesia can be performed at various levels of the spinal cord, it is possible to block only a portion of the spinal cord (segmental blockade). Based on the fact that the innervation of the bladder and urethral sphincter lies between L1 and S4 it can be assumed that TEA within segments T4-6 to T10-12 should have no or minimal influence on lower urinary tract function.
However voiding problems are a common clinical observation during TEA. There has yet been no consensus concerning the appropriate catheterization strategy during TEA. A lower rate of UTI’s through early removal of the bladder catheter in patients receiving TEA has been demonstrated and the rate of recatheterization was low.51 However, leaving the bladder catheter as long as the epidural analgesia was maintained resulted in a higher incidence of UTI’s and a prolonged hospital stay. Basse et al. observed a 9% of incidence of recatheterization in patients undergoing colorectal surgery where epidural analgesia (bupivacaine 0.125%) was sustained during 48 h postoperatively and the transurethral catheter was left 24 h postoperatively.52 The incidence of UTI was 4%. However in colorectal surgery the surgery itself may have an effect on bladder function due to impairment of bladder innervation. Open renal or thoracic surgery cannot be expected to have a direct effect on bladder function. In 2 prospective, open, observational follow-up studies53,54 from our institution we attempted to prove the hypothesis that that lower urinary tract function remains unchanged during TEA within segments T4 to T11 after open renal surgery. Male patients with no pre-existing LUTS (IPSS 7) and a postvoid residual of less than 100 ml underwent urodynamic investigations the day before open renal surgery (lumbotomy) and 2e3 days postoperatively under TEA. Postvoid residual increased significantly from 25 ml before surgery to 420 ml 2e3 days postoperatively under TEA. The underlying factor was an impairment of bladder contractility expressed by a decrease in maximum detrusor pressure, detrusor pressure at maximum flow rate and maximum flow rate under TEA. Bladder capacity and sensation; however remained unaffected by TEA. After cessation of the TEA and removal of the epidural catheter, bladder function recovered and all patients had a postvoid residual of less than 100 ml.54 In women the findings were similar.53 As the result of TEA, there was a significant increase in postvoid residual and a significant decrease in bladder contractility, urinary flow rate and voided volume. Maximum urethral closure pressure at rest decreased significantly under TEA. Again, bladder sensation, maximum cystometric capacity, compliance, and functional urethral length at rest were not influenced by TEA. In these two studies, the main effect of TEA performed at level T8/9 was a significant decrease in detrusor pressure generation during voiding, which is synonymous to detrusor underactivity according to the ICS.20 This resulted in impaired bladder emptying with clinically relevant postvoid residual necessitating indwelling or intermittent catheterization or at the least monitoring of postvoid residuals. Intact bladder sensation during filling in these patients may well protect them from developing acute bladder overdistension. However, in combination with increased postvoid residuals, the normal perception of bladder filling would clinically manifest itself as an increased urinary frequency. One explanation for the effect of TEA on bladder function may be that thoracic segmental sympatholysis is accompanied by normal or increased sympathetic activity in the unblocked regions.55 An intact sympathetic activity at level T12eL1 with stress-induced activation postoperatively and/or an inhibition of the parasympathetic activity could lead to a decrease in detrusor activity/ pressure. Interestingly, detrusor overactivity, defined as involuntary detrusor contractions during filling during urodynamics, which was present in three women preoperatively disappeared under TEA. This finding fits in with the notion of detrusor inhibition through TEA but could also be a completely random observation. The systemic effect of opioids may also impact bladder function. Opioids applied intravenously inhibit detrusor function and stimulate the urethral sphincter, a combination which impedes bladder
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emptying and leads to urinary retention.56 The site of action of epidurally administrated fentanyl remains controversial and probably depends on the mode of administration (bolus versus infusion). Continuous epidural infusion of lipophilic opioids such as fentanyl leads to equal spinal and supraspinal analgesia because of drug redistribution to the brain.57,58 Addition of fentanyl to 0.2% ropivacaine for peripartum epidural analgesia does not seem to increase the risk of urinary retention.45 Niemi and Breivik59 demonstrated that the serum concentration of fentanyl was lowered by half with addition of adrenaline in the epidurally administrated mixture, the same mixture that was applied in the above mentioned two studies.53,54 Major open thoracic surgery is another common field of TEA application where the incidence of POUR, is not well described. Postvoid residual was not significantly changed pre- and postoperatively in men or women with no pre-existing LUTS undergoing thoracotomy.60 However, a significant decrease in bladder capacity when feeling a strong desire to void was observed in women. Transient catheterization was necessary in 23% of the male patients with an initial IPSS 3. All were older than 50 years.60 Based on this observation it may be advantageous to closely monitor male patients over 50 years of age with an IPSS 3 postoperatively as they may be the ones at risk of developing significant postvoid residuals under TEA. 5. Conclusion TEA has a significant effect on detrusor function. The ensuing increased postvoid residual in the majority of patients necessitates catheterization or close monitoring. Prolonged catheterization has an increased risk of CAUTIs, therefore efforts should be made to identify the patients at risk or ameliorate the effects of TEA drugs on bladder function. Increased awareness of these issues should encourage development of strategies to minimize perioperative lower urinary tract dysfunction as well as the need for transurethral catheters, leading to less CAUTI. Conflicts of interest No conflicts of interest. References 1. Wu CL, Cohen SR, Richman JM, Rowlingson AJ, Courpas GE, Cheung K, et al. Efficacy of postoperative patient-controlled and continuous infusion epidural analgesia versus intravenous patient-controlled analgesia with opioids: a meta-analysis. Anesthesiology 2005;103:1079e88 [quiz 1109e10]. 