heroin and Hypoxia

Leukoencephalopathy is a syndrome of neurologic deficits, including alteration of mental status, caused by pathologic changes in the cerebral white matter. The term, toxic leukoencephalopathy, encompasses a wide variety of exposures and clinical presentations. The diagnosis in these Frontiers in Clinical Neurotoxicology syndromes is made by careful attention to the history, clinical features, and radiologic findings. This article details three of the best-defined toxic leukoencephalopathies: delayed posthypoxic leukoencephalopathy, including delayed neurologic sequelae after carbon monoxide poisoning; heroin inhalation leukoencephalopathy; and posterior reversible encephalopathy syndrome.

Topics: Administration, Inhalation; Carbon Monoxide Poisoning; Heroin; Humans; Hypoxia; Leukoencephalopathies; Neuroimaging; Posterior Leukoencephalopathy Syndrome; Prognosis; Radiography

Several mechanisms leading to noncardiac pulmonary edema have been reviewed. Common features are damage to and increased permeability of vascular endothelium, interstitial and alveolar edema fluid high in protein content, increased pulmonary vascular resistance and pressure, nondependent distribution of the edema and normal left atrial or wedge pressure. The available evidence suggests that in some instances the sites of leakage are the pulmonary arterial walls and, perhaps in some, overperfused, damaged capillary beds. Therapeutic obestives differ from those in cardiac pulmonary edema in that efforts are directed toward a reduction in pulmonary blood flow and pulmonary arterial pressure during the period that endothelial healing is taking place.

Topics: Altitude Sickness; Animals; Bacterial Infections; Brain Injuries; Capillaries; Capillary Permeability; Ethchlorvynol; Heroin; Humans; Hypersensitivity; Hypoxia; Lung; Paraquat; Pulmonary Alveoli; Pulmonary Artery; Pulmonary Edema; Respiratory Distress Syndrome; Ultrafiltration

Analgesia provided by either 5 mg diamorphine, or 5 mg methadone administered by the epidural route during elective caesarean section was compared in 40 women. The median time to further analgesia in the methadone group was 395 min, and 720 min in the diamorphine group, P = 0.0003. Linear analogue scores to assess pain were measured 2-hourly for 12 h, then again at 24 h postoperatively. Pain scores were significantly lower in the diamorphine group at 8 and 10 h. The median cumulative i.m. morphine dose administered during the first 24 h was 20 mg in the methadone group and 0 mg in the diamorphine group (P = 0.0005). Nausea and pruritus were common side effects in both groups. Continuous pulse oximetry data were available for 12 h post-operatively in 15 patients receiving methadone, and in 17 patients receiving diamorphine. One or more episodes of significant desaturation (< 90% for 30 s), occurred in three patients receiving methadone, and in nine patients receiving diamorphine. Desaturation to 90-92% occurred in a further three patients given epidural diamorphine, and in one further patient given epidural methadone.

Topics: Analgesia, Epidural; Analgesia, Obstetrical; Cesarean Section; Double-Blind Method; Female; Heroin; Humans; Hypoxia; Incidence; Methadone; Morphine; Nausea; Oxygen; Pain Measurement; Pain, Postoperative; Pregnancy; Prochlorperazine; Pruritus; Time Factors

We have examined postoperative pain in patients allocated randomly to receive extradural bolus diamorphine 3.6 mg, extradural infusion of 0.15% bupivacaine with 0.01% diamorphine or patient-controlled i.v. administration of diamorphine at a maximum rate of 1 mg per 5 min, after total abdominal hysterectomy. Extradural infusion analgesia produced the smallest pain scores from 12 to 24 h after surgery (P < 0.05). More patients in the extradural infusion group were moderately hypoxaemic (SpO2 < 90% > 12 min h-1) after operation, compared with the two other groups (P < 0.05). The group using patient-controlled analgesia received more diamorphine and suffered a greater incidence of emetic sequelae (P < 0.05).

