Abstract
Background:
The vasoactive-ventilation-renal (VVR) score is a disease severity index for predicting outcomes of pediatric patients receiving cardiac surgeries. We investigated whether the VVR score on admission can predict the length of stay (LOS) in the pediatric intensive care unit (PICU) in children diagnosed with heart failure (HF).Methods:
Medical records were reviewed for pediatric HF cases between January 2010 and December 2016. We calculated the VVR score using the electronic data, including measurements obtained at the time of admission and analyzed the correlation between the VVR score and prolonged LOS (PLOS). A PLOS was defined by a longer stay than the median duration for the surviving cases.Results:
A total of 113 pediatric HF cases were reviewed, of which 96 cases were finally included in the study. The median [IQR] LOS was 12 [6, 22] days. The use of a mechanical ventilator and extracorporeal membrane oxygenation (ECMO) were associated with PLOS. The area under the curve (AUC) of the vasoactive-inotropic score (VIS), VVR score, lactic acid level, and brain natriuretic peptide (BNP) for evaluating the association with mechanical ventilator or ECMO use was 0.682 (P = 0.006), 0.823 (P < 0.001), 0.683 (P = 0.006), and 0.783 (P < 0.001), respectively. In multivariable logistic regression analysis, the VVR score was the only significant parameter for predicting PLOS.Conclusions:
The VVR score on admission to the PICU is predictive for mechanical ventilator or ECMO use, which correlates with a PLOS. Therefore, the VVR score at PICU admission in children with HF is a useful LOS marker.Keywords
Heart Failure Pediatrics Pediatric Intensive Care Unit Prolonged Length of Stay Vasoactive-Ventilation-Renal Score
1. Background
Heart failure (HF) is an impairment in the ability of the ventricle to fill with or eject blood due to structural or functional issues. This disorder leads to problems in hemodynamics, oxygen consumption, and exercise capacity and eventually becomes pathologic for almost every organ in the body (1).
The vasoactive-ventilation-renal (VVR) score is a novel disease severity index which includes components reflecting cardiovascular, pulmonary, and renal function. Recently, the usefulness of the VVR score in pediatric patients undergoing cardiac surgery has been reported (2, 3). In some studies (4, 5), the VVR score was shown to be predictive in particular of a prolonged length of stay (PLOS) in the intensive care unit (ICU).
The lactate level has been shown to be associated with the LOS in the ICU or hospital in adult patients who have undergone cardiac surgeries (6, 7). In addition, brain natriuretic peptide (BNP) was previously found to be associated with PLOS in adult HF patients (8). Vasoactive-inotropic score (VIS) was shown to be associated with PLOS in ICU in infants receiving cardiac surgery (9).
2. Objectives
In the current study, we aimed to determine whether the VVR score can predict pediatric ICU (PICU) PLOS in children with HF. We also aimed to compare the usefulness of the VVR score with the lactate or BNP levels in relation to these predictive properties.
3. Methods
We conducted a retrospective cohort study of children with HF patients admitted to the PICU of Asan Medical Center Children's Hospital, Seoul, Republic of Korea, between January 2010 and December 2016. All patients included in the study were admitted to the medical section of PICU, and those with postoperative problems of any kind were excluded. Patients who had undergone heart transplantation or died were excluded, and only the children who had survived to discharge or transfer to the general ward were analyzed. Following our own clinical protocols, laboratory tests including lactate and BNP were immediately done, and echocardiograms were conducted by the attending intensivist or a cardiologist for all PICU cases on admission. The diagnosis of HF was made when all the following criteria were met: (1) the presence of clinical symptoms of HF (dyspnea, feeding difficulty, diaphoresis, etc.); (2) echocardiographic evidence of systolic or diastolic dysfunction; and (3) the BNP level at admission greater than 100 pg/mL (10). We excluded any children who did not meet the above diagnostic criteria based on a medical record review or for whom complete echocardiographic or laboratory test data were not available. This study was approved by the Institutional Review Board of Asan Medical Center (S2019-2723-0001).