2. Kehlet H, Wilmore DW. Multimodal strategies to improve surgical outcome. Am J Surg 2002;183:630e41. 3. Wijeysundera DN, Beattie WS, Austin PC, Hux JE, Laupacis A. Epidural anaesthesia and survival after intermediate-to-high risk non-cardiac surgery: a population-based cohort study. Lancet 2008;372:562e9. 4. Liu SS, Wu CL. Effect of postoperative analgesia on major postoperative complications: a systematic update of the evidence. Anesth Analg 2007;104:689e702. 5. Popping DM, Elia N, Marret E, Remy C, Tramer MR. Protective effects of epidural analgesia on pulmonary complications after abdominal and thoracic surgery: a meta-analysis. Arch Surg 2008;143:990e9. 6. Baldini G, Bagry H, Aprikian A, Carli F. Postoperative urinary retention: anesthetic and perioperative considerations. Anesthesiology 2009;110:1139e57. 7. Foxman B. Epidemiology of urinary tract infections: incidence, morbidity, and economic costs. Am J Med 2002;113(Suppl. 1A):5e13. 8. Klevens RM, Edwards JR, Richards Jr CL, Horan TC, Gaynes RP, Pollock DA. Estimating health care-associated infections and deaths in U.S. hospitals, 2002. Public Health Rep 2007;122:160e6. 9. Schaberg DR, Weinstein RA, Stamm WE. Epidemics of nosocomial urinary tract infection caused by multiply resistant gram-negative bacilli: epidemiology and control. J Infect Dis 1976;133:363e6. 10. Meddings J, Rogers MA, Macy M, Saint S. Systematic review and meta-analysis: reminder systems to reduce catheter-associated urinary tract infections and urinary catheter use in hospitalized patients. Clin Infect Dis 2010;51:550e60.
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Huang AJ, Brown JS, Boyko EJ, Moore EE, Scholes D, Walter LC, et al. Clinical significance of postvoid residual volume in older ambulatory women. J Am Geriatr Soc 2011;59:1452e8. 23. Truzzi JC, Almeida FM, Nunes EC, Sadi MV. Residual urinary volume and urinary tract infectionewhen are they linked? J Urol 2008;180:182e5. 24. van Koeveringe GA, Vahabi B, Andersson KE, Kirschner-Herrmans R, Oelke M. Detrusor underactivity: a plea for new approaches to a common bladder dysfunction. Neurourol Urodyn 2011;30:723e8. 25. Jacobsen SJ, Jacobson DJ, Girman CJ, Roberts RO, Rhodes T, Guess HA, et al. Natural history of prostatism: risk factors for acute urinary retention. J Urol 1997;158:481e7. 26. Keita H, Diouf E, Tubach F, Brouwer T, Dahmani S, Mantz J, et al. Predictive factors of early postoperative urinary retention in the postanesthesia care unit. Anesth Analg 2005;101:592e6. 27. Meigs JB, Barry MJ, Giovannucci E, Rimm EB, Stampfer MJ, Kawachi I. Incidence rates and risk factors for acute urinary retention: the health professionals followup study. J Urol 1999;162:376e82. 28. Toyonaga T, Matsushima M, Sogawa N, Jiang SF, Matsumura N, Shimojima Y, et al. Postoperative urinary retention after surgery for benign anorectal disease: potential risk factors and strategy for prevention. Int J Colorectal Dis 2006;21:676e82. 29. Lamonerie L, Marret E, Deleuze A, Lembert N, Dupont M, Bonnet F. Prevalence of postoperative bladder distension and urinary retention detected by ultrasound measurement. Br J Anaesth 2004;92:544e6. 30. Pavlin DJ, Pavlin EG, Gunn HC, Taraday JK, Koerschgen ME. Voiding in patients managed with or without ultrasound monitoring of bladder volume after outpatient surgery. Anesth Analg 1999;89:90e7. 31. Saito M, Miyagawa I. Bladder dysfunction after acute urinary retention in rats. J Urol 2001;165:1745e7. 32. Saito M, Shimizu S, Kinoshita Y, Satoh I, Shomori K, Dimitriadis F, et al. Bladder dysfunction after acute urinary retention in the rats: a novel over active bladder model. Mol Cell Biochem 2010;333:109e14. 33. Shimizu S, Saito M, Kinoshita Y, Kazuyama E, Tamamura M, Satoh I, et al. Acute urinary retention and subsequent catheterization cause lipid peroxidation and oxidative DNA damage in the bladder: preventive effect of edaravone, a freeradical scavenger. BJU Int 2009;104:713e7. 34. Saito M, Wada K, Kamisaki Y, Miyagawa I. Effect of ischemia-reperfusion on contractile function of rat urinary bladder: possible role of nitric oxide. Life Sci 1998;62:149e56. 35. Hampson SJ, Noble JG, Rickards D, Milroy EJ. Does residual urine predispose to urinary tract infection? Br J Urol 1992;70:506e8. 36. Appell RA, England HR, Hussell AR, McGuire EJ. The effects of epidural anesthesia on the urethral closure pressure profile in patients with prostatic enlargement. J Urol 1980;124:410e1. 37. Cohen SE, Woods WA. The role of epidural morphine in the postcesarean patient: efficacy and effects on bonding. Anesthesiology 1983;58:500e4. 38. Kau YC, Lee YH, Li JY, Chen C, Wong SY, Wong TK. Epidural anesthesia does not increase the incidences of urinary retention and hesitancy in micturition after ambulatory hemorrhoidectomy. Acta Anaesthesiol Sin 2003;41:61e4. 39. Singh SK, Agarwal MM, Batra YK, Kishore AV, Mandal AK. Effect of lumbarepidural administration of tramadol on lower urinary tract function. Neurourol Urodyn 2008;27:65e70. 40. Stricker K, Steiner W. Postoperative urinary retention. Anaesthesist 1991;40:287e90.