Topics: Abdomen; Adult; Aged; Analgesia, Epidural; Analgesia, Patient-Controlled; Bupivacaine; Female; Heroin; Humans; Hypoxia; Hysterectomy; Middle Aged; Pain Measurement; Pain, Postoperative

Arterial oxygen saturation (SaO2) was analysed continuously before and for 24 h after lower abdominal surgery in 30 patients breathing air using one of three postoperative analgesic regimens: i.v. diamorphine using a patient-controlled analgesia system (PCAS), extradural diamorphine or i.m. morphine. Hypoxaemia was defined as SaO2 less than 94% for more than 6 min h-1. Before operation there was no difference between the three analgesia groups assessed by the duration when SaO2 was less than 94%. After operation the pattern of SaO2 vs time distribution was either stable, with little variation from hour to hour with no hypoxaemia, or unstable with large variation with 30% of patients hypoxaemic. Thus three patterns of SaO2 distribution were seen in the postoperative period: stable without hypoxaemia (4/10 PCAS, 0/10 extradural, and 1/10 i.m. patients), unstable without hypoxaemia (4/10 PCAS, 5/10 extradural and 7/10 i.m. patients) and unstable with prolonged nocturnal periods with SaO2 less than 94% for a mean of 17.7 min h-1, 95% confidence limits (CL) 10-25 min h-1, (2/10 PCAS, 2/10 i.m. and 5/10 extradural patients). Before operation, the unstable group with hypoxaemia spent longer at less than 94% SaO2 (mean 4.8 min h-1, 95% CL 1.0-8.6 min h-1) than the stable group (mean 0.4 min h-1, 95% CL 0.17-0.61 min h-1) and this was a predictor of postoperative hypoxaemia. Hypoxaemia occurred in all analgesia groups, but extradural diamorphine tended to cause longer periods. Some patients at risk of postoperative hypoxaemia may be predicted by preoperative monitoring of SaO2 although extradural diamorphine boluses were associated with hypoxaemia in patients with normal preoperative values.

Topics: Abdomen; Adolescent; Adult; Female; Heroin; Humans; Hypoxia; Infusions, Intravenous; Injections, Epidural; Injections, Intramuscular; Male; Middle Aged; Morphine; Oximetry; Oxygen; Pain, Postoperative; Postoperative Complications; Self Administration

Xylazine has emerged in recent years as an adulterant in an increasing number of opioid-positive overdose deaths in the United States. Although its exact role in opioid-induced overdose deaths is largely unknown, xylazine is known to depress vital functions and cause hypotension, bradycardia, hypothermia, and respiratory depression.. In this study, we examined the brain-specific hypothermic and hypoxic effects of xylazine and its mixtures with fentanyl and heroin in freely moving rats.. In the temperature experiment, we found that intravenous xylazine at low, human-relevant doses (0.33, 1.0, 3.0 mg/kg) dose-dependently decreases locomotor activity and induces modest but prolonged brain and body hypothermia. In the electrochemical experiment, we found that xylazine at the same doses dose-dependently decreases nucleus accumbens oxygenation. In contrast to relatively weak and prolonged decreases induced by xylazine, intravenous fentanyl (20 μg/kg) and heroin (600 μg/kg) induce stronger biphasic brain oxygen responses, with the initial rapid and strong decrease, resulting from respiratory depression, followed by a slower, more prolonged increase reflecting a post-hypoxic compensatory phase, with fentanyl acting much quicker than heroin. The xylazine-fentanyl mixture eliminated the hyperoxic phase of oxygen response and prolonged brain hypoxia, suggesting xylazine-induced attenuation of the brain's compensatory mechanisms to counteract brain hypoxia. The xylazine-heroin mixture strongly potentiated the initial oxygen decrease, and the pattern lacked the hyperoxic portion of the biphasic oxygen response, suggesting more robust and prolonged brain hypoxia.. These findings suggest that xylazine exacerbates the life-threatening effects of opioids, proposing worsened brain hypoxia as the mechanism contributing to xylazine-positive opioid-overdose deaths.

Topics: Analgesics, Opioid; Animals; Drug Overdose; Fentanyl; Heroin; Humans; Hypothermia; Hypoxia; Hypoxia, Brain; Oxygen; Rats; Respiratory Insufficiency; Xylazine

Toxic leukoencephalopathy (TLE) is a rare pathology caused by various substances including opioids (notably heroin), immunosuppressants, chemotherapy agents, cocaine, alcohol and carbon monoxide. However, although heroin is metabolised by the body into morphine, there is a striking paucity in cases of primary oral morphine-induced TLE, especially in the adult population. We present the case of a man in his 40s admitted to hospital in respiratory depression with a Glasgow Coma Scale (GCS) score of 6 after taking an overdose of oral morphine sulphate. Following a complete recovery to baseline, he was then readmitted with an acute deterioration in his neurobehavioural condition. Initial investigations returned normal but MRI showed changes characteristic for TLE.In cases of opioid toxicity such as ours, TLE is difficult to differentiate from delayed post-hypoxic leukoencephalopathy, due to their similar clinical presentation, disease progression and radiological manifestation. We explore how clinicians can approach this diagnostic uncertainty.