Patient demographics and data on the length of PICU stay, HF etiology, classification of HF, and need for mechanical ventilation/mechanical circulatory support by extracorporeal membrane oxygenation (ECMO)/renal replacement therapy were collected. PLOS was defined as a value greater than the median LOS for all of our HF patients. HF was classified according to the New York Heart Association (NYHA) guidelines for older children and Ross HF classification in younger children. The VIS was calculated as the dopamine dose (mcg/kg/min) + dobutamine dose (mcg/kg/min) + 100 × epinephrine dose (mcg/kg/min) + 10 × milrinone dose (mcg/kg/min) + 10,000 × vasopressin dose (units/kg/min) + 100 × norepinephrine dose (mcg/kg/min). The VVR was calculated as ventilation index + VIS + Δ creatinine (change in creatinine from baseline × 10). Ventilator index was calculated as the PaCO2 (mmHg) × peak airway pressure (cmH2O) × respiratory rate (breaths/min)/1,000. Concerning the ventilation index, the maximum measurement during the first 6 hours after admission to the PICU was used; if a patient did not receive mechanical ventilation, the ventilation index was defined as ‘0’. The inotrope (s) dose and creatinine measurements were obtained from the measurements first recorded at the time of PICU admission.
Statistical analysis was performed using SPSS software for Windows® version 21 (SPSS, Chicago, IL). Continuous variables were analyzed using the Wilcoxon rank sum test, and presented as a median [interquartile range]. Cross tabulation analysis was performed to analyze the correlation between mechanical life support application and PLOS, and an odds ratio (OR) was presented. Receiver operating characteristic (ROC) curves were created to analyze the usefulness of different clinical parameters in predicting the possible need for mechanical life support application or PLOS. In all analyses, a P-value of less than 0.05 was considered statistically significant.
4. Results
During the study period, 113 children with HF were admitted to our PICU. Twelve of these patients died, and five received heart transplantation and were thus excluded from further analysis. A final sample population of 96 children with HF was finally included in the present study. The median age of the included patients was 0.5 years, and 44 (45.8%) were male. The median PICU LOS was 12 days (IQR 6, 22). Fifty-six (58.3%) of these children required mechanical ventilation, 15 (15.6%) required ECMO, and 11 (11.5%) required renal replacement therapy (Table 1). The baseline characteristics (age, sex, HF etiology, classification of HF, and application of mechanical life support) were not significantly different between the PLOS group versus no-PLOS group (table not shown).
Clinical and Demographic Characteristics of the Study Patients a
| Characteristics | n = 96 |
|---|---|
| Age (y) | 0.5 [0.2, 6.9] |
| Sex, male | 44 (45.8) |
| Length of pediatric intensive care unit stay, days | 12 [6, 22] |
| HF etiology | |
| Congenital heart disease/repaired | 52 (54.2) / 38 (39.6) |
| Cardiomyopathy | 24 (25.0) |
| Myocarditis | 15 (15.6) |
| Arrhythmia | 3 (3.1) |
| Rejection of transplanted heart | 2 (2.1) |
| Classification of heart failure | |
| Class III | 10 (10.4) |
| Class IV | 86 (89.6) |
| Mechanical ventilation | 56 (58.3) |
| ECMO | 15 (15.6) |
| Renal replacement therapy | 11 (11.5) |
The children were divided into PLOS and no-PLOS groups, and their clinical parameters were compared. The VIS, VVR score, lactic acid levels, and BNP concentrations were all greater in the PLOS group (Table 2). The association between the clinical parameters and the PLOS was analyzed using ROC curves, and the VIS, VVR score, lactic acid levels, and BNP amounts were found to have a statistically significant relationship, each yielding an area under the curve (AUC) of 0.636, 0.714, 0.639, and 0.626, respectively (Figure 1).
Clinical Parameters at Admission in the PLOS and No-PLOS Groups a
| Variables | No-PLOS (n = 48) | PLOS (n = 48) | P-Value |
|---|---|---|---|
| VIS | 8.5 [5.0, 18.3] | 14.1 [7.4, 24.3] | 0.018 |
| VVR score | 11.1 [5.5, 20.7] | 27.8 [11.6, 36.2] | < 0.001 |
| Lactic acid (mmol/L) | 1.8 [1.1, 2.5] | 2.8 [1.2, 5.3] | 0.020 |
| B-type natriuretic peptide (pg/mL) | 1478.5 [529.8, 4532.8] | 2340.0 [1234.8, 6836.8] | 0.036 |
| Left ventricular ejection fraction (%) | 44.5 [27.8, 67.0] | 37.0 [21.5, 63.8] | 0.593 |
Receiver operating characteristic (ROC) curve analysis of the associations between the indicated clinical parameters and PLOS (≥ 12 days)
The requirements for the use of a mechanical ventilator and ECMO were found to correlate with a PLOS, with OR of 10.82 and 3.61, respectively (Table 3). The ROC curve analysis of the association between clinical parameters of interest and the need for a mechanical ventilator or ECMO showed statistically significant results for the VIS and VVR values and lactic acid and BNP levels each yielding an AUC of 0.682, 0.823, 0.683, and 0.783, respectively (Figure 2). When the cutoff for the VVR score was set as ≥ 10, the sensitivity, specificity, positive predictive, and negative predictive values for the PLOS were 82.6, 50.0, 60.3, and 75.8%, respectively (Table 4). Multivariable logistic regression analysis revealed that the VVR score was the only significant predictor of PLOS (Table 5).
