PEDIATRICS Vol. 105 No. 4 April 2000, pp. 915

Insulin Infusions in Extremely Low Birth Weight Infants

To the Editor.

We read with interest the article by Fuloria et al on insulin infusions in extremely low birth weight (ELBW) infants.¹ The authors concluded that priming the tubing with a higher concentration of insulin (5 U/mL) before the initiation of a standard insulin infusion therapy should accelerate the achievement of steady-state insulin delivery and correction of hyperglycemia in ELBW.¹ This approach would require two insulin concentrations for the routine preparation of these infusions. In our view, this increases the likelihood of errors, especially during shifts when less experienced personnel are present in the NICU. To combat this problem and minimize the loss of insulin in the infusion system, we have, until recently, added serum albumin to the insulin infusion solutions. However, shortages and costs of albumin have led us to retrospectively compare the effectiveness of insulin infusions in ELBW infants with and without albumin. The albumin insulin solutions had 10 mL of the 5% albumin added to the solution, and the nonalbumin insulin infusions were prepared by flushing the microbore tubing with 10 mL of the insulin admixture. The tubing and syringe were allowed to stand for at least 30 minutes prior to use. The demographics of the patients are presented in Table 1. The insulin infusion rates and blood sugars are shown in Table 2. In comparing the two groups on day 1, the patients whose insulin admixture did not contain albumin demonstrated a slower decline in glucose. However, by 12 hours, the two groups appeared to have very similar insulin requirements and the blood glucose levels were consistently <200 mg/dL (11.1 mmol/L). Although the time difference between the two groups in achieving serum glucose levels of <200 mg/dL is about 12 hours, clinically and physiologically it is not clear whether this would compromise the care of the patient.^2,3

We also analyzed the cost of using albumin in the preparation of the insulin admixtures, and the estimated annual cost was $47 328. Therefore, not adding albumin to the insulin admixture results in a considerable cost savings and avoids the exposure of the patient to human sera.

In conclusion, it appears that adequate control of hyperglycemia is achieved by flushing the intravenous tubing with 10 mL of insulin admixture and allowing the insulin syringe and tubing to sit for 30 minutes.

Minyon Avent, PharmD^* and Jonathan Whitfield, MBChB
^* Department of Pharmacy and  Neonatal Intensive Care Unit, Department of Pediatrics
Baylor University Medical Center
Dallas, TX 75246

REFERENCES

1. Fuloria M, Friedberg MA, DuRant RH, Aschner JL Effect of flow rate and insulin priming on the recovery of insulin from microbore infusion tubing. Pediatrics. 1998; 102:1401-1406 [Abstract/Free Full Text]
2. Pildes RS Neonatal hyperglycemia. J Pediatr. 1986; 109:905-907 [CrossRef][Medline]
3. Lilien LD, Rosenfield RL, Baccaro MM, Pildes RS Hyperglycemia in stressed small premature neonates. J Pediatr. 1979; 94:454-459 [CrossRef][Medline]

In Reply.

We thank Drs. Avent and Whitfield for their comments on our article "Effect of Flow Rate and Insulin Priming on the Recovery of Insulin from Microbore Infusion Tubing," in which we compared insulin recovery from unprimed infusion tubing and tubing primed with a higher concentration of insulin. Similar to our own data, Drs. Avent and Whitfield found a 12-hour delay in correction of hyperglycemia when the insulin infusion was administered through tubing flushed for 30 minutes with 10 mL of the "insulin admixture" (presumably 0.2 U/mL) compared with administration through tubing flushed with 5% albumin. Their information on the cost associated with the use of 5% albumin, in addition to the risk of exposure to human sera, provides a strong disincentive to this practice. They also point out that use of two different insulin concentrations may increase the likelihood of errors in the nursery. We believe this risk can be circumvented with the proper safeguards. It requires less than 1 mL of insulin (5 U/mL) to prime the infusion tubing. This can be dispensed by the pharmacy in a small, properly labeled 1-mL syringe. The standard insulin infusion solution (0.2 U/mL) used to flush the tubing after priming, and for continuous insulin infusion to patients, should be dispensed in a large (20- or 50-mL) syringe. This approach should make the possibility of errors remote.

Drs Avent and Whitfield imply that a delay of 12 hours before correction of hyperglycemia is unlikely to compromise patient care. However, there is little evidence to support or refute that supposition. Persistent hyperglycemia can be detrimental to infants, resulting in osmotic diuresis and alterations in blood osmolality, which can affect the integrity of the blood-brain barrier and increase the risk of intraventricular hemorrhage.^1,2 Ideally, when a continuous infusion of insulin is deemed clinically indicated, the delivery method should result in rapid correction of hyperglycemia and utilize the lowest possible insulin infusion rate. Apropos, we found it interesting that the insulin infusion rates used by Drs. Avent and Whitfield in the no-albumin group were higher than those infused through tubing with albumin. We believe that the higher infusion rates required to correct hyperglycemia in neonates receiving infusions through unprimed tubing increases the risk of hypoglycemia once saturation of the binding sites on the tubing has occurred. We are currently conducting a randomized clinical trial comparing safety and efficacy of insulin delivery to extremely low birth weight infants through unprimed and insulin-primed tubing, which we hope will address some of these important issues.

Mamta Fuloria, MD and Judy L. Aschner, MD
Department of Pediatrics
Wake Forest University School of Medicine
Winston-Salem, NC 27157-1081

REFERENCES

1. Finberg L Dangers to infants caused by changes in osmolar concentration. Pediatrics. 1967; 40:1031-1034 [Abstract/Free Full Text]
2. Dweck HS, Cassady G Glucose intolerance in infants of very low birth weight. I. Incidence of hyperglycemia in infants of birth weight 1100 grams or less. Pediatrics. 1974; 52:189