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41. Weiniger CF, Wand S, Nadjari M, Elchalal U, Mankuta D, Ginosar Y, et al. Postvoid residual volume in labor: a prospective study comparing parturients with and without epidural analgesia. Acta Anaesthesiol Scand 2006;50:1297e303. 42. Weissman A, Grisaru D, Shenhav M, Peyser RM, Jaffa AJ. Postpartum surveillance of urinary retention by ultrasonography: the effect of epidural analgesia. Ultrasound Obstet Gynecol 1995;6:130e4. 43. Howell CJ, Kidd C, Roberts W, Upton P, Lucking L, Jones PW, et al. A randomised controlled trial of epidural compared with non-epidural analgesia in labour. BJOG 2001;108:27e33. 44. Evron S, Muzikant G, Rigini N, Khazin V, Sessler DI, Sadan O, et al. Patientcontrolled epidural analgesia: the role of epidural fentanyl in peripartum urinary retention. Int J Obstet Anesth 2006;15:206e11. 45. Evron S, Samueloff A, Simon A, Drenger B, Magora F. Urinary function during epidural analgesia with methadone and morphine in post-cesarean section patients. Pain 1985;23:135e44. 46. Zaric D, Boysen K, Christiansen C, Christiansen J, Stephensen S, Christensen B. A comparison of epidural analgesia with combined continuous femoral-sciatic nerve blocks after total knee replacement. Anesth Analg 2006;102:1240e6. 47. Fowler SJ, Symons J, Sabato S, Myles PS. Epidural analgesia compared with peripheral nerve blockade after major knee surgery: a systematic review and meta-analysis of randomized trials. Br J Anaesth 2008;100:154e64. 48. Vercauteren MP, Van Den Bergh L, Kartawiadi SL, Van Boxem K, Hoffmann VL. Addition of bupivacaine to sufentanil in patient-controlled epidural analgesia after lower limb surgery in young adults: effect on analgesia and micturition. Reg Anesth Pain Med 1998;23:182e8. 49. Liang CC, Chang SD, Wong SY, Chang YL, Cheng PJ. Effects of postoperative analgesia on postpartum urinary retention in women undergoing cesarean delivery. J Obstet Gynaecol Res 2010;36:991e5. 50. Kim JY, Lee SJ, Koo BN, Noh SH, Kil HK, Kim HS, et al. The effect of epidural sufentanil in ropivacaine on urinary retention in patients undergoing gastrectomy. Br J Anaesth 2006;97:414e8.
51. Zaouter C, Kaneva P, Carli F. Less urinary tract infection by earlier removal of bladder catheter in surgical patients receiving thoracic epidural analgesia. Reg Anesth Pain Med 2009;34:542e8. 52. Basse L, Werner M, Kehlet H. Is urinary drainage necessary during continuous epidural analgesia after colonic resection? Reg Anesth Pain Med 2000;25:498e501. 53. Wuethrich PY, Burkhard FC, Panicker JN, Kessler TM. Effects of thoracic epidural analgesia on lower urinary tract function in women. Neurourol Urodyn 2011;30:121e5. 54. Wuethrich PY, Kessler TM, Panicker JN, Curatolo M, Burkhard FC. Detrusor activity is impaired during thoracic epidural analgesia after open renal surgery. Anesthesiology 2010;112:1345e9. 55. Magnusdottir H, Kirno K, Ricksten SE, Elam M. High thoracic epidural anesthesia does not inhibit sympathetic nerve activity in the lower extremities. Anesthesiology 1999;91:1299e304. 56. Doyle PT, Briscoe CE. The effects of drugs and anaesthetic agents on the urinary bladder and sphincters. Br J Urol 1976;48:329e35. 57. Ginosar Y, Columb MO, Cohen SE, Mirikatani E, Tingle MS, Ratner EF, et al. The site of action of epidural fentanyl infusions in the presence of local anesthetics: a minimum local analgesic concentration infusion study in nulliparous labor. Anesth Analg 2003;97:1439e45. 58. Ginosar Y, Riley ET, Angst MS. The site of action of epidural fentanyl in humans: the difference between infusion and bolus administration. Anesth Analg 2003;97:1428e38. 59. Niemi G, Breivik H. Adrenaline markedly improves thoracic epidural analgesia produced by a low-dose infusion of bupivacaine, fentanyl and adrenaline after major surgery. A randomised, double-blind, cross-over study with and without adrenaline. Acta Anaesthesiol Scand 1998;42:897e909. 60. Wuethrich PY, Henning A, Schweizerhof M, Kessler TM, Burkhard FC. Postvoid residuals remain unchanged in patients with postoperative thoracic epidural analgesia after thoracotomy. Reg Anesth Pain Med 2011;36:46e50.
