Lactate Level in Critical Patients With Upper GI Bleeding
Lactate Level in Critical Patients With Upper GI Bleeding
Our study found that lactate level of 2.1 mmol/L on admission has high sensitivity but low specificity for predicting in-hospital death in patients with acute upper gastrointestinal hemorrhage admitted to the ICU. The addition of the clinical Rockall score to lactate level did not significantly improve the discriminative property of lactate. However, with the combined use of clinical Rockall score and lactate level, no case of in-hospital death would have been missed. Such a highly sensitive strategy comes at the cost of a very low specificity.
The main scoring systems that predict outcomes after UGIB, such as clinical Rockall score, Glasgow-Blatchford score, and AIMS65 score use systolic blood pressure and heart rate as a part of the scoring system, but none of these scores used serum lactate level to predict outcomes.
Koch et al. found elevated serum lactate level in patients with acute gastrointestinal hemorrhage on admission to the ICU to be superior to some of these standard prognostic scores in predicting mortality. Furthermore, elevated serum lactate level on presentation to the ED with acute gastrointestinal hemorrhage was found to be associated with higher in-hospital mortality and it was independently correlated with death.
It is well known that, in severe sepsis, high serum lactate is associated with mortality independent of organ dysfunction and shock. In addition, in septic patients, increased clearance of lactate within the first 6 h has been shown to be associated with decreased 60-day mortality, even in the absence of arterial hypotension. In trauma patients, survival rate was 100% for those who had normalization of their serum lactate level in 24 h.
Animal studies showed that the gut is sensitive to hypoperfusion. During hemorrhage, intestinal oxygen uptake is compromised early, even without changes in systemic oxygen consumption, due to reflex mesenteric vasoconstriction. Furthermore, progressive vasoconstriction of microvasculature can persist after resuscitation and restoration of hemodynamics.
The concept of tissue hypoperfusion despite restoration of hemodynamics was further supported by clinical studies that showed evidence of tissue hypoperfusion, evidenced by lactic acidosis and decreased mixed venous oxygen saturation, despite normalization of vital parameters, including blood pressure, heart rate, and urine output. Also, some patients with acute gastrointestinal hemorrhage have an abnormally elevated lactate level, despite normal hematocrit and heart rate, which point to the potential use of lactate level to identify occultly ill patients.
Besides tissue hypoxia, other mechanisms have been proposed for lactic acidosis in the setting of sepsis. These mechanisms include mitochondrial dysfunction and increased aerobic glycolysis via tissue cytokine-mediated glucose uptake or catecholamine-enhanced Na-K skeletal muscle pump activity, which is a proposed mechanism of lactic acid production in hemorrhage as well. These mechanisms of lactic acid production are not reflected in vital parameters, such as blood pressure and heart rate. These findings support the role of serum lactate as a marker of tissue hypoperfusion in the setting of normal blood pressure and heart rate in early stages of hypoperfusion and after resuscitation. Other proposed methods of lactate production cannot be measured or predicted based solely on hemodynamics as well.
Our study encourages further investigation of the predictive role of serum lactate level in the setting of acute UGIB. Developing scoring systems for an acute UGIB incorporating serum lactate level and other biomarkers can be beneficial for predicting outcomes. The role of serial measurements of serum lactate levels for predicting outcomes in acute UGIB and the role of using serum lactate to help in triage of patients with acute UGIB can be investigated in future studies.
Prospective studies can assess the impact of lactate use in acute UGIB on both resource utilization and patient-oriented outcomes before it is recommended for routine use.
Our study has a number of limitations. The retrospective design leads to a higher risk of misclassification bias with regard to the characteristics of the patients. Because of the reliance on administrative search to identify cases, it is possible that some patients have been left out. Another limitation is that a high number of patients were not included because a lactate test was not available on admission. As a result, there is a potential for selection bias, as the sicker patients might be more likely to be tested for serum lactate levels; therefore, the study population might be biased toward selection of a population with a higher risk of death, which can lead to underestimating negative predictive and overestimating positive predictive value, compared with an unselected population. Although we documented the admitting systolic blood pressure, heart rate, and presence of comorbid conditions that are required to calculate clinical Rockall score, we did not document the presence of other acute comorbid conditions that might have an impact on lactate level and mortality. Median lactate level was significantly higher in nonsurvivors compared to survivors in patients with liver cirrhosis, but the severity of underlying liver disease could not be assessed.
