OBJECTIVES. Hypertonic-hyperoncotic solutions are used for the improvement of micro- and macrocirculation in various types of shock. In pediatric intensive care medicine, controlled, randomized studies with hypertonic-hyperoncotic solutions are lacking. Hypertonic-hyperoncotic solutions may improve cardiac function in children. The primary objective of this controlled, randomized, blinded study was to evaluate the hemodynamic effects and safety of hypertonic-hyperoncotic solution infusions in children shortly after open-heart surgery for congenital cardiac disease. The secondary objective was to determine whether the administration of hypertonic-hyperoncotic solutions could be a potential and effective therapeutic option for preventing a probable capillary leakage syndrome that frequently occurs in children after open-heart surgery.
METHODS. The children were randomly assigned to 2 groups of 25. The hypertonic-hyperoncotic solution group received Poly-(O-2)-hydroxyethyl-starch 60.0 g, with molecular weight of 200 kDa, Na+ 1232 mmol/L and osmolality of 2464 mOsmol/L (7.2% sodium chloride with 6% hydroxyethyl-starch 200 kDa). The isotonic saline solution group received isotonic saline solution (0.9% sodium chloride). Atrial and ventricular septal defects were corrected using a homograft patch. Monitoring consisted of an arterial, a central venous, and a thermodilution catheter (PULSIOCATH). Cardiac index, extravascular lung water index, stroke volume index, mean arterial blood pressure, and systemic vascular resistance index were measured (Pulse Contour Cardiac Output technique). Immediately after surgery, patients were loaded either with hypertonic-hyperoncotic solution or with isotonic saline solution (4 mL/kg). Blood samples (sodium concentration, osmolality, thrombocyte count, fibrinogen, and arterial blood gases) were drawn directly before; immediately after; 15 minutes after; and, 1, 4, 12, and 24 hours after the end of volume loading. Hemodynamic parameters were registered at the same time. The total amount of dobutamine required was documented, as well as the 24- and 48-hour fluid balances.
RESULTS. In the hypertonic-hyperoncotic solution group, cardiac index was 3.6 ± 0.26 L/min per m2 before volume administration and increased to 5.96 ± 0.27 after the administration of the study solution (64%). Fifteen and 60 minutes after administration, the cardiac index remained significantly elevated (5.55 ± 0.29 L/min per m2 and 4.65 ± 0.18 L/min per m2, respectively) and returned to preadministration values after 4 hours. In the isotonic saline solution group, the cardiac index did not change during the entire observation period (3.39 ± 0.21 before and 3.65 ± 0.23 L/min per m2 after isotonic saline solution). The systemic vascular resistance index decreased in the hypertonic-hyperoncotic solution group after administration from 1396 ± 112 to 868 ± 63 dyn/sec per cm−5/m2. The decrease of systemic vascular resistance index in the hypertonic-hyperoncotic solution group was transiently significant within 60 minutes after administration but stayed lower than before volume load (999 ± 70 dyn/sec per cm−5/m2). In the isotonic saline solution group, we found no statistically relevant change in systemic vascular resistance index. Stroke volume index significantly increased after hypertonic-hyperoncotic solution infusion (53.9 ± 3.0 mL/m2 directly after, 48.8 ± 2.46 mL/m2 15 minutes after, and 41.4 ± 2.2 mL/m2 60 minutes after) when compared with stroke volume index before administration (32.4 ± 2.6 mL/m2). In the hypertonic-hyperoncotic solution group, an increase in mean arterial blood pressure remained transiently significant within 60 minutes after administration when compared with the isotonic saline solution group, in which the mean arterial blood pressure remained unchanged. Both central venous pressure and heart rate were unchanged during the whole time of observation in both groups. In the hypertonic-hyperoncotic solution group, extravascular lung water index decreased from 10.6 ± 1.2 to 5.6 ± 1.2 mL/kg and remained significantly decreased 15 minutes after (6.5 ± 1.2 mL/kg) when compared with before volume administration. In the isotonic saline solution group, extravascular lung water index increased from 12.3 ± 1.1 mL/kg to 18.1 ± 1.7 mL/kg directly after administration and remained elevated for 60 minutes after volume loading (15.6 ± 1.5 mL/kg). In all patients, no hypoxia (Pao2<60 mm Hg) or hypercapnia (Paco2 >60 mm Hg) was observed. Arterial blood gas analysis showed pH and base excess within physiologic range, and this did not change throughout the whole period of observation. After infusion of hypertonic-hyperoncotic solution, sodium concentration increased from 139.2 ± 0.7 to 147.5 ± 0.7 mmol/L. The maximum sodium concentration was 153 mmol/L, measured immediately after hypertonic-hyperoncotic solution in 1 patient. The total amount of fluid infused was similar in both groups. The postoperative need for infused dobutamine in the patients in the hypertonic-hyperoncotic solution group was decreased compared with the isotonic saline solution group (46.9 ± 8.8 μg/kg vs 308.2 ± 46.6 μg/kg). No patient presented with severe bleeding. Short- and long-term cardiac and neurologic outcome was not reduced and all patients left the hospital in a clinically sufficient state.
DISCUSSION. This study demonstrates a profound increase of cardiac index after the administration of hypertonic-hyperoncotic solution in children after uncomplicated open-heart surgery, suggesting a positive inotropic effect. The total amount of catecholamine was lower, assuming that hypertonic-hyperoncotic solution reduces the need for positive inotropic support. The observed positive cardiac effect of hypertonic-hyperoncotic solution may even be intensified by the decreased afterload (decreased systemic vascular resistance index). According to the Frank-Starling relation, an effective tool in the treatment of low cardiac output are an elevated preload while afterload is diminished. Therefore, we postulate that hypertonic-hyperoncotic solution may be helpful in preventing or attenuating low cardiac output failure in childhood. Capillary leakage syndrome also is a frequent problem after cardiopulmonary bypass. For quantification of edema formation, extravascular lung water index measurement is a useful tool. Using this approach, we provided evidence that the infusion of hypertonic-hyperoncotic solution is transiently able to reduce extravascular lung water index. This reduction was transient but might prevent the triggering of a clinically relevant capillary leakage syndrome. This is in line with in vitro studies demonstrating that hypertonic-hyperoncotic solution improves microcirculation by reducing vascular permeability. The single administration of hypertonic-hyperoncotic solution infusion was safe, and no adverse effects, such as hemostatic disturbances, were observed.
CONCLUSIONS. A single infusion of hypertonic-hyperoncotic saline solution after cardiac surgery is safe despite the hypertonicity and the colloid component of the hypertonic-hyperoncotic saline solution. In children after cardiopulmonary bypass surgery, the administration of hypertonic-hyperoncotic saline solution increased cardiac index by elevating stroke volume index in combination with a lowered systemic vascular resistance index. Extravascular lung water index transiently decreased, suggesting that hypertonic-hyperoncotic saline solution effectively counteracts the capillary leakage that often occurs after cardiac surgery in children. Additional investigations might elucidate whether the temporary effects of hypertonic-hyperoncotic saline solution are beneficial in the treatment of severe capillary leakage after complicated cardiac surgery. It has to be shown that hypertonic-hyperoncotic saline solution is a long-lasting, effective treatment strategy for low cardiac output failure in children that is caused by sepsis, multiorgan failure, and endothelial edema. We have provided evidence to pediatric intensive care clinicians that the single administration of hypertonic-hyperoncotic saline solution might be a useful and safe treatment in the amelioration of contractility, inotropy, and the possible treatment of early-onset capillary leakage.