Mak K H, Wang Y T, Cheong T H, Poh S C
Dept. of Medicine III, Tan Tock Seng Hospital, Singapore.
Eur Respir J. 1993 Jan;6(1):42-7.
Benzodiazepine have been shown to suppress ventilatory responses to hyperoxic hypercapnia (HCVR) and isocapnic HVR when taken parenterally. Most patients would, however, prefer to take an oral rather than parenteral preparation but the effect of oral benzodiazepine on these ventilatory responses has not been well studied. We therefore studied the effect of oral midazolam (7.5 mg) and diazepam (5 mg) both given orally on resting ventilation and respiratory drive, as assessed by HCVR and HVR. Flumazenil, a specific benzodiazepine antagonist, was administered intravenously to reverse the effect. A mental alertness-drowsiness index in five grades, from 1 (awake and alert) to 5 (asleep), was used to assess the sedation effect. Six normal male subjects, (aged 31 +/- 1.6 yrs) (mean +/- SD), participated in the study. Mean resting ventilation, and ventilatory response to HCVR and HVR were not significantly altered by these drugs when taken orally. Flumazenil also had not significant effect on HCVR and HVR. However the mental alertness-drowsiness index rose from 1 to 2.83 with oral midazolam and reversed to 1.25 with flumazenil. Similarly, this index increased from 1 to 2.25 after oral diazepam and reversed to 1.42 after flumazenil. In conclusion, we found that even though oral midazolam and diazepam produced a significant sedation effect, which was reversed with flumazenil, the drugs had no effect on ventilation at rest and the ventilatory responses to hypoxia and hypercapnia.
苯二氮䓬类药物经肠胃外给药时，已显示出可抑制对高氧性高碳酸血症（HCVR）和等碳酸血症性HVR的通气反应。然而，大多数患者更愿意口服而非肠胃外给药，但口服苯二氮䓬类药物对这些通气反应的影响尚未得到充分研究。因此，我们研究了口服咪达唑仑（7.5毫克）和地西泮（5毫克）对静息通气和呼吸驱动的影响，通过HCVR和HVR进行评估。静脉注射氟马西尼，一种特异性苯二氮䓬类拮抗剂，以逆转其作用。采用从1（清醒警觉）到5（睡着）的五级精神警觉-嗜睡指数来评估镇静效果。六名正常男性受试者（年龄31±1.6岁）（平均值±标准差）参与了该研究。口服这些药物时，平均静息通气以及对HCVR和HVR的通气反应均未发生显著改变。氟马西尼对HCVR和HVR也无显著影响。然而，口服咪达唑仑后精神警觉-嗜睡指数从1升至2.83，使用氟马西尼后又降至1.25。同样，口服地西泮后该指数从1升至2.25，使用氟马西尼后降至1.42。总之，我们发现尽管口服咪达唑仑和地西泮产生了显著的镇静效果，且可被氟马西尼逆转，但这些药物对静息通气以及对低氧和高碳酸血症的通气反应并无影响。
