Temazepam at high altitude reduces periodic breathing without impairing next-day performance: A randomized cross-over double-blind study

Oxford Centre for Respiratory Medicine, Churchill Hospital, Headington, Oxford, UK.
Journal of Sleep Research (Impact Factor: 3.35). 01/2007; 15(4):445-54. DOI: 10.1111/j.1365-2869.2006.00558.x
Source: PubMed


The aim of the study was to examine the efficacy and safety of temazepam on nocturnal oxygenation and next-day performance at altitude. A double-blind, randomized, cross-over trial was performed in Thirty-three healthy volunteers. Volunteers took 10 mg of temazepam and placebo in random order on two successive nights soon after arrival at 5000 m, following a 17-day trek from 410 m. Overnight SaO(2) and body movements, and next-day reaction time, maintenance of wakefulness and cognition were assessed. Compared with placebo, temazepam resulted in a reduction in periodic breathing from a median (range) of 16 (0-81.3)% of the night to 9.4 (0-79.6)% (P = 0.016, Wilcoxon's signed-rank test), associated with a small but significant decrease in mean nocturnal SaO(2) from 78 (65-84)% to 76 (64-83)% (P = 0.013). There was no change in sleep latency (P = 0.40) or restlessness (P = 0.30). Temazepam had no adverse effect on next-day reaction time [241 (201-380) ms postplacebo and 242 (204-386) ms post-temazepam], maintenance of wakefulness (seven trekkers failed to maintain 40 min of wakefulness postplacebo, and four post-temazepam), cognition or acute mountain sickness. At high altitude temazepam reduces periodic breathing during sleep without an adverse effect on next-day reaction time, maintenance of wakefulness or cognition. The 2% reduction in mean SaO(2) post-temazepam is likely to be predominantly because of acclimatization, as by chance more trekkers took temazepam on the first night (19 versus 14). We conclude that at high altitude temazepam is effective in reducing periodic breathing, and is safe to use, without any adverse effect upon next-day performance.

