Effect of temazepam on ventilatory response at moderate altitude

British Medical Journal, Jan 1, 2000 by Georg Roggla, Berthold Moser, Martin Roggla

EDITOR--Dubowitz's study of the effect of temazepam on oxygen saturation at high altitude found that benzodiazepines do not have a depressant effect.[1] He explains the discrepancy between his findings and those of previous studies by the fact that other studies have investigated the effect of long acting benzodiazepines.[2] Dubowitz's probands were investigated after altitude acclimatisation while walking to Everest base camp, whereas climbers in Europe mainly engage in short periods of mountaineering. We therefore evaluated the effect of 10 mg temazepam on respiration in non-acclimatised Alpine climbers at moderate altitude.

We performed a randomised, double blind, placebo controlled, crossover trial in seven healthy men aged 21 to 27. Participants at 171 m altitude were randomised to receive either 10 mg temazepam or placebo. Three days later the men were given the same medication and taken by cable car to 3000 m. The procedure was repeated after one week, with the men crossed to the other arm of the study. Arterial blood samples were obtained from the ear lobe before and one hour after temazepam or placebo was taken.[4] Arterial oxygen partial pressure and carbon dioxide partial pressure were analysed on an IL Synthesis 25 blood gas analyser (Instrumentation Laboratory, Milan, Italy). Differences in blood gas concentrations before and after temazepam or placebo at each altitude were analysed by paired t tests.

The table shows the results of blood gas analysis before and after temazepam. At 171 m blood gas concentrations did not change significantly after temazepam. At 3000 m the arterial oxygen pressure decreased and carbon dioxide pressure increased significantly after temazepam. The mean decrease in arterial oxygen concentration between altitudes was 0.77 (95% confidence interval -- 8.02 to -- 3.69) kPa (P [is less than] 0.01) and the mean increase in arterial carbon dioxide concentration was 0.3 (0.46 to 4.11) kPa (P [is less than] 0.05). Placebo did not affect blood gas concentrations at either altitude.

Arterial oxygen ([Pao.sub.2]) and carbon dioxide ([Paco.sub.2]) concentrations (kPa) of seven men before and one hour after 10 mg temazepam at 171 and 3000 m

                              [Pao.sub.2]
                     171 m                    3000 m

Case No       Before        After         Before     After

1              12.2          12.2          9.3        8.6
2              11.2          11.6          8.6        8.4
3              12.1          12            8.9        8.2
4              11            11.4          9.1        4.9
5              10.9          11            8.5        8.1
6              12.5          12.2          9.1        8.1
7              12            12.2          9.4        8.4
Mean (SD)   11.7 (0.63)   11.8 (0.48)   9 (0.29)   8.3 (0.2)

                           [Pao.sub.2]
                  171 m                    3000 m

Case No     Before         After         Before        After

1             4.5           4.3           4.3           4.4
2             4.7           4.9           4.4           4.7
3             4.4           4.5           4.4           4.7
4             4.9           4.8           4.0           4.3
5             4.7           4.4           4.1           4.4
6             4.5           4.8           4.4           4.7
7             4.4           4.5           4.0           4.8
Mean (SD)   33.4 (1.4)    34.6 (1.8)    4.2 (0.19)    4.5 (0.2)

Although we did not measure respiration directly, our data indicate that a low dose of a short term benzodiazepine can impair respiration at moderate altitude. These findings seem to contradict Dubowitz's conclusion. Treatment with temazepam at stable conditions after altitude acclimatisation may not impair respiration, but initial stages of acute respiratory adaptation to hypoxia at altitude are inhibited. Similar results were found after 50 g alcohol at moderate altitude.[5] Caution in the use of benzodiazepines to treat sleep disorders at altitude is therefore necessary, especially in the initial stages of altitude acclimatisation.

[1] Dubowitz G. Effect of temazepam on oxygen saturation and sleep quality at high altitude: randomised placebo controlled crossover trial. BMJ 1998;316:587-9.

[2] Roggla G, Roggla M, Wagner A, Seidler D, Podolsky A. Effect of low dose sedation with diazepam on ventilatory response at moderate altitude. Wien Klin Wochenschr 1994;106:649-51.

[3] Hills M, Armitage P. The two-period cross-over clinical trial. Br J Clin Pharmacol 1979;8:7-20.

[4] Spiro SG, Dowdeswell IR. Arterialised ear lobe blood sampling for blood gas tensions. Br J Dis Chest 1976;70:263-8.

[5] Roggla G, Roggla H, Roggla M, Binder M, Laggner AN. Effect of alcohol on acute ventilatory adaptation to mild hypoxia at moderate altitude. Ann Intern Med 1995;122:925-927.

Georg Roggla head of department interne@khneunkirchen.at

Berthold Moser student Department of Internal Medicine, Municipal Hospital of Neunkirchen, Neunkirchen, Austria

Martin Roggla lecturer Department of Emergency Medicine, University of Vienna, Austria