Adverse Effects and Parenteral Hydromorphone Use in Renal Failure (310-A)

Abstract

1.Recognize the conditions associated with neurotoxicity when hydromorphone is used in the setting of renal insufficiency.2.Discuss the prevalence of neuroexcitatory symptoms when hydromorphone is given in the setting of renal insufficiency.3.Discuss the toxicities of hydromorphone metabolites. Background. Hydromorphone is a semi-synthetic derivative of morphine that differs structurally from morphine by the presence of a 6-keto group and a hydrogenated double bond at the 7-8 position of the molecule. Hydromorphone is metabolized to hydromorphone-3-glucoronide (H3G), a compound that has no analgesic properties but one that may contribute to the development of neurotoxicity. In renal insufficiency, H3G accumulates and has been shown to cause myoclonus, agitation, and seizures in a dose dependent manner when infused into the cerebrospinal fluid of rats. In humans, there is conflicting evidence as to whether hydromorphone causes neuroexcitatory toxicities when given to patients with renal insufficiency. Research objectives. Determine the prevalence of neuroexcitation in patients with renal failure given hydromorphone, as measured by the glomerular filtration rate and to investigate factors associated with increased risk of neuroexcitation in this patient group. Methods. For the 12-month period from June 2007 through June 2008, charts of inpatient hospice patients with a glomerular filtration rate of < 60 (ml/min/1.73 m2) and who had received hydromorphone for pain control parenterally were reviewed for the occurrence of neuroexcitatory effects including tremor, myoclonus, agitation, cognitive dysfunction, and seizures. The effect of dose and duration of therapy was evaluated. Results. There was a strong and graded increase in neuroexcitatory effects with increasing quartile of dose or duration of hydromorphone for agitation (dose, P < 0.0001; duration, P < 0.0001) and cognitive dysfunction (dose, P < 0.0002; duration, P < 0.002). Consistent but weaker trends were observed for tremor and myoclonus. Conclusion. Parenteral hydromorphone is associated with neuroexcitatory symptoms when a neuroexcitatory threshold is reached. Implications for research, policy, or practice. When hydromorphone is given in the renal failure setting, a neurotoxic threshold can be reached beyond which there is a greater occurrence of neuroexcitatory effects. This means that hydromorphone should be used cautiously in the setting of renal insufficiency. Physical Aspects of Care