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Available from: Jim Milledge, Sep 08, 2014
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    • "While the current study is the first that validates actigraphy by comparison to polysomnography at altitude, the technique has been employed previously to evaluate the effects of hypoxia, acute mountain sickness, and drugs for treatment of altitude insomnia (Barash et al., 2001; Erba et al., 2004; Nickol et al., 2006) illustrating the role of actigraphy for investigation of sleep and its disturbances at altitude. One study revealed that temazepam induced a reduction in periodic breathing over the course of a trek to 5000 m (Nickol et al., 2006) but there was no change in actigraphic sleep latency or nocturnal restlessness. Another study assessing the effects of zolpidem and zaleplon on sleep at 3613 m (Beaumont et al., 2007) revealed a significant decrease in the number of wrist movements by both drugs compared to placebo. "
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    ABSTRACT: Data on sleep at altitude are scant due to the limited availability of polysomnography. Therefore, we investigated whether actigraphy might serve as a simple tool for monitoring sleep during altitude field studies. Fourteen mountaineers participating in studies on dexamethasone prophylaxis of high altitude pulmonary edema were monitored by actigraphy and polysomnography during 1 night at Zurich (490 m) and 4 nights at the Regina Margherita hut (4559 m). Total sleep time (TST) estimated by actigraphy was compared to polysomnography and subjective sleep quality. In 64 comparisons, mean differences±2SD (bias±limits of agreement) between actigraphy and polysomnography were 5±35 min for TST and 1±7% for sleep efficiency. Correlations between subjective and polysomnographic estimates of sleep efficiency and sleep latency were nonsignificant. Medians of nocturnal oxygen saturation were 96% at 490 m and 74%-81% during nights 1 to 4 at 4459 m (p<0.05 vs. 490 m). Medians of polysomnographic TST were similar at 490 m (451 min) and 4559 m (377-456 min during nights 1 to 4, p=NS) but the proportions of slow wave and REM sleep were reduced and arousals were more common (p<0.05 all instances). Actigraphy accurately estimates sleep efficiency and duration. Due to its portability and simple use and the potential application over several weeks, it is a convenient tool for investigating altitude effects on sleep during field studies.
    High altitude medicine & biology 10/2011; 12(3):229-36. DOI:10.1089/ham.2010.1073 · 1.28 Impact Factor
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    • "If still abnormal, prophylactic drug therapy is recommended: acetazolamide (250 mg b.i.d.), dexamethasone (2 mg b.i.d.), sildenafil (20 mg b.i.d.) [11,23], nifedipine slow release (20 mg b.i.d.). In the case of ventilatory (respiratory pump, periodic breathing) insufficiency with and without lung and heart failure: polysomnography should be performed in all patients, if necesssary with and without supplemental O2-breathing and/or mechanical aids at night (CPAP, BiPAP, IPPV, added dead space) and drug therapy [9,12,20,22]. "
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    ABSTRACT: Altitude travel results in acute variations of barometric pressure, which induce different degrees of hypoxia, changing the gas contents in body tissues and cavities. Non ventilated air containing cavities may induce barotraumas of the lung (pneumothorax), sinuses and middle ear, with pain, vertigo and hearing loss. Commercial air planes keep their cabin pressure at an equivalent altitude of about 2,500 m. This leads to an increased respiratory drive which may also result in symptoms of emotional hyperventilation. In patients with preexisting respiratory pathology due to lung, cardiovascular, pleural, thoracic neuromuscular or obesity-related diseases (i.e. obstructive sleep apnea) an additional hypoxic stress may induce respiratory pump and/or heart failure. Clinical pre-altitude assessment must be disease-specific and it includes spirometry, pulsoximetry, ECG, pulmonary and systemic hypertension assessment. In patients with abnormal values we need, in addition, measurements of hemoglobin, pH, base excess, PaO2, and PaCO2 to evaluate whether O2- and CO2-transport is sufficient. Instead of the hypoxia altitude simulation test (HAST), which is not without danger for patients with respiratory insufficiency, we prefer primarily a hyperoxic challenge. The supplementation of normobaric O2 gives us information on the acute reversibility of the arterial hypoxemia and the reduction of ventilation and pulmonary hypertension, as well as about the efficiency of the additional O2-flow needed during altitude exposure. For difficult judgements the performance of the test in a hypobaric chamber with and without supplemental O2-breathing remains the gold standard. The increasing numbers of drugs to treat acute pulmonary hypertension due to altitude exposure (acetazolamide, dexamethasone, nifedipine, sildenafil) or to other etiologies (anticoagulants, prostanoids, phosphodiesterase-5-inhibitors, endothelin receptor antagonists) including mechanical aids to reduce periodical or insufficient ventilation during altitude exposure (added dead space, continuous or bilevel positive airway pressure, non-invasive ventilation) call for further randomized controlled trials of combined applications.
    02/2011; 6(1):38-46. DOI:10.1186/2049-6958-6-1-38
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    • "Similarly,wedidnotfindadifferenceineitherthemeanor minimumsleepingSaO2betweensubjectswithandwithout PB.AstudybyNickoletal.(2006)studiedtheeffectsof temazepamonPB,overnightSaO2andnext-daycognitive performance;theyfoundthattemazepamdidreducePBbut wasassociatedwithasmallbutsignificantdecreasein overnightSaO2;thisdecreaseinSaO2may,however,bedue tothefactthatmostsubjectstooktemazepamonthefirstnight athighaltitude. "
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    ABSTRACT: The aim of this study was to examine sleep architecture at high altitude and its relationship to periodic breathing during incremental increases in altitude. Nineteen normal, sea level-dwelling volunteers were studied at sea level and five altitudes in the Nepal Himalaya. Morning arterial blood gases and overnight polysomnography were performed in 14 subjects at altitudes: 0, 1400, 3500, 3900, 4200 and 5000 m above sea level. Subjects became progressively more hypoxic, hypocapnic and alkalinic with increasing altitude. As expected, sleep architecture was affected by increasing altitude. While time spent in Stage 1 non-rapid eye movement sleep increased at 3500 m and higher (P < 0.001), time spent in slow-wave sleep (SWS) decreased as altitude increased. Time spent in rapid eye movement (REM) sleep was well preserved. In subjects who developed periodic breathing during sleep at one or more altitudes (16 of 19), arousals because of periodic breathing predominated, contributing to an increase in the total arousal index. However, there were no differences in sleep architecture or sleeping oxyhaemoglobin saturation between subjects who developed periodic breathing and those who did not. As altitude increased, sleep architecture became progressively more disturbed, with Stage 1 and SWS being affected from 3500 m, while REM sleep was well preserved. Periodic breathing was commonplace at all altitudes, and while associated with increases in arousal indices, did not have any apparent effect on sleep architecture.
    Journal of Sleep Research 08/2009; 19(1 Pt 2):148-56. DOI:10.1111/j.1365-2869.2009.00745.x · 3.35 Impact Factor
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