|Year : 2021 | Volume
| Issue : 3 | Page : 117-122
Validation of the vasoactive-inotropic score in predicting pediatric septic shock mortality: A retrospective cohort study
Antonius Hocky Pudjiadi, Dwi Lestari Pramesti, Sudung O Pardede, Mulyadi M Djer, Rinawati Rohsiswatmo, Nastiti Kaswandani
Department of Child-Health, Faculty of Medicine, Cipto Mangunkusumo Hospital, Universitas Indonesia, Jakarta, Indonesia
|Date of Submission||30-Jun-2020|
|Date of Acceptance||21-Nov-2020|
|Date of Web Publication||25-Sep-2021|
Dr. Antonius Hocky Pudjiadi
Department of Child-Health, Faculty of Medicine, Cipto Mangunkusumo Hospital, Universitas Indonesia, Jl, Salemba Raya No. 6, Jakarta Pusat 10430
Source of Support: None, Conflict of Interest: None
| Abstract|| |
Introduction: Mortality in pediatric septic shock remains very high. Vasoactive-inotropic score (VIS) is widely used to predict prognosis in patients with heart disease. It is a simple method that was initially used as a predictor of morbidity and mortality in postoperative patients with congenital heart diseases. Previous reports showed that high VIS score was associated with high mortality in pediatric sepsis. However, its discriminative value remains unclear. We aim to explore the discriminative value of VIS in predicting mortality in pediatric septic shock patients.
Methods: We conducted a retrospective cohort study on medical records of septic shock patients who received care in the pediatric intensive care unit (PICU). We screened medical records of pediatric patients which were diagnosed with septic shock and admitted to the PICU and received vasoactive/inotropic score for more than 8 h. Other supporting examination results were recorded, such as organ function evaluation for calculation of Pediatric Logistic Organ Dysfunction-2 (PELOD-2) score. The outcome of patients was recorded. The receiver operating curve was constructed to calculate the area under the curve (AUC), sensitivity, and specificity of each cutoff point.
Results: We obtained the optimum cutoff point of VIS > 11 with 78.87% sensitivity and 72.22% specificity. AUC positive was 0.779 (P < 0.001); predictive value and negative predictive value were 91.80% and 46.43%, respectively.
Conclusion: VIS > 11 has a good ability to predict mortality in children with septic shock.
Keywords: Mortality, pediatrics, sepsis, vasoactive-inotropic score
|How to cite this article:|
Pudjiadi AH, Pramesti DL, Pardede SO, Djer MM, Rohsiswatmo R, Kaswandani N. Validation of the vasoactive-inotropic score in predicting pediatric septic shock mortality: A retrospective cohort study. Int J Crit Illn Inj Sci 2021;11:117-22
|How to cite this URL:|
Pudjiadi AH, Pramesti DL, Pardede SO, Djer MM, Rohsiswatmo R, Kaswandani N. Validation of the vasoactive-inotropic score in predicting pediatric septic shock mortality: A retrospective cohort study. Int J Crit Illn Inj Sci [serial online] 2021 [cited 2022 Jul 6];11:117-22. Available from: https://www.ijciis.org/text.asp?2021/11/3/117/326605
| Introduction|| |
Sepsis describes a state of organ dysfunction due to dysregulated immune response toward infections. Today, uniform diagnostic criteria widely used in research to identify sepsis in the pediatric population are based on the International Pediatric Sepsis Consensus Conference (IPSCC). However, the SPROUT trial found that only 42% of sepsis patients were identified as such by both the clinician and the consensus criteria. According to IPSCC, sepsis is formally defined as systemic inflammatory response syndrome attributed to infection. Severe sepsis is defined as sepsis with either cardiovascular organ dysfunction or acute respiratory distress syndrome or two or more other organ dysfunctions. Septic shock is particularly defined as sepsis with cardiovascular organ dysfunction. Septic shock happens when sepsis causes persistent cardiovascular dysfunction despite ≥40 mL/kg fluid resuscitation. Sepsis is responsible for high morbidity and mortality among children. Today, septic shock mortality in developed countries is as low as 5%, whereas in developing countries, it is around 35%.
