Acute hemodynamic effects of caffeine administration in premature infants.

OBJECTIVE: Administration of caffeine citrate (caffeine) has been a central component of the treatment of apnea of prematurity. However, given its multiple pharmacologic effects, caffeine might be expected to produce hemodynamic changes in heart rate, stroke volume, cardiac output and vascular resistance. STUDY DESIGN: In this prospective observational study, we report the hemodynamic effects of intravenous caffeine administration in a population of premature infants who received caffeine to correct or prevent apnea of prematurity. METHODS: Hemodynamic effects of caffeine were determined in 31 infants. Stroke volume was measured via echocardiogram, using velocity time integral at the aortic root diameter. Statistically univariate analyses were performed parametrically using paired t-test and nonparametrically (sign test). Multivariate linear regression models were used to identify subgroup covariate effects. RESULTS: After intravenous caffeine, cardiac index increased in 31 of 31 trials, by an average of 14.6+/-16.3% (s.d.); stroke volume increased in 24 of 31 trials, by 7.8+/-12.2%; heart rate increased in 28 of 31 trials by 7.7+/-7.2 beats per min; and blood pressure increased in 25 of 31 trials, by 4.1+/-5.8 mm Hg (all P<0.001). Multivariate linear regression revealed no significant effect of dose, birth weight, gestational age or postnatal age. CONCLUSIONS: Intravenous caffeine consistently increases cardiac output and blood pressure in relatively stable premature infants, when given to treat or prevent apnea of prematurity. We speculate that there may be a role for caffeine in the hemodynamic treatment of hypotensive/hypoperfused infants.

Role of iNO in the modulation of pulmonary vascular resistance.

Inhaled nitric oxide (iNO) has quickly become a standard therapy for term and near-term infants with hypoxic respiratory failure and persistent pulmonary hypertension. Its effect on the lung is believed to be through the stimulation of soluble guanylyl cyclase and the increased production of cyclic guanosine 3',5'-monophosphate (cGMP). However, in addition to pulmonary vasodilation and a decrease in pulmonary vascular resistance, nitric oxide (NO) shows several additional potential beneficial effects on the lung. This article reviews NO mechanisms of action, early clinical trial of iNO and clinical aspects for the use of iNO in acute respiratory failure of the term and near-tem neonates.

Orbital growth retardation in retinoblastoma survivors: work in progress.

BACKGROUND: Orbital growth retardation, after enucleation and/or external beam radiation for retinoblastoma (RB), is a serious late effect. We measured orbital volumes of RB survivors treated at Hadassah University Hospital, Jerusalem, between 1980-1998. PROCEDURE: Forty-five orbits of 28 children with RB (17 bilateral, 11 unilateral) were examined. Thirty-six orbits were irradiated, 19 enucleated, and 10 both enucleated and irradiated. The orbital volumes were calculated from a three-dimensional orbital CT reconstruction. The orbits of RB survivors were compared to age-matched controls. RESULTS: The mean age at diagnosis was 13 months, mean follow-up time was 56 months. The mean volume of RB orbits (14.4 cc) was statistically significantly smaller than control orbits (17.8 cc). There was no difference between the mean volume of orbits treated with enucleation, irradiation or both. The orbital volume of children treated before the age of 12 months was statistically significantly smaller than those treated later. There was no difference between mean volume of fellow orbits in unilateral RB and controls. The mean orbital asymmetry index in control children (2.6%) was statistically significantly smaller than in RB survivors (14%). CONCLUSIONS: There was a significant orbital growth retardation after enucleation and/or irradiation for RB. There was no difference between mean orbital volumes after enucleation, radiation or both. Orbital growth retardation was most prominent in children treated in the first year of life. Although small in number, our study suggests that deferring enucleation and/or irradiation until after the age of 12 months may reduce long-term complications.

Prolonged elimination half-life of phenol after dermal exposure.

BACKGROUND: Phenol is a general protoplastic poison which has been in use in medicine and industry for decades. It is readily absorbed through the skin causing both local and systemic toxicity. CASE REPORT: A 47-year-old male had 90% phenol spilled over his left foot and shoe (3% of body surface area). After a 4 1/2-hour exposure, manifestations included confusion, vertigo, faintness, hypotension, ventricular premature beats, atrial fibrillation, dark-green urine, and tense swelling, blue-black discoloration, hypalgesia, and hypoesthesia of the affected area. Treatment consisted of irrigation with copious amounts of water, incisions, and supportive measures. RESULTS: Peak serum phenol was 21.6 micrograms/mL, considered in the fatal range. Peak urine phenol plus urine-conjugated phenol was 13,416 mg/g creatinine, indicating a major absorption. Elimination half-life was 13.86 hours, considerably longer than previously reported. CONCLUSIONS: Prolonged skin contact with concentrated phenol in an occlusive environment may result in a major absorption and a long elimination half-life even if the area involved is small. Prolonged elimination may be explained by extensive tissue distribution or by "slow-release reservoir" properties of the skin. Such exposure may be associated with severe systemic and local toxicities. Immediate removal from exposure and aggressive decontamination of the skin are essential to reduce these risks.

[Fanconi anemia syndrome as a predisposing factor for acquired bone marrow aplasia].

A 4-year old girl who received prophylactic therapy with oral cephalexin for 1 year because of a history of urinary tract infections, was referred for evaluation of short stature. On physical examination mildly dysmorphic features were observed. Blood counts disclosed pancytopenia, and bone marrow examination showed hypoplasia of all 3 cell lines. Chromosome analysis after exposure to a DNA cross-linking agent (diepoxybutane) showed a chromosomal breakage pattern consistent with Fanconi anemia. Discontinuation of cephalexin was followed by improvement in hematological values. This course of events supports the hypothesis that acquired bone marrow depression may be a manifestation of Fanconi anemia, warranting the appropriate diagnostic work up in every case of acquired bone marrow aplasia.