Effects of Analgesic and Anesthetic Medications on Lower Urinary Tract Function

Sammy E. Elsamra, MD; Pamela Ellsworth, MD, FAAP, FACS


Urol Nurs. 2012;32(2):60-67. 

In This Article



Opioids are products, both natural and synthetic, that bind to opioid receptors and result in analgesia. Morphine is commonly used in the post-operative period for analgesia and is a well-known risk factor for POUR. The treatment of pain with opiates or its analogues decreases the sensation of bladder fullness by partially inhibiting the parasympathetic nerves that innervate the bladder. In addition, opiates have been shown to increase the sphincter tone of the urinary bladder via sympathetic over-stimulation, resulting in increased bladder outlet resistance (Durant & Yaksh, 1988). The combination of decreased sensation of fullness and increased outlet resistance may increase the risk of urinary retention. Further, animal and human studies have shown that intravenous morphine directly binds to spinal opioid receptors and results in total bladder relaxation rather than having targeted effects on the detrusor alone (Chen, Shen, & Pan, 2005), and has been reported with epidural anesthesia (Malinovsky et al., 1998). Animal studies have demonstrated increased bladder capacity and compliance following intravenous (IV) and intrathecal injections of tramadol. In humans, similar results on bladder capacity and compliance have been noted, with a reported increase in bladder capacity varying from 20% to 65% depending on the opioid, dose, patient group, and route of administration (Dray, 1988; Kuipers et al., 2004; Malinovsky et al., 1998).

Studies suggest that the half-life of the opioid used has an impact on urinary function and risk of retention. One study found that meperidine, an opioid with a relatively long half-life, use was an independent predictor of difficulty voiding after elective cholecystectomy (Kulacoglu, Dener, & Kama, 2001). In contrast, studies that evaluated orthopedic patients who received fentanyl (short half-life) for post-operative analgesia noted that these patients experienced significantly less risk for urinary retention than those who received morphine (intermediate half-life) (Gallo, Durand, & Pshon, 2008). Thus, the half-life of the narcotic may affect the risk for POUR; however, no prospective, comparative studies have been performed.

The mode of opioid delivery appears to also play a role in the risk of urinary retention (Chaney, 1995; Petros, Mallen, Howe, Rimm, & Robillard, 1993; Petros, Rimm, & Robillard, 1992). While, orally ingested opioids have been associated with an increased risk of urinary retention, the risk of POUR is higher with intravenous (IV) and epidural administration (Dolin & Cashman, 2005). A recent systematic review studied the occurrence of adverse effects (nausea, vomiting, sedation, pruritis, and urinary retention) related to post-operative pain management. Three analgesic techniques were compared: intramuscular (IM) analgesia, patient-controlled an algesia (PCA), and epidural analgesia. Overall, urinary retention occurred in 23% of all patients, and the frequency was highest for the epidural group at 29% (Dolin & Cashman, 2005).

Several authors have demonstrated that the risk of retention is increased in patients using PCA compared to those receiving intermittent IV or IM opioids (Petros et al., 1992, 1993). The highest rates of opioid-mediated urinary retention have generally been associated with epidural administration (Darrah et al., 2009). A meta-analysis of 12,513 patients found that the use of epidural anesthesia for post-operative pain control was associated with urinary retention in nearly 25% of patients, a significant increase over the rate found in patients receiving IM or PCA (Darrah et al., 2009; Dolin & Cashman, 2005). A meta-analysis of patients undergoing colorectal surgery found that the incidence of urinary retention increased from 1% to 10% when patients received epidural anesthesia instead of parenteral opioids (Darrah et al., 2009; Marret, Remy, & Bonnet – Postoperative Pain Forum Group, 2007).