Topics: Adult; Analgesics, Opioid; Drug Overdose; Heroin; Humans; Hypoxia; Leukoencephalopathies; Male; Morphine; Sulfates

Alcohol is the most commonly used psychoactive drug, often taken in conjunction with opioid drugs. Since both alcohol and opioids can induce CNS depression, it is often assumed that alcohol potentiates the known hypoxic effects of opioid drugs. To address this supposition, we used oxygen sensors to examine the effects of alcohol on brain oxygenation and hypoxic responses induced by intravenous heroin in awake, freely moving rats. To eliminate robust sensory effects of alcohol following its oral or intraperitoneal delivery, alcohol was administered directly into the stomach via chronically implanted intragastric catheters at human relevant doses. Alcohol delivered at a 0.5 g/kg dose did not affect brain oxygen levels, except for a weak transient increase during drug delivery. This phasic oxygen increase was stronger at a 2.0 g/kg alcohol dose and followed by a weaker tonic increase. Since alcohol absorption from intragastric delivery is much slower and more prolonged than with intraperitoneal or intravenous injections, the rapid rise of brain oxygen levels suggests that alcohol has a direct action on sensory afferents in the stomach well before the drug physically reaches brain tissue via circulation. Despite slow tonic increases in brain oxygen, alcohol at the 2.0 g/kg dose strongly potentiates heroin-induced oxygen responses, increasing both the magnitude and duration of oxygen decrease. Therefore, under the influence of alcohol, the use of opioid drugs becomes much more dangerous, increasing brain hypoxia and enhancing the probability of serious health complications, including coma and death.

Topics: Administration, Intravenous; Animals; Brain Chemistry; Dose-Response Relationship, Drug; Drug Interactions; Ethanol; Heroin; Hypoxia; Male; Narcotics; Oxygen Consumption; Rats; Rats, Long-Evans; Substance Abuse, Intravenous

Benzodiazepines are important therapeutic drugs, but they are often abused and co-abused with opioids. Clinical evidence suggests that benzodiazepines can inhibit respiration, and when combined with the respiratory-depressive effects of opioids, may increase likelihood of death. In this study we used oxygen sensors coupled with high-speed amperometry and multi-site thermorecording to examine how intravenous (iv) midazolam, a potent benzodiazepine, modulates the brain hypoxic and temperature effects of iv heroin in freely-moving rats. Oxygen levels and brain temperature were assessed with high temporal resolution in the nucleus accumbens (NAc), an important structure in the motivational-reinforcement circuit. When administered alone, midazolam (2 mg/kg) modestly decreased NAc temperature but had no evident effects on oxygen levels in this structure. In contrast, heroin (0.4 mg/kg) induced a strong decrease in NAc oxygen that was followed by a weaker, rebound-like oxygen increase. Midazolam pretreatment did not affect heroin-induced brain hypoxia but potentiated the initial hypothermia induced by heroin. However, co-administration of these drugs potentiated the heroin-induced oxygen decrease and enhanced heroin-induced brain hypothermia. Co-administration of heroin and midazolam also resulted in enhanced locomotor inhibition and loss of motor control. This effect caused some rats to collapse, resulting in nose and mouth occlusion, which caused a secondary hypoxic phase. These results could have important implications for human drug users, as the combined use of benzodiazepines with potent opioids not only results in sustained brain hypoxia but creates conditions of loss of motor control which could result in asphyxia and death. This article is part of the Special Issue entitled 'New Vistas in Opioid Pharmacology'.

Topics: Animals; Asphyxia; Behavior, Animal; Body Temperature; Brain; Drug Interactions; Electrodes, Implanted; Heroin; Hypoxia; Locomotion; Male; Midazolam; Nucleus Accumbens; Oxygen; Rats; Respiratory Insufficiency; Skin Temperature

Topics: Adult; Analgesics, Opioid; Drug Overdose; Fentanyl; Heroin; Heroin Dependence; Humans; Hypoxia; Lung; Male; Naloxone; Narcotic Antagonists; Pulmonary Edema; Radiography, Thoracic; Substance Abuse, Intravenous

This is a collaborative piece of work undertaken between the PCA and a Principal FME. The study is based on 16 cases of internal drug concealment drawn from 43 drug-related deaths in custody in England and Wales between 1997 and 2002. These data are supplemented by three case studies from a county force involving non-fatal drug concealment to illustrate practical custody issues. The majority of the 16 deaths were white (n = 12) and male (n = 13) with a mean age of 34 years. In half of the cases, the deceased was known or believed to have concealed drugs orally at the point of initial contact with police. In 4/16 cases, the individual first showed signs of medical distress in a public place, a further 4 collapsed on arrival at the police station and two more detainees were subsequently found collapsed in their cell. Drug toxicity was the most common cause of death (10/16). In 5 cases death was caused by airway obstruction by swallowed packages. Both cocaine (14/16) and cannabis (8/16) traces were found in post-mortem samples. The report emphasises the need for a safety first approach.

