Anesth Analg 2001;93:92-95
© 2001 International Anesthesia Research Society
PEDIATRIC ANESTHESIA
The Effect on the Hemodynamic Stability of Varying Calcium Chloride Administration During Protamine Infusion in Pediatric Open-Heart Patients
Vorasri Muangmingsuk, MD*,
Thomas F. Tremback, MD*,
Sunthorn Muangmingsuk, MD*,
David A. Roberson, MD*, and
Nancy E. Cipparrone, MA
*Department of Anesthesia, The Heart Institute for Children, Advocate Christ Hospital and Medical Center; and Department of Research and Education, Advocate Health Care, Oak Lawn, Illinois
Address correspondence and reprint requests to Thomas F. Tremback, MD, Department of Anesthesia, Christ Hospital and Medical Center, 4440 W. 95th St., Oak Lawn, IL 60453.
 |
Abstract
|
|---|
Implications: We conducted a randomized study in 147 pediatric patients undergoingcardiopulmonary bypass to determine when there are any differences inhemodynamic effects if CaCl2 20 mg/kg and protamine 5mg/kg are mixed together and infused over 10 min versus administering half ofthe calcium dose (10 mg/kg) as a bolus followed by a 10-min infusion ofprotamine 5 mg/kg and CaCl2 10mg/kg.
|
Introduction
|
|---|
Routine protamine sulfate administration for heparin neutralization after cardiopulmonary bypass (CPB) may be associated with adverse reactions such as transient hypotension (1). Whether protamine-induced systemic hypotension after CPB is caused by impaired myocardial performance, by changes in systemic vascular resistance, or both is unclear. CaCl2 administration can minimize the adverse hemodynamic effect of protamine (2)1 by exerting positive cardiac inotropic and peripheral vascular effects (3,4). Shapira et al. (5) demonstrated an immediate and sustained enhancement of myocardial performance and blood pressure when CaCl2 was given as a bolus injection or as a continuous infusion after CPB in adults. We performed our study to clinically investigate whether bolus and continuous infusion administrations of CaCl2 could maintain hemodynamic stability in our pediatric open heart patients during protamine reversal of heparinization.
|
Methods
|
|---|
After Medical Investigation Committee approval, we obtained informed consent for 151 pediatric patients scheduled for surgical correction of congenital heart lesions requiring CPB. Patients were classified into six subgroups with regard to age (<2 yr, 2–7 yr, and >7 yr) and severity of congenital lesion (simple or complex). Within each of the six subgroups, patients were randomized into one of two groups. Group 1 received protamine 5 mg/kg and CaCl2 20 mg/kg mixed together and infused over 10 min. Group 2 received half of CaCl2 (10 mg/kg) administered as a bolus before infusion of the protamine 5 mg/kg and CaCl2 10 mg/kg admixture (Medfusion pump 2001; Medex Medical, Dulueth, GA). Review of the previous year’s pediatric open heart case volume helped determine our stratified study population size. Envelopes were assigned to each subgroup containing an equal number of cards assigned to Group 1 and Group 2. Investigators randomly picked a card from the envelope matching their patient subgroup.
All patients received balanced general anesthesia, including IV and inhaled anesthetics, at the discretion of the attending anesthesiologist. Before CPB, all patients received beef lung heparin (America Pharmaceutical Partners, Deerfield, IL) to achieve and maintain an activated clotting time of >300 s. After completion of surgical repair, calcium was administered into the pump circuit as needed to maintain satisfactory calcium levels (ionized calcium 1.2 ± 0.2 via GEM PREMIER 5300; Instrumentation Lab, Lexington, MA). Vasoactive drugs were initiated to wean the patients successfully from CPB at the clinical discretion of the surgeon. After separation from CPB, the perfusionist normalized acid-base status and calcium levels (base excess 0 ± 3 and Ca2+ 1.2 ± 0.2, respectively). Blood products, crystalloids, or both were infused to achieve and maintain adequate filling volumes as assessed by direct observation in the surgical field or by transesophageal echocardiography (TEE). The study protocol was initiated only after blood labs, intravascular volume, and vasopressor drugs were titrated to achieve steady state by the surgeon and perfusionist, who were blinded to the patients’ study group.
Hemodynamic variables (heart rate [HR]; systolic, mean, and diastolic blood pressure [BP]; oxygen saturation; mean arterial pressure; and temperature) were obtained before heparin reversal (baseline = 0 min) and continuously collected by a SpaceLabs 90305 monitor (Spacelabs Medical, Redmond, WA) and tabulated at 1-min intervals for a period of 10 min. Where feasible, cardiac function (fractional shortening) was measured via TEE (Hewlett-Packard Sonos 2000; Hewlett-Packard, Andover, MA) at baseline (0 min) and at 2, 4, 6, 8, and 10 min (Table 1). A blinded investigator later reviewed videotaped TEE recordings and made five independent measurements of left ventricle (LV) (or functional ventricle in patients with single-ventricle morphology) short or long axis views. Fractional shortening was calculated with the following formula (6):
equation
where LVIDd is left ventricular (or fractional) ventricular internal dimension diastolic and LVIDs is left ventricular (or functional) ventricular internal dimension systolic. Exclusion criteria for TEE were weight <3.5 kg, circulatory arrest, increased airway pressure after initial attempts at insertion of the TEE probe, and inability to pass an appropriately sized suction catheter via the endotracheal tube after initial attempt at insertion of the TEE probe.
