Paired Data Points Research Articles

Evaluation of the accuracy of different methods of monitoring body temperature in anesthetized brown bears (Ursus arctos).

There is some evidence that the handheld rectal thermometer does not accurately measure core temperature in bears. The objective of this study was to compare body temperature measured by the handheld digital thermometer (HDT), deep rectally inserted core temperature capsules (CTCs), and gastrically inserted CTCs in anesthetized brown bears (Ursus arctos). Twenty-two brown bears were immobilized with a combination of zolazepam-tiletamine and xylazine or medetomidine. After immobilization, one CTC was inserted 15 cm deep into the animal's rectum (DRTC) with a standard applicator, and another CTC was inserted into the stomach (GTC) via a gastric tube inserted orally. Temperature was measured every 5-10 min with an HDT. Paired temperature data points were analyzed with the Bland-Altman technique for repeated measurements and regression analysis with a significance level of 0.05. The mean difference ± SD of the difference between HDT and GTC readings was 0.27 ± 0.47 degrees C and the 95% limits of agreement (LoA) were 1.20 and -0.66 degrees C. The determination coefficient (r2) found between these methods was 0.68 (P < 0.0001). The mean difference ± SD of the difference between HDT and DRTC readings was 0.36 ± 0.32 degreesC and the 95% LoA were 1.0 and -0.28 degrees C. The r2 between HDT and DRTC was 0.83 (P < 0.0001). The mean difference ± SD of the difference between the two insertions of the VitalSense capsules was -0.06 ± 0.24 degrees C and the 95% LoA were 0.42 and -0.54 degrees C. The r2 found between GTC and DRTC was 0.91 (P < 0.0001). This study demonstrates that DRTC provided accurate measurement of core temperature and that HDT did not accurately measure core temperature, compared with GTC in anesthetized brown bears.

Assessing the agreement of biomarker data in the presence of left-censoring.

BackgroundIn many clinical biomarker studies, Lin’s concordance correlation coefficient (CCC) is commonly used to assess the level of agreement of a biomarker measured under two different conditions. However, measurement of a specific biomarker typically cannot provide accurate numerical values below the lower limit of detection (LLD) of the assay, which results in left-censored data. Most researchers discard the data below the LLD or apply simple data imputation methods in the presence of left-censored data, such as replacing values below the LLD with a fixed number less than or equal to the LLD. This is not statistically optimal, because it often leads to biased estimates and overestimates the precision.MethodsWe describe a simple method using a bivariate normal distribution in this situation and apply SAS statistical software to arrive at the maximum likelihood (ML) estimate of the parameters and construct the estimate of the CCC. We conduct a computer simulation study to investigate the statistical properties of the ML method versus the data deletion and simple data imputation method. We also contrast the methods with real data using two urine biomarkers, Interleukin 18 and Cystatin C.ResultsThe computer simulation studies confirm that the ML procedure is superior to the data deletion and simple data imputation procedures. In all of the simulated scenarios, the ML method yields the smallest relative bias and the highest percentage of the 95% confidence intervals that include the true value of the CCC. In the first simulation scenario (sample size of 100 paired data points, 25% left-censoring for both members of the pair, true CCC of 0.238), the relative bias is −1.43% for the ML method, −40.97% for the data deletion method, and it ranges between −12.94% and −21.72% for the simple data imputation methods. Similarly, when the left-censoring for one of the members of the data pairs increases from 25% to 40%, the relative bias displays the same pattern for all methods.ConclusionsWhen estimating the CCC from paired biomarker data in the presence of left-censored values, the ML method works better than data deletion and simple data imputation methods.

Performance characterization of an abiotic and fluorescent-based continuous glucose monitoring system in patients with type 1 diabetes

A continuous glucose monitoring (CGM) system consisting of a wireless, subcutaneously implantable glucose sensor and a body-worn transmitter is described and clinical performance over a 28 day implant period in 12 type 1 diabetic patients is reported. The implantable sensor is constructed of a fluorescent, boronic-acid based glucose indicating polymer coated onto a miniaturized, polymer-encased optical detection system. The external transmitter wirelessly communicates with and powers the sensor and contains Bluetooth capability for interfacing with a Smartphone application. The accuracy of 19 implanted sensors were evaluated over 28 days during 6 in-clinic sessions by comparing the CGM glucose values to venous blood glucose measurements taken every 15min. Mean absolute relative difference (MARD) for all sensors was 11.6±0.7%, and Clarke error grid analysis showed that 99% of paired data points were in the combined A and B zones.

