|Year : 2020 | Volume
| Issue : 6 | Page : 321-326
Prediction of early intensive care unit mortality with serial serum lactate levels and its clearance in children with septic shock and multiorgan dysfunction syndrome
Krishna Mohan Gulla1, Tanushree Sahoo2, Dhiren Gupta3, Anil Sachdev3
1 Division of Pediatric Emergency and Critical Care, Institute of Child Health, Sir Ganga Ram Hospital, New Delhi; Department of Pediatrics, All India Institute of Medical Sciences, Bhubaneswar, Odisha, India
2 Department of Neonatology, All India Institute of Medical Sciences, Bhubaneswar, Odisha, India
3 Division of Pediatric Emergency and Critical Care, Institute of Child Health, Sir Ganga Ram Hospital, New Delhi, India
|Date of Submission||19-Jul-2020|
|Date of Decision||24-Aug-2020|
|Date of Acceptance||10-Sep-2020|
|Date of Web Publication||11-Nov-2020|
Dr. Krishna Mohan Gulla
Department of Pediatrics, All India Institute of Medical Sciences, Bhubaneswar, Odisha
Source of Support: None, Conflict of Interest: None
Introduction: Serum lactate is an important parameter to assess adequacy of microcirculation in septic shock. However, prediction of outcome in pediatric septic shock with mutli organ dysfunction (MODS) based on serial lactate levels and it's clearance is not well studied.
Materials and Methods: In this prospective study from a tertiary PICU in India, 43 children with septic shock and MODS aged 1month to 16 years were enrolled over one year. Our objective was to predict early ICU mortality (within 72 hours) as well as in-hospital mortality using serial serum lactate levels and it's rate of clearance. Serial serum lactate levels were measured at admission to PICU (0 hours) and 6 hourly for initial 24 hours and 12 hourly till 120 hours.
Results: The median (IQR) age of enrolled children was 32 (4.5,96) months. Median (IQR) PRISM-12 score was 16.5 (12,22). Seventeen children died. Serum lactate ≥2.6 mmol/L at 24 hours predicted early ICU mortality with sensitivity and specificity of 83.3% and 85.7% (AUC: 0.873, 95% CI 0.727, 1.000). In hospital mortality could be predicted with sensitivity and specificity of 60% and 73% (AUC: 0.734, 95% CI 0.571, 0.897) when serum lactate ≥1.8 mmol/L at 24 hours. Percentage of lactate clearance (median, IQR) at 24 hours of ICU stay were 15.1 (-21.4, 24.6) and -33.2 ( -262, 0.4) (p=0.04) between survivors and non-survivors at 72 hours of ICU stay.
Conclusion: Pediatric septic shock and MODS carries high mortality and serum lactate of ≥2.6 mmol/L predicted early ICU mortality with good precision.
Keywords: Children, lactate, mortality, sepsis, shock
|How to cite this article:|
Gulla KM, Sahoo T, Gupta D, Sachdev A. Prediction of early intensive care unit mortality with serial serum lactate levels and its clearance in children with septic shock and multiorgan dysfunction syndrome. J Pediatr Crit Care 2020;7:321-6
|How to cite this URL:|
Gulla KM, Sahoo T, Gupta D, Sachdev A. Prediction of early intensive care unit mortality with serial serum lactate levels and its clearance in children with septic shock and multiorgan dysfunction syndrome. J Pediatr Crit Care [serial online] 2020 [cited 2020 Nov 30];7:321-6. Available from: http://www.jpcc.org.in/text.asp?2020/7/6/321/300576
| Introduction|| |
Septic shock with multiorgan dysfunction syndrome (MODS) in pediatric patients is one of the major causes of morbidity and mortality in spite of advancements in the treatment of multiple organ failure.,, Serum lactate elevation is an important marker of impaired tissue perfusion in patients with sepsis and often elevated even in the absence of arterial hypotension. Lactate is frequently measured to estimate the extent of hypoxia at cellular level which elevates when the systemic oxygen delivery (hemoglobin level, oxygen saturation, and cardiac output) no longer maintains the extraction of oxygen by cells to meet their demands., Clinical studies also indicate the relationship between the supply dependent state of oxygen consumption and increased lactate levels similar to animal studies., A health technology assessment on the use of lactate levels in critically ill patients showed that blood lactate levels are important in risk-stratification of patients in emergency department and intensive care unit (ICU). Apart from one time point measurement of lactate levels, duration and area under the curve of increased lactate levels are linked to morbidity (organ failure) as well as mortality in different patient groups.