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Trends in Anaesthesia and Critical Care journal homepage: www.elsevier.com/locate/tacc
REVIEW
Thoracic epidural analgesia: What about the urinary bladder? Patrick Y. Wuethrich a, *, Fiona C. Burkhard b a b
University Department of Anaesthesiology and Pain Therapy, University Hospital Bern, Inselspital, CH-3010 Berne, Switzerland Department of Urology, University Hospital Bern, Switzerland
s u m m a r y Keywords: Thoracic epidural analgesia Urinary retention Bladder function
The impact of thoracic epidural analgesia (TEA) on lower urinary tract function, although a common observation in everyday clinical practice, has not been examined in depth. One factor often observed in patients with TEA is postoperative urinary retention (POUR). POUR is linked to several factors including age, gender, postoperative pain, type of surgical procedure, use of opioids and neuraxial anaesthesia/ analgesia. Its inadequate management can lead to urinary tract infections and/or bladder overdistension with long term debilitating morbidities and associated high costs. This paper discusses the effects and potential modulatory mechanisms of the TEA on lower urinary tract function. Ó 2012 Elsevier Ltd. All rights reserved.
1. Introduction In recent years, epidural analgesia has been shown to be an effective method of postoperative pain management,1 which facilitates postoperative rehabilitation,2 and reduces the 30-day mortality after surgery3 as well as being an established part of fast tract surgery protocols. Thoracic epidural analgesia (TEA) favourably benefits physiological functions such as respiration, coagulation, bowel function and hormonal stress response.4,5 Postoperative urinary retention (POUR) is one of the most common complications of epidural anaesthesia/analgesia with an incidence of up to 75% after major surgery.6 It is a common practice to place an indwelling catheter in the bladder of patients receiving epidural analgesia and to leave the catheter as long as the epidural analgesia is maintained despite a lack of evidence supporting this approach. However, transurethral catheterization is associated with significant morbidity such as patient discomfort, urethral trauma and urinary tract infections (UTI). Prolonged catheterization is the primary risk factor for catheter associated urinary tract infections (CAUTI) and is the most common site of nosocomial infections in the United States.7 CAUTI account for more than 1 million cases each year, 900,000 additional hospitalization days per year and are directly responsible for 13% of the deaths related to nosocomial infections.8 In addition, bacteriuria leads to unnecessary antimicrobial use and urinary catheters often serve as a reservoir for multidrug-resistant bacteria.9 For this reason, increasing focus is placed on limiting the duration of catheterization and
* Corresponding author. Tel.: þ41 316322483; fax: þ41 6320554. E-mail address: [email protected] (P.Y. Wuethrich). 2210-8440/$ e see front matter Ó 2012 Elsevier Ltd. All rights reserved. doi:10.1016/j.tacc.2012.02.003
finding methods to avoid unnecessary catheterization in perioperative medicine.10,11 This review article offers an overview of lower urinary tract function including anatomy and physiology of the lower urinary tract and outlines the impact of epidural analgesia on bladder function with a focus on TEA. 2. Anatomy and physiology of lower urinary tract The lower urinary tract is composed of two functional units: a reservoir (bladder) and an outlet (bladder neck, urethra and urethral sphincter). The two essential functions of the lower urinary tract are to store and periodically expel liquid waste. An average adult human empties the bladder 5e7 times a day and has a bladder capacity of about 400e500 ml. The predominant role of the bladder is to store urine at low pressure even during filling to capacity. When necessary the bladder is also dynamic and able to empty essentially any volume at any time and as often as necessary in a short time by actively contracting. Normal lower urinary tract function requires the integrity of the central and peripheral nervous systems supplied by the somatic and autonomous systems which are under both voluntary and involuntary control. 2.1. Anatomy of the lower urinary tract The bladder is a hollow smooth muscle organ, composed of the bladder body located above the ureteral orifices and the base, consisting of the trigone and the urethrovesical junction. The bladder or detrusor muscle is composed of three layers of typical smooth muscle cells, where the inner and outer layers are oriented longitudinally and the middle one circularly. This orientation is
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important because it determines the bladder’s shape and intraluminal pressure. During the storage phase, the muscle cells have to relax and to elongate for a long time interval for storage, whereas during the voiding phase they have to shorten in a synchronized way over a short time period to expel the urine as quickly as possible. The urethra allows urinary outflow to the exterior and prevents leakage of urine during storage by generating a higher pressure than in the bladder. In men, the urethra is divided into the bladder neck, prostatic, membranous, bulbar and penile sections, in women the urethra is shorter and has a more uniform structure.12 The urethra is composed of smooth muscle, striated muscle and a lamina propria which has a submucosa and a mucosal layer. Striated muscle structures compose the external urethral sphincter (also called intramural sphincter or rhabdosphincter) and contribute to the resting urethral pressure.12 Smooth muscle structures are found throughout the length of the urethra in women and in the membranous urethra in men. Circular and longitudinal layers are well defined, generating spontaneous myogenic tone. The circular muscle layer seems to play an important role in maintaining urethral pressure during the storage phase. In contrast the function of the longitudinal muscle layer is less clear: contraction of the muscle fibers may lead to shortening and opening of the urethra during micturition. The submucosal layer plays an important role in mediating the pressure generated by the muscle layers and keeping the lumen closed. This function is of particular importance in women, as it is advocated to contribute to urinary continence. 