Angiographic Lumen Changes Associated with Oversized Intracranial Stent Implantation for Aneurysm Treatment

The effect of oversized intracranial stent implantation, and potential excessive neointimal hyperplasia from the chronic outward radial force, has not been reported. We sought to compare the angiographic narrowing associated with implantation of oversized stents. We reviewed an aneurysm database and identified patients treated with stent-assisted embolization involving a vessel size transition. Demographics and lesion characteristics were extracted. The relationship between lumen diameter and stent oversizing was compared. Twenty vessels were identified in 18 patients, providing 80 paired data points. Mean follow-up time was 8 months (SD 6). The average oversizing in the smaller diameter parent vessel landing-zone was 1.75 mm. Mean change in lumen size from pre-stent implantation was not significantly different for any of the four sites. There was a significant difference in change of lumen size at the stent tines when compared with the respective mid-stent segment for both the proximal (P = 0.02) and distal (P = 0.0004) landing zones. A small significant lumen loss occurs at stent tines when compared to midstent struts. However, there is no overall significant stenosis from highly oversized stents. Persistent luminal gain from the oversized stent radial force likely predominates over any neointimal hyperplasia.

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Introduction: Medication safety is crucial for critically ill patients with organ dysfunction exposed to polypharmacy. Our objective was to test an ‘Inventory for Medication Safety Interventions in the ICU’ (IMSI-ICU), developed based on a systematic review of strategies that impact on medication safety through error reduction, enhanced communication or institutional culture change. Hypothesis: We hypothesized that community and academic colleagues would find it to have face validity, and be easy to use, clear, complete, sensible, and reproducible. Methods: Preliminary drafts of the IMSI-ICU were created by medication safety experts from medicine, pharmacy, and nursing from ISMP Canada, ISMP US, McMaster University, University of Toronto, and Johns Hopkins University. For piloting testing, the IMSI-ICU was reviewed by 12 experts (3 pharmacists [Ph], 4 nurses [RNs], 4 physicians [MDs] and 1 ICU manager). Respondents were asked to provide feedback on item wording, flow, organization, and ease of completion. Formal clinical sensibility testing was completed by 1 Ph, 2 RNs, 5 MDs, and 1 manager using a 1 to 5 scale. For the test-retest exercise, the IMSI-ICU was administered 2 weeks apart to 16 persons in 4 centers in 3 cities. Results: Comments were favourable; pilot testing feedback was to shorten instructions, clarify item stems, allow selection of ‘unsure’, and provide examples, which resulted in a modified 44 item IMSI-ICU instrument. Clinical sensibility mean scores indicated that the items were important (4.6), complete (4.3), understandable (4.1), suitable (4.6), not redundant (4.7), and potentially discriminable (3.6). Of the 704 test-retest paired data points, 108 pairs had different responses, although most were mismatched by only 1 category and 23 pairs were mismatched by >1 category. Conclusions: The IMSI-ICU is a novel instrument for measuring effective medication safety interventions in practice. This 3 phase testing suggests that the IMSI-ICU has been pre-tested, is clinically sensible and reliable, and is ready to be completed by a multidisciplinary ICU team to examine its responsiveness in multicenter studies.

Pilot Study of a Prototype Minimally Invasive Intradermal Continuous Glucose Monitor