In early phase of shock resuscitation, lactate level seems to be more closely related to outcome when compared to macrocirculatory parameters such as blood pressure. Hence, a holistic approach incorporating macrocirculatory parameters such as heart rate, blood pressure, pulse volume, and microcirculatory parameters such as blood lactate would be more appropriate to predict outcome during resuscitation of sepsis with shock. In clinical practice, serum lactate level can be measured at bed side with rapid turnaround time for treating sepsis with shock. However, it is not being evaluated on large scale in critically ill children with septic shock. Hence, we conducted this prospective study to predict the outcome by serial lactate levels in critically ill children with septic shock and multiorgan failure.
| Materials and Methods|| |
This prospective observational study was conducted in a tertiary care teaching pediatric ICU (PICU) of Sir Ganga Ram Hospital, New Delhi, India. Our primary objective was prediction of early ICU mortality (within 72 h) using serial serum lactate levels and it is rate of clearance. Secondary objective was to predict in hospital mortality using serial lactate levels and it is clearance rate. Consecutive patients with septic shock and multiorgan failure (MOF) aged from 1 month to 16 years were prospectively enrolled in the study over a period of 1 year. Septic shock with MOF was defined as per International Pediatric Sepsis Consensus conference definition. Patients with inborn errors of metabolism with lactic acidosis, chronic kidney disease, and chronic liver disease were excluded. Patients were managed as per standard unit protocol for the management of septic shock. Written informed consent was obtained from parents/legal guardian prior to enrolment in the study. Serial arterial serum lactate levels at admission to PICU (0 h) and 6 hourly for initial 24 h and then 12 hourly till 120 h of stay were measured as a part of unit's protocol in managing septic shock. Lactate levels were measured in arterial blood using a blood gas analyzer (GEM Premier 3000 with i QM, displayed ranges of lactate 0.3–15.0 mmol/l). Once daily vasoactive inotropic score (VIS) and pediatric logistic organ dysfunction score (PELODS) were measured.
Lactate clearance (in percentage) was calculated by the formula: (Serum lactate at admission to ICU – serum lactate at specified time)/serum lactate at admission to ICU multiplied by 100. Inotropic Score was calculated as used by Gaies et al., in their study on outcome after infant cardiac surgery.
(Inotropic score [IS] = Dopamine dose [mcg/kg/min] + Dobutamine [mcg/kg/min] + 100 × epinephrine dose [mcg/kg/min]).
VIS = IS + 10 × Milrinone dose (mcg/kg/min) + 10,000 × vasopressin dose (units/kg/min) + 100 × nor epinephrine dose (mcg/kg/min). Institutional ethics committee clearance was obtained for the study.
Data were analyzed using Stata Corp LP College Station, Texas, USA. Continuous variables were measured using descriptive statistics such as mean, median, and mode, while for categorical variables proportion was used. Comparison of continuous variables between survivors and nonsurvivors was done by Student's t-test (uniformly distributed data) and Mann–Whitney test (for skewed data). Receiver operating characteristic (ROC) curves were used to analyze the ability of serial lactate values (0 h, 6 h, 12 h, 18 h, and 24 h) and lactate clearance (6 h, 12 h, 18 h, and 24 h) to predict outcome and optimal cut off points were subsequently selected for the calculation of sensitivity and specificity. Area under curve (AUC) >0.5 was taken as significant. We compared survival between two groups based on lactate level below or above 2.6 mmol/L at 24 h of ICU admission using log rank test. Lactate clearance rate was compared at 6 h, 12 h, 18 h, and 24 h between survivors and nonsurvivors by 72 h of ICU admission. The relation between serial serum lactates and daily PELODS scoring was obtained using spearman correlation coefficient. P < 0.05 was taken as statistically significant for all measurements. Using the best prediction value of lactate, we constructed Kaplan–Meier survival curve.