Animal studies have demonstrated that opioid mu-receptors are concentrated in the dorsal horn of the spinal cord, where the bladder afferents merge (Coggeshall & Carlton, 1997; Singh, Agarwal, Batra, Kishore, & Mandal, 2008). Delta and kappa receptors are also present, but in lower concentrations. Both mu and delta (but not kappa) receptors are involved in bladder realization and impaired sensations by inhibiting the sensory input at the level of the dorsal horn and PAG. This is supported by the absence of such action by non-mu-agonist opioids (such as nalbuphine [Nubain®] [kappa agonist and mu antagonist] or pentazocine [Talwin®] [kappa and delta agonist]) (Malinovsky et al., 1998; Singh et al., 2008). The inhibition of bladder afferents at the dorsal horn via mu-receptor activation diminishes bladder sensations and may delay the micturition threshold, thus increasing compliance and bladder capacity. Furthermore, a direct effect of opioid receptor activation at the sacral parasympathetic innervations also improves compliance (Drenger, Magora, Evron, & Caine, 1986).

The role of opioid antidotes has been assessed in the management of opioid-related urinary retention. Opioid-mediated depression of bladder motility is largely secondary to action at the mu-opioid receptor, and can be reversed by intravenous naloxone (Narcan®), which results in the promotion of detrusor contraction and sphincter relaxation. Small doses of IV naloxone (0.1 mg) have been shown to decrease bladder distention without reversing analgesia (Gallo et al., 2008; Wren, 1996).

Naloxone, an antidote to morphine and its analogues, has been tested for the treatment of urinary retention after epidural and intrathecal anesthesia. Although naloxone was found to be very effective in reversing urinary retention, it also reversed the analgesic effect, and thus, was not recommended for the treatment of POUR (Rawal, Mollefors, Axelsson, Lingardh, & Widman, 1981; Verhamme et al., 2008). In fact, low dose naloxone in the treatment of urinary retention during extradural fentanyl (Actiq®, FentoraTM Duragesic®) use resulted in excessive reversal of analgesia (Wang, Pennefather, & Russel, 1993). However, nalbuphine, another opioid receptor inhibitor, appears to be effective in reversing urinary retention without compromising the analgesic effect (Verhamme et al., 2008), although further studies are warranted.

In an effort to decrease the effects of opioids on the LUT, studies have evaluated whether a decrease in the dose of opioid administered (by combining with NSAIDs) results in a decreased risk of POUR. In one meta-analysis, Remy, Marret, and Bonnet (2005) showed that morphine use can be reduced significantly by the combination of acetaminophen and morphine; however, there was no effect in the incidence of morphine-related side effects, including urinary retention. Another recent meta-analysis demonstrated that while the addition of NSAIDs to PCA may decrease nausea and vomiting, the risk of urinary retention, pruritis, and respiratory depression was not significantly reduced (Marret, Kurdi, Zufferey, & Bonnett, 2005). Similarly, a third meta-analysis concluded that while the concurrent use of COX- 2 inhibitors reduced opioid consumption by 35%, as well as decreased the risks of associated nausea, vomiting, pruritis, and constipation, there was no decrease in the risk of acute urinary retention (Romsing, Moiniche, Mathiesen, & Dahl, 2005).


NSAIDs are commonly used in surgical and nonsurgical settings. Pharmacologically, NSAIDs inhibit the metabolism of arachidonic acid to prosta glandins and thromboxanes by cycloxegenase (COX)-1 and 2. Prostaglandins, especially prostaglandin E 2 (PGE2), play an important role in LUT function. PGE2 is up-regulated within the bladder as a result of bladder inflammation, trauma, or over distention. PGE2 stimulates the release of tachykinins, which stimulate neurokinin receptors on afferent nerves and the detrusor smooth muscle and as a result promote detrusor contraction (Andersson & Hedlund, 2002; Verhamme et al., 2008).

One recent study discovered that NSAID users have a two-fold increased risk of acute urinary retention (Verhamme et al., 2005). Similar outcomes were seen even with COX-2 specific inhibitors because there have been reports of acute urinary retention that occurred within one week of starting such medications (Gruenenfelder, McGuire, & Faerber, 2002). By inhibiting the COX-2, PGE2, and tachykinin/neurokinin pathway, NSAIDs may decrease bladder contractility (Andersson & Hedlund, 2002; Darrah et al., 2009).

The effect of NSAIDs on urinary retention may be dose-specific. Verhamme et al. (2005) studied the association between NSAIDs and acute urinary retention and found the risk of acute urinary retention increased with higher doses of NSAIDs.


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