Correlation Between the Requirement for a Mechanical Ventilator/RRT/ECMO Intervention and PLOS a
| Variables | No-PLOS (n = 48) | PLOS (n = 48) | Odds Ratio | P-Value |
|---|---|---|---|---|
| Mechanical ventilator | 16 (33.3) | 40 (83.3) | 10.82 | < 0.001 |
| ECMO | 4 (8.3) | 11 (22.9) | 3.61 | 0.048 |
| RRT | 3 (6.3) | 8 (16.7) | 3.30 | 0.111 |
Receiver Operating Characteristic (ROC) Curve Analysis of the Associations between the Indicated Clinical Parameters and Requirement for a Mechanical Ventilator/ECMO Intervention
Predictability of the VVR Score for PLOS and Mechanical Ventilator/ECMO Interventions when the Cutoff was Set at ≥ 10
| Variables | Sensitivity | Specificity | PPV | NPV |
|---|---|---|---|---|
| Prolonged length of stay | 82.6 | 50.0 | 60.3 | 75.8 |
| Mechanical ventilator/ECMO | 85.7 | 62.5 | 76.2 | 75.8 |
Multivariate Logistic Regression Analysis for Predictors of PLOS
| Variables | Odds Ratio | 95% Confidence Interval | P-Value |
|---|---|---|---|
| VIS | 0.920 | 0.839 - 1.009 | 0.075 |
| VVR score | 1.091 | 1.016 - 1.172 | 0.016 |
| Lactic acid | 1.112 | 0.920 - 1.346 | 0.273 |
| B-type natriuretic peptide | 1.000 | 1.000 - 1.000 | 0.543 |
| Left ventricular ejection fraction | 0.996 | 0.972 - 1.020 | 0.730 |
5. Discussion
Based on our findings, the VVR score at admission is significantly higher in children with HF who will eventually require a PLOS in the PICU. In addition, the application of a mechanical ventilator or ECMO in these cases showed an association with a PLOS, and the VVR score was the best predictor of the requirement for these interventions.
A longer hospitalization for HF treatment was previously reported to be associated with poorer patient outcomes (11, 12). This prompted efforts to elucidate predictive or associated factors with a longer LOS in HF patients. Omar HR et al. identified higher BNP levels in their longer-than-average LOS group (13). In our study, we used the median LOS as the cutoff for defining PLOS. The BNP level was a significant factor in univariable analysis for predicting PLOS, but not in subsequent multivariable analysis in which VVR score was the only significant predictor. Consistently, further ROC curve analysis revealed that the AUC of the VVR score was the largest among the tested parameters.
Organ impairment is frequently observed in HF patients. HF also leads to congestion and hypoperfusion, which can eventually lead to the failure of other organs such as the lung and kidney (14). Mechanical life support systems such an ECMO, ventilator, and renal replacement therapy (RRT) are required in these cases (15). In previous studies, the application of mechanical ventilators was shown to be associated with an ICU PLOS (16, 17), and ECMO interventions were shown to further increase this duration (18, 19). Similarly in our present study in children with HF, the need for mechanical ventilation or ECMO was associated with a PLOS in the PICU. Because the VVR score is a calculation formula consisting complementary pulmonary and renal components in addition to VIS, it is theoretically and clinically plausible that the greater the VVR score, the need for not only ECMO but also mechanical life support system like ventilator and RRT increases. Based on our findings, the VVR score was found to be the best predictor of the requirement for this support, which likely underlies its superior predictive properties in relation to PLOS.