| Results|| |
A total of 43 children (male-29) with sepsis and multiorgan dysfunction were enrolled. Their median age (months) and weight (kg) were 32 (4.5, 96) and 10 (5, 22), respectively. Comorbid conditions of the children enrolled in the study are shown in [Table 1]. Median (interquartile range [IQR]) pediatric risk of mortality (PRISM)-12 scores in survivors and nonsurvivors were 16 (12, 19) and 19 (12, 27), respectively (P = 0.30). Seventeen children (39.5%) died during hospital stay and 7 children died in initial 72 h of admission.
Early ICU mortality (within 72 h) could be predicted with sensitivity and specificity of 83.3% and 85.7% (AUC: 0.873, 95% confidence interval [CI] 0.727, 1.000) respectively when serum lactate was more than >2.6 mmol/L at 24 h of ICU stay. In-hospital mortality could be predicted with sensitivity and specificity of 66.6% and 76.9% (AUC: 0.71, 95% CI 0.54, 0.89), respectively, when serum lactate was more than >2 mmol/L at 18 h of ICU admission [Table 2]. Serum lactate value of ≥2.6 mmol/L at 24 h of admission was significantly associated with in-hospital mortality [Figure 1]. Prediction of mortality using lactate, PELODS, and VIS at 24 h of stay is shown in [Figure 2]. Percentage of lactate clearance (median, IQR) at 24 h of ICU stay was 15.1 (−21.4, 24.6) and − 33.2 (−262, 0.4) (P = 0.04), respectively, between survivors and nonsurvivors before 72 h of ICU stay. Comparison of VIS and PELODS between survivors and nonsurvivors is depicted in [Table 3]. Median (IQR) duration of ventilation in survivors was 197 h (150, 240) and that of nonsurvivors was 60 h (33, 96) (P ≤ 0.001) and of inotropic support duration in survivors and nonsurvivors were 72 h (49, 120) and 48 h (45, 78), respectively
|Table 2: Serial lactate measurement for prediction of early intensive care unit mortality and in hospital mortality|
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|Figure 1: Kaplan–Meier survival curves for hospital mortality based on lactate levels|
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|Figure 2: Receiver operating characteristic curves for mortality prediction using lactate, pediatric logistic organ dysfunction score and vasoactive inotropic score at 24 h of pediatric intensive care unit stay|
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|Table 3: Comparison of vasoactive inotropic score and pediatric logistic organ dysfunction score between survivors and nonsurvivors from day 1 to 5|
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(P = 0.09). Serum lactate levels between survivors and nonsurvivors were compared till 96 h of ICU admission [Table 4] and [Figure 3]. Statistically significant positive correlation between PELODS and lactate was seen from 2nd day to 5th day of ICU admission [Table 5].
|Table 4: Comparison of lactate concentration between survivors and nonsurvivors till 96 h during intensive care unit stay|
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|Figure 3: Comparison of lactate concentration between survivors and non survivors|
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|Table 5: Correlation between lactate and pediatric logistic organ dysfunction score (day1-5)|
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| Discussion|| |
In our study, we measured serial arterial lactate value till 120 h in children with septic shock and constructed ROC curves. We found that absolute serum lactate at 24 h of PICU stay best predicted early mortality (within 72 h) while serum lactate value at 18 h was the best predictor of in-hospital mortality. Predictive ability of lactate was better for early mortality as compared to overall in-hospital mortality. There was a positive correlation between organ dysfunction measured by PELODS and serum lactate level from second day to 5th day of ICU admission. Overall mortality was 39.5% in our cohort.
