naloxone and Acidosis

Poisonings, adverse drug effects, and envenomations continue to be commonly encountered. Patients often present critically ill and warrant ICU admission. Many other patients who are initially stable have the potential for rapid deterioration and require continuous cardiopulmonary and neurologic monitoring. Given the potential for rapid deterioration, and because patients need continuous monitoring, ICU admission is frequently required. This article is the first of a three-part series to be published in CHEST; it discusses general management, laboratory tests, enhanced elimination, and emerging therapies. The second article will address the management of specific overdoses; the last will cover plants, mushrooms, envenomations, and heavy metals.

Topics: Acid-Base Equilibrium; Acidosis; Fat Emulsions, Intravenous; Humans; Hydroxocobalamin; Intensive Care Units; Naloxone; Narcotic Antagonists; Neuroleptic Malignant Syndrome; Osmolar Concentration; Poisoning; Renal Dialysis; Serotonin Syndrome; Therapeutic Irrigation; Xenobiotics

Topics: Acidosis; Adrenal Cortex Hormones; Anticoagulants; Barbiturates; Blood Viscosity; Brain Edema; Calcium Channel Blockers; Carbon Dioxide; Cerebrovascular Disorders; Dextrans; Hemodilution; Humans; Hypothermia, Induced; Lactates; Naloxone; Vasodilator Agents

Topics: Acidosis; Adult; Alcohol Drinking; Alkalosis; Animals; Child, Preschool; Circadian Rhythm; Dogs; Electrolytes; Female; Humans; Hypercapnia; Hypertension; Hypotension; Hypoxia; Infant; Lung; Male; Mice; Naloxone; Narcotics; Neurotransmitter Agents; Rats; Temperature; Thyroid Gland; Time Factors

A 74-year-old man was referred to our hospital due to deteriorating level of consciousness and desaturation. His Glasgow Coma Scale was 6, and his pupils were constricted but responded to light. Chest radiograph was negative for significant findings. Arterial blood gas evaluation on supplemental oxygen revealed severe acute on chronic respiratory acidosis: pH 7.15; PCO2, 133 mm Hg; PO2,64 mm Hg; and HCO3, 31 mmol/L. He regained full consciousness (Glasgow Coma Scale, 15) after receiving a 0.4 mg dose of naloxone, but because of persistent severe respiratory acidosis (pH 7.21; PCO2, 105 mm Hg), he was immediately commenced on noninvasive positive pressure ventilation (NIV) displaying a remarkable improvement in arterial blood gas values within the next few hours. However, in the days that followed, he remained dependent on NIV, and he was finally discharged on a home mechanical ventilation prescription. In cases of drug-induced respiratory depression, NIV should be regarded as an acceptable treatment, as it can provide ventilatory support without the increased risks associated with invasive mechanical ventilation.

Topics: Acidosis; Aged; Analgesics, Opioid; Combined Modality Therapy; Fentanyl; Humans; Hypercapnia; Male; Naloxone; Narcotic Antagonists; Positive-Pressure Respiration; Tramadol

Ibuprofen overdose is usually characterized by GI upset, dizziness, and mild sedation. On rare occasions, severe complications such as respiratory failure, metabolic acidosis, renal failure, coma, and death have been reported in both adults and children. Presently, treatment of acute ibuprofen intoxication with complications requires supportive therapy until the symptoms resolve over 24 to 48 hours. We report the case of an 11-month-old female infant with a depressed level of consciousness after ingestion of ibuprofen whose mental status markedly improved with administration of naloxone.

Topics: Acidosis; Anti-Inflammatory Agents, Non-Steroidal; Antidotes; Central Nervous System; Central Nervous System Diseases; Drug Overdose; Female; Humans; Ibuprofen; Infant; Naloxone

