Health & Medical Children & Kid Health

Cardiac Preload in Children With CV Dysfunction or Dilated CM

Cardiac Preload in Children With CV Dysfunction or Dilated CM

Discussion


In this study, we have established "normal" GEDVI values in children and defined normalized GEDVI limits of cardiac preload responsiveness in children with acute cardiovascular dysfunction and dilated cardiomyopathy.

Fluid loading is the center of treatment in hypovolemia; however, only about 50% of patients respond with a significant increase in CO after fluid loading. Additionally, predicting cardiac preload responsiveness is critical because inappropriate fluid administration can result in pulmonary edema and in positive fluid balance, which is associated with increased mortality.

Clinical evaluation and measurements of cardiovascular pressures or volumes do not reliably predict fluid responsiveness. Although several studies have demonstrated that pressure pulse variation and stroke volume variation are highly predictive of fluid responsiveness, they are of limited use in children as they can only be applied to patients under controlled positive pressure ventilation failing to predict fluid responsiveness in the presence of spontaneous breathing activity, low tidal volume, low respiratory system compliance, high oscillatory frequency ventilation or respiratory rates greater than 40 breaths/min, arrhythmias, and during increased intra-abdominal pressure.

For predicting fluid responsiveness, it has been recommended that it should be determined on the part of the Frank-Starling relationship that the heart is working. GEDV behaves as a reliable indicator of preload both in children and adults in different clinical conditions. However, there are no "normal" GEDVI values in children, and the proposed normal values in adults (680–800 mL/m) are based on measurements in healthy volunteers and are neither appropriate for children nor directly applicable for critically ill patients. Since during growth cardiac end-diastolic blood volume increases by a factor of 3, whereas BSA by a factor of 5, a further normalization of GEDVI is required for children. We found that the GEDV-PBSA relationship closely fits a power-law in patients with normal cardiovascular status during the TPTD assessment. Interestingly, both GEDV and left ventricular end-diastolic volume (LVEDV) exhibit a similar power-law relationship with body size, as supported by the similarities of their particular scaling exponents. Assuming a proportional relationship between LVEDV and total cardiac volume, the power-law relationships strongly suggest that the GEDV's increase with body size parallels cardiac volume increase, providing support to the relationship GEDV = 488.8·PBSA for obtaining "normal" values of GEDVI (GEDVIN = 488.8·PBSA) and normalized levels of cardiac preload in children (GEDVI/GEDVIN).

GEDVI/GEDVIN versus SVI (CI) curves emulate the Frank-Starling biventricular relationship in two groups of patients with distinct contractile states (Fig. 3). These curves depict the probability (AUC) that a subject with a defined cardiac preload status will exhibit a different SVI or CI after a step change in their preload status. Therefore, according to our results, the magnitude of ΔSVI (ΔCI) and the probability for a subject to have a clinically meaningful increase in SVI (CI) after the GEDVI's increase will decrease when his initial preload status is greater than 1.33 times GEDVIN (starting of the plateau phase), being almost nonexistent above 1.51 times GEDVIN.

These findings are supported by Renner et al who found that GEDVI was a good predictor (AUC, 0.77; sensitivity, 66%; and specificity, 78%) of volume responsiveness (ΔSVI ≥ 15%) after repair of congenital heart disease in 26 anesthetized infants (BSA = 0.46 m). Receiver-operating characteristic curve analysis yielded a threshold value of GEDVI less than or equal to 400 mL/m equivalent to 1.11 times GEDVIN. Additionally, Michard et al studied adult patients response to volume in three preinfusion GEDVI groups—low 413–611 mL/m, intermediate 615–781 mL/m, and high 816–1,174 mL/m—and found an increase in the rate of a positive response to volume loading (ΔSVI > 15%) of 77%, 45%, and 23%, respectively. Interestingly, these GEDVI limits correspond with those of our study at 1.80 m PBSA with 816 mL/m matching 1.33 times GEDVIN. In addition, the rate of a positive response was 0% at a preinfusion GEDVI of 950 mL/m, equivalent to 1.55 times GEDVIN.

Furthermore, although the number of available fluid loading observations may be insufficient to draw definitive conclusions, data presented in Figure 1 show evidence of patent fluid responsiveness below 1.33 times GEDVIN in both the cardiovascular dysfunction and dilated cardiomyopathy groups. In fact, the lower the preinfusion preload status, the higher were ΔSVI, ΔGEDVI/GEDVIN, and AUC. By contrast, above 1.33 times GEDVIN, the response to volume loading was less consistent both in magnitude (ΔSVI) and rate of responsiveness, and ΔGEDVI/GEDVIN was at its minimal level, indicating that the maximum cardiac end-diastolic volume had been reached. Additionally, SVI was at its maximum between 1.33 and 1.51 times GEDVIN, indicating that the subjects were operating at maximum efficacy of the Frank-Starling response with no additional preload reserve.

