OBJECTIVE -Current criteria for the diagnosis of diabetic ketoacidosis (DKA) are limited by their nonspecificity (serum bicarbonate [HCO 3 ] and pH) and qualitative nature (the presence of ketonemia/ketonuria). The present study was undertaken to determine whether quantitative measurement of a ketone body anion could be used to diagnose DKA. RESEARCH DESIGN AND METHODS-A retrospective review of records from hospitalized diabetic patients was undertaken to determine the concentration of serum -hydroxybutyrate (OHB) that corresponds to a HCO 3 level of 18 mEq/l, the threshold value for diagnosis in recently published consensus criteria. Simultaneous admission OHB and HCO 3 values were recorded from 466 encounters, 129 in children and 337 in adults. RESULTS -A HCO 3 level of 18 mEq/l corresponded with OHB levels of 3.0 and 3.8 mmol/l in children and adults, respectively. With the use of these threshold OHB values to define DKA, there was substantial discordance (ϳՆ20%) between OHB and conventional diagnostic criteria using HCO 3 , pH, and glucose. In patients with DKA, there was no correlation between HCO 3 and glucose levels on admission and a significant but weak correlation between OHB and glucose levels (P Ͻ 0.001).CONCLUSIONS -Where available, serum OHB levels Ն3.0 and Ն3.8 mmol/l in children and adults, respectively, in the presence of uncontrolled diabetes can be used to diagnose DKA and may be superior to the serum HCO 3 level for that purpose. The marked variability in the relationship between OHB and HCO 3 is probably due to the presence of other acid-base disturbances, especially hyperchloremic, nonanion gap acidosis. Diabetes Care 31:643-647, 2008R ecently published consensus criteria for diagnosing diabetic ketoacidosis (DKA) include a serum bicarbonate (HCO 3 ) level Յ18 mEq/l, pH Յ7.30, the presence of ketonuria/ ketonemia, an anion gap Ͼ10 mEq/l, and a plasma glucose concentration Ͼ250 mg/dl (13.9 mmol/l) (1). The development of a consensus statement represents an advance in view of the divergence of opinion that has existed concerning what the standards for diagnosis of DKA should be (2). However, these diagnostic criteria have limitations. Anion gap, HCO 3 , and pH are relatively nonspecific for DKA because they can be affected by the degree of respiratory compensation or the presence of a separate acid-base disturbance. Ketonuria and ketonemia are usually determined with the nitroprusside assay, which detects acetoacetate (AcAc) but not the most abundant ketone body, -hydroxybutyrate (OHB) (3). Moreover, the measurement is not quantitative (4).Ketone body anion concentrations (i.e., AcAc and OHB), on the other hand, directly reflect the rate of ketone body production (5), which is accompanied by equimolar production of hydrogen ions (6). The present study was undertaken to investigate how a laboratory-based measurement of serum OHB might be used as part of simplified diagnostic criteria for the diagnosis of DKA. RESEARCH DESIGN AND METHODS -We retrieved electronic medical records da...
Correlation to plasma hexokinase values and hematocrit interference are the main variables that differentiate glucose meters. Meters that correlate with plasma glucose measured by a reference method over a wide range of glucose concentrations and minimize the effects of hematocrit will allow better glycemic control for critically ill patients.
We compared the clinical concordance of estimated glomerular filtration rate (eGFR) based on 3 whole blood creatinine assays with the eGFR calculated from a reference plasma creatinine assay. Whole blood creatinine on the Radiometer ABL800 FLEX (Radiometer A/S, Bronshoj, Denmark) demonstrated the best correlation and concordance to plasma creatinine/eGFR compared with the i-STAT (i-STAT, East Windsor, NJ) and StatSensor (Nova Biomedical, Waltham, MA). The i-STAT had better sensitivity (compared with Radiometer) but poorer specificity for prediction of plasma eGFR less than 60 mL/min/1.73 m(2). The StatSensor demonstrated lower concordance of whole blood to plasma eGFR but offered a slope and an intercept offset feature that partially compensates for this effect. The optimal device for use in rapid determination of eGFR from whole blood creatinine may depend on whether it is more important in a given practice to optimize sensitivity, specificity, or overall concordance for determining plasma eGFR less than 60 mL/min/1.73 m(2).
Intravenous insulin protocols are increasingly common in the intensive care unit to maintain normoglycemia. Little is known about the accuracy of point-of-care glucometers for measuring glucose in this patient population or the impact of sample source (capillary, arterial, or venous whole blood) on the accuracy of glucometer results. We compared capillary, arterial, and venous whole blood glucose values with laboratory plasma glucose values in 20 patients after cardiac surgery. All 4 samples (capillary, arterial, and venous whole blood and laboratory plasma glucose) were analyzed hourly for the first 5 hours during intravenous insulin therapy in the intensive care unit. There were no significant differences between median capillary whole blood (149 mg/dL [8.3 mmol/L]) and laboratory plasma (151 mg/dL [8.4 mmol/L]) glucose levels. The median arterial (161 mg/dL [8.9 mmol/L]) and venous (162 mg/dL [9.0 mmol/L]) whole blood glucose levels were significantly higher than the median laboratory plasma glucose level. Capillary whole blood glucose levels correlate most closely with laboratory plasma glucose levels in patients receiving intensive intravenous insulin therapy after cardiac surgery.
We have studied the molecular mechanism of Ca-ATPase activation in sarcoplasmic reticulum (SR) by the volatile anesthetic halothane. Using time-resolved phosphorescence anisotropy, we determined the rotational correlation times and mole fractions of different oligomeric states of the enzyme, as a function of halothane and temperature. Lipid fluidity was measured independently, using EPR of spin-labeled lipids. At 4 and 7 degrees C, the principal effects of halothane were to increase the activity of the Ca-ATPase and to promote the formation of monomers and dimers of the enzyme from larger aggregates. At higher temperatures (up to 25 degrees C), halothane activated the enzyme, but to a lesser extent than observed at lower temperatures. While the functional effects of halothane were temperature dependent, the effects of halothane on lipid fluidity and protein aggregation state were similar at all temperatures tested. We conclude that at low temperatures Ca-ATPase activity is dominated by aggregation state, so halothane activates the enzyme primarily by promoting the formation of monomers and dimers of the enzyme from larger aggregates. At higher temperatures, the activity of the enzyme is dominated by lipid fluidity, so halothane activates the enzyme by increasing the lipid fluidity. The physical mechanism of Ca-ATPase activation, dominated by aggregation state at low temperature and lipid fluidity at higher temperature, provides an explanation for the break in the Arrhenius plot of Ca-ATPase activity (in the absence of halothane) at approximately 20 degrees C.
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