Morphine, the opioid-agonist, and the antagonists naloxone and levallorphan exerted direct effects on spontaneously-contracting cultures of cardiac myocytes from neonatal rats. Naloxone and levallorphan induced an increase in the amplitude of systolic cell motion (ASM) and in the size of [Ca2+]i-transients, measured as indo-1 fluorescence ratio (IFR), whereas morphine caused an increase in IFR with no change in ASM. Both morphine and naloxone caused a transient increase in 45Ca2+ influx into the cardiomyocytes. Analysis of the relationship between changes in ASM and IFR indicated dual action of the drugs: (a) An increase in [Ca2+]i-transients elicited by morphine and the antagonists, apparently resulting from a transient increase of Ca2+ influx. (b) Altered myofibril responsiveness to Ca2+; the agonists decreased it, and the antagonists increased it. Intracellular pHi measurements in cardiomyocytes loaded with the fluorescent indicator BCECF revealed that morphine caused acidosis and the antagonists caused alkalosis. These pH changes were inhibited by pertussis-toxin, protein kinase inhibitor K323a, phorbol-ester and ethylisopropyl-amiloride, indicating pathways mediated by GTP-binding proteins and altered activities of protein kinase C and Na+/H+ exchanger. Preincubation with pertussis toxin prior to the addition of morphine prevented the decrease in the myofibril responsiveness to Ca2+ as well as the decrease in pHi but did not affect the increase in [Ca2+]i-transients and the increase in the rate of Ca2+ influx. As a result, addition of morphine after preincubation with pertussis toxin caused a positive inotropic effect. Our results indicate that morphine acts by two different pathways distinguishable by their sensitivity to pertussis toxin (1), increased Ca2+ influx leading to increased Ca(2+)-transients and (2) decreased intracellular pH leading to reduced myofibril responsiveness to Ca2+.

Topics: Acidosis; Alkalosis; Animals; Animals, Newborn; Calcium; Cells, Cultured; Fluorescent Dyes; Heart Ventricles; Hydrogen-Ion Concentration; Indoles; Morphine; Myocardial Contraction; Myocardium; Naloxone

The effects of continuous naloxone infusion on the response to intestinal ischemia-reperfusion were studied in a rat model. Naloxone was given as a bolus injection (2 mg/kg bw) followed by a continuous infusion (4 mg/kg bw/h) starting before (-10 min) intestinal ischemia was applied (0-60 min) and continuing 2 h after reperfusion of the intestine. Blood pressure, acidosis and survival were determined. Saline-infused shocked rats and untreated shocked rats served as comparisons and non-shocked animals as controls. Blood pressure was slightly higher before and during the continuous naloxone infusion but did not differ after reperfusion in the three shock groups. Acidosis was less pronounced in naloxone compared to untreated shocked rats. Survival rates were significantly higher in naloxone-treated shocked rats compared to untreated shock and significantly lower in saline treated shocked rats compared to non-shocked controls. In conclusion a naloxone effect on acidosis and survival in shock after intestinal ischemia and reperfusion is possible.

Topics: Acid-Base Equilibrium; Acidosis; Animals; Blood Pressure; Hematocrit; Infusions, Intravenous; Intestines; Ischemia; Naloxone; Rats; Rats, Wistar; Reperfusion; Shock

Using the opiate receptor antagonist naloxone, we tested the hypothesis that endorphins act on opiate receptors to cause cardiovascular depression in primate shock. Mean arterial pressure (MAP), cardiac output, and left ventricular contractility (LV dP/dtmax) were measured in 34 anesthetized cynomolgus monkeys. Hemorrhagic shock was induced by bleeding into a heparinized reservoir to achieve (t = 0) and maintain MAP at 45 mm Hg. At t = 60 min, the reservoir was clamped and the animals were treated with 2 mg/kg plus 2 mg/kg.h naloxone (n = 5) or 0.9% NaCl as a control (n = 5). There were no significant differences in the cardiovascular responses to naloxone and saline when acid-base balance and core body temperature were not controlled. Pressor responses to naloxone, however, were present in proportion to arterial pH and body temperature. When these factors were controlled, naloxone (n = 6) significantly increased MAP and LV dP/dtmax by 48% and 83%, respectively, whereas saline (n = 6) had no significant effect. Blood was reinfused at t = 120 min, and survival rate at 72 h was significantly (p = .01) higher with naloxone (3/6) than saline controls (0/6). In the endotoxic shock model, cynomolgus monkeys were treated with 2 mg/kg plus 2 mg/kg.h naloxone (n = 6) or 0.9% NaCl (n = 6) when MAP reached 75 mm Hg or its nadir 60 to 90 min after Escherichia coli endotoxin, 5 mg/kg iv. Naloxone significantly increased MAP and LV dP/dtmax by 24% and 22%, respectively, whereas saline had no effect. Survival rate at 48 h was significantly (p = .01) higher with naloxone (6/6) than saline (1/6). Plasma beta-endorphin and beta-lipotropin concentrations rose three to five-fold in both shock models and were not affected by treatment. We conclude that endorphins are activated in primate shock and act on opiate receptors to contribute to the cardiovascular depression found with hemorrhage and endotoxemia.