Several scoring systems have been validated to predict mortality in pediatric sepsis; for instance, pediatric sequential organ failure assessment and Pediatric Logistic Organ Dysfunction-2 (PELOD-2) scores. However, the requirement for extensive laboratory examinations limit their use in terms of availability and affordability. Thus, availability and affordability limit their use.
The vasoactive-inotropic score (VIS) was originally used to predict morbidity and mortality in patients with cardiac diseases. It represents the need for medications to support the cardiovascular function. A study by Haque et al. demonstrates high VIS score's association with mortality in septic children with refractory shock.
Calculating VIS is relatively easier than PELOD-2 score, however its use as mortality predictor in pediatric septic shock has yet to be explored.
| Methods|| |
We conducted a retrospective cohort study on pediatric patients diagnosed with septic shock and admitted to the pediatric intensive care unit (PICU) of Cipto Mangunkusumo Hospital between December 2015 and November 2019. This study obtained ethical approval from the Faculty of Medicine Universitas Indonesia Ethical Committee with approval number KET.1198/UN2.FI/ETIK/PPM.00.02/2019 on October 2019.
Inclusion criteria were pediatric patients aged 1 month to 18 years, with ICD 10 administrative coding of “other sepsis” (A41) and/or “streptococcal sepsis” (A40) and/or septic shock (R65.21) and received treatment at the PICU. We further screen for patient presenting with sepsis directly admitted to the PICU from the emergency room, exclusive of patients who developed septic shock during their hospital stay and transferred to the PICU (floor admission). Exclusion criteria were incomplete information to calculate VIS and PELOD-2 score, the patient referred by other PICU, and those with hospital LOS <8 h (including those who died or transferred to other hospitals). PELOD-2 score calculated was based on the examination performed within the first 24 h of sepsis diagnosis. VIS was calculated based on the maximum dose of vasoactive and inotropic drugs used within the first 24 h since the septic shock diagnosis. The value of VIS equals to dopamine dosage (μg/kg/min) + dobutamine dosage (μg/kg/min) + 100 × epinephrine dosage (μg/kg/min) + 10 × milrinone dosage (μg/kg/min) + 10,000 × vasopressin dosage (U/kg/min) + 100 × norepinephrine dosage (μg/kg/min).
The minimal sample size was calculated using that of diagnostic value cutoff point estimation, with 5% significance, absolute accuracy of 10%, and expected sensitivity of 85%. The minimal sample size calculated was 85 samples. We identified 213 medical records through electronic health record (Integra eOffice© SEVIMA, Surabaya, Indonesia). Incomplete records were excluded upon physical medical records screening. We collected the following variables for each data set: demographics data, chief complaint (related to sepsis diagnosis), history of surgery during hospital stay, history of mechanical ventilator use during hospital stay, PICU LOS, mortality outcome, maximum VIS score calculated on the 1st day of vasoactive-inotropic use, laboratory and physical examination data needed for PELOD-2 score on the 1st day of sepsis diagnosis, any diagnosis/suspected congenital heart defects, and immunosuppression (any presence/suspect of either malignancy or immunological cause of impaired immune system). We performed statistical analysis using SPSS version 17.0 (IBM Corp, Armonk, USA). Descriptive data are presented as percentage. Discriminative value of VIS was obtained using receiver operator characteristic (ROC) curve and expressed as area under the curve. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) are presented as 95% confidence interval.
| Results|| |
The study team reviewed 114 medical records, 12 were excluded due to incomplete data, and 13 were screened doubly. A final total of 89 medical records of pediatric patients diagnosed with septic shock who were admitted to PICU were reviewed and analyzed.
The distribution of patient characteristics is described in [Table 1]. The majority of septic shock patients were <5 years of age and admitted with a respiratory chief complaint. During hospitalization, 23.6% of patients underwent surgery, 79.8% required mechanical ventilation, and 67.5% stayed in the PICU for more than 48 h. The overall patient mortality was 79.8%.
