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Abstract

The respiratory effects of benzodiazepines have been controversial. This investigation aimed to study the effects of oral alprazolam on ventilation. In a randomised, double-blind cross-over protocol, 20 healthy men ingested 1 mg of alprazolam or placebo in random order, 1 week apart. Ventilation was unobtrusively monitored by inductance plethysmography along with end-tidal PCO₂ and pulse oximetry 60–160 min after drug intake. Subjects were encouraged to keep their eyes open. Mean ± SD minute ventilation 120 min after alprazolam and placebo was similar (6.21 ± 0.71 vs 6.41 ± 1.12 L/min, P = NS). End-tidal PCO₂ and oxygen saturation did also not differ between treatments. However, coefficients of variation of minute ventilation after alprazolam exceeded those after placebo (43 ± 23% vs 31 ± 13%, P < 0.05). More encouragements to keep the eyes open were required after alprazolam than after placebo (5.2 ± 5.7 vs 1.3 ± 2.3 calls, P < 0.05). In a multiple regression analysis, higher coefficients of variation of minute ventilation after alprazolam were related to a greater number of calls. Oral alprazolam in a mildly sedative dose has no clinically relevant effect on ventilation in healthy, awake men. The increased variability of ventilation on alprazolam seems related to vigilance fluctuations rather than to a direct drug effect on ventilation.

Keywords

benzodiacepin anxiolythic ventilation apnea hypoventilation control of breathing anxiety

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References

Bloch KE Barandun J Sackner MA (1995) Effect of mouthpiece breathing on cardiorespiratory response to intense exercise. Am J Respir Crit Care Med 151: 1087–1092.

Bloch KE Li Y Sackner MA Russi EW (1997a) Breathing pattern during sleep disruptive snoring. Eur Respir J 10: 576–586.

Bloch KE Li Y Zhang J Bingisser R Kaplan V Weder W Russi EW (1997b) Effect of surgical lung volume reduction on breathing patterns in severe pulmonary emphysema. Am J Respir Crit Care Med 156: 553–560.

Bonnet MH Dexter JR Arand DL (1990) The effect of triazolam on arousal and respiration in central sleep apnea patients. Sleep 13: 31–41.

Brack T Senn O Russi EW Bloch KE (2005) Transtracheal high-flow insufflation supports spontaneous respiration in chronic respiratory failure. Chest 127: 98–104.

Camacho ME Morin CM (1995) The effect of temazepam on respiration in elderly insomniacs with mild sleep apnea. Sleep 18: 644–645.

Carey MP Faulstich ME Carey TC (1994) Assessment of anxiety in adolescents - concurrent and factorial validities of the trait anxiety scale of spielberger state-trait anxiety inventory for children. Psychol Rep 75: 331–338.

Carley DW Trbovic SM Radulovacki M (1998) Diazepam suppresses sleep apneas in rats. Am J Respir Crit Care Med 157: 917–920.

Clark JS Votteri B Aragno RL Cheung P Eichhorn JH Fallat RJ Lee SE Newth CJL Rotman H Sue DY (1992) Noninvasive assessment of blood gases. Am Rev Respir Dis 145: 220–232.

10.

Dodson ME Youssef Y Maddison S Pleuvry B (1976) Letter: respiratory effects of lorazepam. Br J Anaesth 48: 611–612.

11.

Greenblatt DJ Wright CE (1993) Clinical pharmacokinetics of alprazolam. Therapeutic implications. Clin Pharmacokinet 24: 453–471.

12.

Gross JB Zebrowski ME Carel WD Gardner S Smith TC (1983) Time course of ventilatory depression after thiopental and midazolam in normal subjects and in patients with chronic obstructive pulmonary disease. Anesthesiology 58: 540–544.

13.

Hoijer U Hedner J Ejnell H Grunstein R Odelberg E Elam M (1994) Nitrazepam in patients with sleep apnoea: a double-blind placebo-controlled study. Eur Respir J 7: 2011–2015.

14.