2.2. Neurophysiology of the lower urinary tract Motoneurons of both urethra and bladder are located in the sacral spinal cord (S2-4) in the nucleus of Onuf and reach the periphery through the pudendal nerves (Fig. 1).13 The detrusor smooth muscle is innervated by parasympathetic fibers, which reside in the sacral intermediolateral cell group and are located in S2-4. These fibers exit the spinal cord through the anterior roots, intermingle with somatic fibers forming the spinal nerves, continue in the anterior spinal rami and travel via the pelvic splanchnic nerves to ganglion cells in the pelvic plexus, the vesical plexus and the cavernous nerves. Cholinergic transmitters are the major excitatory mechanism in the human bladder, resulting in detrusor contraction via M3 and M2 muscarinic receptors. In contrast the trigone muscle is sparsely innervated by parasympathetic fibers, while sympathetic fibers are prevalent.14 Sympathetic fibers innervating the bladder and urethra originate in the intermediolateral cell column of the spinal cord (T11L2)13 and play an important role in promoting continence.15 These fibers exit the spinal cord by the anterior root and intermingle with somatic efferent fibers to form the spinal nerve. They either synapse in one of the nearby paravertebal ganglia or continue peripherally with associated somatic segmental fibers to reach the pelvic floor or pass directly through the paravertebral ganglia and exit as splanchnic nerves to synapse on prevertebral or collateral ganglia and then continue as the right and left hypogastric nerves which contribute to the pelvic plexus. The pelvic plexus consists of a dense network of pre- and postganglionic sympathetic and parasympathetic nerve fibers and ganglia, which give rise to, beside others, the vesical plexus to the bladder and urethra and the cavernous nerves to the urethral sphincter complex. Stimulation of a1-adrenoceptors in the bladder base and urethra by the postganglionic fibers of the sympathetic nervous system has an excitatory effect while b-adrenoreceptors lead to an inhibition of the detrusor muscle. These fibers may also inhibit parasympathetic
Fig. 1. Innervation of the lower urinary tract. Figure reproduced with permission, from 13 Ó (2010) Elsevier.
ganglia of the bladder via a2-adrenoceptors or facilitate bladder parasympathetic ganglia via a1-adrenoceptors. It appears that inhibition and facilitation occur at different firing frequencies thus allowing the same mechanism to facilitate emptying and storage. During the filling phase, noradrenaline activates the b-adrenergic inhibitory receptors in the detrusor muscle to contribute to bladder relaxation as well as the a-adrenergic excitatory receptors in the urethra and the bladder neck14 which contribute to the outlet closure. Most afferent fibers from the lower urinary tract enter the sacral spinal cord through the pelvic nerve at segments L1-S2. These afferents consist firstly of myelinated Ad fibers, which are stimulated by passive distension and active contraction of the bladder, giving information on the state of filling. They seem to be low threshold mechanoreceptors with activation by pressure ranging from 5 to 15 cm H2O. Secondly, afferent unmyelinated C fibers are also present and respond to chemical irritation of the bladder mucosa (cold) and may become mechanosensitive. These fibers are normally inactive. 2.3. Storage phase In more than 90% of the time the bladder is in the storage phase. Afferent information on bladder filling is conveyed through afferent visceral fibers of the sympathetic and parasympathetic nervous system to the neurons in the lumbar and sacral spinal cord and then to the periaqueductal grey (PAG). The PAG has a coordinating function. During the filling phase it maintains input to an area of the ventral pons (lateral region) which results in an increase in urethral closing pressure and relaxation of the detrusor muscle to
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maintain continence and an intravesical pressure lower than 10 cm H2O. During the filling phase, parasympathetic innervation of the detrusor is inhibited and both urethral sphincters are activated, an urethral reflex known as the guarding reflex.14 Adrenergic inhibitory modulation in the bladder is effective during storage through b-adrenergic receptors and excitation of the bladder base and urethra via a-adrenoreceptors. Some inputs from the lateral pons (“pontine storage centre”) contribute to sphincter reflexes and involuntary sphincter control (Fig. 1). Three different normal sensations during the filling phase have been described and applied during cystometry: first sensation of filling (at a mean of 40% of the bladder capacity), first desire to void (60% of the total bladder capacity) and strong desire to void. Sensation dysfunction may cause urgency or high micturition frequency including nocturia. Sensations related to the desire to void are transmitted by the pelvic nerves and the sensation of imminent micturition through the pudendal nerves. 