STUDY ON ROLE OF SERUM LACTATE LEVELS AND LACTATE CLEARANCE TO PREDICT THE OUTCOME OF PATIENTS WITH PAEDIATRIC SHOCK IN RURAL TERTIARY CARE TEACHING HOSPITAL

In thePaediatric Intensive Care Unit (PICU), though shock is one of the most commonly diagnosed etiology, it is still poorly understood. Academic definitions of shock include an acute state that results from cardiovascular malfunction and the circulatory system's inability to effectively supply nutrients and oxygen to fulfil the metabolic demands of essential organs. (1) The diagnosis is still based on the clinical element of the criteria, and hypotension is not a requirement. Septic shock is the most prevalent life-threatening illness affecting children globally. Because it provides 90% of the body's energy requirements, aerobic metabolism requires oxygen. When there is tissue-level hypoxia, cells switch to anaerobic metabolism, which is less effective since it is unable to maintain normal aerobic cellular metabolism. Lactic acid is a by-product of anaerobic metabolism, which occurs when the body's cells are not easily accessible to oxygen. (2)

Lactate is the end product of anaerobic glycolysis, the final step of which is the conversion of pyruvate into lactate by the enzyme lactate dehydrogenase (LDH). Lactic acid is produced by various cells in the body, including muscle cells, red blood cells and neurons. Lactic acid is often considered the waste product of glycolysis. But as always with metabolism, there is no such thing as waste. In a fasted state, lactate can be taken up by other organs and continue its way to the tricarboxylic acid (TCA) cycle. In addition, lactate can serve as a substrate in signalling pathways.(3,4)

Oxygen debt, which results in lactic acidosis and gradual clinical deterioration, is caused when there is an imbalance between the amount of oxygen delivered to the tissue and the amount of oxygen that is needed. The estimation of the blood's lactic acid content makes the serum lactate level a relatively sensitive and reliable biomarker of tissue hypoxia and hypoperfusion. (5,6)Various underlying disease processes commonly result in reduced tissue perfusion in sick children. The development of Multi-Organ Dysfunction Syndrome (MODS) may result from delayed identification of tissue hypoperfusion.If not promptly identified and rectified, this has an adverse effect on mortality and morbidity rates. (7)

Regardless of whether the primary underlying pathophysiologic change is hypovolemic, cardiogenic, obstructive, or distributive, lactate concentrations rise in all types of shock.(8)

The purpose of the current study was to assess the serial lactate levels in children experiencing septic shock and to link such levels with the outcome.

Objectives:

To assess the relationship between serial lactate levels monitoring and lactate clearance and correlate the outcome in the children with shock.

SOFA SCORE: Sequential Organ Failure Assessment Score (11)

Definitions

·         Critically Ill Children:

Children admitted in PICU requiring continuous monitoring due to various medical and surgical pathophysiologies. (1)

·         Shock:

Is an acute process characterised by the body's inability to provide enough oxygento meet the metabolic demands of vital organs and tissues. (1)

·         Sepsis:

Sepsis is defined as SIRS (Systemic Inflammatory Response Syndrome) that has an infectious origin that is either suspected or confirmed.(10)

Criteria for PICU admission:

ü  Shock

ü  GCS < 8

ü  Hypoxia

ü  Respiratory distress

ü  Hepatic failure

ü  Post GI surgery

ü  Requiring mechanical ventilation

ü  Requiring Non-Invasive Ventilation

ü  Requiring Post Op care

Investigations:

After a complete clinical examination, investigations viz.,Complete Blood Count (CBC), Liver Function Test, Kidney Function Test, Blood Gas were sent. Serum lactate levels at the time of presentation of shock and 12-24 hours after the initial presentation were done.

SOFA score was measured by taking platelet count, bilirubin, sr. creatinine and PaO2/FiO2 ratio into account.Chest radiograph was done wherever indicated.

Instrumentation:

1.       The results were obtained using ABX-Pentra XL 80. The levels of hemoglobin, total and differential leucocyte count, total platelet count were recorded.

2.       LFT, KFT and Serum lactate levels were determined using VITROS 5600 integrated system and manufactured by Ortho Clinical Diagnostics.

3.       The normal values were taken as:

Sr Albumin- 3.5 to 5.5 g/dl

Sr Creatinine- < 1 mg/dl

SrLactate- 0 to 4 mmol/L

4.       Chest radiogram was done and abnormal findingsrecorded.

5.       The duration of stay of each child was recorded

Flow chart:

Statistical analysis:

Data was entered into Microsoft Excel sheet and statistical analysis was done. Relationship of various demographic, clinical characteristics and etiology with outcome were evaluated employing Chi- square test, Fischer’s exact test for categorical data and independent T test for continuous data with normal distribution. p value was considered significant if less than 0.05.       

