Airway protection following simulated gastro-oesophageal reflux in sedated and sleeping neonatal piglets during active sleep.

1. In infants, promethazine has been implicated in the pathogenesis of sleep apnoea, apparent life threatening events (ALTE) and the Sudden Infant Death syndrome (SIDS). The aim of the present study was to investigate, in a neonatal animal, the effects of a commonly used promethazine-containing medication on airway protective mechanisms and cardiorespiratory reflexes following simulated gastro-oesophageal reflux (GER) to different levels in the oesophagus and pharynx. 2. Physiological and radiographic recordings were made in 21 naturally sleeping (controls) and 21 sedated (1.5 mg/kg, p.o., promethazine) piglets. On 3 consecutive days physiological recordings were made in all piglets during active sleep. Gastro-oesophageal reflux was simulated by the injection of boluses of 0.5 mL HCl, pH 2 or 3, or NaCl (0.9%) at 37 degrees C into the pharynx, upper or lower oesophagus. 3. In healthy neonatal piglets, minimal sedation with promethazine, which did not affect behaviour during wakefulness, revealed previously unreported findings during active sleep. 4. The most significant effects were observed following simulated GER to the pharynx, with no effect observed in the lower oesophagus. In sedated piglets, compared with naturally sleeping piglets, there was a significant reduction in swallowing (P < 0.01), delayed radiological clearance of fluid (P < 0.05), a reduction in breathing rate, oxygen saturation and heart rate and an increase in apnoea. 5. These findings are consistent with a low dose of promethazine producing a significant attenuation of airway protective mechanisms and, thus, stimulation of the laryngeal chemoreflex. The results suggest a mechanism for the association observed between promethazine use and the occurrence of ALTE and SIDS. The results support continued caution and suggest the need for greater regulation of promethazine-containing medications in infants.

Sedation with promethazine profoundly affects spontaneous airway protection in sleeping neonatal piglets.

1. Phenothiazine use in infants has been implicated in apparent life-threatening events, sleep apnoea and Sudden Infant Death Syndrome. 2. The aim of this study was to investigate the cumulative effects of a commonly used antihistamine medication containing promethazine on airway protective mechanisms and cardiorespiratory responses in 42 healthy neonatal piglets (21 naturally sleeping, 21 sedated sleeping). 3. Sedated piglets were given 1.5 mg/kg, p.o., promethazine 2 h prior to each recording session. Control animals slept naturally with no sedative given. On three consecutive days in all piglets, physiological recordings were made during sleep; on at least one of these days, simultaneous physiological and radiological observations were made. 4. Following sedation, sleep time and time in active sleep were increased significantly (P < 0.01). The spontaneous occurrence of swallowing, arousal, body movement, gastrooesophageal reflux and apnoea was compared between naturally and sedated sleeping piglets. Sedation with promethazine significantly decreased the spontaneous occurrence of swallowing (P < 0.05) and arousal (P < 0.05) and increased the occurrence of both central (P < 0.05) and obstructive sleep apnoea (P < 0.0001). 5. By the third day, a cumulative effect of promethazine was seen; the rate of swallowing and body movement significantly decreased (P < 0.01). 6. In summary, a low dose of promethazine profoundly altered sleep characteristics, airway protective mechanisms and cardiorespiratory responses in normal healthy sleeping piglets. Continued use of promethazine over several days may attenuate airway protective mechanisms to a potentially life-threatening degree. Our findings support continued caution in the use of promethazine-containing medications for the sedation of infants.

Effects of promethazine on porcine gastroduodenal function: a sonographic study.

This sonographic study was aimed at examining the effect of sedation with promethazine (1.5 mg x kg(-1)), on gastroduodenal function in neonatal piglets. On 3 consecutive days, observations of gastroduodenal motility during the first 3 postprandial h were made in 13 animals (3 to 5 days old; 7 sleeping naturally and 6 sedated 2 h prior to feeding). Promethazine significantly reduced both the closures per min of the terminal part of the pyloric antrum and pyloric canal and the percentage of gastric contractions that were followed by closure of the terminal pyloric antrum and canal. Such actions of promethazine on motility of the gastroduodenal junction could lead to a delay in gastric emptying of ingesta with a consequent increased risk of reflux of gastric contents into the esophagus. Because gastroesophageal reflux has been associated with the pathogenesis of sudden infant death syndrome (SIDS), care should be taken if promethazine is to be used as a sedative in neonates.

Sonographic observations of the gastroduodenal junction in neonatal piglets.

Knowledge of the function of the gastroduodenal junction is important, as changes in its motility are associated with gastrointestinal disorders. Sonographic observations were made of the stomach and duodenum of 19 neonatal piglets, 2-6 d of age. Contractions of the stomach and duodenum were identified clearly; the overall rate of gastric contractions was about 4 min-1. The percentage of contractions in which there was a closure of the terminal pyloric antrum and pyloric canal varied, being 57.2% +/- 4.6% in the first postprandial hour and 43.1% +/- 3.0% in the third. Antegrade flow of digesta principally occurred preceding a closure of the pyloric antrum and canal. During contractions of the pyloric antrum, the torus pyloricus moved caudally to fill the lumen of the pyloric canal. Our sonographic method provided a noninvasive technique for studying the form and function of gastroduodenal motility in the neonate, suitable for investigating factors that alter gastric emptying.