Topics: Acidosis; Animals; beta-Endorphin; beta-Lipotropin; Cold Temperature; Female; Hemodynamics; Macaca fascicularis; Male; Naloxone; Shock, Hemorrhagic

We evaluated the hypothesis that increased endogenous opioid activity mediates part or all of the left ventricular contractile and pump dysfunction previously demonstrated in HCl-induced metabolic acidemia. Eighteen Western newborn lambs were catheterized and instrumented; pacing wires were sutured to the right atrial appendage; a catheter mounted micromanometer pressure transducer was inserted into the left ventricle; and a 2.5 F thermistor was inserted into the distal abdominal aorta. The lambs were studied 3 days after surgery. Metabolic acidemia was produced with an infusion of 0.5 N HCl into the inferior vena cava. Inhibition of endogenous opioids was achieved with a bolus of 2 mg/kg of intravenous naloxone, which was demonstrated to inhibit morphine sulfate-induced myocardial dysfunction. The effects of opioid inhibition were contrasted with our previously published results after restoration of a normal arterial pH with intravenous sodium bicarbonate. In agreement with our previous study, we found that reducing the arterial pH from 7.41 +/- 0.01 to 6.97 +/- 0.04 was associated with a 45% reduction in cardiac output which resulted from a 50% reduction in stroke volume. These changes in turn were mediated by a 35% reduction in the maximal first derivative of left ventricular pressure and/or a 63% increase in systemic vascular resistance which we used to estimate contractility and afterload, respectively. Left ventricular end diastolic pressure increased during acidemia. Although opioid inhibition produced a consistent increase in the maximal first derivative of left ventricular pressure, this increase was relatively small and was not associated with a significant change in cardiac output, stroke volume, or systemic vascular resistance.

Topics: Acidosis; Animals; Animals, Newborn; Asphyxia Neonatorum; Bradycardia; Cardiac Output, Low; Disease Models, Animal; Endorphins; Heart Ventricles; Humans; Hydrochloric Acid; Infant, Newborn; Naloxone; Sheep; Stroke Volume

Naloxone treatment of endotoxin shock has been shown to alter many cardiovascular parameters. However, since opioids can affect ventilatory function we thought it important to assess the effects of naloxone on some respiratory variables during endotoxin shock. Male Sprague-Dawley rats (300-400 g) were surgically prepared with carotid artery and jugular vein cannulas 24 hours before experiments were begun. Conscious, unrestrained rats were challenged with 10 mg/kg E. coli endotoxin or saline. Measurements of blood gases, pH, respiratory rate, serum lactate, and medullary/pontine blood flow (radio labelled microsphere method) were made 0, 10, 30, and 60 minutes postchallenge. Rats were treated with either 2 mg/kg naloxone or saline at 25 minutes postchallenge. Arterial PO2 rose and PCO2 fell in a stepwise fashion in saline-treated endotoxic rats. These changes were unrelated to medullary/pontine perfusion or to arterial pH (up to 30 minutes postchallenge). In naloxone-treated endotoxic rats the increased ventilatory drive at 60 minutes was attenuated, apparently as a result of prevention of acidosis at this time. These data further support uncoupling of ventilatory drive and arterial pH reported earlier and also indicate that naloxone's ability to prevent acidosis in these animals is not mediated through respiratory compensation.

Topics: Acid-Base Equilibrium; Acidosis; Animals; Endorphins; Gases; Hemodynamics; Male; Naloxone; Rats; Rats, Inbred Strains; Respiration; Shock, Septic

A patient who ingested 1.5 g pentazocine developed status epilepticus, coma, respiratory depression, acidosis, profound hypotension, and ventricular arrhythmias. Although this patient survived after institution of general supportive measures, she did not respond to usual doses of naloxone. We describe the clinical symptoms and course of recovery of a patient with pentazocine overdose. Our case suggests that pentazocine overdose may require higher doses of naloxone (5 to 20 mg) than are customarily used for narcotic overdoses.

Topics: Acidosis; Arrhythmias, Cardiac; Coma; Critical Care; Electrocardiography; Female; Humans; Hypotension; Middle Aged; Naloxone; Pentazocine; Respiratory Insufficiency; Status Epilepticus; Substance-Related Disorders