Our present study had some limitations of note, principally arising from the retrospective nature of the analyses. In addition, the administration of vasoactive medication or the degree of mechanical ventilation is likely to have varied according to the judgment and practices of the attending physician. However, the intensivist team members at our hospital who treated these children were unchanged during the study period, which would have minimized the bias in terms of clinical decision making processes. Another shortcoming of our current report was the small sample size. Future prospective studies of larger cohorts are warranted to validate our preliminary findings, and further elucidate the factors that may affect the VVR score under a consistent practice protocol.
Another hypothesis is that the VVR score at PICU admission would be associated with a higher risk for major adverse outcomes like death and heart transplantations. During the study period, 12 patients died, and five patients received heart transplantations, so the small numbers presenting major adverse outcomes restricted us from conducting supplementary analysis on this issue. Future studies, including a larger sample size are needed to further analyze the detailed variables of major adverse outcomes.
In conclusion, the VVR score for pediatric HF patients at admission to the PICU is a useful predictor of the need for mechanical ventilator or ECMO support. Since mechanical support interventions correlate with PLOS in such cases, the VVR score at admission can also be a useful predictor of an extended stay in the PICU for pediatric HF patients.
References
-
1.
Dickstein K, Cohen-Solal A, Filippatos G, McMurray JJ, Ponikowski P, Poole-Wilson PA, et al. ESC guidelines for the diagnosis and treatment of acute and chronic heart failure 2008: The task force for the diagnosis and treatment of acute and chronic heart failure 2008 of the European Society of Cardiology. Developed in collaboration with the Heart Failure Association of the ESC (HFA) and endorsed by the European Society of Intensive Care Medicine (ESICM). Eur J Heart Fail. 2008;10(10):933-89. [PubMed ID: 18826876]. https://doi.org/10.1016/j.ejheart.2008.08.005.
-
2.
Cashen K, Costello JM, Grimaldi LM, Narayana Gowda KM, Moser EAS, Piggott KD, et al. Multicenter validation of the vasoactive-ventilation-renal score as a predictor of prolonged mechanical ventilation after neonatal cardiac surgery. Pediatr Crit Care Med. 2018;19(11):1015-23. [PubMed ID: 30095748]. https://doi.org/10.1097/PCC.0000000000001694.
-
3.
Scherer B, Moser EA, Brown JW, Rodefeld MD, Turrentine MW, Mastropietro CW. Vasoactive-ventilation-renal score reliably predicts hospital length of stay after surgery for congenital heart disease. J Thorac Cardiovasc Surg. 2016;152(5):1423-1429 e1. [PubMed ID: 27649997]. https://doi.org/10.1016/j.jtcvs.2016.07.070.
-
4.
Miletic KG, Delius RE, Walters H3, Mastropietro CW. Prospective validation of a novel vasoactive-ventilation-renal score as a predictor of outcomes after pediatric cardiac surgery. Ann Thorac Surg. 2016;101(4):1558-63. [PubMed ID: 26872731]. https://doi.org/10.1016/j.athoracsur.2015.11.006.
-
5.
Miletic KG, Spiering TJ, Delius RE, Walters H3, Mastropietro CW. Use of a novel vasoactive-ventilation-renal score to predict outcomes after paediatric cardiac surgery. Interact Cardiovasc Thorac Surg. 2015;20(3):289-95. [PubMed ID: 25487233]. https://doi.org/10.1093/icvts/ivu409.
-
6.
Andersen LW, Holmberg MJ, Doherty M, Khabbaz K, Lerner A, Berg KM, et al. Postoperative lactate levels and hospital length of stay after cardiac surgery. J Cardiothorac Vasc Anesth. 2015;29(6):1454-60. [PubMed ID: 26456273]. https://doi.org/10.1053/j.jvca.2015.06.007.
-
7.
Kogan A, Preisman S, Bar A, Sternik L, Lavee J, Malachy A, et al. The impact of hyperlactatemia on postoperative outcome after adult cardiac surgery. J Anesth. 2012;26(2):174-8. [PubMed ID: 22113490]. https://doi.org/10.1007/s00540-011-1287-0.
-
8.
Whellan DJ, Zhao X, Hernandez AF, Liang L, Peterson ED, Bhatt DL, et al. Predictors of hospital length of stay in heart failure: Findings from get with the guidelines. J Card Fail. 2011;17(8):649-56. [PubMed ID: 21807326]. https://doi.org/10.1016/j.cardfail.2011.04.005.
-
9.