2.4. Voiding phase Voiding is initiated by relaxation of the pelvic floor and urinary sphincter. Voiding is associated with activation of the prefrontal cortex, the hypothalamus and the PAG before reaching the pontine micturition centre (PMC). For micturition the PAG activates a region of the dorsomedial pontine tegmentum, the PMC. This in turn activates descending pathways to excite parasympathetic neurons in the sacral spinal cord leading to a detrusor contraction while simultaneously stimulating inhibitory neurons which relax the urethral sphincter. 3. Clinical assessment of lower urinary tract function The first step starts with the assessment of the patient’s history and risk factors of lower urinary tract symptoms (LUTS). Various questionnaires with scoring systems, have been developed to screen and track the symptoms of LUTS.16 The International Prostate Symptom Score (IPSS) has gained wide acceptance. Conventional urodynamic studies including mictiography, uroflowmetry, pressure flow and cystometry allow a direct assessment of lower urinary tract function by measuring all relevant physiological bladder parameters of the storage and voiding phase. They usually involve artificial filling of the bladder. Postvoid residuals can be easily measured with bedside ultrasound or bladder scan. 3.1. International prostate symptom score (IPSS) The IPSS, created by the American Urological Association in 1992, is a questionnaire consisting of 8 questions covering frequency, nocturia, weak urinary stream, hesitancy, intermittence, incomplete emptying, urgency and quality of life, which is used to screen for LUTS (Table 1). Originally thought to be used for tracking the symptoms of the benign prostatic hyperplasia, the IPSS is a clinically sensible, reliable, valid and responsive questionnaire for daily clinical practice as well as research17 and can be used for both sexes.18 An IPSS score greater than 7 is considered to indicate relevant LUTS. 3.2. Urodynamic techniques: pressure flow and filling cystometry Urodynamic investigations assess parameters of both storage and voiding phases, voided volume, postvoid residual and pelvic electromyographic activity. Gold standard of the urodynamic investigation is filling cystometry with a pressure flow study which is a method by which the pressureevolume relation of the bladder is
assessed to determine detrusor activity (maximum detrusor pressure, detrusor pressure at maximum flow rate, maximum flow rate), bladder sensation (bladder volume at first desire to void, bladder volume at strong desire to void), maximum cystometric capacity and bladder compliance which are not possible with uroflowmetry or cystometry alone. Briefly, after placement of a transurethral dual channel catheter and a rectal balloon catheter, the bladder is filled with Ringer’s lactate solution at a speed of 25e50 ml/min and storage and voiding phases parameters are then recorded. Urethral pressure measurements, maximum urethral closure pressure at rest and functional profile length at rest, are determined to assess urethral function. In this specific procedure, a dual sensor catheter is pulled through the urethra at a slow but continuous rate according to the standardization of urethral pressure measurement report.19 The resulting curve illustrates the function of the urethra from the bladder neck to the meatus urethrae. One of the most relevant values resulting from the urethral pressure measurement is the maximum urethral closure pressure at rest, which is around 100 30 cm H2O and decreases with age. Terminology, assessment of the urodynamic parameters and units have been standardized by the International Continence Society (ICS).20 3.3. Urinary retention 3.3.1. Definition Urinary retention is the inability to completely empty the bladder and can be acute or chronic. There is no consensus on what is to be considered a pathological postvoid residual. The retention of more than 300 ml can be considered chronic however some investigators have defined postvoid residual between 100 and 500 ml.21,22 A postvoid residual of less than 50 ml indicates adequate bladder emptying. It is clear that the larger the postvoid residual is linked to the higher risk of cystitis.23 3.3.2. Risk factors The reported incidence of POUR ranges from 5 to 75%.6 Overall, there are various risk factors for POUR (Table 2).6 Advancing age strongly contributes to the incidence of acute urinary retention: patients in their 50s have an incidence of 0.5e0.7/1000 person-years whereas patients in their 70s have an incidence of 4e9/1000 personyears. Aging decreases the muscle to collagen ratio and M3 muscarinic receptor density, resulting in reduced autonomous activity of the bladder through altered excitation-contraction mechanisms of the muscle cells.24 In addition to aging, males have a two-fold increased risk of POUR because of bladder outlet obstruction. More than 50% of men aged gt; 50 years have LUTS, mainly due to prostatic hyperplasia, the symptoms of which can be assessed by the IPSS. A history of urinary retention before surgery increases the risk of POUR.21 Men with an IPSS greater than 7 are at increased risk of POUR with an RR of 3.2 (95% CI 1.9e5.4).25 The amount of intraoperative fluid received and a bladder volume of more than 270 ml on entry to the post anaesthesia care unit were independent predictive factors for POUR.26 Even after adjusting for age, IPSS, and peak urinary flow the RR remains 5 fold higher for patients in their 70s.27 Some types of surgery have a higher risk of POUR: for example in anorectal surgery the incidence of POUR is near 16%,28 whereas in patient undergoing arthroplastic surgery the incidence varies between 11 and 84%.6 4. Epidural anaesthesia/analgesia The incidence of POUR during epidural analgesia varies widely, depending on the type of surgery, the level insertion of the epidural
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Table 1 International prostate symptom score (IPSS) questionnaire.