In patients with dilated cardiomyopathy, GEDVI/GEDVIN-SVI (CI) curves shift downward as expected from their reduced myocardial contractility. Although their slopes are lower than in the cardiovascular dysfunction group, they still keep a well-defined steep part below 1.33 times GEDVIN as supported by the fact that 75% of the fluid infusion observations with preinfusion preload status less than 1.33 times GEDVIN responded with an increase in SVI greater than 15% (Fig. 1) even though the median of the infused volume were as low as 5.8 mL/kg. It is not possible to conclude that there is an absence of fluid responsiveness above 1.33 times GEDVIN because although none of the three patients responded to volume infusion, the median volume infused was too low (median, 3.3 mL/kg) to consistently increase cardiac preload. However, the 8% drop in SVI above 1.51 times GEDVIN (Fig. 3) suggests afterload mismatch due to the limit of preload (Frank-Starling) reserve had been reached.

Pulmonary edema is an expected consequence of high preload, especially in the failing heart. EVLWI can detect small (10–20%) increases in lung water. EVLWI greater than 10 mL/kg is associated with pulmonary edema and greater than 14 mL/kg with increased mortality in critically ill adults patients. EVLWI is higher in children than in adults, and values associated with pulmonary edema are still to be determined. In pediatric patients with respiratory failure, Lubrano et al found that EVLWI remained higher than 23 ± 9 mL/kg in nonsurvivors and lower than 17 ± 8 mL/kg in survivors. According to our results, in the cardiovascular dysfunction group with a cardiac preload status below 1.33 times GEDVIN, the EVLWI upper limit of the 95% CI is 16 mL/kg. By contrast, the EVLWI lower limit of the 95% CI is 19 mL/kg between 1.33 and 1.51 times GEDVIN and 22 mL/kg above 1.51 times GEDVIN, supporting our conclusion that above 1.33 times GEDVIN the heart is functioning in the "flat" part of the Frank-Starling curve (Fig. 3) where it is known that fluid loading has little effect on CO and only serves to increase lung tissue edema. Accordingly, Aman et al recently found that the plateau of CI rather than permeability or pressures predicted a ΔEVLWI greater than 10% during fluid loading in presumed hypovolemic critically ill patients, independent of the presence of sepsis and the volume and type of loading fluid.

This study has some limitations. Most of the patients did not have an echocardiogram at the time of the TPTD assessments, so we could not evaluate the impact of atrioventricular regurgitation on GEDVI. In addition, volume infusion may either increase intravascular blood volume (venous pooling) or interstitial fluid volume (capillary leak) but not necessarily affect cardiac preload. Therefore, GEDVI/GEDVIN-SVI (CI) curves allow assessment of a patient's preload responsiveness provided that a sufficient amount of the infused volume is able to reach the heart.

The increase in SV in response to an increase in cardiac preload depends mainly on the slope of the Frank-Starling curvilinear relationship which is influenced by afterload. In our study, there were no significant differences for SBP—a surrogate of afterload in the absence of aortic or pulmonary stenosis—between the four preload status levels. Accordingly, a SBP beyond the limits of our study may affect the prediction of cardiac preload responsiveness based on the GEDVI/GEDVIN-SVI (CI) relationships.

There is also the concern regarding possible mathematical coupling between the GEDV and CO. Michard et al observed a positive relationship between changes in GEDVI and mean arterial pressure, two variables that cannot be mathematically coupled. We did not observe significant differences in SBP and MBP between the different preload levels, possibly because catecholamines were used to maintain normal blood pressure. However, our data show that the SVI stops increasing when the GEDVI exceeded 1.33 times GEDVIN, a response more in keeping with cardiac physiology than with mathematical coupling.

As with most of the observational pediatric studies with a wide range of ages and disease origins, several confounding factors may have distorted our results. Noncardiogenic pulmonary edema could have contributed to the EVLWI increase in some patients. Patients with cardiovascular dysfunction are a heterogeneous group in regard to the origin of shock, dose of catecholamines, ventilatory assistance, and the time course of disease, all of which may affect cardiac preload responsiveness, afterload, and pulmonary edema. The inhomogeneity in the types of fluids used (NS, HS3%, Ab5%, FFP, PRBCs, platelets) and in the duration of the infusion of the fluid challenges and volume loadings may have affected the results of fluid responsiveness shown in Figure 1. However, the sample we studied represents the complex PICU population with hemodynamic instability, a situation which physicians face on a daily basis.

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