Gaies MG, Jeffries HE, Niebler RA, Pasquali SK, Donohue JE, Yu S, et al. Vasoactive-inotropic score is associated with outcome after infant cardiac surgery: an analysis from the pediatric cardiac critical care consortium and virtual picu system registries. Pediatr Crit Care Med. 2014;15(6):529-37. [PubMed ID: 24777300]. [PubMed Central ID: PMC4159673]. https://doi.org/10.1097/PCC.0000000000000153.
-
10.
Maisel AS, Krishnaswamy P, Nowak RM, McCord J, Hollander JE, Duc P, et al. Rapid measurement of B-type natriuretic peptide in the emergency diagnosis of heart failure. N Engl J Med. 2002;347(3):161-7. [PubMed ID: 12124404]. https://doi.org/10.1056/NEJMoa020233.
-
11.
Reynolds K, Butler MG, Kimes TM, Rosales AG, Chan W, Nichols GA. Relation of acute heart failure hospital length of stay to subsequent readmission and all-cause mortality. Am J Cardiol. 2015;116(3):400-5. [PubMed ID: 26037295]. https://doi.org/10.1016/j.amjcard.2015.04.052.
-
12.
Cotter G, Davison BA, Milo O, Bourge RC, Cleland JG, Jondeau G, et al. Predictors and associations with outcomes of length of hospital stay in patients with acute heart failure: Results from VERITAS. J Card Fail. 2016;22(10):815-22. [PubMed ID: 26721775]. https://doi.org/10.1016/j.cardfail.2015.12.017.
-
13.
Omar HR, Guglin M. Longer-than-average length of stay in acute heart failure: Determinants and outcomes. Herz. 2018;43(2):131-9. [PubMed ID: 28168428]. https://doi.org/10.1007/s00059-016-4532-3.
-
14.
Harjola VP, Mullens W, Banaszewski M, Bauersachs J, Brunner-La Rocca HP, Chioncel O, et al. Organ dysfunction, injury and failure in acute heart failure: From pathophysiology to diagnosis and management. A review on behalf of the Acute Heart Failure Committee of the Heart Failure Association (HFA) of the European Society of Cardiology (ESC). Eur J Heart Fail. 2017;19(7):821-36. [PubMed ID: 28560717]. [PubMed Central ID: PMC5734941]. https://doi.org/10.1002/ejhf.872.
-
15.
Ponikowski P, Voors AA, Anker SD, Bueno H, Cleland JG, Coats AJ, et al. 2016 ESC guidelines for the diagnosis and treatment of acute and chronic heart failure: The task force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC). Developed with the special contribution of the Heart Failure Association (HFA) of the ESC. Eur J Heart Fail. 2016;18(8):891-975. [PubMed ID: 27207191]. https://doi.org/10.1002/ejhf.592.
-
16.
Arabi Y, Venkatesh S, Haddad S, Al Shimemeri A, Al Malik S. A prospective study of prolonged stay in the intensive care unit: Predictors and impact on resource utilization. Int J Qual Health Care. 2002;14(5):403-10. [PubMed ID: 12389806]. https://doi.org/10.1093/intqhc/14.5.403.
-
17.
Higgins TL, McGee WT, Steingrub JS, Rapoport J, Lemeshow S, Teres D. Early indicators of prolonged intensive care unit stay: Impact of illness severity, physician staffing, and pre-intensive care unit length of stay. Crit Care Med. 2003;31(1):45-51. [PubMed ID: 12544992]. https://doi.org/10.1097/00003246-200301000-00007.
-
18.
Maxwell BG, Powers AJ, Sheikh AY, Lee PH, Lobato RL, Wong JK. Resource use trends in extracorporeal membrane oxygenation in adults: An analysis of the nationwide inpatient sample 1998-2009. J Thorac Cardiovasc Surg. 2014;148(2):416-21 e1. [PubMed ID: 24183903]. https://doi.org/10.1016/j.jtcvs.2013.09.033.
-
19.
Aiello S, Loomba RS, Kriz C, Buelow M, Aggarwal S, Arora RR. The need for extracorporeal membrane oxygenation in adults undergoing congenital heart surgery: Impact and trends of utilization. Indian J Crit Care Med. 2017;21(9):547-51. [PubMed ID: 28970652]. [PubMed Central ID: PMC5613604]. https://doi.org/10.4103/ijccm.IJCCM_169_17.