catheter (lumbar more than thoracic), the epidural mixture and the infusion rate.6 Under the influence of epidural analgesia bladder sensitivity is reduced and the urge to void depressed, which can result in acute urinary retention and bladder overdistension. Bladder overdistension is a serious adverse effect of POUR with an incidence of between 20 and 40%.29,30 Overfilling of the bladder can induce stretch related damage to the detrusor muscle as increased intravesical pressure leads to a decreased blood flow. Partial ischaemia and hypoxia with oxidative DNA damage and lipid peroxydation following reperfusion injury after catheterization can lead to the irreversible urinary tract dysfunction. In animal models, administration of free radical scavengers like mannitol and edaravone has been shown to reduce bladder dysfunction after acute urinary retention.31e34 Impaired bladder emptying and increased postvoid residuals are associated with UTIs.23,35 4.1. Lumbar epidural anaesthesia/analgesia There are few studies of the urodynamic effects of various anaesthetic agents on lower urinary tract function,36e42 and the
majority pertain to lumbar epidural anaesthesia. The use of lumbar epidural analgesia during labourlabor and delivery has frequently been implicated as a causative factor for postpartum urinary retention; however micturition is impaired during labourlabor per se. Greater postvoid residuals and a higher incidence of catheterization (83%) in parturients with epidural analgesia strongly suggested that lumbar epidural analgesia influences lower urinary tract function during labourlabor.41 In contrast, Howell et al. could not find a difference in the incidence of urinary retention in parturients randomised with (52%) or without (56%) lumbar epidural analgesia.43 Evron et al. found an overall incidence of urinary retention of 21e53% with lumbar epidural analgesia in labouring women or after caesarean sections.44,45 CAUTI is a dreaded complication after orthopaedic surgery which increases the risk for infection of the prosthetic joints. Lumbar epidural analgesia (ropivacaine 0.75%) following total knee replacement was associated with a higher rate of urinary retention and need for catheterization than when a peripheral nerve blockade was applied.46 The risk of prosthetic infection due to postoperative bacteriuria is increased by a factor of 3e6 in male
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Table 2 Overall risk factors for POUR. Age >50 yrs Internationale prostate symptome score >7 Gender: male > female Decreased bladder contractility: 1. Motor neuron injury (cauda equina, radiculopathy, neuropathy) 2. Rapidbladder overdistension 3. Anticholinergica 4. Medications with anticholinergic properties (antipsychotic drugs, antidepressants) 5. Calcium channel antagonists 6. Antiarrhythmics 7. Beta-blockers 8. Constipation Decreased afferent function: 1. Motor neuron injury (cauda equina, radiculopathy, neuropathy) 2. Systemic analgesics (morphine) Outlet obstruction: 1. Prostatic hypertrophy 2. Pelvic organ prolapse 3. Urethral stricture 4. Detrusor sphincter dyssynergia 5. Adrenergic agonist Type of surgery (anorectal surgery, inguinal repair, pelvic surgery) Prolonged surgery Spinal anaesthesia (long acting drugs, high dose of local anaesthetics, m-receptor agonists) Epidural anaesthesia (lumbar > thoracic) Hypnotics/Sedative (thiopental, benzodiazepines ketamine, halogenics)
patients with risk for POUR.6 For the same type of surgery, a metaanalysis reported a combined Odds ratio of 0.07 (95% CI: 0.02e0.27, p < 0.001) for POUR with epidural analgesia.47 A direct relationship between the incidence of POUR and the concentration of epidural bupivacaine could be detected in patients undergoing limb surgery.48 However these studies did not focus on the mechanistic impact of the epidurally administered drugs on lower urinary tract function, and urodynamic analysis were lacking. The composition of the epidural solution may also influence bladder function. Lipophilic opioids such as sufentanil and fentanyl have a higher systemic uptake than hydrophilic morphine, which remains available longer in the lumbar region and diffuses into the intrathecal space. The sustained presence of morphine in combination with its affinity to m-receptors in the spinal cord lead to decreased parasympathetic firing in the sacral region and decreased afferent inputs from the bladder to the spinal cord, which may explain the more pronounced effect of morphine on bladder function. The effect of opioids in patient-controlled epidural analgesia on urinary retention rate is ambiguous.44,49 The addition of opioids to the epidural mixture seems to increase the risk of POUR, depending on the pharmacokinetics and the receptor affinities of the different opioids. In a recently published study, Liang et al. found that the cadence of POUR was higher in parturients receiving an epidural morphine bolus (33%) than in patients receiving patient-controlled epidural analgesia with ropivacaine-fentanyl (15%) after elective cesarean delivery.49 However, intramuscular administration of pethidin was associated with an incidence of POUR of 17%.49 In patients undergoing a gastric bypass epidurally administrated morphine again was associated with more POUR than sufentanil.50 4.2. Thoracic epidural analgesia Because epidural analgesia can be performed at various levels of the spinal cord, it is possible to block only a portion of the spinal cord (segmental blockade). Based on the fact that the innervation of the bladder and urethral sphincter lies between L1 and S4 it can be assumed that TEA within segments T4-6 to T10-12 should have no or minimal influence on lower urinary tract function.
However voiding problems are a common clinical observation during TEA. There has yet been no consensus concerning the appropriate catheterization strategy during TEA. A lower rate of UTI’s through early removal of the bladder catheter in patients receiving TEA has been demonstrated and the rate of recatheterization was low.51 However, leaving the bladder catheter as long as the epidural analgesia was maintained resulted in a higher incidence of UTI’s and a prolonged hospital stay. Basse et al. observed a 9% of incidence of recatheterization in patients undergoing colorectal surgery where epidural analgesia (bupivacaine 0.125%) was sustained during 48 h postoperatively and the transurethral catheter was left 24 h postoperatively.52 The incidence of UTI was 4%. However in colorectal surgery the surgery itself may have an effect on bladder function due to impairment of bladder innervation. Open renal or thoracic surgery cannot be expected to have a direct effect on bladder function. In 2 prospective, open, observational follow-up studies53,54 from our institution we attempted to prove the hypothesis that that lower urinary tract function