Majority of studies in children have demonstrated prognostic role of lactate in postoperative cardiac patients (congenital heart disease/cardiopulmonary bypass or patients with postarrest state), post trauma and in sepsis/infection.,,,,,,,, Children with septic shock are usually very sick with higher mortality. However, relatively few studies have evaluated role of lactate in children with septic shock and multi organ dysfunction., In a pediatric septic shock cohort from North India (n = 30), Jat et al. measured lactate values at 3 points till 24 h and found that a value of >5 mmol/L at 12 h has good prediction of mortality (positive predictive value, negative predictive value 70%–80%) and overall mortality was 50%. In an another study by Choudhary et al. three-point estimation of serum lactate at 0 h, 24 h, and 48 h was done in 148 children with septic shock and lactate clearance was calculated at 24 h. A clearance of <10% at 24 h had moderate sensitivity and specificity (nearly 70%–80%) and an absolute value of >4 mmol/L at admission had best prediction of mortality with overall mortality of 64%. In study from China by Yan Hai et al. enrolled 484 children with sepsis out of which 69 had septic shock. The authors found serum lactate value >2.25 mmol/L has high probability of septic shock with sensitivity and specificity of 80% while an admission lactate of >4 mmol/L had 67% chance of mortality. The mortality rate of children with septic shock varies from 10% to 60% and in our cohort, overall mortality was 39.5% which is lower as compared to other studies reported from India. In our cohort, predictability of early mortality by serial serum lactate levels was maximum at 24 h of PICU stay with lactate cut off >2.6 mmol/L. Apart from absolute lactate value, some other studied lactate parameters are time to normalization of lactate to <2 mmol/dL from baseline (known as Lactime), lactate clearance, and lactate area.,,,, Few pediatric studies have used single-point estimation of lactate at admission,, while others have used lactate clearance (2-point estimation:First at admission and second varying from 6 to 24 h).,, A recent study had shown that compared to lactate clearance, absolute lactate value at 6 h of admission had better predictive ability. We chose serial lactate values as well as lactate clearance at specified points till 120 h of ICU stay to look at disease progression and its dynamicity. As compared to previous studies which measured serial lactate levels till 48 h of PICU stay, we measured the serial lactate levels till 120 h of ICU stay. In our study, we found significant difference in lactate clearance between survivors and nonsurvivors at 24 h of ICU stay which indirectly indicates that it takes at least some time for the therapeutic interventions such as fluid boluses, vasoactive inotropic support, maintaining normal metabolic milieu, and antibiotics to restore microcirculation. In our study, few children who died after 72 h of ICU stay and after shifting from ICU to ward and who went LAMA were counted under in-hospital mortality. This might be the reason for lower cut offs in lactate levels in predicting in-hospital in comparison to cut offs obtained for early ICU mortality.
We measured daily PELODS and VIS for assessing disease progression and correlated them with serial lactate levels. Previous studies looked at correlation of admission lactate with pediatric index of mortality score,,, and PRISM score., In our cohort, there was good positive correlation between PELODs and lactate from day 3 to 5 which may indirectly suggest that serial lactate levels can be used as marker to monitor clinical course as compared to more cumbersome PELODS scoring and it needs further validation.
Strengths of our study are its prospective nature, uniform disease spectrum (restricted to children with diagnosis of sepsis with septic shock and MODS) and serial lactate measurement till 120 h of PICU stay and its correlation with VIS and PELOD score. We do acknowledge few limitations such as small sample size.
| Conclusion|| |
Children with septic shock and MODS are a vulnerable group with high mortality and predictability of early ICU mortality was maximum at 24 h of ICU stay with lactate value >2.6 mmol/L in our cohort of children with septic shock and MODS.
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Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2], [Figure 3]
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5]