Influence of sedation on arousal and cardiorespiratory responses to airflow obstruction in sleeping lambs.
Our aim was to determine the effects of two commonly used sedatives, promethazine and diazepam, on arousal and cardiorespiratory responses to airflow obstruction in sleeping lambs. In eight lambs fitted with obstructable rubber face masks, we recorded electrocortical, electroocular, and electromyographic activities to identify sleep-wake states; intrapleural pressure, heart rate, and percentage O2 saturation (Sao2) were also recorded. In each lamb, arousal and respiratory responses were measured after tidal airflow was obstructed during rapid eye movement (REM) and nonREM sleep. Each lamb was studied, on different days, when unsedated and after being mildly sedated with either promethazine or diazepam. Seven of the lambs were studied while sleeping after being sedated with promethazine (1.6 +/- 0.07 mg/kg, orally with milk) and six were studied after sedation with diazepam (0.31 +/- 0.03 mg/kg, intramuscularly). In unsedated lambs, airflow obstruction led to augmentation of respiratory efforts, bradycardia, hypoxemia, and arousal; in REM sleep, arousal was delayed and occurred at lower Sao2 (16 +/- 3 s; 75.3 +/- 3%) compared with nonREM sleep (8 +/- 1 s; 90 +/- 1%). Sedation increased the arousal latency in both REM and nonREM sleep and caused arousal to occur at lower Sao2; in some sedated lambs Sao2 fell to less than 30% before arousal. The augmentation of inspiratory and expiratory efforts immediately before arousal was increased after sedation. We conclude that promethazine and diazepam depress arousal responses in sleeping lambs leading to profound hypoxia, and that this may be due to impaired sensitivity to augmented respiratory efforts and other physiologic changes during airflow obstruction.
Department of Physiology, Monash University, Melbourne, Victoria, Australia.
A E
AE
Jakubowska
G J
GJ
McCrabb
R
R
Harding
D000818:Animals; D000831:Animals, Newborn; D001143:Arousal; D003975:Diazepam / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects*; D006993:Hypnotics and Sedatives / Q000494:pharmacology*; D010101:Oxygen Consumption / Q000187:drug effects; D010296:Parietal Lobe / Q000502:physiology; D011398:Promethazine / Q000494:pharmacology*; D012119:Respiration / Q000187:drug effects*; D012756:Sheep; D012890:Sleep / Q000187:drug effects / Q000502:physiology*; D012895:Sleep, REM / Q000187:drug effects / Q000502:physiology
D006993:Hypnotics and Sedatives; D011398:Promethazine; D003975:Diazepam