Potentially dangerous misuse of the Hartford once-daily nomogram for gentamicin.


Sir, Much of the gentamicin prescribed in the UK is given once daily and can be controlled by using the Hartford nomogram. Using the Hartford method gives time for assay of the blood sample before the next dose is due to be given, allowing appropriate dose modification to be made if necessary. This is not possible with control of therapy by ascertaining pre-dose levels. As clearly stated by its authors, this nomogram is designed only for 7 mg/kg/24 h. Experience of interactions with other hospitals indicates that lower dosages are being used, some as low as 3 mg/kg/24 h and, anecdotally, the Hartford nomogram may still be used to adjust dosages. We describe here a study of the potential errors that could occur if dosages lower than 7 mg/kg are controlled by using this nomogram. Blood level data for patients with normal renal function [estimated glomerular filtration rate (eGFR) .90 mL/min/1.73 m] and receiving 7 mg/kg of gentamicin were abstracted from Figure 2 in a paper by the Hartford group. These showed that with normal renal function, the simulated blood level at 1 h (the end of the infusion) was 19.6 mg/L, the concentrations decreased linearly when plotted semi-logarithmically and the plasma t1/2 was 2.5 h. The corresponding 1 h concentrations for three lower doses (5, 4 and 3 mg/kg) were then calculated proportionally since the pharmacokinetics of aminoglycosides are linear in this dose range. The decision concentrations for altering the dosage interval were taken from the nomogram. These were 7.6 mg/L for a sample taken 6 h after the start of the infusion and 2.0 mg/L for a sample at 14 h. These values were plotted on a semi-logarithmic graph of concentration versus time, and blood concentration lines from the four 1 h values were taken through the 6 h and 14 h decision concentrations. With doses lower than 7 mg/kg a sample at 6 h would not detect an increase in t1/2 from that expected in a patient with normal function as reliably as one at 14 h. Taking a concentration of 7.6 mg/L at 6 h, the t1/2 values for the four doses that would trigger a change in dosage using the nomogram, and the corresponding 24 h concentrations are shown in Figure 1. The maximum t1/2 of gentamicin detectable using the 6 h nomogram decision point and the likely concentration at 24 h were: 7 mg/kg, 3.7 h and 0.2 mg/L; 5 mg/kg, 5.7 h and 0.8 mg/L; 4 mg/kg, 8.9 h and 1.8 mg/L; and 3 mg/kg, 34.7 h and 5.2 mg/L. The corresponding values for the 14 h decision point were: 7 mg/kg, 3.9 h and 0.3 mg/L; 5 mg/kg, 4.6 h and

DOI: 10.1093/jac/dkp323

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@article{Lovering2009PotentiallyDM, title={Potentially dangerous misuse of the Hartford once-daily nomogram for gentamicin.}, author={Andy Lovering and David S Reeves}, journal={The Journal of antimicrobial chemotherapy}, year={2009}, volume={64 5}, pages={1117-8} }