Prevalence and significance of lactic acidosis in diabetic ketoacidosis

doi:10.1016/j.jcrc.2011.07.071

Journal of Critical Care

Volume 27, Issue 2, April 2012, Pages 132-137

https://doi.org/10.1016/j.jcrc.2011.07.071 Get rights and content

Abstract

Purpose

The prevalence and clinical significance of lactic acidosis in diabetic ketoacidosis (DKA) are understudied. The objective of this study was to determine the prevalence of lactic acidosis in DKA and its association with intensive care unit (ICU) length of stay (LOS) and mortality.

Methods

Retrospective, observational study of patients with DKA presenting to the emergency department of an urban tertiary care hospital between January 2004 and June 2008.

Results

Sixty-eight patients with DKA who presented to the emergency department were included in the analysis. Of 68 patients, 46 (68%) had lactic acidosis (lactate, >2.5 mmol/L), and 27 (40%) of 68 had a high lactate (>4 mmol/L). The median lactate was 3.5 mmol/L (interquartile range, 3.32-4.12). There was no association between lactate and ICU LOS in a multivariable model controlling for Acute Physiology and Chronic Health Evaluation II, glucose, and creatinine. Lactate correlated negatively with blood pressure (r = −0.44; P < .001) and positively with glucose (r = 0.34; P = .004).

Conclusions

Lactic acidosis is more common in DKA than traditionally appreciated and is not associated with increased ICU LOS or mortality. The positive correlation of lactate with glucose raises the possibility that lactic acidosis in DKA may be due not only to hypoperfusion but also to altered glucose metabolism.

Introduction

Diabetic ketoacidosis (DKA) is a life-threatening complication of diabetes mellitus that occurs when circulating insulin levels are low or absent. This state is characterized by acidosis, hyperglycemia, and the presence of serum ketones. Diabetic ketoacidosis affects nearly 8 per 1000 persons with diabetes annually and is associated with a mortality of less than 5% [1], [2], [3].

Lactate levels have been found to be predictive of illness severity in several critical illnesses including sepsis, burns, ST-elevation myocardial infarction, postcardiac arrest, and trauma [4], [5], [6], [7], [8], [9], [10], [11]. At present, there are very little data on the clinical significance of lactate levels in DKA or the association with disease severity. Furthermore, in the relatively small body of literature on this subject, there is controversy surrounding the prevalence of lactic acidosis in this population. Although Fulop et al [12] report that “elevations of blood lactate concentration are not uncommon in patients with hypovolemia, hypotension, and hyperventilation, which are abnormalities often found in patients with diabetic ketoacidosis”; other reports suggest that DKA and lactic acidosis are distinct entities that rarely occur concomitantly. In a study of lactic acidosis in 23 diabetics with clinically suspected DKA, Watkins et al [13] concluded that “lactic acid may contribute to the metabolic acidosis in patients with true diabetic ketoacidosis, but the blood lactate concentrations in these patients are not usually very high.” In a review article from 2001, Kitabchi et al [2] state that “measuring blood lactate concentration easily establishes the diagnosis of lactic acidosis (>5 mmol/L) because DKA patients seldom demonstrate this level of serum lactate.” This statement suggests that DKA should be differentiated from lactic acidosis because lactic acidosis in the setting of DKA is a rare event.

Based on previous data from non-DKA populations, one might expect that high lactate levels in DKA would be associated with clinical outcome measures such as increased mortality or increased ICU length of stay (LOS), as seen in other disease states. Watkins et al [13] concluded that persons with diabetes with “lactic acidosis generally have a serious underlying disorder and poor prognosis.” The clinical significance of the predictive value of lactic acidosis in DKA is important given the increasing practice of measuring this variable. At present, clinicians may associate a high lactate in DKA as an indicator of illness severity, but this assumption may not be valid. Our study aims to establish the prevalence and significance of lactic acidosis in patients with DKA. We hypothesized that lactic acidosis is common in DKA and that lactic acidosis would not be a predictor of clinical outcomes, specifically ICU LOS.