The purpose of this study was to assess point accuracy, rate-of-change accuracy, and safety of a prototype, minimally invasive continuous glucose monitoring (CGM) device over a 12 h in-clinic study. The CGM system consisted of a wireless electronics module with a disposable glucose sensor attached to the bottom. The electronics module was affixed to the abdomen using an adhesive pad on the bottom of the disposable sensor housing. Two CGM sensors were inserted into the abdominal tissue (left and right) of 15 adults aged 26-67 years, 5 with normoglycemia, 5 with type 1 diabetes, and 5 with type 2 diabetes. Over a 12 h period, each participant was fed three meals. Reference venous blood samples were drawn at periodic intervals (12.4 ± 5.3 min), and glucose was measured at the bedside using a laboratory reference method. For each participant, a single plasma equivalent glucose concentration was used for retrospective sensor calibration. A total of 1082 paired data points were obtained from 15 subjects and 25 of 30 sensors. Statistical analysis yielded a mean absolute relative difference of 12.6% and a mean absolute difference of 16.0 mg/dl. Continuous glucose error grid analysis showed the combined point and rate-of-change accuracy was 97.4% in zone A and 1.5% in zone B (98.9% A+B), with 1.1% erroneous readings. The prototype CGM system provided clinically accurate results 98.9% of the time and was well tolerated by participants, with little or no pain and no adverse events.

Continuous glucose monitoring: quality of hypoglycaemia detection

To evaluate the accuracy of a (widely used) continuous glucose monitoring (CGM)-system and its ability to detect hypoglycaemic events. A total of 18 patients with type 1 diabetes mellitus used continuous glucose monitoring (Guardian REAL-Time CGMS) during two 9-day in-house periods. A hypoglycaemic threshold alarm alerted patients to sensor readings <70 mg/dl. Continuous glucose monitoring sensor readings were compared to laboratory reference measurements taken every 4 h and in case of a hypoglycaemic alarm. A total of 2317 paired data points were evaluated. Overall, the mean absolute relative difference (MARD) was 16.7%. The percentage of data points in the clinically accurate or acceptable Clarke Error Grid zones A + B was 94.6%. In the hypoglycaemic range, accuracy worsened (MARD 38.8%) leading to a failure to detect more than half of the true hypoglycaemic events (sensitivity 37.5%). Furthermore, more than half of the alarms that warn patients for hypoglycaemia were false (false alert rate 53.3%). Above the low alert threshold, the sensor confirmed 2077 of 2182 reference values (specificity 95.2%). Patients using continuous glucose monitoring should be aware of its limitation to accurately detect hypoglycaemia.

Abstract 2884: Angiographic Lumen Changes From Oversized Neuroform Stent Implantation

Introduction: The effect of oversized intracranial stent implantation, and the potential for excessive neointimal hyperplasia from the resulting chronic outward radial force, has not been previously reported. We sought to compare the angiographic narrowing associated with implantation of oversized Neuroform stents overlapping vessels of different diameters. Methods: We reviewed an aneurysm database and identified patients treated with stent-assisted coil embolization involving stent placement overlapping a vessel size transition. Patient demographics and lesion characteristics were extracted from chart review. A submillimeter digital caliper was used for angiogram measurement of lumen diameter at four sites ( figure ). The relationship between lumen diameter and stent oversizing was compared with student’s t-test and Pearson’s correlation. Results: Twenty vessels were identified in 18 patients, providing 80 paired data points. Mean age was 52 years (SD 12), with mean follow-up time of 8 months (SD 6). The distribution of vessel transitions included BA to PCA (n = 8), A1 to A2 or M1 to M2 (n = 8), ICA to ACA or MCA (n = 3), and Vertebral artery to PICA (n = 1). Stent diameter ranged from 3 mm to 4.5 mm, and the average oversizing in the smaller diameter parent vessel landing-zone was 1.75 mm (range 0.8 to 2.9 mm) greater than the vessel diameter. The mean change in lumen size from pre-stent implantation to follow-up was not significantly different for any of the four sites; the proximal end-stent decreased by 5.5% (SD 19.7), proximal mid-stent increased by 7.3% (SD 18.8), distal mid-stent increased by 14.7% (SD 13.8), and the distal end-stent decreased by 0.9% (SD 13.1). Stent oversizing by less than a factor of 1.65 resulted in a mean lumen loss of 4.1% (SD 15.6), while oversizing by greater than a factor of 1.65 resulted in a mean lumen gain of 11.1% (SD = 17.2), (p = 0.006). Conclusions: These data suggest oversized Neuroform stent implantation within the intracranial vasculature does not lead to increased stenosis. Stent oversizing by a factor of 1.65 or more leads to significant persistent luminal gain. The non-significant trend toward lumen loss at the stent tines suggests diminished radial force or greater neointimal hyperplasia at these sites, however persistent luminal gain from the oversized stent radial force likely predominates over any neointimal hyperplasia. Figure . A NF stent overlapping the M1 and M2 segments (A, tines indicated by white arrows). Four points of measurement (B), proximal tines (1.), mid-stent in proximal landing zone (2.), mid-stent in distal landing zone (3.), and distal tines (4.).

