oxymorphone and Respiratory-Insufficiency

Prescription drug abuse is a major public health problem in the United States, with the rate of opioid-related deaths nearly quadrupling between 2000 and 2014. Extended-release oral oxymorphone hydrochloride (Opana ER) is a long-acting opioid prescribed for chronic pain; however, it also has the potential to be abused via intravenous injection. This retrospective review sought to analyze specific complications and sequelae requiring intensive care unit resources for patients intravenously abusing extended-release oral oxymorphone.. We retrospectively reviewed the medical records of patients identified for drug abuse between January 2012 and December 2015, identifying patients who intravenously abused extended-release oral oxymorphone. Medical charts were reviewed to identify associated sequelae and patients requiring an intensive care unit level of care.. We identified 53 patients who required treatment in an intensive care unit setting as a consequence of intravenously abusing extended-release oral oxymorphone. Twenty-eight patients (52.8%) required endotracheal intubation with mechanical ventilation for either acute hypoxic respiratory failure or protection of airway. Acute kidney injury developed in 48 patients (90.6%); 28.3% of these patients failed to regain renal function and required renal replacement therapy. Bacteremia was diagnosed in 36 patients (67.9%) and 30 patients (56.6%) were diagnosed as having acute infective bacterial endocarditis.. Our patients demonstrated a great need for critical care resources and severe sequelae related to intravenous drug abuse. Clinicians should be vigilant for the possibility for clinical decompensation when initially evaluating patients reporting intravenous abuse of extended-release oral oxymorphone.

Topics: Abscess; Acute Kidney Injury; Adult; Analgesics, Opioid; Bacteremia; Cellulitis; Delayed-Action Preparations; Endocarditis, Bacterial; Female; Humans; Intensive Care Units; Intubation, Intratracheal; Male; Middle Aged; North Carolina; Opioid-Related Disorders; Oxymorphone; Patient Admission; Prescription Drug Misuse; Renal Replacement Therapy; Respiration, Artificial; Respiratory Insufficiency; Retrospective Studies; Substance Abuse, Intravenous; Young Adult

In 2012, a nephrologist reported the development of a multiorgan thrombotic syndromic complex resembling thrombotic thrombocytopenic purpura (TTP) in patients who were abusing long acting oxymorphone hydrochloride; all patients had hemolytic anemia and thrombocytopenia.. Herein, we report another case involving a 31-year-old woman who self intravenously administered dissolved oral oxymorphone resulting in thrombotic sequelae resembling Degos disease.. Formalin-fixed and paraffin embedded skin biopsies were prepared according to standard protocols for H&E and immunohistochemistry.. The clinical presentation and biopsy findings were held to be indicative of Degos disease/malignant atrophic papulosis (MAP) but with unusual clinical features including renal failure and severe respiratory insufficiency. Given the efficacy of eculizumab in the treatment of the acute thrombotic phase of Degos disease/MAP, the patient received this drug, resulting in rapid resolution of signs and symptoms associated with her multiorgan failure. Although she developed recurrent cutaneous ulcers despite complete complement inhibition with eculizumab., her other extracutaneous manifestations did not recur. The patient's pre and post eculizumab skin biopsies showed a striking pauci-inflammatory thrombogenic vasculopathy associated with marked endothelial cell injury along with deposits of C3d and C4d within the cutaneous vasculature; the C5b-9 deposits were limited to the pre-eculizumab biopsy. We discovered that her syndromic complex was a self-inflicted one related to the localized administration of dissolved oxymorphone.. Our patient's biopsy along with the rapid response to eculizumab indicates that this distinct thrombotic microangiopathy is another complement mediated thrombotic microangiopathy syndrome. Opioid thrombotic microangiopathy has a varied clinical presentation and can mimic other catastrophic microangiopathy syndromes, all of which have in common a responsiveness to complement inhibition.

Topics: Acute Kidney Injury; Adult; Analgesics, Opioid; Diagnosis, Differential; Female; Humans; Malignant Atrophic Papulosis; Oxymorphone; Respiratory Insufficiency; Substance Abuse, Intravenous; Tablets; Thrombosis

Differences in the receptor mechanisms of opiate analgesia and respiratory depression have been studied with three novel irreversible opiates. A single injection of the irreversible agonist oxymorphazone produces analgesia in mice, lasting over 24 hours. Conversely, the irreversible antagonist naloxazone dramatically reduces the analgesic effectiveness of a variety of opiate alkaloids and enkephalin analogs for over a day. Despite this marked reduction in analgesia after naloxazone treatment, morphine lethality (LD50) is unchanged in similarly treated mice. Receptor binding studies show that naloxazone irreversibly and selectively blocks a subpopulation of opiate receptors (the mu1 sites) to which all classes of opiates and enkephalins bind with highest affinity, whereas the drug has little to no effect on their lower-affinity sites (mu, and delta). The return of high-affinity receptor (mu1) binding to normal levels corresponds closely to the return of analgesic sensitivity and possibly represents receptor turnover in the central nervous system. These studies suggest that both opiate and opioid peptide analgesia is mediated through a single receptor subpopulation distinct from those involved with respiratory depression, and raise the possibility of specific opiate analgesics without respiratory depression.

Topics: Analgesia; Animals; Humans; Lethal Dose 50; Morphine; Muridae; Naloxone; Naltrexone; Oxymorphone; Receptors, Opioid; Respiration; Respiratory Insufficiency

Topics: Adolescent; Adult; Anesthesia, Inhalation; Blood Pressure; Heart Rate; Humans; Hypoventilation; Levallorphan; Middle Aged; Nalorphine; Narcotic Antagonists; Nitrous Oxide; Oxymorphone; Pulse; Respiration; Respiratory Insufficiency; Thiopental

Topics: Analgesics; Analgesics, Non-Narcotic; Antipyretics; Biomedical Research; Blood Gas Analysis; Carbon Dioxide; Narcotic Antagonists; Oxymorphone; Respiratory Function Tests; Respiratory Insufficiency