naloxone and Sleep-Apnea-Syndromes

Guidelines for the medical therapy of obstructive sleep apnea are difficult to define precisely. While some elegant investigations have been completed, most study populations have been small. Also, the long-term effects of most forms of therapy are not known. Some patients will respond to a given form of therapy or combination of therapies while others will not. In most instances the responders cannot be recognized prior to the institution of therapy and a cycle of trial and error ensues. One of the best nonsurgical approaches appears to be weight loss, albeit unsuccessful in most cases. Almost all experts would agree, however, that in nonemergent situations weight loss should be strongly suggested. Nasal CPAP appears to be the single most promising device. Protriptyline may have a role, although in our opinion its true efficacy remains to be determined. Oxygen will probably serve more an adjunctive role in therapy, and medroxyprogesterone appears to be beneficial only in the treatment of the obesity-hypoventilation syndrome. A reasonable approach to the medical treatment of the obstructive sleep apnea patient should include, first, by history, physical examination, and appropriate laboratory testing, elimination of anatomically correctable, pharmacologic, or endocrinologic causes of OSA. If apnea length, degree of desaturation, cardiac arrhythmias, or levels of hypersomnolence are so severe as to be potentially life threatening, immediate tracheostomy is suggested. In specialized centers, nasal CPAP would be used. In less severely affected patients, medical management, as discussed above, should begin. We believe that in view of the lack of controlled trials demonstrating which form of therapy is best, the clinician must recommend therapy on the basis of local clinical experience and patient acceptance. Of fundamental importance is the need for serial reevaluation so that the impact of therapeutic failure can be minimized.

Topics: Almitrine; Central Nervous System Stimulants; Diet, Reducing; Humans; Intubation; Male; Naloxone; Nasopharynx; Obesity; Oxygen Inhalation Therapy; Piperazines; Positive-Pressure Respiration; Progesterone; Protriptyline; Sleep Apnea Syndromes; Theophylline

Patients using chronic opioids are at risk for exceptionally complex and potentially lethal disorders of breathing during sleep, including central and obstructive apnoeas, hypopnoeas, ataxic breathing and nonapnoeic hypoxaemia. Buprenorphine, a partial μ-opioid agonist with limited respiratory toxicity, is widely used for the treatment of opioid dependency and chronic nonmalignant pain. However, its potential for causing sleep disordered breathing has not been studied. 70 consecutive patients admitted for therapy with buprenorphine/naloxone were routinely evaluated with sleep medicine consultation and attended polysomnography. The majority of patients were young (mean±sd age 31.8±12.3 years), nonobese (mean±sd body mass index 24.9±5.9 kg·m(-2)) and female (60%). Based upon the apnoea/hypopnoea index (AHI), at least mild sleep disordered breathing (AHI ≥5 events·h(-1)) was present in 63% of the group. Moderate (AHI ≥15- <30 events·h(-1)) and severe (AHI ≥30 events·h(-1)) sleep apnoea was present in 16% and 17%, respectively. Hypoxaemia, defined as an arterial oxygen saturation measured by pulse oximetry, of <90% for ≥10% of sleep time, was present in 27 (38.6%) patients. Despite the putative protective ceiling effect regarding ventilatory suppression observed during wakefulness, buprenorphine may induce significant alterations of breathing during sleep at routine therapeutic doses.

Topics: Adolescent; Adult; Buprenorphine; Female; Humans; Male; Middle Aged; Naloxone; Narcotic Antagonists; Opioid-Related Disorders; Polysomnography; Respiration; Sleep Apnea Syndromes; Young Adult

The medial pontine reticular formation (mPRF) is a cholinoceptive brain stem region known to play a key role in regulating rapid eye movement (REM) sleep and state-dependent ventilatory depression. Numerous lines of evidence have shown that opioids inhibit both cholinergic neurotransmission and REM sleep. The present study examined the hypothesis that morphine applied to the cholinoceptive mPRF would inhibit REM sleep and alter ventilation. In six cats, guide cannulas were chronically implanted to permit pontine microinjection of morphine sulfate, naloxone, and the cholinergic agonist carbachol. After each mPRF microinjection, 2-h polygraphic recordings quantified respiratory frequency and the percent of time spent in states of wakefulness, non-REM sleep, and REM sleep. The results show that mPRF administration of morphine significantly inhibited REM sleep and that this REM sleep inhibitory effect was blocked by pretreating the mPRF with naloxone. Apneic episodes were increased after injection of morphine alone, and the apneas were decreased by the cholinergic agonist carbachol. The results also demonstrated that the ability of microinjected morphine to inhibit REM sleep was dose-dependent and site-dependent. Considered together, the site-localization, pharmacologic blocking, and dose-response data support the hypothesis that specific regions of the mPRF can contribute to the long-recognized ability of morphine to inhibit REM sleep and alter respiratory control.