We performed bivariate analysis on each risk factor that may affect patient's survival. The use of mechanical ventilator and PICU LOS were significantly associated with mortality. However, on further adjustment to other variables using multiple logistic regressions, no significant association was found [Table 2]. The mortality rate was statistically different between patients with high VIS score (VIS > 25) and low VIS score, P = 0.0051. Similarly, the mortality rate was statistically different between patients with PELOD-2 score >9, PELOD-2 score 4–9, and PELOD-2 score 0–3 [Table 3].
|Table 3: Relationship between vasoactive-inotropic score, PELOD-2 score, and mortality in shock septic patients|
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We obtained cutoff value for VIS and PELOD-2 score to predict mortality. VIS score of 11 was shown to be the optimum cutoff point with 78.87% (67.56%–87.97%) sensitivity, 72.22% (46.52–90.30) specificity, 91.80% (84.04–95.97) PPV, and 46.43% (33.71–59.63) NPV in predicting septic shock mortality in our study. The AUC of VIS score was 0.757 and was shown to be able to discriminate nonsurvivors among our pediatric septic shock patients (P = 0.001) [Table 4] and [Figure 1].
|Table 4: Discriminative value of PELOD-2 score, PELOD-2 score without lactate, and vasoactive-inotropic score in predicting mortality outcome in pediatric shock sepsis patients|
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|Figure 1: Receiver operating curve of vasoactive inotropic score,Pediatric Logistic Organ Dysfunction-2 score without lactate in predicting mortality in pediatric septic shock|
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Using ROC, PELOD-2 without lactate score was able to discriminate nonsurvivors with AUC of 0.753 (P < 0.001). Using PELOD-2 without lactate, we obtain optimal cutoff point of >9 with 67.61 (55.45–78-24) sensitivity and 66.67 (40.99–86.66) specificity. Similarly, PELOD-2 score (with lactate) was able to discriminate nonsurvivors with AUC of 0.779 (P = 0.001). Using PELOD-2 cutoff point of >10, sensitivity and specificity were 78.87 (67.56–87.67) and 72.22 (46.52–90.31), respectively [Table 4].
| Discussion|| |
This study demonstrates that VIS can be used to predict mortality in our pediatric septic shock patients. Secondarily, we also re-validate the use of PELOD-2 score in predicting clinical outcome in pediatric shock sepsis. In addition, we also found that omitting the lactate component in PELOD-2 did not compromise its discriminative value, however different cutoff value should be used.
Our data demonstrate high prevalence of pediatric sepsis cases that fell into septic shock of 17.6% with mortality rate reaching 78.6%. Our mortality rate is considerably higher compared to previously published data. A meta-analysis by Tan et al. comprised of 94 studies with a cumulative of 7561 severe sepsis and septic shock patients demonstrate that mortality rate is significantly higher in developing countries compared to developed countries. Our even higher mortality rate may be due to the single-center nature of our study which took place in a tertiary hospital. Cipto Mangunkusumo is a teaching hospital and a national referral center. Hence, most pediatric septic shock cases included in this study have underlying disease.
In this study, none of the risk factors identified independently affect the mortality outcome [Table 2]. This is contrary to the findings of Shime et al. that identified hematological diseases, malignancy, and shock as factors that affect mortality among severe sepsis subjects. We think that this may be due to the minimal sample size in this study as the sample size calculated was for determination of cutoff for VIS score and not to find difference in proportion between identified risk factors.
In this study, the value of VIS score used to predict mortality was the maximum dosage of vasopressor and inotropes used in the first 24 h of septic shock diagnosis. This was based on previous study by Musick et al. on 20752 patients admitted to the PICU. Their study found that the initial 24h VIS was better than the following 48h VIS in predicting mortality in critically ill PICU patients (AUC 0.736 vs 0.788 respectively).
We obtained the optimal cutoff value of VIS in predicting mortality in pediatric septic shock of > 11 with AUC 0.779 [Table 4]. This supports previous study by Musick et al. and Haque et al. that demonstrate the usefulness of VIS in predicting mortality in critically ill patients., In their study, Haque et al. used different cutoff or VIS of 20 to analyze the increased risk of mortality among their pediatric septic shock patients. However, the nature of their study was to find a correlation between high VIS score, instead of finding the optimum cutoff point for VIS in predicting mortality in pediatric septic shock patients. Using our data ROC, VIS > 20 has an AUC of 0.734, which is lower than VIS > 11. Furthermore, using VIS > 20, the sensitivity calculated was 57.75%, hence certain cases in which mortality risk should be anticipated might be underestimated (data not shown).
