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The American Journal of Managed Care January 2015
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Prognostic Factors of Mortality Among Patients With Severe Hyperglycemia
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Prognostic Factors of Mortality Among Patients With Severe Hyperglycemia

Ya-Wun Guo, MD; Tzu-En Wu, MD, MS; and Harn-Shen Chen, MD, PhD
Sepsis, renal impairment with electrolyte imbalance, and low blood pressure were independent prognostic factors of mortality among patients with severe hyperglycemia in the emergency department.
Patients in the 90-day mortality group were older and more likely to have sepsis, including more leukocytosis and elevated C-reactive protein; more azotemia and hypotension were also noted. Both hyperthermia and hypothermia increased the mortality rate, but hyperthermia was nonsignificant. Lower blood pressure (BP) and reduced hemoglobin, as well as elevated respiratory rate, white blood cell count, absolute neutrophil count, C-reactive protein, blood urea nitrogen, creatinine, blood urea nitrogen-creatinine ratio, and potassium were related to elevated mortality rate. Increasing pulse rate, sodium, and osmolality were also related to higher mortality rate but were not statistically significant. Lower BP and reduced hemoglobin were related to higher mortality. However, elevated blood glucose (>500 mg/dL) was associated with decreasing mortality rate among these extremely hyperglycemic patients.

Some studies have previously addressed mortality associated with hyperglycemia. Chung et al showed that the crude mortality rate associated with hyperglycemia crises was 17.7% and increased significantly with age. The strongest predictor of mortality in that study was change of mental status.14 The factors predictive of mortality in a study by Ogbera et al were sepsis, foot ulceration, newly diagnosed diabetes mellitus, hypokalemia, and older age.17 Anthanont et al found a mortality rate of 8.4%, observing that infections and noncompliance with treatment were the 2 most common factors precipitating mortality. The most common etiology of death was infection, and serum sodium levels on admission were an independent risk factor.8 In general, the mortality in hyperglycemic crises was near 15%, increasing substantially with aging and the presence of concomitant life-threatening illnesses.9 In our study, the mortality rate was 14.6%, which was essentially the same as in previous reports.

Stress hyperglycemia is common among patients in critical condition. Some studies have found that infection is the most common precipitating factor in the development of severe hyperglycemia,8-12 and is the leading cause of death in these patients.10,12,17 Patients in our study also showed an excess of death from infectious disease (Table 1), with sepsis defined as infection combined with a systemic inflammatory response syndrome. Patients commonly presented with fever or hypothermia, tachycardia, tachypnea, hyperglycemia in the absence of diabetes, altered mental status, leukocytosis or leucopenia, elevated C-reactive protein and procalcitonin, arterial hypotension, and hypoxemia.18,19 Our study found that several factors compatible with a diagnosis of sepsis were also independent risk factors in 90-day mortality, including hypothermia, tachycardia, tachypnea, leukocytosis, and elevated C-reactive protein. Thus, it seems that sepsis is an important contributing factor to mortality associated with hyperglycemia, and absolute neutrophil count (HR, 7.34; 95% CI, 1.93-27.96) was the best predictive factor.

Dehydration is an important characteristic of hyperglycemia hyperosmolality states and was found to be prognostic of mortality in medical admissions.8,20,21 Patients with hyperglycemia have osmotic diuresis, which results in high effective serum osmolality.8,13 Methods to evaluate dehydration include BP, osmolality, and ratio of blood urea nitrogen to creatinine.22 Patients with hypotension in the ED have poorer prognoses than patients with normal BP,23,24 and our study similarly found the mortality rate increased with decreasing SBP (Figure 2d). Among patients whose SBP was lower than 110 mm Hg, the hazard ratio for mortality was 3.167 when compared with those who had SBP above 168 mm Hg. The elevated BP is a physical response resulting from stimulation of the sympathetic system when stress is presented. We did not have data about serial BP readings in the ED; future studies should consider this. Elevated blood urea nitrogen, elevated creatinine, and elevated blood urea nitrogen to creatinine ratio were all independent risk factors of 90-day mortality. It might not be necessary to calculate the ratio of blood urea nitrogen to creatinine in order to evaluate the degree of dehydration. Osmolality was not a prognostic factor in our study.