Topics: Animals; Carbachol; Cats; Male; Morphine; Naloxone; Pons; Reticular Formation; Sleep Apnea Syndromes; Sleep, REM

Defense of ventilatory homeostasis against recurrent hypercapnia, hypoxia, and acidosis resulting from apnea in obstructive sleep apnea syndrome (OSAS) is dependent on compensatory mechanisms operative between episodes of airway obstruction. This investigation was designed to examine whether endogenous opiate activity modulates the compensatory ventilatory response to apnea in OSAS. Polysomnography and quantitative measurement of tidal volume was performed in 12 patients with moderate to severe OSAS during a morning nap study before and after intravenous administration of 10 mg of naloxone. Apnea index was not significantly altered. There was a small but significant shortening of apneas (postnaloxone apnea duration, 91.2% of prenaloxone; p = 0.002 by ANOVA). Tidal volume of the first postapnea breath and minute ventilation extrapolated from the first two postapnea breaths, but not frequency, increased significantly after naloxone (postnaloxone first breath volume, 112.7% of prenaloxone value [p = 0.03], with a similar increase for minute ventilation, 115.1% [p = 0.007]). The volume of the first postapnea breath was correlated with the duration of the previous apnea, both before (r = 0.59, p = 0.0001) and after naloxone. Despite this, analysis of covariance with apnea duration as the covariate confirmed a significant independent increase in postapnea breath volume after naloxone (p = 0.001). Naloxone also altered sleep architecture, increasing percent time awake during the study period (prenaloxone, 36.3 +/- 15.6%; postnaloxone, 56.7 +/- 22.4%; p = 0.0003) and decreasing total sleep time and percent time in Stage 1. Furthermore, naloxone increased continuity of awake periods (mean length of awake periods increased from 27.0 +/- 8.4 to 66.0 +/- 66.6 s after naloxone, p = 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Analysis of Variance; Endorphins; Humans; Naloxone; Reaction Time; Respiration; Sleep; Sleep Apnea Syndromes; Wakefulness

A simple blind study with small doses of naloxone (0.8-1.6 mg i.v.) was carried out in 11 patients with hypersomnia with sleep apnoea (HSA). The effect was studied by diurnal polysomnography. It was found that the administration of naloxone was followed by significant prolongation of wakefulness and by significant shortening of the total duration of the second stage of NREM sleep. The duration of the apnoeic episodes was also significantly shortened after naloxone, although their number did not alter. Increased activity of the endorphinergic system (which naloxone inhibits by receptor competition) evidently plays a role in the pathophysiology of HSA.

Topics: Adult; Disorders of Excessive Somnolence; Female; Humans; Male; Middle Aged; Naloxone; Single-Blind Method; Sleep Apnea Syndromes; Sleep Wake Disorders; Sleep, REM

A patient not known in advance to have the sleep apnoea syndrome (SAS) was administered a combined epidural-general anaesthetic for a proposed radical prostatectomy. After surgery which had to be discontinued due to extensive tumoural spread, morphine 5 mg was administered through the epidural catheter for analgesia. Severe respiratory depression occurred eight hours later and was successfully reversed by repeated injections of naloxone. The potential danger of epidural morphine administration to SAS patients is discussed.

Topics: Aged; Anesthesia, Epidural; Anesthesia, General; Blood Gas Analysis; Humans; Male; Morphine; Naloxone; Oxygen Inhalation Therapy; Pain, Postoperative; Prostatectomy; Respiratory Insufficiency; Sleep Apnea Syndromes

Topics: Adult; Coma; Humans; Hypnotics and Sedatives; Male; Meperidine; Naloxone; Physostigmine; Promethazine; Respiration; Sleep Apnea Syndromes

The effects of intravenous injections of the opiate antagonist naloxone (0.005-0.4 mg/kg body weight) on respiratory pattern, apnoea duration and frequency were investigated in six infants with severe sleep apnoea syndrome. Since several authors found elevated plasma- and CSF-levels of endogenous opioids (endorphines) in infants with sleep apnoea syndrome, we wanted to determine whether the impairment of the control mechanisms of respiration during sleep is due to an effect of endogenous opioids. Independent of the dose, naloxone did not exert any effect on respiratory pattern and occurrence of periodic apnoea. We were unable to prove that endorphines play a major role in pathogenesis of sleep apnoea syndrome in infancy and possibly in sudden infant death syndrome (SIDS). We speculate that elevated levels of endorphines reported by some investigators rather seem to be a consequence of hypoxic stress than a cause for sleep apnoeas.

Topics: Aminophylline; Drug Therapy, Combination; Female; Humans; Infant; Male; Naloxone; Respiration; Risk; Sleep; Sleep Apnea Syndromes; Sudden Infant Death

To test the hypothesis that endogenous opiates play a role in the etiology of the sleep apnea syndrome, we administered naloxone, an opiate antagonist, to ten obese humans with sleep apnea. On two separate nights we measured the frequency and severity of sleep apnea during naloxone infusion vs saline control infusion. The number of oxyhemoglobin desaturation episodes was not significantly lowered but the average maximal oxyhemoglobin desaturation fell significantly (P less than 0.01) with naloxone. The desaturation index (average maximal oxyhemoglobin desaturation times desaturations per hour) fell by 21 percent (P less than 0.05) on the night of naloxone infusion. Nine of the ten patients had a lower desaturation index with naloxone. REM sleep decreased by 80 percent (P less than 0.05) in the subjects in whom it was measured. We conclude that opiate antagonists hold promise in the treatment of sleep apnea and that the endogenous opiate system may be involved in the production of sleep apnea.

Topics: beta-Endorphin; Endorphins; Female; Humans; Male; Naloxone; Obesity; Sleep Apnea Syndromes; Sleep, REM