Baseline blood calcium levels were recorded after the induction of anesthesia and also before and 3 min after the CaCl2/protamine administration study period. Return of activated clotting time to baseline was confirmed 3–5 min after completion of protamine infusion.
Repeated-measures analysis of variance was performed to detect between- and within-group differences over the 10-min interval. Statistical significance was determined at P < 0.05. Subsequent statistical analysis focused on HR, BP, and FS only for the youngest patients (
6 mo) with complex heart disease because we anticipated that those patients with poor myocardial reserve and the least mature sympathetic nervous system might better dramatize any potential differences in the drug administration regimen.
|
Results
|
|---|
Demographic data were not statistically different between the two groups (Table 1). There were no differences found between Groups 1 and 2 for any of the baseline hemodynamic data (Table 2).
For the entire sample, we detected no significant difference between groups at any of the times measured in any of the hemodynamic variables. Within groups, there was a significant (P 0.001) positive increase over time for all hemodynamic variables, with the exception of oxygen saturation.
No significant differences were found for the youngest, complex patients between Groups 1 (n = 22) and 2 (n = 25) in the hemodynamic variables studied (HR and BP), but a within-group difference was detected (P 0.04) for both HR and BP again, with a positive increase over time.
Complete fractional shortening data were obtained for 63 patients. Overall, a borderline significant difference (P = 0.050) was found between Group 1 (n = 35) and Group 2 (n = 28) over time, and also a significant (P = 0.047) within-group difference was detected (Fig. 1). No differences were detected in the youngest, complex patients, either between or within Group 1 (n = 13) and Group 2 (n = 13).
View larger version (15K):
[in this window]
[in a new window]
|
Figure 1. Change in fractional shortening over time (n = 63). Between-group difference, P = 0.050, repeated-measures analysis of variance (ANOVA); within-group difference, P = 0.047, repeated-measures ANOVA.
|
|
|
Discussion
|
|---|
Transient hypotension occurs in adults within three to four minutes of protamine administration, especially in patients with poor ventricular function (1,7). CaCl2 is the most frequently used adjunct to protamine for improving hemodynamic stability. Clinical studies of the hemodynamic responses to protamine and calcium administration in the post-CPB period in pediatric patients are lacking. At our institution, we anticipated seeing hemodynamic benefits from the bolus administration of CaCl2 given before the administration of protamine. However, in this study we found no measurable difference in HR or BP in those patients receiving the CaCl2 either as a bolus before the protamine administration or with protamine/CaCl2 administration. Shapira et al. (5) reported in adults that an initial augmentation of cardiac index was a consistent hemodynamic response to CaCl2. Our observation of FS augmentation in pediatric patients (Group 2) concurs with those results reported in adult patients. It is interesting to note that objective benefits were not detected by significant HR or BP changes.
The adult study of Gourin et al. (7) suggested that protamine may have a negative inotropic effect that is apparent in patients with impaired ventricular function. We further subcategorized each protocol arm into simple versus complex cardiac lesions with the assumption that complex lesions have less myocardial reserve. Again we found no significant difference in hemodynamics during protamine administration.
We were able to obtain TEE evaluations in only 63 of our patients because of limitations of patient size, lack of justification of added cost, or limited availability of this fairly specialized pediatric diagnostic tool. Yet our study shows that HR and BP may be inadequate variables for assessment of hemodynamic function and supports the FS as a more sensitive measure of contractile function, as demonstrated in Figure 1.
Future studies should include FS as the absolute measure of hemodynamic effects, because our study suggests that the assessment of vital sign variables proves less than adequate. Also, future studies can then address whether an increased FS attributed to the positive effect of CaCl2 improves the clinical outcome in pediatric patients, especially focusing on pediatric patients with normal versus poor baseline contractility.
|
Footnotes
|
|---|
1Wassil VM, Hill GE, Jacoby RM. Antagonism of the cardiovascular depressant effects of protamine by calcium [abstract]. Anesth Analg 1980;59:564. 
|
References
|
|---|
-
Horrow JC. Protamine: a review of its toxicity. Anesth Analg 1985; 64: 348–61.[Free Full Text]
-
Shapira N, Schaff HV, Piehler J, et al. Cardiovascular effects of protamine sulfate in man. J Thorac Cardiovasc Surg 1982; 84: 505–14.[Abstract]
-
Drop LJ, Scheidegger D. Plasma ionized calcium concentration. J Thorac Cardiovasc Surg 1980; 79: 425–31.[Medline]
-
Cote’ CJ, Drop LJ, Daniels AL, Hoaglin DC. Calcium chloride versus calcium gluconate: comparison of ionization and cardiovascular effects in children and dogs. Anesthesiology 1987; 66: 465–70.[Medline]
-
Shapira N, Schall HV, White RD, Pluth JR. Hemodynamic effects of calcium chloride injection following cardiopulmonary bypass: response to bolus injection and continuous infusion. Ann Thorac Surg 1984; 37: 133–40.[Abstract]
-
Feigen H. Echocardiographic evaluation of cardiac chambers. In: Feigenbaum H. Echocardiography. Philadelphia: Lea & Febiger, 1994;134–80.
-
Gourin A, Streisand RL, Greineder JK. Protamine sulfate administration and the cardiovascular system. J Thorac Cardiovasc Surg 1971; 62: 193–204.[ISI][Medline]
Accepted for publication February 22, 2001.
Top
Abstract
Introduction
