Relationship between lactate value and mortality in critical patients diagnosed with diabetic ketoacidosis

Authors

Abstract

AimIn this study, we aimed to investigate the lactate value and lactate clearance (LC) at the time of presentation to the emergency department and within the first two hours in predicting mortality in patients diagnosed with diabetic ketoacidosis (DKA).
MethodsThis retrospectively and observationally planned cohort study was conducted with patients with DKA who presented to the hospital between January 2021 and December 2022. The patients’ demographic characteristics, biochemistry, hemogram, and blood gas results at the time of presentation, second-hour lactate value, and outcome parameters were recorded. Then, LC was calculated for each patient. The patients were divided into groups according to the mortality status and the length of hospital stay. The groups were compared in terms of age, blood gas pH, osmolarity, glucose level, lactate level at presentation and at the second hour, LC, and bicarbonate, blood urea nitrogen, potassium levels, length of stay in hospital, intensive care unit admission, inotropic agent requirement, invasive mechanical ventilation requirement and mortality.
ResultsThe overall mortality rate was 15.6% (16/102). Age, pH, osmolarity, bicarbonate and sodium levels, and second-hour lactate level significantly differed between the groups (Mann-Whitney U test, p<0.05). The cut-off and area under the curve values of LC were not significant in predicting mortality (p>0.05).
ConclusionAmong the patients with DKA who presented to the emergency department, age, the presence of comorbidities, glucose levels at presentation, admission and second-hour lactate values, pH, bicarbonate, potassium, and intensive care unit admission were useful in predicting mortality.

Keywords

Introduction

The number of patients presenting to emergency departments due to complications related to diabetes mellitus (DM) is currently increasing.¹ According to World Health Organization data, deaths due to diabetes rank 19th globally. In the USA, DM is the eighth leading cause of mortality.² Diabetic ketoacidosis (DKA) and hyperglycemic hyperosmolar state (HHS) are hyperglycemic emergencies with the highest mortality due to diabetes.³ Rapid diagnosis of these conditions in emergency departments, and detection and treatment of the underlying causes, are essential to reduce mortality.
One of the complications of DM with which patients usually present to emergency departments is DKA, characterized by hyperglycemia, increased anion gap, ketonemia/ketonuria, and metabolic acidosis.⁴ DKA is observed in 0.8% of patients with DM and is potentially fatal if not recognized and treated quickly.^5,6 Deaths due to DKA have been reported to occur most frequently within the first three days of hospital presentation and within the first 48 hours of ICU admission.⁷
Although lactate is mainly produced in muscle cells, it is the end product of increased anaerobic metabolism when oxygen delivery cannot meet oxygen consumption.⁸ Increased lactate levels may be associated with increased production in diseases that cause decreased oxygen delivery or reduced elimination, or both, in a multifactorial manner.⁹ A high lactate concentration associated with low blood pH is useful for demonstrating the severity of mismatch between supply, demand, and energy consumption.¹⁰ Elevated blood lactate is an important finding in predicting prognosis in critical diseases.⁴ It is frequently detected in both adult and pediatric patients diagnosed with DKA in emergency departments.^11,12
Lactate clearance (LC) is the difference between the lactate value taken at a selected time and the first measured lactate value, expressed as the ratio of the initial lactate value in percentage.¹³ Some studies have underlined the importance of LC measurement in conditions that may lead to hypoperfusion, such as trauma and sepsis.^14,15
In contrast to patients with sepsis, there are limited studies investigating the role of lactate changes in patients with DKA for evaluating severity, treatment response, ICU requirement, and prognosis.^16,17 Therefore, the primary aim of this study was to retrospectively investigate the relationship of lactate values at presentation and LC with mortality in patients who presented to the emergency department with hyperglycemia and were diagnosed with DKA in 2021 and 2022. The secondary aim was to evaluate the relationship of these parameters with hospital and ICU length of stay, mechanical ventilation requirement, and inotropic agent requirement.

Materials and Methods

This research was performed as a retrospective observational cohort study. Approval was obtained from the Ethics Committee of University of Health Sciences, Kartal Dr. Lutfi Kirdar City Hospital (Decision number: 2022/514/240/21, Date: 2022-12-28). Patients who presented to the emergency department with the diagnosis of DKA from January 1, 2021 to December 31, 2022 were included. Data were retrospectively screened from the hospital’s automation system.
Exclusion criteria were: age < 18 years, pregnancy, chronic renal failure, trauma, refusal of treatment or transfer to another healthcare institution due to ICU requirement, not meeting ADA diagnostic criteria for DKA, and missing or erroneous data. Results of routine blood tests conducted in the emergency department, including hemoglobin, hematocrit, glucose, urea, creatinine, troponin, lactate, bicarbonate (HCO3-), carbon dioxide, pH, and base excess values, were recorded. In our emergency department, DKA is diagnosed using ADA Guideline I.¹⁸ According to these criteria, DKA is diagnosed based on plasma glucose > 250 mg/dL, arterial pH < 7.3, serum HCO3- < 18 mmol/L, and ketone positivity.¹⁹
Patients’ admission and second-hour lactate values were used to calculate LC as follows:
LC (%) = (lactate admission – lactate hour 2) / lactate admission × 100
Additionally, age, gender, and comorbidities were recorded. Hospital and ICU length of stay, discharge, and mortality status were also documented.
Ethical Approval
Ethics Committee approval for the study was obtained.
Statistical Analysis
SPSS v 25 was used for statistical analyses. Data were summarized using descriptive statistics (mean ± SD, frequency, minimum–maximum values). The Shapiro-Wilk test was used to determine normality for continuous variables. Differences between mean values were investigated with the two-sample t-test for normally distributed data, and with the Mann-Whitney U test for non-normal data. Fisher’s exact test was used for categorical variables. ROC curve analysis was undertaken to determine the ability of parameters to predict mortality. The significance level was set at p<0.05.