OBSERVATION AND RESULTS:

In the present study of 144 cases, 1^stserum lactate levels were sent at the time of admission and 2^nd lactate levels were sent 12-24 hours after admission. The relation between lactate levels, lactate clearance and clinical outcome is as mentioned below.There were 83 males and 60 females. 32.17% were in the age group of 1 month to 1 year, 27.97% were between 10-18 years of age, 22.38% were in the age group of 5-10 years of age and 17.49% were between 1-5 years of age.Majority of the patients had cardiogenic shock and maximum number of deaths were among the patients with cardiogenic shock followed by septic shock.

Majority of the patients with poor prognosis had septic shock and cardiogenic shock.There was significant decrease in the clearance of lactate in the presence of hepatic dysfunction in presence of shock. Majority of patients with higher duration of complaints had higher lactate levels comparatively than those with less duration of complaints.58 study cases died and all the cases had elevated lactate levels.The most common causes were systemic illnesses like pneumonia, congenital heart disease, gastroenteritis, seizures etc.Malnutrition and multi organ dysfunction syndrome were highly associated in patients who died.The mean change in lactate levels in those patients that died was -4.19 which indicates that the 2^nd lactate levels were more than the initial levels on admission.Patients with 2^nd lactate levels > 4 mmol/L had higher mortality rate.

DISCUSSION

In the present study, out of 144 patients, 61 patients had a lactate level < 4mmol/L, among which 27 (44.27%) died. 82 patients had initial lactate value   > 4 mmol/L, among which 31 (37.8%) died. 76 patients (53.14%) had 2^nd lactate level < 4 mmol/L, among which 12 patients (15.79%) died. 67 patients (46.86%) had lactate values > 4 mmol/L, among which 46 (68.65%) died.

Majority of the patients who died had initial lactate levels < 4 mmol/L which is within the normal limits. These patients were admitted in PICU during the initial stages of shock and 1^st lactate level was sent immediately after admission. 7 patients that died had diagnosis of pneumonia, leukemia, heart failure and chronic kidney disease. All these patients were started on ionotropic support but did not improve and their condition deteriorated over a period of time and the mean lactate clearance was - 7.6 mmol/L which indicates that the 2^nd lactate level was elevated indicating the bad prognosis of the patient.

The lactate levels in shock usually may take as late as 3-6 hours to increase. This may also depend on the severity of the illness, prognosis to treatment and presence of MODS. This explains the increased death rates when the 1^st lactate level at admission was normal. The 2^nd lactate level sent 12-24 hours after admission was associated with higher mortality rates.

The mean of 2^nd lactate levelwas more than 1^st lactate level among those that died and the negative mean value of change in lactate levels among those dead indicates that the lactate clearance was less among the dead.

Based on serial blood gas readings, increased mortality was associated with lactate and unidentified anions (Strong Ion Gap = SIG). Metabolic acidosis (both lactic and non-lactic) seemed to be associated with high mortality and increased length of stay in hospital and in the ICU. (12)

In a study done by Rocha A et al(13), 93 patients (37.3%) with a maximal lactate level of more than 2.0 mmol/L on D1 were profiled. In this patient group (n = 93), there were 11 deaths (11.8%) while in the PICU and one additional patient passed away after 28 days, for a total mortality rate of 12.9%. When lactate concentrations either rose or slightly reduced (less than 0.05 mmol/L) from D1 to D2, mortality was predicted with the highest sensitivity (0.636) and specificity (0.890). Higher serum lactate readings (L 0.05 mmol/L) from D1 to D2 were linked to higher mortality during PICU stays (L 0.05 mmol/L).

In a study byJat K et al (14), 3 lactate levels at 0-3 hours, 12 hours and 24 hours of admission were considered. In their study, lactate value of > 5 mmol/L was taken as elevated lactate and all three lactate levels were elevated in patients with mortality and all the lactate levels had significant values in patients with mortality.

A study done by Patriawati KA et al(15) also had taken 3 lactate values into consideration, 1^st at admission, 2^nd at 6 hours and 3^rd at 24 hours of admission. In their study, the 1^st and 3^rd lactate values had significant association with mortality i.e, the patients with high (> 4mmol/L) initial and third lactate levels had higher mortality rates. 2^nd lactate level at 6 hours of admission did not have much significance with the outcome.  The lactate clearance rate is more important than the single serum lactate value.

