How to Manage Pain in Patients with Renal Insufficiency or End-Stage Renal Disease on Dialysis?

Tramadol is metabolized in the liver, producing one active compound. Approximately 30% of the tramadol dose is excreted unchanged in the urine, whereas 60% of the dose is excreted as metabolites. It is recommended to reduce the dose and increase the dosing interval in patients with renal insufficiency, but tramadol is generally well-tolerated in patients with renal insufficiency and dialysis. It is significantly removed by hemodialysis; therefore, redosing after a session may be necessary.^18,19

Oxycodone can be used in patients with mild to moderate renal insufficiency but should be used at reduced dosing; it has been associated with significant sedation with usual doses in renal failure patients.¹⁶ Its use is generally not recommended in dialysis patients due to lack of data.³

Methadone and its metabolites are excreted in the urine and feces. Methadone has been used safely in patients with renal insufficiency, but it is poorly removed by dialysis and no specific recommendations are available regarding its dosing in dialysis.^3,16

Fentanyl is primarily metabolized in the liver to inactive metabolites. Fentanyl clearance is reduced in patients with moderate to severe uremia (BUN >60 mg/dL). It is not expected that fentanyl be dialyzable because of its pharmacokinetic properties (high protein-binding, low water solubility, high molecular weight, and high volume of distribution). Data suggests that fentanyl can be used at usual doses in mild to moderate renal insufficiency and in dialysis patients, although reduced doses may be prudent. Such patients should be monitored for signs of gradual accumulation of the parent drug.^3,16

Morphine is metabolized in the liver to morphine-6-glucuronide (M6G) and morphine-3-glucuronide (M3G), all of which are excreted renally, along with the parent compound. Only M6G has analgesic properties, and when it accumulates, it can lead to CNS depression. M3G is associated with behavioral excitation, a side effect that is further magnified in patients with renal insufficiency. Although morphine is dialyzable, it should generally be avoided in patients with any level of renal insufficiency.^16,17,20,21

Codeine is metabolized to several active metabolites, all of which are renally excreted. Lower-than-usual doses are recommended in patients with renal insufficiency, and it should be avoided altogether in dialysis patients.^3,16

Meperidine is metabolized in the liver to various metabolites, primarily normeperidine, which is toxic and has a long half-life, five to 10 times longer then meperidine. Meperidine should not be used in patients with renal insufficiency or dialysis.³

Adjunctive therapeutic options. Lidocaine patches currently are only FDA-indicated for postherpetic neuralgia but are used for a wide variety of local pain syndromes. Absorption of lidocaine is determined by the duration of application and the surface area over which it is applied. There is no appreciable accumulation of lidocaine or its metabolites in renal insufficiency; therefore, dose adjustments are not required.^22,23

Gabapentin is FDA-indicated for partial seizures and postherpetic neuralgia but is also used for a wide variety of neuropathic pain syndromes, including postoperative pain.²⁴ Gabapentin is not metabolized and is excreted in the urine unchanged. Renal clearance of gabapentin is reduced by 40% and the elimination half-life is increased up to 52 hours in renal insufficiency, but it is dialyzable. Therefore, dose adjustments are required with gabapentin in patients with moderate to severe renal insufficiency, and supplemental doses should be administered in patients after receiving dialysis.^25-27