naloxone and Renal-Insufficiency

Opioid abuse is a devastating, costly, and growing problem in the United States, and one for which treatment can be complicated by barriers such as access to care and legal issues. Only 12% to 15% of the opioid-dependent population is enrolled in methadone maintenance programs. A significant breakthrough occurred with passage of the Drug Addiction Treatment Act of 2000 (DATA 2000). For the first time in approximately 80 years, physicians could legally prescribe opioid medications for the treatment of opioid addiction. The opiate, so designated, was buprenorphine (Subutex).

Topics: Anesthesia; Buprenorphine; Humans; Naloxone; Narcotic Antagonists; Opioid-Related Disorders; Renal Insufficiency

Hospitalized patients are at risk for opioid overdose. Little is known about the risk factors for these events.. Opioid overdose cases were identified by naloxone orders in computerized order entry system from a single institution. For each case, two controls were randomly selected. Data were collected on factors including age, gender, weight, opioid dose, route of administration, concomitant CNS depressants, renal function and comorbid conditions.. Between 2010 and 2013, we identified 44 cases of opioid overdose (OD), none of which were fatal, and matched these to 88 controls (no OD). Patients with a history of substance use disorder were excluded from the study. Factors associated with opioid overdose included age of 65 or older (40.9% OD vs 29.5% no OD, P = .026), being in an ICU (MICU/CICU 27.3% OD vs. 3.4% no OD, P < .001; SICU 18.1% OD vs 5.7% no OD, P = .031) and renal impairment (eGFR ≤60, 50.0% OD vs 28.4% no OD, P = .034). Total 24-hour opioid dose was lower in OD group, but the difference was not statistically significant (71.9 vs 107.2 mg morphine equivalent, P = .116). OD cases were more likely to have received concomitant CNS depressants, but the difference was statistically significant only for those who received 3 or more (15.9% OD vs 0% no OD, P = <.001). Heart disease was the only comorbidity significantly associated with an increased risk of opioid overdose (43.2% vs 20.5%, P = .025). Patient's BMI, duration of opioid use, route of administration and history of COPD and/or psychiatry were not associated with opioid overdoses.. Among hospitalized patients, risk factors of opioid overdose include age of 65 or greater, being in an ICU, renal impairment and concomitant administration of CNS depressant medications. These findings may help with the development and implementation of measures to prevent overdose.

Topics: Age Factors; Aged; Analgesics, Opioid; Drug Interactions; Drug Overdose; Female; Hospitalization; Humans; Intensive Care Units; Male; Middle Aged; Naloxone; Narcotic Antagonists; Renal Insufficiency; Risk Factors

Renal ischemia produces sympathoexcitation, which is responsible for the development of ischemic acute kidney injury. Stimulation of central opioid receptors activates the renal sympathetic nerve. The present study examined the effect of an opioid receptor antagonist naloxone on the ischemia/reperfusion-induced renal dysfunction in mice. Blood urea nitrogen (BUN) and plasma creatinine increased 24 h after the renal ischemia/reperfusion. Intraperitoneal or intracerebroventricular, but not intrathecal, pretreatment with naloxone suppressed the renal ischemia/reperfusion-induced increases in BUN and plasma creatinine. This effect of naloxone was reversed by subcutaneous pretreatment with morphine. Selective MOP receptor antagonist β-funaltrexamine (FNA) also suppressed the renal ischemia/reperfusion-induced increases in BUN and plasma creatinine. Moreover, tyrosine hydroxylase expression in the renal tissue increased 24 h after renal ischemia/reperfusion, which was abolished by intraperitoneal or intracerebroventricular pretreatment with naloxone and FNA. Immunohistochemical experiments revealed a significant increase in the number of the Fos family proteins (c-Fos, FosB, Fra-1, and Fra-2) positive cells in the paraventricular nucleus of hypothalamus and supraoptic nucleus 24 h after the renal ischemia/reperfusion. Intracerebroventricular pretreatment with naloxone attenuated the renal ischemia/reperfusion-induced increase in the number of the Fos family proteins positive cells in these areas. Finally, we observed that i.c.v. pretreatment with antiserum against β-endorphin also suppressed the increased blood urea and plasma creatinine. These results suggest that the blockade of central opioid receptors can attenuate the ischemic acute kidney injury through the inhibition of renal sympathoexcitation. The central opioid receptors may thus be a new target for the treatment of ischemic organ failures.

Topics: Analgesics, Opioid; Animals; Dose-Response Relationship, Drug; Hypothalamus, Anterior; Injections, Intraperitoneal; Injections, Intraventricular; Kidney; Male; Mice; Mice, Inbred ICR; Molecular Targeted Therapy; Naloxone; Naltrexone; Narcotic Antagonists; Nerve Tissue Proteins; Neurons; Proto-Oncogene Proteins c-fos; Receptors, Opioid, mu; Renal Insufficiency; Reperfusion Injury

We have surgically treated 771 patients for thoracic and thoracoabdominal aortic aneurysms since 1983. Our primary effort has been to develop experimentally validated strategies to reduce paraplegia, renal failure, and mortality in these high-risk patients. This approach has led to a spinal cord protection protocol that has reduced paraplegia risk by 80% (observed/expected ratio = 0.19) with the use of cerebral spinal fluid drainage, moderate hypothermia (31°C-33°C), endorphin receptor antagonist (naloxone), and thiopental burst suppression while optimizing mean arterial pressure (> 90 mm Hg) and cardiac index. The elective mortality rate is 2.80% (17% for acute patients), and with rapid renal cooling for renal protection, only 0.88% required permanent dialysis. These results were achieved without the use of assisted circulation. We have reattached intercostal arteries since 2005 using preoperative magnetic resonance angiographic localization, but it remains unclear whether intercostal reimplantation reduces paraplegia risk, as we had initially proposed. We strongly believe that a consistent anesthetic and postoperative care protocol uniformly built and applied around these principles greatly enhances our surgical outcomes. We also show that improved outcomes with assisted circulation and hypothermic arrest in treatment of thoracoabdominal aortic disease follow similar principles of spinal cord and end-organ protection.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anesthetics, Intravenous; Aortic Aneurysm, Thoracic; Assisted Circulation; Cerebrospinal Fluid Shunts; Child; Constriction; Female; Heart Arrest, Induced; Hemodynamics; Humans; Hypothermia, Induced; Male; Middle Aged; Naloxone; Narcotic Antagonists; Paraplegia; Postoperative Care; Renal Insufficiency; Replantation; Risk Assessment; Risk Factors; Spinal Cord Ischemia; Suture Techniques; Thiopental; Thoracic Arteries; Treatment Outcome; Vascular Surgical Procedures; Wisconsin; Young Adult