Apneic preterms and methylxanthines: arousal deficits, sleep fragmentation and suppressed spontaneous movements.

OBJECTIVE: To determine if apneic preterm infants currently treated with methylxanthines develop evidence of sleep deprivation from cumulative arousal and motor activational effects. STUDY DESIGN: Sleep, wake, arousal and actigraphic movements were monitored in extubated clinically stable premature infants (N=37). Neonates were free of other medications for >72 h and were grouped based on methylxanthine exposure: >5 days with caffeine (n=14), >5 days theophylline (n=13) or no prior exposure (n=10). RESULT: Duration of methylxanthine treatment predicted increased arousals, wakefulness and actigraphic movements, and decreased active sleep. Recording from 1200 to 0500 hours, methylxanthine-treated groups showed reductions in all arousal parameters: waking state, number of wake epochs, brief arousals and composite arousal index, and shorter fast-burst, sleep-related motility than untreated controls. CONCLUSION: In apneic preterms, chronic methylxanthine treatment appears to produce sleep deprivation secondary to the stimulatory action of methylxanthines on arousal and motor systems.

Effects of unilateral lesions of retrotrapezoid nucleus on breathing in awake rats.

In anesthetized rats, unilateral retrotrapezoid nucleus (RTN) lesions markedly decreased baseline phrenic activity and the response to CO2 (E. E. Nattie and A. Li. Respir. Physiol. 97:63-77, 1994). Here we evaluate the effects of such lesions on resting breathing and on the response to hypercapnia and hypoxia in unanesthetized awake rats. We made unilateral injections [24 +/- 7 (SE) nl] of ibotenic acid (IA; 50 mM), an excitatory amino acid neurotoxin, in the RTN region (n = 7) located by stereotaxic coordinates and by field potentials induced by facial nerve stimulation. Controls (n = 6) received RTN injections (80 +/- 30 nl) of mock cerebrospinal fluid. A second control consisted of four animals with IA injections (24 +/- 12 nl) outside the RTN region. Injected fluorescent beads allowed anatomic identification of lesion location. Using whole body plethysmography, we measured ventilation in the awake state during room air, 7% CO2 in air, and 10% O2 breathing before and for 3 wk after the RTN injections. There was no statistically significant effect of the IA injections on resting room air breathing in the lesion group compared with the control groups. We observed no apnea. The response to 7% CO2 in the lesion group compared with the control groups was significantly decreased, by 39% on average, for the final portion of the 3-wk study period. There was no lesion effect on the ventilatory response to 10% O2. In this unanesthetized model, other areas suppressed by anesthesia, e.g., the reticular activating system, hypothalamus, and perhaps the contralateral RTN, may provide tonic input to the respiratory centers that counters the loss of RTN activity.

Acute digoxin overdose in a newborn with renal failure: use of digoxin immune Fab and peritoneal dialysis.

Digitalis intoxication is a common problem, mainly because of the narrow margin of safety of digoxin. These patients may have concomitant renal failure. In patients who have renal failure and who have been treated with digoxin-Fab, the elimination of the digoxin-Fab complex is significantly delayed, and there is a risk of dissociation of the complex with rebound of free digoxin and recurrence of toxicity. The high molecular weight of digoxin and digoxin-Fab complex prevents its elimination by hemodialysis or continuous arteriovenous hemofiltration. A 3-day-old newborn with digoxin overdose and acute renal failure was treated with digoxin immune Fab and peritoneal dialysis. Low levels of total digoxin were measured in the dialyzate, indicating poor elimination of the digoxin-Fab complex through peritoneal dialysis.