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QT interval lengthening in premature infants treated with doxapram
C Maillard1, M J Boutroy, J Fresson
1Neonatal Intensive Care and Perinatal Pharmacology, Maternité Régionale Universitaire, Nancy, France.
Insights
Doxapram use in premature infants may prolong the corrected QT (QTc) interval, potentially leading to dangerous heart rhythm disorders. Close electrocardiogram monitoring is essential during doxapram treatment for apnea of prematurity.
Area of Science:
- Neonatal pharmacology
- Pediatric cardiology
- Clinical toxicology
Background:
- Doxapram is commonly used for apnea of prematurity unresponsive to methylxanthines.
- Concerns exist regarding doxapram's potential to cause cardiac conduction disorders.
Purpose of the Study:
- To evaluate the cardiac and general tolerance of doxapram in very premature infants.
- To assess the relationship between doxapram plasma concentrations and adverse effects.
Main Methods:
- Prospective evaluation of 40 premature infants receiving intravenous doxapram.
- Electrocardiogram monitoring (including corrected QT interval - QTc) before and during treatment.
- Measurement of drug plasma concentrations and recording of side effects.
Main Results:
- A statistically significant, moderate lengthening of the QTc interval was observed during doxapram treatment.
- Six infants experienced QTc prolongation exceeding the 440 ms threshold without other rhythm disorders.
- No correlation was found between adverse effects and drug plasma concentrations.
Conclusions:
- Doxapram can prolong the QTc interval in premature infants, increasing the risk of exceeding the life-threatening 440 ms threshold.
- Electrocardiogram monitoring is crucial when administering doxapram to neonates.
Objective:
Doxapram, routinely used in premature infants treated for apnea of prematurity unresponsive to methylxanthines, has been related to cardiac conduction disorders. This study was designed to evaluate doxapram cardiac and general tolerance and its relationship to drug plasma concentrations in very premature infants.
Methods:
Forty infants (mean +/- SEM, 28.9 +/- 0.3 weeks of gestation) who were given intravenous doxapram, 0.5 to 1 mg/kg per hour, at 15.9 +/- 2.4 days of life were evaluated prospectively. Electrocardiograms were monitored before and during the first 3 days of treatment. QT interval corrected for heart rate (QTc) longer than 440 ms was regarded as clinically pertinent, given that it is considered a significant risk of conduction disorder leading to torsades de pointes and sudden death. Other side effects were recorded. Toxic plasma concentration of doxapram and ketodoxapram was set at >4 mg/L.
Results:
A statistically significant but moderate lengthening of QTc interval has been observed from 394 +/- 4 ms before doxapram to 409 +/- 4 ms at 48 and 72 hours of treatment (P =.0065). For 6 patients, QTc interval became longer than 440 ms without any other rhythm or conduction disorder. Digestive disorders were observed in 20 infants but 9 presented with concomitant septicemia. No relationship was found between presence or absence of adverse effects and drug plasma concentrations.
Conclusion:
Our study enlightened the lengthening effect of doxapram on QTc interval in premature infants with a risk of exceeding the 440 ms threshold that is considered life-threatening. This finding emphasizes the need for electrocardiogram follow-up when using doxapram in neonates.