naloxone and Hypoventilation

Persons with chronic mountain sickness (CMS) hypoventilate and are more hypoxemic than normal individuals, but the cause of the hypoventilation is unclear. Studies of 14 patients with CMS and 11 healthy age-matched control subjects residing in Lhasa, Tibet, China (3,658 m) were conducted to test the hypothesis that hypoventilation, blunted hypoxic ventilatory responsiveness (HVR), and hypoxic ventilatory depression of CMS were due to increased endogenous opioid production. Patients with CMS compared with control subjects exhibited hypoventilation (end-tidal carbon dioxide pressure [PETCO2] = 36.6 +/- 1.0 versus 31.5 +/- 0.5 mm Hg, p less than 0.05), lower tidal volume (VT = 0.54 +/- 0.02 versus 0.61 +/- 0.02 ml BTPS, p less than 0.05), blunted HVR (shape parameter A = 17 +/- 8 versus 114 +/- 22 mm Hg/L BTPS/min, p less than 0.05), and a depressant effect of ambient hypoxia on ventilation (delta PETCO2 with acute hyperoxia = -3.5 +/- 0.5 versus -1.0 +/- 0.6 mm Hg, p less than 0.05). Reduced forced expiratory volume in 1 s to vital capacity ratios (FEV1/VC) and a higher proportion of cigarette smokers in the group of patients with CMS compared with control subjects suggested that at least some patients with CMS had mild airway obstructive lung disease. Naloxone infusion (0.14 mg/kg) to six patients with CMS did not change resting VT, PETCO2, HVR, or SaO2.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Altitude Sickness; China; Chronic Disease; Endorphins; Humans; Hypoventilation; Hypoxia; Male; Middle Aged; Naloxone

Naloxone was used in 20 patients divided into two series: series A consisted of 10 adults with an average age of 50.6 years (+/- 12.03) and series B 10 children with an average age of 8.5 years (+/- 5.16). Naloxone was given in the treatment of postoperative respiratory depression related to persistence of morphine impregnation, the patients having received either fentanyl (mean dose 0.04 mg/kg/h) or dextromoramide (mean dose 1.15 mg/kg/h). The mean dose of naloxone was 0.26 mg +/- 0.10, i.e. 3.9 microgram/kg in series A, and 0.13 mg +/- 0.11, i.e. 5.3 microgram/kg in series B. In both series, study of ventilatory function showed correction and stabilisation of the various parameters (F/min, Vt and V) up to 180 minutes after the injection. Recovery was rapid in both groups (7 to 10 min) and of good quality. Whilst it was accompanied in a number of cases by the recurrence of pain, the latter never required specific relief. The administration of naloxone was associated with an increase in heart rate (non-significant) at 10 min in series A and 30 min in series B. Apart an episode of nausea in one case of series A, no disagreeable side effects were observed.

Topics: Adolescent; Adult; Aged; Cardiovascular System; Child; Child, Preschool; Clinical Trials as Topic; Consciousness; Female; Humans; Hypoventilation; Male; Middle Aged; Naloxone; Neuroleptanalgesia; Pain, Postoperative; Postoperative Complications; Respiratory Function Tests

The object of this study was the use of naloxone to correct hypoventilation related to the use of morphinomimetics without suppressing the analgesic effect of these agents. The study involved ten patients undergoing gynaecological surgery under neuroleptanalgesia and who at the end of surgery had hypoventilation due to the use of fentanyl (average dose : 4.87 microgram/kg/h) or phenoperidine (average dose : 48.7 microgram/kg/h). Naloxone was administered intravenously in an average dose of 1.37 microgram/kg (in one or two injections) followed by an intramuscular injection of an average of 0.73 microgram/kg. Under these conditions, respiratory depression was completely corrected in all cases, the effect being durable. Good analgesia was retained and there was a normal return to consciousness without undesirable effects.

Topics: Adult; Clinical Trials as Topic; Consciousness; Drug Evaluation; Female; Fentanyl; Genital Diseases, Female; Humans; Hypoventilation; Middle Aged; Naloxone; Neuroleptanalgesia; Pain, Postoperative; Phenoperidine; Respiration

Topics: Animals; Fentanyl; Hypoventilation; Male; Mice; Molecular Structure; Naloxone; Narcotic Antagonists; Plethysmography; Receptors, Opioid, mu; Respiratory Mechanics

A possible approach to handling the harmful side effects of an analgesic overdose, without losing its therapeutic potential, involves feedback regulated delivery of an antidote. For example, overdose of morphine causes hypoventilation, an inadequate ventilation to perform gas exchanges in lungs leading to increased CO2 concentration in the blood. Taking advantage of CO2 as a toxicity marker, a hydrogel-based delivery vehicle containing dimethylamino groups [poly(N,N-dimethylaminoethyl methacrylate) cross-linked by trimethylolpropane trimethacrylate] was designed. Stimulus controlled swelling of these hydrogels in naloxone delivery is discussed. A remarkable control over naloxone release was achieved against the concentration of the biomarker. The overall stimuli response of the gel could be enhanced further by encapsulating carbonic anhydrase, a metalloenzyme known to catalyze the reversible hydration of CO2. Thus, a feedback regulated drug delivery vehicle based on toxicity biomarker strategy was modeled successfully, which has the potential to mitigate risks associated with drug overdose.

Topics: Analgesics; Antidotes; Biomarkers; Carbon Dioxide; Cations; Drug Delivery Systems; Drug Overdose; Feedback, Physiological; Hydrogels; Hypoventilation; Models, Biological; Morphine; Naloxone; Narcotic Antagonists

Topics: Anesthetics; Humans; Hypoventilation; Naloxone; Neuromuscular Blocking Agents; Nursing Assessment; Nursing Process; Postoperative Complications; Respiration; Respiratory Function Tests

Topics: Body Temperature; Brain; Cardiovascular System; Female; Humans; Hypoventilation; Liver; Maternal-Fetal Exchange; Morphine; Naloxone; Pregnancy; Protein Binding; Respiration; Structure-Activity Relationship; Substance-Related Disorders