PubMed2000
OBJECTIVES: Maternal cigarette smoking is established as a major dose-dependent risk factor for sudden infant death syndrome (SIDS). Both prenatal and postnatal exposures to constituents of tobacco smoke are associated with SIDS, but no mechanism of death attributable to nicotine has been found. Breastfeeding gives a substantial increase in absorbed nicotine compared with only environmental tobacco smoke when the mother smokes, because the milk:plasma concentration ratio of nicotine is 2.9 in smoking mothers. Furthermore, many SIDS victims have a slight infection and a triggered immune system before their death, thus experiencing a release of cytokines like interleukin-1beta (IL-1beta) that may depress respiration. Because apneas in infancy are associated with SIDS, we have tested the hypothesis that postnatal exposure to tobacco constituents and infections might adversely affect an infant's ability to cope with an apneic episode. This is performed by investigating the acute effects of nicotine and IL-1beta on apnea by laryngeal reflex stimulation and on the subsequent autoresuscitation. DESIGN: Thirty 1-week-old piglets (+/-1 day) were sedated with azaperone. A tracheal and an arterial catheter were inserted during a short halothane anesthesia. The piglets were allowed a 30-minute stabilization period before baseline values were recorded and they were randomized to 4 pretreatment groups (avoiding siblings in the same group): 1) immediate infusion of 10 pmol IL-1beta intravenously/kg (IL-1beta group; n = 8); 2) slow infusion of 5 microg nicotine intravenously/kg 5 minutes later (NIC group; n = 8); 3) both IL-1beta and NIC combined (NIC + IL-1beta group; n = 6); or 4) placebo by infusion of 1 ml .9% NaCl (CTR group; n = 8). Fifteen minutes later, apnea was induced by insufflation of .1 ml of acidified saline (pH = 2) in the subglottic space 5 times with 5-minute intervals, and variables of respiration, heart rate, blood pressure, and blood gases were recorded. RESULTS: Stimulation of the laryngeal chemoreflex by insufflation of acidified saline in the subglottic space produced apneas, primarily of central origin. This was followed by a decrease in heart rate, a fall in blood pressure, swallowing, occasional coughs, and finally autoresuscitation with gasping followed by rapid increase in heart rate, rise in blood pressure, and (in the CTR group) an increase of respiratory rate. Piglets pretreated with nicotine had more spontaneous apneas, and repeated spontaneous apneas caused an inability to perform a compensatory increase of the respiratory rate after induced apnea. This resulted in a lower SaO(2) than did CTR at 2 minutes after apnea (data shown as median [interquartile range]: 91% [91-94] vs 97% [94-98]). The pretreatment with IL-1beta caused prolonged apneas in piglets and an inability to hyperventilate causing a postapneic respiratory rate similar to the NIC. When nicotine and IL-1beta were combined, additive adverse effects on respiratory control and autoresuscitation compared with CTR were observed: NIC + IL-1beta had significantly more spontaneous apneas the last 5 minutes before induction of apnea (2 [.3-3] vs 0 [0-0]). Apneas were prolonged (46 seconds [39-51] vs 26 seconds [22-31]) and followed by far more spontaneous apneas the following 5 minutes (6.6 [4.0-7.9] vs.5 [.2- .9]). Instead of normal hyperventilation after apnea, a dramatic decrease in respiratory rate was seen (at 20 seconds: -45% [-28 to -53] vs +29% [+24-+50], and at 60 seconds: -27% [-23 to -32] vs +3% [-2-+6), leading to SaO(2) below 90% 3 minutes after end of apnea: 89% (87-93) versus 97% (95-98). These prolonged adverse effects on ventilation were reflected in lowered PaO(2), elevated PaCO(2) and lowered pH 2 minutes, and even 5 minutes, after induction of apnea. CONCLUSIONS: Nicotine interferes with normal autoresuscitation after apnea when given in doses within the range of what the child of a smoking mother could receive through environmental t