The Need for Clinical Accuracy Guidelines for Blood Glucose Monitors

The performance of blood glucose (BG) monitors can be classified based on analytical accuracy or clinical accuracy.1 Analytical accuracy represents a quantitative approach to describing how closely the result of a measurement method being evaluated compares with a measurement by a reference method. Clinical accuracy is a qualitative approach that describes the clinical outcome of basing a treatment decision on the result of a measure-ment method being evaluated.2 Analytical accuracy is measured by various statistical metrics, including precision and bias, among others. Clinical accuracy is currently measured by comparing paired data points of the results of the measurement being evaluated along with the results from a reference method, with the paired data points plotted on a grid, known as an error grid.

Evaluation of mean systemic filling pressure from pulse contour cardiac output and central venous pressure

The volemic status of a patient can be determined by measuring mean systemic filling pressure (Pmsf). Pmsf is obtained from the venous return curve, i.e. the relationship between central venous pressure (Pcv) and blood flow. We evaluated the feasibility and precision of Pmsf measurement. In ten piglets we constructed venous return curves using seven 12 s inspiratory holds transiently increasing Pcv to seven different steady state levels and monitored the resultant blood flow, by pulse contour (COpc) and by flow probes around the pulmonary artery (COr) and aorta (COl). Pmsf is obtained by extrapolation of the venous return curve to zero flow. Measurements were repeated to evaluate the precision of Pmsf. During the inspiratory holds, 133 paired data points were obtained for COr, COl, COpc and Pcv. Bland-Altman analysis showed no difference between COr and COl, but a small significant difference was present between COl and COpc. All Pcv versus flow (COl or COpc) relationships were linear. Mean Pmsf was 10.78 with COl and 10.37 mmHg with COpc. Bland-Altman analysis for Pmsf with COl and with COpc, showed a bias of 0.40 ± 0.48 mmHg. The averaged coefficient of variation for repeated measurement of Pmsf with COl was 6.2% and with COpc 6.1%. During an inspiratory hold pulmonary flow and aortic flow equilibrate. Cardiac output estimates by arterial pulse contour and by a flow probe around the aorta are interchangeable. Therefore, the venous return curve and Pmsf can be estimated accurately by pulse contour methods.

Improved function of prototype 4.3‐mm Medtronic Quadcut microdebrider blade over standard 4.0‐mm Medtronic Tricut microdebrider blade

Test performance of a new prototype microdebrider blade. The commercially-available, standard 4.0-mm Medtronic straight Tricut blade was tested against the new, prototype 4.3-mm Medtronic straight Quadcut blade in experimental surgical conditions utilizing both a nasal polyp (NP) analog (raw oysters) and an allergic fungal sinusitis (AFS) analog (minced beef cat food). Both sides of 5 thawed, fresh-frozen cadaver heads were utilized for NP analog removal. AFS analog was removed out of specimen containers. A total of 10 paired data points were collected for time of surgical removal and number of clogs comparing the 2 blades. For simulated AFS debris, the prototype clogged less than the standard blade (0 vs 4.5, p < 0.0001). There were no clogs noted for either blade with the NP analog. Time for debris eradication was significantly improved for both AFS analog (147.4 vs 262.0 seconds, p < 0.0001) and NP analog (43.7 vs 112.1 seconds, p < 0.0001). The prototype blade offers faster debris and polyp removal and clogs less in the setting of allergic fungal debris. As the new blade is faster and more aggressive, introduction into a surgical setting should be guarded with an appropriate degree of caution.