Results

The screening of hospital records revealed a total of n = 125 patients diagnosed with DKA in the emergency department over the study period who underwent blood gas measurements at presentation and at the second hour. However, 23 patients did not meet inclusion criteria (n = 9 aged < 18 years, n = 9 transferred to another hospital with ICU indications, n = 3 refused treatment, n = 2 had missing data). After exclusions, n = 102 patients were included. Of these, 45 (44.11%) were female and 57 (55.88%) were male. The mean age was 45.5 ± 21 years. While 48 (47%) were followed up in the emergency department, 54 (53%) were followed up in the ICU. The mortality rate was 15.6% (16/102).
The mortality group had significantly higher mean age, glucose, potassium at presentation, and lactate at both hours, and significantly lower pH at presentation (Mann–Whitney U test, p<0.05) (Table 1). Hospital and ICU stay lengths were also significantly higher in the mortality group (Table 1).
Comorbidities, ICU admission, mechanical ventilation (MV) requirement, and inotropic agent requirement were significantly higher in the mortality group (Fisher’s exact test, p<0.05) (Table 2). Patients with hospital stay > 5 days had lower HCO3 values and higher BUN and base excess values at presentation (Fisher’s exact test, p<0.05).
No significant correlation was found between hospital stay length and initial glucose, admission and second-hour lactate, or LC. Table 3 presents ROC curve analysis results for mortality prediction.
According to ROC curve p-values, all variables except pH and hospital stay length were significant in predicting mortality (p<0.05). The highest Youden index for mortality prediction belonged to MV requirement, followed by inotropic agent requirement. Patients with positive MV and inotropic agent results had higher mortality risk. Sensitivity was high for comorbidities, ICU admission, potassium, MV requirement, inotropic agent requirement, and second-hour lactate. Specificity was high for MV and inotropic agent requirements, hospital and ICU stay length, BUN, and glucose.
Overall, MV and inotropic agent requirements were the most determinant factors for mortality, followed by ICU stay length, BUN, and second-hour lactate values.

Discussion

Among the metabolic complications of diabetes, DKA and HHS constitute emergencies with the highest mortality rates.^3,18 In the USA, 220,000 patients were hospitalized due to DKA in 2018, and the mortality rate was approximately 1%.^16,17 Although the mortality rate of DKA is < 1% in developed countries such as the USA and UK, this rate is higher, ranging from 3-13% in developing countries.^20,21 Mortality is affected by the adequacy of healthcare services, rapid diagnosis of the condition, and rapid initiation of treatment. The mortality rate of our patients was 15.6%, which is consistent with the literature. Researchers have focused on the use of various biomarkers in the prediction of mortality. In the current study, we aimed to evaluate the relationship of mortality with the first-hour and second-hour lactate values and LC in patients who presented to the emergency department with DKA. Our study has certain limitations, such as retrospective design and data being obtained from the hospital’s automation system. Various drugs and metabolic disorders are known to trigger DKA, and insulin deficiency is the most important cause,^22,23 however, we were not able to access such data through the hospital records.
Blood gas analyses in emergency departments are extremely valuable for presenting rapid results and providing important information about the metabolic status of parameters, including lactate, pH, base excess, and HCO3. Changes in blood lactate values help interpret tissue hypoxia when evaluated together with clinical manifestation and treatment, especially in diseases where perfusion is impaired. According to the Surviving Sepsis Campaign, lactate levels should be monitored to reflect the severity of the disease in sepsis and follow up patients on targeted therapy.¹⁵ DKA is a clinical condition presenting with high lactate levels. In our study, there was a significant correlation between elevated first- and second-hour lactate levels and mortality, which is consistent with the literature.²² However, lactate values were not significant in determining the length of hospital stay.
Many studies have shown that LC follow-up results in better clinical outcomes.^13,23 According to our findings, LC was lower in the group with a hospital stay of > 5 days, although this did not reach a statistically significant level. In some studies, LC has been shown to be significant in predicting 30-day mortality.²⁴ In our study, no significant correlation was observed between LC and mortality, but LC was lower in the mortality group.
We found that the glucose level at the time of presentation to the emergency department and patient age were significantly associated with mortality. We consider that this may be due to the presence of resistant hyperglycemia and age-related comorbidities. This idea is supported by the literature.^3,19 In clinical practice, especially in emergency departments, rapid, practical, and effective biochemical markers are needed to predict patient prognosis and determine the optimal treatment process. This can reduce mortality in metabolic emergencies such as DKA. We consider that the most effective biochemical and clinical markers will be identified through further studies.
In this study, a significant correlation was found between mortality and important parameters for ICU indication, pH, HCO3, and potassium at the time of presentation (p<0.05). Similar to the studies in the literature,⁷ the mortality rate was significantly higher in the patients admitted to the ICU. In addition, the presence of comorbidities and inotropic agent and MV requirements were among the significant factors that increased mortality. Glucose value at presentation, patient age, blood gas parameters, severity of metabolic acidosis, course of lactate values from presentation to the second hour, and the length of ICU and hospital stay were determined to be appropriate and clinically useful diagnostic markers for patients with DKA.

Declarations

References

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About This Article

Received:

January 31, 2023

Accepted:

March 2, 2023

Published Online:

March 11, 2023

Printed:

March 25, 2023