Electrolyte imbalance was a prognostic factor for 90-day mortality, and significantly elevated or decreased serum levels often are associated with increased mortality. When severe hyperglycemia occurs, the hyponatremia does not reflect true plasma hypoosmolality; the initial hyperosmolality produced by severe hyperglycemia causes an osmotic shift of water from intracellular fluid to extracellular fluid, which in turn produces a dilutional decrease in serum sodium levels. Mild hyponatremia indicates the patient has the ability to compensate for the osmolality change caused by hyperglycemia, and among our study patients, hyponatremia did not increase mortality. Hypernatremia significantly increased mortality, however, which may be explained by patients losing the ability to compensate for the osmolality and severe dehydration. We also found that hyperkalemia (potassium level above 5.2 mmol/L) was prognostic of mortality. The most common etiologies of hyperkalemia in the ED included renal failure, status of cardiopulmonary resuscitation, and severe metabolic acidosis. Hypokalemia was associated with a nonstatistically significant increase in mortality (HR, 1.847; 95% CI, 0.932-3.661), a finding that may call for further study to prove or disprove the concept.

Our results revealed that the nadir of mortality rate was in the second highest, rather than the highest, blood glucose group, so higher blood glucose levels did not indicate higher mortality rates, per se. Hyperglycemia may serve not only as a risk factor, but also as a risk marker of underlying disease, which may play a more important role in eventual mortality than the severity of the hyperglycemia. Therefore, our data suggests that clinicians should do more examinations to determine the cause of hyperglycemia and treat that, rather than treating the single value of blood glucose.

Limitations

First, this is a retrospective study done in only 1 medical center, so it may not apply universally. Second, as the data were from ED reports, we could not be certain how the underlying diseases influenced mortality. Third, some factors that predict mortality rate, including lactate and blood gas levels25 were not included in our study because they were not part of a routine examination in our ED. The advantages of our study include the fact that the study population was larger than in previous studies11,12,14,15 and showed clear cutoffs for each parameter. However, all of the parameters we enrolled were determined by the routine examinations in the ED. Further studies may be designed as prospective ones and could include greater study populations to better evaluate the prognostic factors.

CONCLUSIONS

Severe hyperglycemia is an important indicator in diabetes, and the 90-day mortality rate among patients with severe hyperglycemia in our ED was nearly 15%. We found age combined with hyperglycemia, sepsis, renal impairment with electrolyte imbalance, and lower BP were independent prognostic factors.

Author Affiliations: Division of Endocrinology and Metabolism, Department of Medicine, Taipei Veterans General Hospital (Y-WG, H-SC), Taipei, Taiwan; Department of Medicine, Taipei City Hospital, Zhongxing Branch (Y-WG), Taipei, Taiwan; National Yang-Ming University School of Medicine (T-EW, H-SC), Taipei, Taiwan.

Source of Funding: Taipei Veterans General Hospital (V102C-043) and the National Science Council (NSC 101-2314-B-010-023-). These institutes played no role in the study design, conduction, data analysis, and manuscript writing.

Author Disclosures: The authors report no relationship or financial interest with any entity that would pose a conflict of interest with the subject matter of this article.

Authorship Information: Concept and design (H-SC); acquisition of data (Y-WG, H-SC, T-EW); analysis and interpretation of data (Y-WG, H-SC, T-EW); drafting of the manuscript (Y-WG); statistical analysis (Y-WG, H-SC, T-EW); obtaining funding (H-SC).

Address correspondence to: Harn-Shen Chen, MD, PhD, Division of Endocrinology and Metabolism, Department of Medicine, Taipei Veterans General Hospital, No 201, Sec 2, Shih-Pai Rd, Taipei, Taiwan. E-mail: chenhs@vghtpe.gov.tw.
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