Topics: Adolescent; Adult; Airway Obstruction; Amphetamines; Cannabinoids; Cocaine; Crime; Deglutition; Dopamine Uptake Inhibitors; Drug Packaging; Female; Foreign Bodies; Forensic Medicine; Hallucinogens; Heroin; Humans; Hypoxia; Male; Middle Aged; N-Methyl-3,4-methylenedioxyamphetamine; Narcotics; Police; Prisoners; Substance-Related Disorders

Topics: Adult; Female; Heroin; Humans; Hypoxia; Male; Methadone; Narcotics; Oximetry

Pulmonary edema complicating heroin overdosage is a well recognized entity and regarded as the major mechanism contributing to death in heroin addicts. It's pathogenesis is unknown, several mechanisms are discussed: hypoxia-induced increase of pulmonary capillary permeability, depressed myocardial contractility, centrally induced respiratory depression, primary toxic effects on the alveolar capillaries and acute anaphylactic shock. The present study included opiate-related deaths (n=23) and a control group of sudden cardiovascular deaths (n=12) to verify the hypothesis, that defects of the alveolar capillary membranes and/or an acute anaphylactic reaction leads to pulmonary congestion, edema and hemorrhages. Lung specimens were obtained from these 35 autopsies of persons autopsied in the Institute of Forensic Medicine, University of Bonn, in 1997 and 1998. All specimens were examined with hematoxylin-eosin, prussian blue and investigated with immunohistological methods using primary antibodies against collagen IV, laminin and IgE. Defects of the basal laminae of the alveoli were found, demonstrated by laminin and collagen IV, and the number of IgE-positive cells was counted in both groups. There was an increased but not significant number of IgE-positive cells in the heroin-group and defects of the epithelial and endothelial basal laminae were found in both groups without significant differences.

Topics: Anaphylaxis; Antibodies; Basement Membrane; Capillaries; Capillary Permeability; Cause of Death; Collagen; Coloring Agents; Death, Sudden, Cardiac; Drug Overdose; Endothelium, Vascular; Epithelial Cells; Female; Hemorrhage; Heroin; Heroin Dependence; Humans; Hypoxia; Immunoglobulin E; Immunohistochemistry; Laminin; Male; Myocardial Contraction; Narcotics; Pulmonary Alveoli; Pulmonary Edema; Respiration

The occurrence of pallidal lesions with or without other hypoxic/ischaemic brain injuries was evaluated in 100 intravenous (i.v.) heroin addicts. The brains were collected consecutively from forensic autopsies during the period from January 1995 to June 1996. The autopsies were required by the police and performed at The Institute of Forensic Medicine, The National Hospital, Oslo. There were 21 women and 79 men, median age 32 (range 21-47) and 34 (19-60) years, respectively. Of 38 brains with abnormalities, twenty-five cases showed isolated or combined lesions of hypoxic/ischaemic origin. Pallidal lesions were found in nine brains; six lesions were old, one was subacute (a couple of weeks), and two were part of recent, generalized hypoxia/ischaemia. Six persons had old infarcts in the hippocampal formation, and one of them in combination with old pallidal infarcts. In seven brains small and old infarcts were found in watershed areas in the cerebellum. Between five and ten percent of i.v. heroin addicts might have pallidal infarcts, either as the sole lesion, or combined with other manifestations of hypoxic/ischaemic brain injury. This might give severe mental disturbances in the affected persons.

Topics: Adult; Brain; Brain Ischemia; Cause of Death; Female; Forensic Medicine; Heroin; Humans; Hypoxia; Male; Middle Aged; Narcotics; Substance Abuse, Intravenous

