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Chappell and Newman1 have asked for urgent initiatives to ensure the manufacture of neonatal targeted products to reduce the risks associated with intravenous drug administration. We endorse their view and report a little recognised problem with the use of adult formulations in neonatal nurseries.
This investigation was conducted after we noticed symptoms of digoxin overdose (bradyarrhythmia) in a neonate. Retrospective review of the case suggested that the overdose received was due to the unaccounted for drug in the dead space of a 1 ml syringe.
The nursing drug dose manual Pediatric drugs and nursing implications2 gives the maintenance dose of intravenous digoxin as 2.5 μg/kg/dose. The nursing instruction3 states that the dose must be diluted, with at least four times the volume, using normal saline or 5% dextrose, and the drug must be given over five minutes. In practice, for a 2 kg neonate who is to receive a 5 μg digoxin intravenous injection (250 μg/ml), the drug volume required is 0.02 ml. This is drawn up in a 1 ml syringe up to the 0.02 ml mark. The nursing practice in our nursery was to draw up normal saline to dilute this four times and give it intravenously, slowly over five minutes. Cognizance is not taken of the dead space in the needle hub and syringe.
We estimated this dead space by drawing up saline in the 1 ml syringe and flushing out the syringe (Syringe and Precision Glide Needle; 1 ml; 26 G; 0.5 inch; Becton-Dickinson, Singapore). The syringe piston was then withdrawn again, and the volume of saline in the dead space was drawn into the syringe barrel. This volume was noted. The dead space volume is 0.07 ml in this syringe. When the diluent is drawn up, the drug in the dead space is also drawn up resulting in toxicity. In the case of digoxin, the baby received 0.09 ml digoxin instead of 0.02 ml.
Ordinarily if the digoxin is drawn up to the 0.02 ml mark and injected directly, the drug in the dead space is retained in the syringe, and there is no overdose delivered. However, when the diluent is drawn up into the syringe for dilution, the drug in the dead space is also drawn up, and this results in the overdosing.
We looked at the magnitude of error induced by the dead space in some of the drugs routinely used in the nursery. Table 1 shows the standard volume of drug required for a 2 kg neonate and the magnitude of error introduced by the dead space of a 1 ml syringe. Its is assumed that these drugs were first drawn in a 1 ml syringe and then diluted in the same syringe. The neonate will get 4.5 times the recommended dose if 250 μg/ml digoxin is used, and 2.4 times the recommended dose if 100 μg/ml digoxin is used. The inadvertent extra dosing factors using a 1 ml syringe for different drugs used in the neonatal unit have been calculated. The dose of adrenaline can be exceeded by a factor of 2.16, for furosemide by 1.35, for dexamethasone by 2.4, and for midazolam by a factor of 2.75.
To avoid this inadvertent overdosing of neonates, prediluted drug formulations are required. Until such drug formulations are more widely available, especially in developing countries, awareness of this error can help circumvent the problem.
A method that can be used to circumvent the problem is to draw up the required volume in a 1 ml syringe and transfer it to a larger volume syringe, leaving the dead space drug behind in the first syringe. This is a crude method and it is not a closed system (as it requires transfer of the drug from one syringe to another).
The insulin syringe (U-40 insulin; 29 G; 0.5 inch ultra-fine 1 ml needle; Becton-Dickinson Consumer Products, Franklin Lakes, New Jersey, USA) does not have a dead space and its needle is fixed to the syringe. Use of this syringe can also obviate the problem.
Another way would be to add the drug contained in this dead space (0.07 ml) to the calculation for dilution.
Although no reports of life threatening adverse effects have been reported in the literature, this inadvertent dosing error has the potential of being serious.
Competing interests: none declared