Trafficking and Surface Expression of Hyperpolarization-activated Cyclic Nucleotide-gated Channels in Hippocampal Neurons

Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels mediate the hyperpolarization-activated current I(h) and thus play important roles in the regulation of brain excitability. The subcellular distribution pattern of the HCN channels influences the effects that they exert on the properties and activity of neurons. However, little is known about the mechanisms that control HCN channel trafficking to subcellular compartments or that regulate their surface expression. Here we studied the dynamics of HCN channel trafficking in hippocampal neurons using dissociated cultures coupled with time lapse imaging of fluorophore-fused HCN channels. HCN1-green fluorescence protein (HCN1-GFP) channels resided in vesicle-like organelles that moved in distinct patterns along neuronal dendrites, and these properties were isoform-specific. HCN1 trafficking required intact actin and tubulin and was rapidly inhibited by activation of either NMDA or AMPA-type ionotropic glutamate receptors in a calcium-dependent manner. Glutamate-induced inhibition of the movement of HCN1-GFP-expressing puncta was associated with increased surface expression of both native and transfected HCN1 channels, and this surface expression was accompanied by augmented I(h). Taken together, the results reveal the highly dynamic nature of HCN1 channel trafficking in hippocampal neurons and provide a novel potential mechanism for rapid regulation of I(h), and hence of neuronal properties, via alterations of HCN1 trafficking and surface expression.

Validation of Cartilage Thickness Calculations Using Indentation Analysis

Different methods have been used to cross-validate cartilage thickness measurements from magnetic resonance images (MRIs); however, a majority of these methods rely on interpolated data points, regional mean and/or maximal thickness, or surface mean thickness for data analysis. Furthermore, the accuracy of MRI cartilage thickness measurements from commercially available software packages has not necessarily been validated and may lead to an under- or overestimation of cartilage thickness. The goal of this study was to perform a matching point-to-point validation of indirect cartilage thickness calculations using a magnetic resonance (MR) image data set with direct cartilage thickness measurements using biomechanical indentation testing at the same anatomical locations. Seven bovine distal femoral condyles were prepared and a novel phantom filled with dilute gadolinium solution was rigidly attached to each specimen. High resolution MR images were acquired, and thickness indentation analysis of the cartilage was performed immediately after scanning. Segmentation of the MR data and cartilage thickness calculation was performed using semi-automated software. Registration of MR and indentation data was performed using the fluid filled phantom. The inter- and intra-examiner differences of the measurements were also determined. A total of 105 paired MRI-indentation thickness data points were analyzed, and a significant correlation between them was found (r=0.88, p<0.0001). The mean difference (+/-std. dev.) between measurement techniques was 0.00+/-0.23 mm, with Bland-Altman limits of agreement of 0.45 mm and -0.46 mm. The intra- and inter-examiner measurement differences were 0.03+/-0.22 mm and 0.05+/-0.24 mm, respectively. This study validated cartilage thickness measurements from MR images with thickness measurements from indentation by using a novel phantom to register the image-based and laboratory-based data sets. The accuracy of the measurements was comparable to previous cartilage thickness validation studies in literature. The results of this study will aid in validating a tool for clinical evaluation of in-vivo cartilage thickness.

Accuracy of a New Real-Time Continuous Glucose Monitoring Algorithm

Through minimally invasive sensor-based continuous glucose monitoring (CGM), individuals can manage their blood glucose (BG) levels more aggressively, thereby improving their hemoglobin A1c level, while reducing the risk of hypoglycemia. Tighter glycemic control through CGM, however, requires an accurate glucose sensor and calibration algorithm with increased performance at lower BG levels. Sensor and BG measurements for 72 adult and adolescent subjects were obtained during the course of a 26-week multicenter study evaluating the efficacy of the Paradigm REAL-Time (PRT) sensor-augmented pump system (Medtronic Diabetes, Northridge, CA) in an outpatient setting. Subjects in the study arm performed at least four daily finger stick measurements. A retrospective analysis of the data set was performed to evaluate a new calibration algorithm utilized in the Paradigm Veo insulin pump (Medtronic Diabetes) and to compare these results to performance metrics calculated for the PRT. A total of N = 7193 PRT sensor downloads for 3 days of use, as well as 90,472 temporally and nonuniformly paired data points (sensor and meter values), were evaluated, with 5841 hypoglycemic and 15,851 hyperglycemic events detected through finger stick measurements. The Veo calibration algorithm decreased the overall mean absolute relative difference by greater than 0.25 to 15.89%, with hypoglycemia sensitivity increased from 54.9% in the PRT to 82.3% in the Veo (90.5% with predictive alerts); however, hyperglycemia sensitivity was decreased only marginally from 86% in the PRT to 81.7% in the Veo. The Veo calibration algorithm, with sensor error reduced significantly in the 40- to 120-mg/dl range, improves hypoglycemia detection, while retaining accuracy at high glucose levels.