Discussion
Our study found that lactate level of 2.1 mmol/L on admission has high sensitivity but low specificity for predicting in-hospital death in patients with acute upper gastrointestinal hemorrhage admitted to the ICU. The addition of the clinical Rockall score to lactate level did not significantly improve the discriminative property of lactate. However, with the combined use of clinical Rockall score and lactate level, no case of in-hospital death would have been missed. Such a highly sensitive strategy comes at the cost of a very low specificity.
The main scoring systems that predict outcomes after UGIB, such as clinical Rockall score, Glasgow-Blatchford score, and AIMS65 score use systolic blood pressure and heart rate as a part of the scoring system, but none of these scores used serum lactate level to predict outcomes.
Koch et al. found elevated serum lactate level in patients with acute gastrointestinal hemorrhage on admission to the ICU to be superior to some of these standard prognostic scores in predicting mortality. Furthermore, elevated serum lactate level on presentation to the ED with acute gastrointestinal hemorrhage was found to be associated with higher in-hospital mortality and it was independently correlated with death.
It is well known that, in severe sepsis, high serum lactate is associated with mortality independent of organ dysfunction and shock. In addition, in septic patients, increased clearance of lactate within the first 6 h has been shown to be associated with decreased 60-day mortality, even in the absence of arterial hypotension. In trauma patients, survival rate was 100% for those who had normalization of their serum lactate level in 24 h.
Animal studies showed that the gut is sensitive to hypoperfusion. During hemorrhage, intestinal oxygen uptake is compromised early, even without changes in systemic oxygen consumption, due to reflex mesenteric vasoconstriction. Furthermore, progressive vasoconstriction of microvasculature can persist after resuscitation and restoration of hemodynamics.
The concept of tissue hypoperfusion despite restoration of hemodynamics was further supported by clinical studies that showed evidence of tissue hypoperfusion, evidenced by lactic acidosis and decreased mixed venous oxygen saturation, despite normalization of vital parameters, including blood pressure, heart rate, and urine output. Also, some patients with acute gastrointestinal hemorrhage have an abnormally elevated lactate level, despite normal hematocrit and heart rate, which point to the potential use of lactate level to identify occultly ill patients.
Besides tissue hypoxia, other mechanisms have been proposed for lactic acidosis in the setting of sepsis. These mechanisms include mitochondrial dysfunction and increased aerobic glycolysis via tissue cytokine-mediated glucose uptake or catecholamine-enhanced Na-K skeletal muscle pump activity, which is a proposed mechanism of lactic acid production in hemorrhage as well. These mechanisms of lactic acid production are not reflected in vital parameters, such as blood pressure and heart rate. These findings support the role of serum lactate as a marker of tissue hypoperfusion in the setting of normal blood pressure and heart rate in early stages of hypoperfusion and after resuscitation. Other proposed methods of lactate production cannot be measured or predicted based solely on hemodynamics as well.
Implications for Future Research
Our study encourages further investigation of the predictive role of serum lactate level in the setting of acute UGIB. Developing scoring systems for an acute UGIB incorporating serum lactate level and other biomarkers can be beneficial for predicting outcomes. The role of serial measurements of serum lactate levels for predicting outcomes in acute UGIB and the role of using serum lactate to help in triage of patients with acute UGIB can be investigated in future studies.
Prospective studies can assess the impact of lactate use in acute UGIB on both resource utilization and patient-oriented outcomes before it is recommended for routine use.
Limitations
Our study has a number of limitations. The retrospective design leads to a higher risk of misclassification bias with regard to the characteristics of the patients. Because of the reliance on administrative search to identify cases, it is possible that some patients have been left out. Another limitation is that a high number of patients were not included because a lactate test was not available on admission. As a result, there is a potential for selection bias, as the sicker patients might be more likely to be tested for serum lactate levels; therefore, the study population might be biased toward selection of a population with a higher risk of death, which can lead to underestimating negative predictive and overestimating positive predictive value, compared with an unselected population. Although we documented the admitting systolic blood pressure, heart rate, and presence of comorbid conditions that are required to calculate clinical Rockall score, we did not document the presence of other acute comorbid conditions that might have an impact on lactate level and mortality. Median lactate level was significantly higher in nonsurvivors compared to survivors in patients with liver cirrhosis, but the severity of underlying liver disease could not be assessed.