The use of VIS in septic shock patients has a good correlation with mortality as demonstrated in our study [Table 3] and Haque et al. The calculation of VIS takes into account the dosage of vasoactive and inotropic agents used to support cardiovascular performance in the event of shock. The use of VIS was originally applied to predict the outcome based on the hemodynamic supports in patients post cardiac surgery., Since then, VIS has been widely used in cardiogenic shock. We identified two prior studies in pediatric septic shock which used VIS. Mcintosh et al. evaluated VIS in pediatric sepsis and concluded that VIS was independently associated with clinical outcome such as PICU LOS, length of ventilator use, cardiac arrest incidence, extracorporeal membrane oxygenation use, and mortality. A study by Haque et al. also demonstrated that high VIS score (>21) was associated with mortality. This significance of VIS in pediatric sepsis may be due to the fact that hemodynamic characteristics in pediatric septic shock are similar to those of cardiogenic shock.
The use of the PELOD-2 score to predict mortality in pediatric patients has been well documented. A study by Zhong et al. demonstrated that the PELOD-2 score assessed on the first 24 h of admission has a good association to mortality outcome. Moreover, their study settings have similar characteristics to ours in which both were conducted in developing countries and in pediatric patients receiving care at the PICU. They also concluded that in developing countries, the PELOD-2 score can be used to standardize the diagnosis of sepsis using the new sepsis definition which includes the involvement of organ dysfunction.
In addition, we also validated the use of PELOD-2 score without lactate component that yielded the same predictive value as PELOD-2 in predicting mortality in pediatric septic shock patients. The incorporation of lactate in the PELOD-2 score may be due to it being an indirect marker of tissue hypoperfusion. However, previous studies in children demonstrated inconsistent results in determining the threshold of lactate value in pediatric sepsis to predict mortality., Similar to our study, Yuniar et al. demonstrated that lactate >2.5 mmol/L was not associated with mortality. Their study demonstrated that only 37% of pediatric shock patients had increased lactate. A previous study by Scott et al. demonstrated normalization of lactate within 2–4 h of presentation, with decreased risk of persistent organ dysfunction. In our study, PELOD-2 score without lactate shows similar predictive value in pediatric sepsis outcome compared to PELOD-2 score with lactate. This may be explained by the lactate value used for PELOD-2 score calculation that was examined within the first 24h, while lactate levels actually fluctuates within a narrower time frame.
Despite significant results, our study has its limitations. First, the retrospective nature of this study may overlook inconsistency in medical data recorded by different treating physicians. Furthermore, there is also a potential of recall bias as the administrative diagnosis was retrospectively assigned, which may have some discrepancy with the actual clinical diagnosis. Second, the small sample size and single-center nature of the study may limit the generalizability of the result. Potential selection bias may occur as we conducted a study in a national referral hospital. This may result in overrepresentation of septic shock in the more severe spectrum. Third, we only analyzed VIS score within the first 24 h and not serial VIS assessment. Furthermore, although with comparable discriminative value as PELOD-2 score, VIS cannot be used to substitute PELOD-2 score in detecting organ dysfunction used in the diagnosis of pediatric sepsis. However, its use to predict mortality is recommended as it is simpler and cost less than PELOD-2 examination. To our knowledge, this is the first study which identifies cutoff of VIS score in predicting mortality in pediatric sepsis patient. It is hoped that it can be used in appropriate clinical setting to help determine the management and prognosis of pediatric sepsis patients.
| Conclusion|| |
In conclusion, VIS can be used as predictor for mortality in pediatric septic shock with good discriminative ability. The use of VIS is comparable with the PELOD-2 score in predicting septic shock mortality, and it should be considered in appropriate setting. A future prospective, multicentered validation study needs to be conducted to extend the generalizability of its use in predicting mortality in pediatric septic shock.
Research quality and ethics statement
This study was approved by the Institutional Review Board / Ethics Committee (Approval # 1212092-1; Approval date Oct 28, 2019). The authors followed the applicable EQUATOR Network (http://www.equator-network.org/) guidelines during the conduct of this research project.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Weiss SL, Fitzgerald JC, Pappachan J, Wheeler D, Jaramillo-Bustamante JC, Salloo A, et al
. Global epidemiology of pediatric severe sepsis: The sepsis prevalence, outcomes, and therapies study. Am J Respir Crit Care Med 2015;191:1147-57.