A Comparison of Mixed and Central Venous Oxygen Saturation in Patients during and after Cardiac Surgery

Monitoring of mixed venous oxygen saturation (Sv̄O2) allows assessment of the global balance between oxygen supply and demand. Sv̄O2 measurement requires the insertion of a pulmonary artery catheter (PAC) whereas central venous oxygen saturation (ScvO2) monitoring only requires a central venous catheter. The aim of this study was to assess how continuous measurements of ScvO2 relate to simultaneous measurements of Sv̄O2 during and after cardiac surgery. Continuous Sv̄O2 and ScvO2 measurements in 15 patients undergoing elective cardiac surgery were recorded each minute for 24 hours. Bland-Altman analysis of 9,382 paired data points for Sv̄O2 and ScvO2 revealed a mean bias of 4.4% (95% Cl +22.3, −13.6%). Considerable inter- and intra-individual variability was noted. Based on these data and previous studies, ScvO2 and Sv̄O2 are not interchangeable variables.

The Accuracy and Efficacy of Real-Time Continuous Glucose Monitoring Sensor in Patients with Type 1 Diabetes

The accuracy and efficacy of the Medtronic Diabetes (Northridge, CA) Real-Time (RT)-Continuous Glucose Monitoring (CGM) sensor were analyzed in 72 subjects with type 1 diabetes. This was a retrospective analysis of 60,050 temporally paired data points (sensor and glucose meter values) obtained during the course of an outpatient ambulatory study evaluating the efficacy of a sensor-augmented pump system in adults and adolescents. Subjects uploaded sensor values and self-monitoring blood glucose data to the CareLink Clinical Application (Medtronic Diabetes) via the Internet, every 2 weeks during the course of the study. The overall percentage of sensor readings within +/-20% or +/-30% agreement of reference glucose readings was 75.6% and 86.8%, respectively. The highest rate of agreement occurred in the 240-400 mg/dL range, where 79.9% of sensor readings were within +/-20% of meter values and 91.5% of sensor readings were within 30% of meter values. The mean absolute relative difference for all subjects was 15.8%, and the median absolute relative difference was 10.9%. The bias was -2.13 mg/dL. Paired glucose measurements from the RT-CGM and meter demonstrated that 95.9% of paired points in the overall subject population fell in zones A and B of the Clarke Error Grid. Consensus Error Grid Analysis established that 99.2% of paired data points were in zones A and B. This study reports the accuracy of a continuous glucose sensor with a large number of paired data points (60,050). RT-CGM is safe and well tolerated and provides readings that are in close agreement with glucose meter values.

On-line Monitoring of End-tidal Propofol Concentration in Anesthetized Patients

Propofol (2,6-diisopropylphenol) has some volatility, so it can be detected in expired breath of individuals receiving intravenous propofol. This study measured volatile propofol exhaled by patients and investigated the relation between exhaled and plasma propofol concentrations. Nineteen patients with American Society of Anesthesiologists physical status I or II who were undergoing elective surgery participated in this two-part study. In study 1 (n = 11), anesthesia was induced with 2 mg/kg propofol, 0.1 mg/kg vecuronium, and 2 microg/kg fentanyl. After intubation, propofol was administered continuously for 60 min at each of three rates: 3, 6, and 9 mg x kg(-1) x h(-1). Blood samples were obtained just before each change in the infusion rate, and the plasma concentrations of propofol were measured. The exhaled propofol concentration was measured continuously by means of proton transfer mass spectrometry. End-tidal propofol concentrations during blood sampling were averaged and compared with plasma propofol concentrations. In study 2 (n = 8), after induction of anesthesia, patients received a bolus injection of 2 mg/kg propofol, and the exhaled propofol concentration was measured. Volatile propofol was detected in expired gas from all study patients. From study 1, the authors obtained 24 paired data points, i.e., concentrations of end-tidal and plasma propofol. With Bland-Altman analysis, bias +/- precision was 5.2 +/- 10.4 with 95% limits of agreement of -15.1 and 25.6. In study 2, the exhaled propofol concentration curve showed an obvious peak in all patients. Agreement between plasma and exhaled propofol concentrations suggests that proton transfer mass spectrometry can be used for real-time propofol monitoring.