Distribution of Study Population by Age: The study predominantly involved infants (1 month - 1 year) comprising 32.17% of the cohort, followed by adolescents (10-18 years).

Mortality Rate by Serum Lactate Level: This chart highlights the study's central finding. While initial lactate levels > 4 mmol/L had a mortality rate of 37.8%, the 2nd lactate level > 4 mmol/L (taken 12-24 hours post-admission) was associated with a significantly higher mortality rate of 68.7%. This supports the conclusion that persistent hyperlactatemia is a stronger predictor of death than the initial level.

Patient Outcomes: Survival vs Death: This stacked bar chart visualizes the absolute numbers. Notice the dramatic shift in the "2nd Level > 4" column, where the number of deaths (red) exceeds survivors (green), unlike the "2nd Level < 4" group where survival is very high. This visually reinforces the importance of lactate clearance.

Gender Distribution: The study included a higher proportion of males (58.0%) compared to females (42.0%).

This study posits that both lactate level estimation for prognostic purposes and early shock recognition for timely intervention are critical factors in preventing negative patient outcomes.Multiple lactate levels estimation is better than single lactate values in determining the outcome of the patients in shock.

1.       Larsen GY, Mecham N, Greenberg R. An emergency department septic shock protocol and care guidelines for children initiated at triage. Pediatrics 2011; 127: e1585-e92.

2.       Choudhury J, Routray SS. Effectiveness of predicting outcome in septic shock in critically ill children by assessing serum lactate levels. Pediatr Rev Int J Pediatr Res. 2016;3(1):9-12.

3.       Okorie ON, Dellinger P. Lactate: biomarker and potential therapeutic target. Crit Care Clin. 2011 Apr;27(2):299-326.

4.       Araki T. As to the formation of lactic acid and glucose in the body with oxygen deficiency. Physiol Chem. 1892;16:453-9.

5.       Munde A, Kumar N, Beri RS, Puliyel JM. Lactate clearance as a marker of mortality in pediatric intensive care unit. Indian Pediatr. 2014 Jul;51(7):565-7.

6.       Gorgis N, Asselin JM, Fontana C, Heidersbach RS, Flori HR, Ward SL. Evaluation of the association of early elevated lactate with outcomes in children with severe sepsis or septic shock. PediatrEmerg Care. 2019 Oct;35(10):661-5.

7.       Jones AE, Trzeciak S, Kline JA. The Sequential Organ Failure Assessment score for predicting outcome in patients with severe sepsis and evidence of hypoperfusion at the time of emergency department presentation. Crit Care Med. 2009 May;37(5):1649-54.

8.       Siddiqui I, Jafri L, Abbas Q, Raheem A, Haque AU. Relationship of serum procalcitonin, C-reactive protein, and lactic acid to organ failure and outcome in critically ill pediatric population. Indian J Crit Care Med. 2018 Feb;22(2):91-5.

9.       Gunnerson KJ, Saul M, He S, Kellum JA. Lactate versus non-lactate metabolic acidosis: a retrospective outcome evaluation of critically ill patients. Crit Care. 2006 Feb;10(1):R22.

10.   Nguyen HB, Rivers EP, Knoblich BP, Jacobsen G, Muzzin A, Ressler JA, et al. Early lactate clearance is associated with improved outcome in severe sepsis and septic shock. Crit Care Med. 2004 Aug;32(8):1637-42.

11.   Jones AE, Trzeciak S, Kline JA. The Sequential Organ Failure Assessment score for predicting outcome in patients with severe sepsis and evidence of hypoperfusion at the time of emergency department presentation. Crit Care Med. 2009 May;37(5):1649-54.

12.   Scherer. Employed chemical and microscopic studies on the pathology in the Departments of Julius Hospitales to Wurzburg. Heidelberg (Germany): C.F. Winter; 1843.

13.   Rocha AC. The prognostic value of delta-lactate in critically ill children. J Paediatr Child Health. 2022 Jan;58(1).

14.   Jat KR, Jhamb U, Gupta VK. Serum lactate levels as the predictor of outcome in pediatric septic shock. Indian J Crit Care Med. 2011 Apr;15(2):102-7.

15.   Patriawati KA, Nurnaningsih N, Suryantoro P. Serial blood lactate levels as a prognostic factor for sepsis mortality. PaediatrIndones. 2014 May;54(3):168.