remains unchanged during TEA within segments T4 to T11 after open renal surgery. Male patients with no pre-existing LUTS (IPSS 7) and a postvoid residual of less than 100 ml underwent urodynamic investigations the day before open renal surgery (lumbotomy) and 2e3 days postoperatively under TEA. Postvoid residual increased significantly from 25 ml before surgery to 420 ml 2e3 days postoperatively under TEA. The underlying factor was an impairment of bladder contractility expressed by a decrease in maximum detrusor pressure, detrusor pressure at maximum flow rate and maximum flow rate under TEA. Bladder capacity and sensation; however remained unaffected by TEA. After cessation of the TEA and removal of the epidural catheter, bladder function recovered and all patients had a postvoid residual of less than 100 ml.54 In women the findings were similar.53 As the result of TEA, there was a significant increase in postvoid residual and a significant decrease in bladder contractility, urinary flow rate and voided volume. Maximum urethral closure pressure at rest decreased significantly under TEA. Again, bladder sensation, maximum cystometric capacity, compliance, and functional urethral length at rest were not influenced by TEA. In these two studies, the main effect of TEA performed at level T8/9 was a significant decrease in detrusor pressure generation during voiding, which is synonymous to detrusor underactivity according to the ICS.20 This resulted in impaired bladder emptying with clinically relevant postvoid residual necessitating indwelling or intermittent catheterization or at the least monitoring of postvoid residuals. Intact bladder sensation during filling in these patients may well protect them from developing acute bladder overdistension. However, in combination with increased postvoid residuals, the normal perception of bladder filling would clinically manifest itself as an increased urinary frequency. One explanation for the effect of TEA on bladder function may be that thoracic segmental sympatholysis is accompanied by normal or increased sympathetic activity in the unblocked regions.55 An intact sympathetic activity at level T12eL1 with stress-induced activation postoperatively and/or an inhibition of the parasympathetic activity could lead to a decrease in detrusor activity/ pressure. Interestingly, detrusor overactivity, defined as involuntary detrusor contractions during filling during urodynamics, which was present in three women preoperatively disappeared under TEA. This finding fits in with the notion of detrusor inhibition through TEA but could also be a completely random observation. The systemic effect of opioids may also impact bladder function. Opioids applied intravenously inhibit detrusor function and stimulate the urethral sphincter, a combination which impedes bladder
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emptying and leads to urinary retention.56 The site of action of epidurally administrated fentanyl remains controversial and probably depends on the mode of administration (bolus versus infusion). Continuous epidural infusion of lipophilic opioids such as fentanyl leads to equal spinal and supraspinal analgesia because of drug redistribution to the brain.57,58 Addition of fentanyl to 0.2% ropivacaine for peripartum epidural analgesia does not seem to increase the risk of urinary retention.45 Niemi and Breivik59 demonstrated that the serum concentration of fentanyl was lowered by half with addition of adrenaline in the epidurally administrated mixture, the same mixture that was applied in the above mentioned two studies.53,54 Major open thoracic surgery is another common field of TEA application where the incidence of POUR, is not well described. Postvoid residual was not significantly changed pre- and postoperatively in men or women with no pre-existing LUTS undergoing thoracotomy.60 However, a significant decrease in bladder capacity when feeling a strong desire to void was observed in women. Transient catheterization was necessary in 23% of the male patients with an initial IPSS 3. All were older than 50 years.60 Based on this observation it may be advantageous to closely monitor male patients over 50 years of age with an IPSS 3 postoperatively as they may be the ones at risk of developing significant postvoid residuals under TEA. 5. Conclusion TEA has a significant effect on detrusor function. The ensuing increased postvoid residual in the majority of patients necessitates catheterization or close monitoring. Prolonged catheterization has an increased risk of CAUTIs, therefore efforts should be made to identify the patients at risk or ameliorate the effects of TEA drugs on bladder function. Increased awareness of these issues should encourage development of strategies to minimize perioperative lower urinary tract dysfunction as well as the need for transurethral catheters, leading to less CAUTI. Conflicts of interest No conflicts of interest. References 1. Wu CL, Cohen SR, Richman JM, Rowlingson AJ, Courpas GE, Cheung K, et al. Efficacy of postoperative patient-controlled and continuous infusion epidural analgesia versus intravenous patient-controlled analgesia with opioids: a meta-analysis. Anesthesiology 2005;103:1079e88 [quiz 1109e10]. 2. Kehlet H, Wilmore DW. Multimodal strategies to improve surgical outcome. Am J Surg 2002;183:630e41. 3. Wijeysundera DN, Beattie WS, Austin PC, Hux JE, Laupacis A. Epidural anaesthesia and survival after intermediate-to-high risk non-cardiac surgery: a population-based cohort study. Lancet 2008;372:562e9. 4. Liu SS, Wu CL. Effect of postoperative analgesia on major postoperative complications: a systematic update of the evidence. Anesth Analg 2007;104:689e702. 5. Popping DM, Elia N, Marret E, Remy C, Tramer MR. Protective effects of epidural analgesia on pulmonary complications after abdominal and thoracic surgery: a meta-analysis. Arch Surg 2008;143:990e9. 6. Baldini G, Bagry H, Aprikian A, Carli F. Postoperative urinary retention: anesthetic and perioperative considerations. Anesthesiology 2009;110:1139e57. 7. Foxman B. Epidemiology of urinary tract infections: incidence, morbidity, and economic costs. Am J Med 2002;113(Suppl. 1A):5e13. 8. Klevens RM, Edwards JR, Richards Jr CL, Horan TC, Gaynes RP, Pollock DA. Estimating health care-associated infections and deaths in U.S. hospitals, 2002. Public Health Rep 2007;122:160e6. 9. Schaberg DR, Weinstein RA, Stamm WE. Epidemics of nosocomial urinary tract infection caused by multiply resistant gram-negative bacilli: epidemiology and control. J Infect Dis 1976;133:363e6. 10. Meddings J, Rogers MA, Macy M, Saint S. Systematic review and meta-analysis: reminder systems to reduce catheter-associated urinary tract infections and urinary catheter use in hospitalized patients. Clin Infect Dis 2010;51:550e60.
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