Section snippets

Materials and methods

We performed a retrospective chart review of patients presenting to the emergency department (ED) of an urban tertiary care hospital with 50,000 ED visits per year. The study was approved by the institutional review board, and waiver of the requirement for informed consent was obtained under institutional review board regulation.

Patients were identified through an electronic query of the ED registry. Consecutive adult (age, ≥18 years) patients admitted to the hospital through the ED between

Results

There were 254 patients admitted between January 2004 and June 2008 with an admitting diagnosis of DKA, and 68 of these patients met the inclusion criteria for this study. The lactate levels observed in our cohort ranged from 1.2 to 8.3 mmol/L and are reported in Fig. 1. Lactic acidosis (lactic acid level, >2.5 mmol/L) was observed in 46 (68%) of 68 patients with DKA in this study. A high lactate level (>4 mmol/L) was observed in 27 (40%) of 68 patients. Only 1 patient in the high-lactate group

Discussion

Lactic acidosis is more common in DKA than traditionally appreciated. Although there is some disagreement in the literature about the association of lactic acidosis with DKA [12], [13], our findings suggest that lactic acidosis commonly occurs in patients with DKA. Although metformin is known to cause lactic acidosis in diabetics, no patients in the high-lactate group were known to be using metformin in this cohort, suggesting that the degree of lactic acidosis observed in this study cannot be

Limitations

The current investigation has several limitations. First, lactate levels were not collected in all patients who presented in DKA. Only 52% (68/132) of patients who were identified as meeting clinical criteria for DKA had a lactate level drawn within 3 hours of arrival to the ED. However, there were no deaths in the cohort of patients with DKA without a measured lactate. In addition, although mortality was not the primary end point, the low incidence of mortality observed in this study limits

Conclusion

Lactic acidosis is common in DKA. Lactic acidosis in patients with DKA is not associated with worse clinical outcomes, specifically increased ICU LOS. Lactate levels should, therefore, be interpreted in the context of a specific disease state.

Acknowledgments

The authors thank Francesca Montillo for her editorial assistance with this manuscript.

References (17)

J. Bakker et al.
Serial blood lactate levels can predict the development of multiple organ failure following septic shock
Am J Surg
(1996)
M.W. Donnino et al.
Effective lactate clearance is associated with improved outcome in post-cardiac arrest patients
Resuscitation
(2007)
J.C. Jeng et al.
Serum lactate, not base deficit, rapidly predicts survival after major burns
Burns
(2002)
J.H. James et al.
Lactate is an unreliable indicator of tissue hypoxia in injury or sepsis
Lancet
(1999)
A.E. Kitabchi et al.
Hyperglycemic crises in adult patients with diabetes: a consensus statement from the American Diabetes Association
Diabetes Care
(2006)
A.E. Kitabchi et al.
Management of hyperglycemic crises in patients with diabetes
Diabetes Care
(2001)
J.F. Wilson
In clinic. Diabetic ketoacidosis
Ann Intern Med
(2010)
D. Abramson et al.
Lactate clearance and survival following injury
J Trauma
(1993)

There are more references available in the full text version of this article.

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^☆: Conflicts of Interest: The authors have no conflicts of interest to declare.

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Metabolism/GlucosePrevalence and significance of lactic acidosis in diabetic ketoacidosis☆

Abstract

Purpose

Methods

Results

Conclusions

Introduction

Section snippets

Materials and methods

Results

Discussion

Limitations

Conclusion

Acknowledgments

Am J Surg

Resuscitation

Burns

Lancet

Hyperglycemic crises in adult patients with diabetes: a consensus statement from the American Diabetes Association

Diabetes Care

Management of hyperglycemic crises in patients with diabetes

Diabetes Care

In clinic. Diabetic ketoacidosis

Ann Intern Med

Lactate clearance and survival following injury

J Trauma

Metabolism/Glucose
Prevalence and significance of lactic acidosis in diabetic ketoacidosis☆