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  • Letter to the Editor
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Gentamicin Pharmacokinetics in Term Newborn Infants Receiving High-frequency Oscillatory Ventilation or Conventional Mechanical Ventilation: A Case-controlled Study

Journal of Perinatology volume 24, pages 266–267 (2004)Cite this article

Dear Editor:

We read with interest Bhatt-Mehta et al.'s article “Gentamicin Pharmacokinetics in Term Newborn Infants Receiving High-frequency Oscillatory Ventilation or Conventional Ventilation: a Case-controlled Study,”1 which found that gentamicin pharmacokinetics are altered in patients receiving high-frequency oscillatory ventilation (HFOV). However, our enthusiasm was dampened by several concerns. Firstly, we were surprised by the failure of the authors to include any data to support their contention that altered vascular volume did not contribute to the altered pharmacokinetics observed in their study. In reading their article and the data presented,1 we would tend to agree that the patients who received HFOV would indeed be more critically ill than patients receiving conventional mechanical ventilation (CMV). As postnatal age at time of treatment was significantly greater in the HFOV group (11.7±11 vs 4.63±4.6 hours, p<0.001) than the CMV group and maintenance of adequate intravascular volume is critical for patients treated with HFOV, we speculate that the HFOV group might have received far greater fluid intake (L/kg/day) than the CMV group. The HFOV group is also more likely to have received more fluid boluses for blood pressure support, if, as reported, many of them needed “high-dose pressors”. As gentamicin is a water-soluble drug whose volume of distribution is dramatically altered by increases in extracellular fluid volume, the substantially greater Vd of the HFOV patients might merely be a reflection of their substantially greater extracellular fluid status. While the authors comment “fluid overload does not appear to be a consistent problem in infants who receive HFOV”, they do not provide any data to clarify whether this is a generic statement or a reference to the patients reported on. Given that they have access to the medical records and input/output data, it would be seemingly easy and imminently useful to clarify this issue. At the very least, a comparison of the change (if any) in infants’ weights during the study period rather than a comparison of birthweights would be more relevant and useful. While clarifying this point will not preclude other pathophysiological mechanisms being responsible, it would support the fact that concomitant fluid therapy rather than ventilator therapy might be responsible for the differences in the two groups. Indeed, increases in extracellular fluid contributing to greater Vd of gentamicin (than the 0.49±0.09 l/kg of the CMV group) have previously been reported by the author2 and others3,4 in other critically ill infants treated with extracorporeal membrane oxygenation.

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References

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Author information

Authors and Affiliations

  1. Department of Pediatrics Baylor College of Medicine, Houston, TX, USA

    Caraciolo J Fernandes MD & Donough J O'donovan MD

  2. Department of Pharmacy Texas Children's Hospital, Houston, TX, USA

    Ngoc-Yen T Nguyen PharmD

Authors
  1. Caraciolo J Fernandes MD
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  2. Donough J O'donovan MD
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  3. Ngoc-Yen T Nguyen PharmD
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Additional information

Dear Editor:

The data presented by Drs. Bhatt-Mehta and Donn have added to our knowledge of gentamicin pharmacokinetics in neonates undergoing high-frequency ventilation. Their recommended dosage of 2.5 mg/kg every 18 hours is suspect, however, and cannot be validated since peak and trough concentrations were not reported. The most significant finding in their report was the doubling of the volume of distribution (Vd). A doubling of the Vd will decrease the peak concentration by approximately one half. The reported Vd of 0.98 l/kg in the HFOV group predicts peak concentrations of approximately 2.5 μg/ml, which are significantly subtherapeutic. A more appropriate recommendation would be to increase the dose to at least 5 mg/kg. The reported serum half-life of 9.23 hours in the HFOV group predicts that a dosing interval of 36 hours (∼ four half-lives) would be more appropriate.

Thomase Young, MDWakeMed Faculty Physicians, University of North Carolina School of Medicine, Raleigh, NC, USA

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Fernandes, C., O'donovan, D. & Nguyen, NY. Gentamicin Pharmacokinetics in Term Newborn Infants Receiving High-frequency Oscillatory Ventilation or Conventional Mechanical Ventilation: A Case-controlled Study. J Perinatol 24, 266–267 (2004). https://doi.org/10.1038/sj.jp.7211070

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  • DOI: https://doi.org/10.1038/sj.jp.7211070

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