Goldstein B, Giroir B, Randolph A; International Consensus Conference on Pediatric Sepsis. International pediatric sepsis consensus conference: Definitions for sepsis and organ dysfunction in pediatrics. Pediatr Crit Care Med 2005;6:2-4.
Weiss SL, Fitzgerald JC, Maffei FA, Kane JM, Rodriguez-Nunez A, Hsing DD, et al
. Discordant identification of pediatric severe sepsis by research and clinical definitions in the SPROUT international point prevalence study. Crit Care 2015;19:325.
Tan B, Wong JJ, Sultana R, Koh JC, Jit M, Mok YH, et al
. Global case-fatality rates in pediatric severe sepsis and septic shock: A systematic review and meta-analysis. JAMA Pediatr 2019;173:352-62.
Leteurtre S, Duhamel A, Salleron J, Grandbastien B, Lacroix J, Leclerc F, et al
. PELOD-2: An update of the PEdiatric logistic organ dysfunction score. Crit Care Med 2013;41:1761-73.
Gaies MG, Gurney JG, Yen AH, Napoli ML, Gajarski RJ, Ohye RG, et al
. Vasoactive-inotropic score as a predictor of morbidity and mortality in infants after cardiopulmonary bypass. Pediatr Crit Care Med 2010;11:234-8.
Haque A, Siddiqui NR, Munir O, Saleem S, Mian A. Association between vasoactive-inotropic score and mortality in pediatric septic shock. Indian Pediatr 2015;52:311-3.
Shime N, Kawasaki T, Saito O, Akamine Y, Toda Y, Takeuchi M, et al
. Incidence and risk factors for mortality in paediatric severe sepsis: Results from the national paediatric intensive care registry in Japan. Intensive Care Med 2012;38:1191-7.
Musick MA, Loftis LL, Kennedy CE. Comparing vasoactive-inotropic score reporting strategies in the PICU relative to mortality risk. Pediatr Crit Care Med 2018;19:1130-6.
Wernovsky G, Wypij D, Jonas RA, Mayer JE Jr., Hanley FL, Hickey PR, et al
. Postoperative course and hemodynamic profile after the arterial switch operation in neonates and infants. A comparison of low-flow cardiopulmonary bypass and circulatory arrest. Circulation 1995;92:2226-35.
Na SJ, Chung CR, Cho YH, Jeon K, Suh GY, Ahn JH, et al
. Vasoactive inotropic score as a predictor of mortality in adult patients with cardiogenic shock: Medical therapy versus ECMO. Rev Esp Cardiol (Engl Ed) 2019;72:40-7.
McIntosh AM, Tong S, Deakyne SJ, Davidson JA, Scott HF. Validation of the vasoactive-inotropic score in pediatric sepsis. Pediatr Crit Care Med 2017;18:750-7.
Carcillo JA, Pollack MM, Ruttimann UE, Fields AI. Sequential physiologic interactions in pediatric cardiogenic and septic shock. Crit Care Med 1989;17:12-6.
Zhong M, Huang Y, Li T, Xiong L, Lin T, Li M, et al
. Day-1 PELOD-2 and day-1 “quick” PELOD-2 scores in children with sepsis in the PICU. J Pediatr (Rio J) 2020;96:660-5.
Hernandez G, Bellomo R, Bakker J. The ten pitfalls of lactate clearance in sepsis. Intensive Care Med 2019;45:82-5.
Schlapbach LJ, MacLaren G, Festa M, Alexander J, Erickson S, Beca J, et al
. Prediction of pediatric sepsis mortality within 1 h of intensive care admission. Intensive Care Med 2017;43:1085-96.
Bai Z, Zhu X, Li M, Hua J, Li Y, Pan J, et al
. Effectiveness of predicting in-hospital mortality in critically ill children by assessing blood lactate levels at admission. BMC Pediatr 2014;14:83.
Yuniar I. Lactate profiles of pediatric shock patients in Cipto Mangunkusumo General Hospital 2015: A pilot study. Paediatr Indones 2017;57:12-7.
Scott HF, Brou L, Deakyne SJ, Fairclough DL, Kempe A, Bajaj L. Lactate clearance and normalization and prolonged organ dysfunction in pediatric sepsis. J Pediatr 2016;170:149-55.e1.
[Table 1], [Table 2], [Table 3], [Table 4]