Editor's column

Hypocalcemia and critical illness in children

Background/Purpose: Disturbances in calcium homeostasis are common at initiation of extracorporeal life support (ECLS). At the authors' institution many neonates undergoing ECLS have developed hypercalcemia. To determine the frequency of hypercalcemia in neonates during ECLS we performed retrospective chart review of neonates that required ECLS at our neonatal intensive care unit. Methods: The authors identified 76 consecutive neonates who underwent ECLS before 10 days of age at Cincinnati Children's Hospital Medical Center from July 1, 1991 to June 30, 1996. The hospital charts and ELSO forms were reviewed. Demographic, clinical, and laboratory data for each of the patients were reviewed, both before initiation and during ECLS. Hypercalcemia was defined as total serum calcium concentration of greater than 11 mg/dL (2.74 mmol/L) on at least one occasion beyond the first 24 hours of ECLS. Results: The hospital charts and ELSO forms from 70 patients were available for review. One patient was excluded because he was only on ECLS for 33 hours, and there were no calcium levels obtained after 24 hours of ECLS and until death. Twenty-five (36%) neonates undergoing ECLS had hypercalcemia (serum Ca > 11 mg/dL [2.74 mmol/L]). Hypercalcemia was associated with longer duration of ECLS (hypercalcemia group, 243 ± 115 hours and normocalcemia group, 139 ± 64 hours) and greater requirements for platelet transfusions (hypercalcemia group, 538 ± 282 mL and normocalcemia group, 372 ± 233 mL). This could not be explained by differences in primary diagnosis, amounts of calcium administered, and acid-base status. Conclusions: Hypercalcemia was found to be common in neonates that require ECLS and is associated with longer duration of ECLS support. Conservative calcium administration for neonates while on ECLS may be warranted. J Pediatr Surg 36:493-497. Copyright © 2001 by W.B. Saunders Company.

The clinical characteristics and neurologic outcome of 15 newborn infants with seizures due to hypocalcemia and hypomagnesemia have been studied with careful exclusion of those patients who had other possible etiologies for seizures. Associated diagnoses included severe congenital heart disease in 7 of 15 (47%) patients. Possible causes for this association with congenital heart disease include a forme fruste of DiGeorge syndrome, hypocalcemia and hypomagnesemia due to critical illness, and subtle embolic cerebral ischemia. In contrast with previous studies, no abnormalities of formula milk feeding were observed. Five patients (36%) died of causes unrelated to seizures. Follow-up in 8 of 9 patients who had no cerebral insults other than neonatal seizures at a mean age of 57.8 ± 10.5 months found neurologic abnormalities in 2 (22%), both with an endocrine etiology for hypocalcemia. We conclude that infants with severe congenital heart disease should be investigated for hypocalcemia and hypomagnesemia. Previous observations of a universally favorable neurologic outcome in newborns with hypocalcemic or hypomagnesemic seizures may be valid for those who have a nutritional etiology for the metabolic disturbance but are less relevant to the current population in whom hypocalcemia or hypomagnesemia due to errors in formula milk feeding is seldom observed. In this group, neurologic prognosis may be more related to associated medical conditions.

The goal of resuscitation pharmacology is to restart the heart as quickly as possible while preserving vital organ function during chest compression. Unfortunately, the application of advanced life support to pediatric cardiac arrest patients is often unsuccessful. The goal of this paper is to review the scientific rationale and educational considerations used to derive the guidelines for medication use in the pediatric patient during CPR.

The first step in drug delivery during CPR is to achieve vascular access. The endotracheal route and intraosseous route may be used, although the former is not reliable. To maximize endotracheal drug effect, a larger dose should be instilled into the airway as deeply as possible. Any vascular access, including intraosseous, is preferable to endotracheal drug administration.

Although other α-adrenergic agents are theoretically superior, epinephrine remains the drug of choice in pediatric resuscitation. The previously recommended dose, however, may be inadequate; a dose 10 to 20 times larger (100–200 μg/kg) should be considered, particularly if the standard dose is ineffective. Lacking convincing data, the indications and dose for calcium are unchanged. Similarly, there are no data advocating a change in the indications or dose for lidocaine, bretylium, or atropine.

The treatment of arrest-induced acidosis remains controversial. The mainstay of therapy consists of efforts to maximize oxygenation and tissue perfusion. Bicarbonate is not a first-line drug; its use should be considered when the patient fails to respond to advanced life support efforts, including the administration of high-dose epinephrine. Bicarbonate may be helpful in the postresuscitation setting, but its use should not supplant efforts to maximize tissue perfusion.

Adenosine is an effective and generally safe medication for the treatment of supraventricular tachycardia in infants and children. Therefore, its indications, dose, and toxicities should be included in the new guidelines.

Finally, a summary of research initiatives are included, including a call for the development of a multi-institutional pediatric clinical resuscitation research group. Large numbers of patients must be enrolled in a standardized manner to better evaluate the benefits and adverse effects of various therapies. This includes the use of high-dose epinephrine, calcium, bicarbonate, and other buffer agents such as Carbicarb® and THAM. Animal models simulating the etiology and pathophysiology of pediatric arrest also are needed. In both clinical and animal studies, neurologic outcome and long-term survival should be assessed rather than simply the rate of restoration of spontaneous circulation.

Ionized calcium is a physiologically critical calcium pool. It is easily determined, although accuracy depends on sample handling. As a clinical parameter, directly measured ionized calcium has particular import in the care of neonates, patients with sepsis or other cardiovascular instability, massively transfused patients, and those undergoing cardiopulmonary bypass or liver transplantation.

The purpose of this study was to assess the association of calcium replacement therapy with morbidity and mortality in infants after cardiac surgery involving cardiopulmonary bypass.

Retrospective chart review.

The cardiac intensive care unit at a tertiary care children's hospital.

Infants undergoing cardiac surgery involving cardiopulmonary bypass between October 2002 and August 2004.

None.

Total calcium replacement (mg/kg calcium chloride given) for the first 72 postoperative hours was measured. Morbidity and mortality data were collected. The total volume of blood products given during the first 72 hrs was recorded. Infants with confirmed chromosomal deletions at the 22q11 locus were noted. Correlation and logistic regression analyses were used to generate odds ratios and 95% confidence intervals, with p < .05 being significant. One hundred seventy-one infants met inclusion criteria. Age was 4 ± 3 months and weight was 4.9 ± 1.7 kg at surgery. Six infants had deletions of chromosome 22q11. Infants who weighed less required more calcium replacement (r = −.28, p < .001). Greater calcium replacement correlated with a longer intensive care unit length of stay (r = .27, p < .001) and a longer total hospital length of stay (r = .23, p = .002). Greater calcium replacement was significantly associated with morbidity (liver dysfunction [odds ratio, 3.9; confidence interval, 2.1–7.3; p < .001], central nervous system complication [odds ratio, 1.8; confidence interval, 1.1–3.0; p = .02], infection [odds ratio, 1.5; confidence interval, 1.0–2.2; p < .04], extracorporeal membrane oxygenation [odds ratio, 5.0; confidence interval, 2.3–10.6; p < .001]) and mortality (odds ratio, 5.8; confidence interval, 5.8–5.9; p < .001). Greater calcium replacement was not associated with renal insufficiency (odds ratio, 1.5; confidence interval, 0.9–2.3; p = .07). Infants with >1 sd above the mean of total calcium replacement received on average fewer blood products than the total study population.

Greater calcium replacement is associated with increasing morbidity and mortality. Further investigation of the etiology and therapy of hypocalcemia in this population is warranted.