Michael D. Waite

Association between intensive care unit-acquired dysglycemia and in-hospital mortality.

Objective:Our objective was to quantify the association between intensive care unit–acquired dysglycemia (hyperglycemia, hypoglycemia, and high variability) and in-hospital mortality. Design:Retrospective, observational study. Setting:eICU Research Institute participating hospitals with an active tele-ICU program between January 1, 2008, and September 30, 2010, representing 784,392 adult intensive care unit patients. Patients:A total of 194,772 patients met inclusion criteria with an intensive care unit length of stay >48 hrs. Interventions:None. Measurements and Main Results:Acute Physiology and Chronic Health Evaluation IV standardized mortality ratios were calculated for dysglycemia present at admission and acquired in the intensive care unit. Intensive care unit–acquired dysglycemia was modeled using multivariable modified Poisson regression to account for confounding not incorporated in Acute Physiology and Chronic Health Evaluation. Dysglycemia severity was assessed by the relative risk of in-hospital mortality associated with the maximum, time-weighted average daily glucose; lowest glucose value throughout the intensive care unit stay; and quintiles of variability (coefficient of variation). The association of duration beyond thresholds of dysglycemia on mortality was also modeled. The adjusted relative risk (95% confidence interval) of mortality for the maximum intensive care unit average daily glucose was 1.13 (1.04–1.58), 1.43 (1.30–1.58), 1.63 (1.47–1.81), 1.76 (1.55–1.99), and 1.89 (1.62–2.19) for 110–150 mg/dL, 151–180 mg/dL, 180–240 mg/dL, 240–300 mg/dL, and >300 mg/dL, respectively, compared to patients whose highest average daily glucose was 80–110 mg/dL. The relative risk of mortality for the lowest glucose value was 1.67 (1.37–2.03), 1.53 (1.37–1.70), 1.12 (1.04–1.21), and 1.06 (1.01–1.11) for <20 mg/dL, 20–40 mg/dL, 40–60 mg/dL, and 60–80 mg/dL, respectively, compared to patients whose lowest value was 80–110 mg/dL. The relative risk of mortality increased with greater duration of hyperglycemia and with increased variability. The relative risk for the highest compared to lowest quintile of variability was 1.61 (1.47–1.78). The association of duration of hyperglycemia on mortality was more pronounced with more severe hyperglycemia. Conclusions:The risk of mortality progressively increased with severity and duration of deviation from euglycemia and with increased variability. These data suggest that severe intensive care unit–acquired hyperglycemia, hypoglycemia, and variability are associated with similar risks of mortality.

Postischemic inotropic support of the dysfunctional heart

Objective To determine relative adenine nucleotide regeneration and improvement in left ventricular (LV) function using three commonly used adrenergic agents—epinephrine, dobutamine, and phenylephrine—during reperfusion after a period of global ischemia. After initial resuscitation from cardiac arrest, adrenergic agents are frequently required to support postischemic LV dysfunction. However, the relative effectiveness and associated bioenergetic changes associated with these agents in the postischemic heart are unclear. Design Prospective, controlled laboratory study. Setting University research laboratory. Subjects Isolated, perfused Sprague-Dawley rat hearts. Interventions After 20 mins of global ischemia, isolated rat hearts were reperfused for 30 mins with Krebs-Henseleit solution alone (control, n = 8), or with the addition of equipotent doses of epinephrine 1 &mgr;M (n = 8), dobutamine 0.3 &mgr;M (n = 8), or phenylephrine 50 &mgr;M (n = 8). In a second experiment, an &agr;-1 antagonist, prazosin was given with phenylephrine to block the presumed &agr;-1 agonist effect of phenylephrine. Measurements and Main Results A constant volume balloon was placed in the left ventricle to measure LV pressure and derived parameters of LV function. Adenine nucleotide concentrations were derived at various time points using high-performance liquid chromatography. During reperfusion, the phenylephrine group had significant improvement in LV function and cardiac efficiency in contrast to epinephrine and dobutamine. Total adenine nucleotides tended to be highest in the phenylephrine group with significant increases in adenosine diphosphate and adenosine monophosphate and no significant loss of adenosine triphosphate. The phenylephrine-induced increase in heart rate and developed pressure could be blocked with an &agr;-1 antagonist, prazosin. Conclusions In the isolated reperfused heart, phenylephrine, mediated by &agr;-1 agonism, significantly improves postischemic LV dysfunction without worsening the overall myocardial metabolic state.

Left ventricular myocardial adenosine triphosphate changes during reperfusion of ventricular fibrillation: the influence of flow and epinephrine.

Objective: To determine whether epinephrine in combination with high flow worsens left ventricular (LV) myocardial high‐energy phosphate stores during reperfusion of ischemic ventricular fibrillation (VF). Design: Blinded, prospective block randomized, placebo controlled study. Setting: University medical center research laboratory. Subjects: A total of 22 mixed breed swine weighing 22.0 ± 3.3 kg (SD). Interventions: Open‐chest swine, anesthetized with α‐chloralose, underwent 10 mins of nonperfused VF followed by reperfusion with cardiopulmonary bypass for 90 mins and then defibrillation. Animals were block randomized to four groups for reperfusion: Group 1 (n = 5), high flow (100 mL/kg/min) and epinephrine (2.5 μg/kg/min); Group 2 (n = 5), high flow and placebo; Group 3 (n = 6), low flow (30 mL/kg/min) and epinephrine; and Group 4 (n = 6), low flow and placebo. Measurements and Main Results: In vivo LV creatine phosphate (CP) and adenosine triphosphate (ATP) were determined using whole wall and spatially localized 31P NMR spectroscopy at 4.7 Tesla. During perfusion of the fibrillating myocardium, epinephrine significantly increased aortic pressure (p < .05) and improved defibrillation rates (p < .01). ATP levels during reperfusion were significantly decreased within all groups compared with baseline. There were no differences in ATP levels between groups. High flow, independent of epinephrine, was associated with increased preservation of ATP (p < .05), increased CP/ATP ratios (p < .02) in all layers of the LV wall, and decreased aortic and cardiac vein lactates (p < .001). Conclusions: Epinephrine, in combination with flow higher than standard cardiopulmonary resuscitation flows, increased perfusion pressure and defibrillation rates, but did not significantly alter myocardial ATP during VF reperfusion in the in vivo heart. Reperfusion flow, independent of epinephrine, is a critical determinant of myocardial ATP preservation.