Early Increase in Blood Glucose in Patients Resuscitated From Out-of-Hospital Ventricular Fibrillation Predicts Poor Outcome

This retrospective population-based observational study used prospectively collected cardiac arrest registry data complemented with laboratory data. An institutional review board approved the study protocol, and consent of subjects was not required.

We included all emergency medical services personnel–confirmed out-of-hospital cardiac arrests in Helsinki during 2005–2009 fulfilling the following criteria: age ≥18 years, arrest witnessed by bystander, ventricular fibrillation as a first recorded rhythm, and survival to hospital admission. Patients with missing glucose values either in the prehospital phase or at admission were excluded. The Helsinki Cardiac Arrest Register is a prospectively collected dataset including all out-of-hospital cardiac arrests in Helsinki. Cerebral Performance Category 1–2 at the time of hospital discharge was used as a survival end point (4).

Glucose-containing fluids were not used in prehospital treatment. Blood glucose was analyzed using the Optimum Xceed glucometer (Abbott Laboratories, Alameda, CA). Blood glucose values measured in the hospital within 24 h after emergency call, as well as HbA_1c (closest value measured within 1 year of cardiac arrest) values, were obtained from an electronic laboratory database.

For analysis, patients were divided into groups based on surviving status and change in blood glucose between prehospital and admission time points. Increasing blood glucose was defined as blood glucose higher measured at admission than that measured in a prehospital setting after return of spontaneous circulation (ROSC).

For proportions, 95% CIs were measured. Categorical data were analyzed using either Fisher’s exact or χ² test. Unpaired and paired t, Kruskal-Wallis, and Mann-Whitney U tests were used to compare groups as appropriate. Normally distributed data are reported as means ± SD and skewed variables as median (interquartile range) (IQR). Statistical analyses were carried out using GraphPad Prism 5.0 for Mac OS X (GraphPad Software, San Diego, CA).

During the study period, resuscitation was attempted in 1,075 cases. Of those, 170 patients fulfilled the study criteria and 134 (79%) had sufficient data for analysis. The number of survivors, defined as discharged in Cerebral Performance Category 1 or 2, was 87 (65% [95% CI 57–73]). Characteristics of the patients and treatment given during and after cardiac arrests are presented in Table 1.

The sample for prehospital glucose measurement was capillary blood in 106, arterial blood in 24, and venous blood in 4 cases. Time between emergency call and glucose measurement at admission was 105 min (IQR 85–132) in survivors and 114 min (91–129) in nonsurvivors, respectively (P = 0.3157).

Significant changes in blood glucose were not observed between prehospital (10.5 ± 4.1 mmol/L) and admission (10.0 ± 3.7 mmol/L) measurements in surviving patients (P = 0.3483), whereas in nonsurvivors blood glucose increased 2.0 mmol/L from 11.8 ± 4.6 mmol/L measured after ROSC to 13.8 ± 3.3 mmol/L measured at admission (P = 0.0025). No associations were observed between increasing glucose and HbA_1c (n = 81). Within 24 h after emergency call, a total of 1,275 glucose measurements were performed. Nonsurvivors had significantly higher blood glucose concentration than survivors, respectively, in 0–3 h (13.5 ± 3.9 vs. 10.4 ± 4.3 mmol/L, P < 0.0001), 3–6 h (10.2 ± 4.4 vs. 8.2 ± 2.7 mmol/L, P < 0.001), and 6–12 h (7.5 ± 2.2 vs. 6.6 ± 1.6 mmol/L, P < 0.001) but not 12–24 h (6.2 ± 1.9 vs. 5.9 ± 1.3 mmol/L, P = 0.3509) after emergency call.

The current study demonstrates that patients who are successfully resuscitated from out-of-hospital ventricular fibrillation but with unfavorable outcome are characterized by significant increase of blood glucose in the ultraacute phase before hospital admission. The increased glucose values persisted during the early reperfusion phase, i.e., the first 12 h, in the patients with poor outcome.

Hyperglycemia at the time of hospital admission is an independent predictor of poor outcome in conditions involving ischemia and reperfusion pathology, including acute myocardial infarction (5) and ischemic stroke (6). Hyperglycemia appears to be especially detrimental during ischemia and the very early reperfusion phase. Less is known about implications of ultraacute hyperglycemia during the first hours after cardiac arrest. In animals, ventricular fibrillation with subsequent resuscitation suppresses insulin secretion and causes a more than threefold rise in blood glucose (7), peaking immediately after ROSC and declining to baseline within 2–3 h (8,9). However, in humans hyperglycemia is still commonly observed at the time of intensive care unit admission (2).

The clinical studies assessing the effects of acute glucose control in ischemia and reperfusion conditions (ischemic stroke and acute myocardial infarction) have failed to provide effective and timely glucose control. In the largest studies, the insulin has been given 4.7–13.3 h after onset of symptoms (10–12). In animal studies, the delay from onset of ischemia to insulin treatment has been shorter, varying from immediate to 60 min (13). The optimal timing of glucose control after cardiac arrest warrants further studies, since hyperglycemia in a prehospital setting is moderately easy to treat. In our previous study (14), paramedics successfully initiated insulin infusion for stroke patients, resulting in a 1.9 mmol/L decrease in blood glucose before reaching the hospital.

The current observational study cannot account for whether treatment of acute hyperglycemia after cardiac arrest could improve outcome. The hyperglycemia after ROSC may have only indicated the patient’s condition, as it was observed more commonly in patients with longer duration of resuscitation and higher cumulative adrenaline dose. Also, the glucose trends after admission need to be interpreted cautiously and not as a natural course of glucose fluctuations after cardiac arrest, since insulin is commonly given to the patients. However, hyperglycemia per se poses many detrimental effects in acutely ill patients, including upregulation of proinflammatory cytokines, endothelial dysfunction, and aggregation of thrombocytes (15).

This study was supported by a personal grant from the Laerdal Foundation for Acute Medicine (to J.N.).

No potential conflicts of interest relevant to this article were reported.

J.N. researched data and wrote the manuscript. J.B. obtained data and reviewed and edited the manuscript. N.A. researched data and reviewed and edited the manuscript. J.W. contributed to discussion and reviewed and edited the manuscript. M.K. contributed to discussion and reviewed and edited the manuscript. J.N. is the guarantor of this work and, as such, had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Parts of this study were presented in abstract form at the Sixth Mediterranean Emergency Medicine Congress, Kos, Greece, 10–14 September 2011.