الفهرس 
INTRODUCTIONOnly 14 pages are availabe for public view
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Abstract
Lactate is a byproduct of glycolysis and a major cause of muscle fatigue. When a muscle contracts in an anaerobic medium, glycogen disappears and lactate appears as the principal end product. In sepsis, muscles may generate lactate under aerobic conditions. So, hyperlactatemia can also result from aerobic glycolysis. Under normal conditions, the generation and consumption of lactate are equivalent. Failure of oxidative mechanisms can increase production and decrease clearance of lactate.
Hyperlactatemia reflects severity of illness with significant prognostic implications. Hyperlactatemia is defined as a persistent, mild to moderate (2-4 mmol/L) increase in blood lactate concentration. The duration as well as the severity of hyperlactatemia is related to mortality in septic shock patients. The main etiologies for severe hyperlactatemia were Sepsis (34.0%) and cardiogenic shock (19.3%). Increased blood lactate concentra¬tion is a powerful predictor of mor¬tality in critically ill patients. Also there is a proportional relationship between lactate levels and mortality: the higher the level, the greater the risk of death.
Lactate clearance in the hospital course may indicate a resolution of global tissue hypoxia and is associated with decreased mortality rate. Patients with higher lactate clearance after 6 hours of medical intervention have improved outcome compared with those with lower lactate clearance. Failure of blood lactate levels to decline after the initiation of treatment is an omi¬nous sign. In patients with sepsis, a serum lactate concentration of more than 4 mmol/l is used as a marker of severe disease with an associated high risk of death.
There is contradiction between intensivists about the role of lactate clearance as a predictor of mortality, while some believed that ‘lactate clearance’ should not be used as the end-point of resuscitation in patients with sepsis. Recent studies considered that the addition of lactate clearance to the SSC (surviving sepsis campaign) resuscitation bundle was associated with improved outcome. Repeated and timely monitoring is therefore important in the management of patients with sepsis. Some studies showed that a single early lactate measurement has important prognostic significance and predicts mortality in populations of patients with infection.
The clinical relevance of lactate and its clearance have been repetitively evaluated. The time course of blood lactate levels could be helpful to assess a patient’s response to therapy. Lactate clearance has been suggested as a parameter to evaluate the effectiveness of resuscitation. Early lactate normalization is associated with decreased mortality. The usefulness of lactate-guided therapy remain under investigation. This study aimed at evaluating the importance of lactate clearance after 6 hours in prediction of mortality in children admitted to the pediatric intensive care unit and correlating it with PIM 2 score.
This prospective observational study was conducted over one hundred and eighteen patients over a period of six months starting from March 2016 to September 2016. We excluded 42 patients because of the presence of one or more of the exclusion criteria so, the final studied patients were 76. Our patients were 56.6% males (n=43) and 43.4% females. Most of our patients belonged to (1-6) months age group (44.7%) and (>6-12) month age group (21.1%).Most of our patients had pulmonary disease (25%). 68% of our patients were discharged and 32% of them were deceased.
We divided our study cases according to lactate clearance after 6 hours of admission into two groups; group A (lactate clearance at 6 hours > 0) (71.1%) and group B (lactate clearance at 6 hours ≤ 0) (28.9%). The patients with sepsis were statistically significantly more distributed on the group B patients whose lactate clearances after 6 hours of admission are ≤ 0 %. Mean PIM2 score and risk of mortality was statistically significantly higher in group B patients. There were statistically significant differences between the two groups in serum albumin, serum potassium, serum calcium, oxygen saturation, admission lactate and admission lactate/pyruvate ratio, lactate after 6 hours of admission and lactate/pyruvate ratio after 6 hours of admission. While there were no statistically significant difference in other laboratory findings.
The ability to predict the patients’ mortality in PICU was assessed using the area under the receiver operating characteristic (ROC) curves (AUC), multivariate logistic regression analysis of the variables and Kaplan-Meier survival curve. Using Kaplan-Meier survival curve, we found that group A patients had statistically significant better overall survival probability than group B patients.
Statistical analysis proved that there was positive significant correlation between lactate clearance and arterial oxygen saturation, while there were negative significant correlations with white blood cells, partial thromboplastin time, serum lactate and lactate/pyruvate ratio after 6 hours of admission,PIM2 score and risk of mortality. Multivariate logistic regression modeling approved that both lactate clearance after 6 hours of admission and PIM2 score had independent prognostic significance as regard fate of patient.
The diagnostic test of accuracy using the AUC values revealed that there is a strong significant predictive power for the PIM2 score, which represents the largest AUC (AUC :0.935) followed by that of lactate clearance after 6 hours of admission(AUC: 0.766) .
This study demonstrated that the concept of lactate clearance is fundamental even after the golden six hours. We followed the lactate levels for only six hours from admission and we think that longer follow up may be more accurate.
The current study concluded that early and effective lactate clearance is associated with decreased mortality. Serial evaluations of serum lactate may have greater value over measuring serum lactate only at the time of presentation. Lactate clearance through 24 hours may be more accurate in prediction of mortality among patients admitted to PICU. PIM2 score is still better predictor of mortality as it avoids problems of early treatment bias, however lactate clearance is fast, easy determined and of accepted prognostic capability.