Temazepam

Introduction

Sleep is impaired in people who have recently arrived at

high altitude.[1 2] Impairment is caused by a combination of

factors, which include being in a new environment, the low

temperature, general discomfort, and development of acute

mountain sickness. A feature of sleep at high altitude is

periods of awakening or arousal that are associated with

pronounced oxygen desaturation and periodic breathing.[3-7]

These episodes of periodic breathing may cause more

unconsolidated sleep, which may lead to further episodes

of periodic breathing.[8] Consequently, daytime symptoms

of drowsiness and reduced performance may occur.[9] The

use of benzodiazepine hypnotics may lessen the effects of

periodic breathing and desaturation.[7 8]

This study compared the effects of a comparatively

low dose (10 mg) of the short acting benzodiazepine

temazepam with placebo on the sleep patterns of subjects

recently arrived at high altitude.

Subjects and methods

Shortly after arrival at 5300 in on Mount Everest nine men

and two women (age range 26-46) were randomly

selected from the 78 members of the British Mount

Everest Medical Expedition. All participants gave

informed consent. The study was approved by the Oxford

regional ethics committee. A coin was tossed to randomly

allocate participants to either temazepam (Norton

Pharmaceuticals, Essex) or placebo (Advisory Services,

London) on the first night followed by the other treatment

on the second night. Participants were unaware which

treatment they were given. However, the investigator was

aware of participants' allocation at the time treatment was

given because of the different sizes of tablets, but was not

aware when data were analysed. Arterial oxygen saturation

was measured continuously during the night (every 5 s)

with a pulse oximeter and finger probe (Minolta Pulseox 7,

De Vilbiss, Middlesex). Each morning quality of sleep

was appraised subjectively by direct questioning.

The data on saturation and pulse rate were

downloaded to a computer and analysed to find the mean

saturation values and variation in saturation (die number of

times saturation dropped [is greater than] 4% below mean value). Values

were analysed with a paired, two tailed Student's t test

(Statview SE and Graphics, version 1.04, Abacus

Concepts, Berkeley, CA). P [is less than] 0.05 was considered

significant.

Results

Six participants took temazepam on the first night and

placebo on the second and five took placebo on the first

and temazepam on the second. The mean duration of

recordings made during sleep was 408 minutes (SD 35

min). Length of recording was limited by sleep duration or

oximeter battery life (whichever was shorter).

Mean arterial oxygen saturation--Temazepam had no

significant effect on mean oxygen saturation during sleep

when compared with placebo (table). The difference of

1.05% was not significant using a paired t test (P = 0.54,

df= 10, 95% confidence interval -4.73 to 2.65). However,

when participants took temazepam there was a significant

decrease in the number of times that saturation fell [is greater than] 4%

below the mean (P=0.0036); there were 25.81 fewer falls

per hour that were [is greater than] 4% below the mean when

participants took temazepam when compared with

placebo (df= 10, 10.7 falls per hour on temazepam v 40.9

falls per hour on placebo). The effect was more

pronounced in the early hours of sleep. These effects were

found regardless of whether participants were assigned to take temazepam

or placebo first (figure).

Mean arterial oxygen saturation in 11 participants at high altitude

who took placebo or temazepam

[11] Laserre E. Insomnies d'altitude: efficacite du fluritiazepam. [High

altitude insomnia: efficacy of fluritrazepam.] Nouv Presse Med 1979;8:2577-8.

[12] Goldenberg F, Richalet JP, Jouhandin M, Gisquet A, Keromes A, Larmignat

P. Respiration periodique pendant le sommeil en altitude. Effets d'une

benzodiazepine hypnotique, le loprazolam. [Periodic respiration dining

sleep at high altitude. Effect of a benzodiazepine hypnotic, loprazolam.]

Presse Med 1988; 17:471-4.

[13] Sutton JR, Gray GW, Houston CS, Powles ACP. Effects of acclimatization

on sleep hypoxaemia at altitude. In: West JB, Lahiri S, eds. High altitude

and man. Washington, DC: American Physiological Society, 1983.

[14] Powles SCP, Sutton JR. Sleep at Altitude. Semin Resp Med 1983;5:175-80.

(Accepted 28 October 1997)

RELATED ARTICLE: Key messages

* Poor sleep at high altitude is common and may

be due to a combination of physiological and

physical factors

* Frequent arousals, periodic breathing, and

episodes of oxygen desaturation lead to poor

sleep and daytime symptoms of drowsiness and

reduced performance

* In this study 10 mg temazepam improved

subjective reports of the quality of sleep and

reduced episodes of arterial desaturation, with

no significant effect on mean oxygen saturation

during sleep

British Mount

Everest Medical

Expedition, The

Pinfold, Hyssington,

Montgomery, Powys

SY15 6AY

Gerald Dubowitz,

expedition medical

officer

Correspondence to:

Dr G Dubowitz, 25

Middleton Road,

London

NW11 7NR

gerald@ii.co.uk

BMJ 1998;316:587-9

COPYRIGHT 1998 British Medical Association
COPYRIGHT 2000 Gale Group