Effect of Lepirudin on the International Normalized Ratio

Many patients receiving direct thrombin inhibitor (DTI) therapy require transition to warfarin. This transition may be complicated by DTI-induced elevations in the international normalized ratio (INR). While the effect of argatroban on the INR has been characterized, data assessing the effect of lepirudin on the INR are limited. To evaluate the effect of lepirudin on the INR. Patients receiving lepirudin therapy between January 2000 and May 2001 were identified using the pharmacy database, and a retrospective chart review was conducted. Patients were included for analysis if they had paired activated partial thromboplastin time (aPTT) and INR data while receiving lepirudin monotherapy. Fifty-three paired aPTT and INR data points from 8 patients receiving lepirudin monotherapy were collected. The Organon MDA 180 instrument was used for aPTT and prothrombin time (PT) determination. Organon MDA Platelin L reagent was used for the aPTT and Organon Simplastin L reagent was used for the PT. The international sensitivity index (ISI) of the Simplastin L thromboplastin was 2.0. The mean +/- SD lepirudin dose was 0.05 +/- 0.04 mg/kg/h. Linear regression was used to identify the INRs that correspond to a therapeutic aPTT value of 45-75 seconds (1.5-2.5 times mean laboratory normal of 30 sec). The correlation between aPTT and INR was 0.77. An aPTT of 45-75 seconds with lepirudin correlated to an INR of 1.6-3.2. Based on laboratory results, when using a thromboplastin with an ISI of 2, lepirudin appears to elevate the INR in the absence of warfarin.

Cerebral saturations trend with mixed venous saturations in patients undergoing extracorporeal life support.

Cerebral saturation (SCO2) monitors are noninvasive tools that continuously measure saturations in the cerebral cortex, a predominately venous bed. The purpose of this study was to see if a trend existed between measurements of SCO2 and mixed venous saturation values (SVO2) for patients on extracorporeal life support (ECLS). Six patients required ECLS for cardiac failure after congenital cardiac surgery, and one patient required ECLS for pulmonary failure. Patients were divided into two groups, those without systemic/pulmonary venous mixing (n = 3, Group I) and those with mixing due to an intraatrial shunt or left ventricular vent (n = 4, Group II). The age of patients was 0.4 +/- 0.5 years (mean +/- SD), weight was 5.2 +/- 2.3 kg, and time on ECLS was 8.3 +/- 4.8 days. No significant abnormalities were seen on head imaging. A total of 786 paired data points were collected. Mean values were different; however, there was a significant trend between SCO2 and SVO2 for the entire sample (R2 = 0.66, p < 0.001). Cerebral saturation trends follow mixed venous trends and, therefore, may be helpful in combination with other physical and laboratory findings in the care of the critically ill child.

The Use of a Continuous Glucose Monitoring System in Hypoglycemic Disorders

To evaluate the use of a continuous glucose monitoring system (CGMS) in the evaluation and treatment of infants and children with hypoglycemic disorders. Patients with hypoglycemic disorders wore the CGMS device in the Pediatric Clinic Research Center during their evaluation and treatment. Capillary blood glucose (CBG) values were obtained at least 3 times each day and entered into the device for calibration purposes. We evaluated the number of hypoglycemic episodes below 3.3 mmol/l (60 mg/dl) detected by CGMS compared to CBG values and characterized episodes by their duration and intensity. Five patients with hypoglycemic disorders were included in the study. There were a total of 13,369 sensor points, 343 paired sensor and CBG data points, and 57 days included. A total of 180 episodes of hypoglycemia occurred in these five patients, with an average duration of 55 +/- 13 minutes. Using a cut-off of 3.3 mmol/l (60 mg/dl) for hypoglycemia, the sensor had a sensitivity of 65.4%, specificity of 90.6%, and false positive rate of 42.9%. The positive and negative predictive values were 57.1% and 93.2%, respectively. CGMS is a useful adjunct in the diagnosis and evaluation of hypoglycemia, and for documentation of euglycemia in these patients following therapy.