Their frequency is estimated with difficulty, although on autopsy pulmonary edema is found almost routinely. It is a major complication of overdoses (48 p. 100 of severe intoxications). Their formation can be suspected, when after the first phase of respiratory depressions, with coma, myosis, and a variable latent period, a second attack of respiratory insufficiency occurs with tachypnea, and cyanosis. The chest X-ray shows diffuse alveolar infiltration, sparing the apices. The heart being generally of normal size. Rapid disappearance of this infiltrate (24 to 48 hours) enables the elimination of two diagnoses: pneumonia due to inhalation of gastric fluid, an infectious pneumonia. Their pathogenesis remains very debatable: - in the majority of cases abrupt L.V.F. can be eliminated: -on the other hand it could be an allergic accident of the anaphylactic type, or local liberation of histamine, or a local toxic action on the pulmonary capillaries; - hypoxia, secondary to respiratory depression, could lead to pulmonary edema, by the same mechanism as at altitude; - finally, owing to the central neurological disorders a neurogenic theory can be put forward. Their treatment is essentially a combination of Nalorphine with oxygen therapy (by mask, or if necessary by assisted, controlled ventilation) with prevention of inhalation of gastric fluid (gastric emptying) or curative treatment of possible aspiration by antibiotics, and cortico-steroids. Diuretics can be useful, as well as cardiotonics.

Topics: Acute Disease; Hemodynamics; Heroin; Humans; Hypoxia; Pulmonary Edema

Severe heroin-induced pulmonary edema occurred in three previously healthy young men. Adequate arterial PO2 could only be achieved with the use of positive endexpiratory pressure (PEEP). Recovery was characterized by the gradual clearing of the pulmonary infiltrates and a gradual lessening of the severe restrictive ventilatory defects over many weeks. Concomitant aspiration of gastric acid was thought to be the explanation for the severity of these cases. In cases such as these, initial vigorous therapy, including PEEP for hypoxia, corticosteroids for possible aspiration and volume replacement for hypotension, is recommended.

Topics: Adrenal Cortex Hormones; Adult; Gastric Juice; Heroin; Humans; Hypotension; Hypoxia; Inhalation; Male; Positive-Pressure Respiration; Pulmonary Edema; Vital Capacity

Topics: Adult; Bronchiectasis; Heroin; Heroin Dependence; Humans; Hypoxia; Inhalation; Lung Diseases, Obstructive; Male; Radiography; Respiratory Function Tests; Respiratory Insufficiency; Substance-Related Disorders

Topics: Heroin; Humans; Hypoxia; Lung; Pulmonary Edema; United States

Topics: Acidosis; Acidosis, Respiratory; Airway Obstruction; Carbon Dioxide; Heroin; Humans; Hypercapnia; Hypothyroidism; Hypoventilation; Hypoxia; Lung Diseases, Obstructive; Neuromuscular Diseases; Oxygen; Pulmonary Alveoli; Pulmonary Circulation; Pulmonary Edema; Pulmonary Embolism; Respiration; Respiratory Insufficiency; Ventilation-Perfusion Ratio; Work of Breathing

Topics: Adolescent; Atrial Fibrillation; Blood Gas Analysis; Blood Pressure; Female; Heroin; Humans; Hypoxia; Intubation, Intratracheal; Levallorphan; Male; Nalorphine; Naloxone; Pneumonia, Aspiration; Positive-Pressure Respiration; Pulmonary Edema; Pupil; Respiration; Substance-Related Disorders

Topics: Altitude; Brain Injuries; Central Nervous System Diseases; Heart Failure; Heroin; Humans; Hypoxia; Pulmonary Edema; Shock; Substance-Related Disorders

Topics: Acidosis; Acidosis, Respiratory; Adolescent; Adult; Carbon Dioxide; Coma; Female; Heroin; Humans; Hypoventilation; Hypoxia; Lung; Lung Compliance; Male; Pulmonary Alveoli; Pulmonary Circulation; Pulmonary Diffusing Capacity; Pulmonary Edema; Pulmonary Ventilation; Radiography; Respiration; Spirometry; Substance-Related Disorders; Vital Capacity

Topics: Adolescent; Adult; Anti-Bacterial Agents; Arrhythmias, Cardiac; Black or African American; Body Temperature; Coma; Drug Combinations; Ethnicity; Female; Heroin; Humans; Hypoxia; Male; Nalorphine; New York City; Pneumonia; Puerto Rico; Pulmonary Edema; Retrospective Studies; Substance-Related Disorders

Topics: Adolescent; Brain Diseases; Coma; Decerebrate State; Electroencephalography; Heroin; Humans; Hypoxia; Male; Neurologic Examination; Substance-Related Disorders; Time Factors; Vision Disorders

Topics: Adolescent; Adult; Aged; Carbon Dioxide; Child; Heroin; Humans; Hydrogen-Ion Concentration; Hypoxia; Male; Middle Aged; Neurologic Manifestations; Oxygen; Partial Pressure

Topics: Adult; Heroin; Humans; Hypoxia