Mak KH Wang YT Cheong TH Poh SC (1993) The effect of oral midazolam and diazepam on respiration in normal subjects. Eur Respir J 6: 42–47.

15.

Marteau TM Bekker H (1992) The development of A 6-Item Short-Form of the State Scale of the Spielberger State Trait Anxiety Inventory (STAI). Br J Clin Psychol 31: 301–306.

16.

Martinez JM Kent JM Coplan JD Browne ST Papp LA Sullivan GM Kleber M Perepletchikova F Fyer AJ Klein DF Gorman JM (2001) Respiratory variability in panic disorder. Depress Anxiety 14: 232–237.

17.

Midgren B Hansson L Skeidsvoll H Elmqvist D (1989) The effects of nitrazepam and flunitrazepam on oxygen desaturation during sleep in patients with stable hypoxemic nonhypercapnic COPD. Chest 95: 765–768.

18.

Miller MR Hankinson J Brusasco V Burgos F Casaburi R Coates A Crapo R Enright P van der Grinten CP Gustafsson P Jensen R Johnson DC MacIntyre N McKay R Navajas D Pedersen OF Pellegrino R Viegi G Wanger J (2005) Standardisation of spirometry. Eur Respir J 26: 319–338.

19.

Mora CT Torjman M White PF (1995) Sedative and ventilatory effects of midazolam infusion – effect of flumazenil reversal. Can J Anaesth 42: 677–684.

20.

Murciano D Armengaud MH Cramer PH Neveux E Lheritier C Pariente R Aubier M (1993) Acute effects of zolpidem, triazolam and flunitrazepam on arterial blood-gases and control of breathing in severe COPD. Eur Respir J 6: 625–629.

21.

Nickol AH Leverment J Richards P Seal P Harris GA Cleland J Dubowitz G Collier DJ Milledge J Stradling JR Morrell MJ (2006) Temazepam at high altitude reduces periodic breathing without impairing next-day performance: a randomized cross-over double-blind study. J Sleep Res 15: 445–454.

22.

Oshima T Masaki Y Toyooka H (1999) Flumazenil antagonizes midazolam-induced airway narrowing during nasal breathing in humans. Br J Anaesth 82: 698–702.

23.

Sackner MA Krieger BP (1989) Noninvasive respiratory monitoring. In: SM Scharf SS Cassidy , (eds), Heart–Lung Interactions in Health and Disease. New York, Basel: Marcel Dekker Inc., pp. 663–805.

24.

Sackner MA Watson H Belsito AS Feinerman D Suarez M Gonzalez G Bizousky F Krieger B (1989) Calibration of respiratory inductive plethysmograph during natural breathing. J Appl Physiol 66: 410–420.

25.

Smoller JW Pollack MH Otto MW Rosenbaum JF Kradin RL (1996) Panic anxiety, dyspnea, and respiratory disease. Theoretical and clinical considerations. Am J Respir Crit Care Med 154: 6–17.

26.

Steens RD Pouliot Z Millar TW Kryger MH George CF (1993) Effects of zolpidem and triazolam on sleep and respiration in mild to moderate chronic obstructive pulmonary disease. Sleep 16: 318–326.

27.

Steer RA Ranieri WF Beck AT Clark DA (1993) Further evidence for the validity of the Beck Anxiety Inventory with psychiatric outpatients. J Anxiety Disord 7: 195–205.

28.

Thomson S Morrell MJ Cordingley JJ Semple SJ (2005) Ventilation is unstable during drowsiness before sleep onset. J Appl Physiol 99: 2036–2044.

29.

Trinder J Whitworth F Kay A Wilkin P (1992) Respiratory instability during sleep onset. J Appl Physiol 73: 2462–2469.

30.

Wilhelm FH Roth WT (1997) Acute and delayed effects of alprazolam on flight phobics during exposure. Behav Res Ther 35: 831–841.

31.

Zacharias M Hunter KM Parkinson R (1996) Respiratory effects of intravenous midazolam. N Z Dent J 92: 76–79.

Does oral alprazolam affect ventilation? A randomised,double-blind,placebo-controlled trial

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