Jamin L. Alexander

Real-Time Continuous Glucose Monitoring in Pediatric Patients During and After Cardiac Surgery

OBJECTIVES. Given the demonstrated benefit of euglycemia in critically ill patients as well as the risk for hypoglycemia during insulin infusion in children, we sought to validate a subcutaneous sensor for real-time continuous glucose monitoring in pediatric patients during and after cardiac surgery. METHODS. Children up to 36 months of age who were undergoing cardiac bypass surgery were recruited. After anesthetic induction, a continuous glucose-monitoring system sensor (CGMS, Medtronic Minimed, Northridge, CA) was inserted subcutaneously. Sensors remained in place for up to 72 hours. Arterial blood glucose was measured intermittently in the central laboratory (Bayer Rapidlab 860, Tarrytown, NY). Sensor data, after prospective calibration with 6-hourly laboratory values using the proprietary Medtronic Minimed Guardian RT algorithm, were compared with all laboratory glucose values. Statistical analysis was performed to test whether sensor performance was affected by body temperature, inotrope dose, or body-wall edema. RESULTS. Twenty patients were enrolled in the study for a total of 40 study days and 246 paired sensor and laboratory glucose values. Consensus error grid analysis demonstrated that 72.0% of sensor value comparisons were within zone A (no effect on clinical action), and 27.6% of comparisons were within zone B (altered clinical action of little or no effect on outcome), with a mean absolute relative deviation of 17.6% for all comparisons. One comparison (0.4%) was in zone C (altered clinical action likely to affect outcome). No significant correlations were found between sensor performance and body temperature, inotrope dose, or body-wall edema. All patients tolerated the sensors well without bleeding or tissue reaction. CONCLUSIONS. Guardian RT real-time subcutaneous blood glucose measurement is safe and potentially useful for continuous glucose monitoring in critically ill children. Subcutaneous sensors performed well in the setting of hypothermia, inotrope use, and edema. These sensors facilitate identifying and following the effects of interventions to control blood glucose.

Tight glycemic control in critically Ill children

Background In multicenter studies, tight glycemic control targeting a normal blood glucose level has not been shown to improve outcomes in critically ill adults or children after cardiac surgery. Studies involving critically ill children who have not undergone cardiac surgery are lacking. Methods In a 35‐center trial, we randomly assigned critically ill children with confirmed hyperglycemia (excluding patients who had undergone cardiac surgery) to one of two ranges of glycemic control: 80 to 110 mg per deciliter (4.4 to 6.1 mmol per liter; lower‐target group) or 150 to 180 mg per deciliter (8.3 to 10.0 mmol per liter; higher‐target group). Clinicians were guided by continuous glucose monitoring and explicit methods for insulin adjustment. The primary outcome was the number of intensive care unit (ICU)–free days to day 28. Results The trial was stopped early, on the recommendation of the data and safety monitoring board, owing to a low likelihood of benefit and evidence of the possibility of harm. Of 713 patients, 360 were randomly assigned to the lower‐target group and 353 to the higher‐target group. In the intention‐to‐treat analysis, the median number of ICU‐free days did not differ significantly between the lower‐target group and the higher‐target group (19.4 days [interquartile range {IQR}, 0 to 24.2] and 19.4 days [IQR, 6.7 to 23.9], respectively; P=0.58). In per‐protocol analyses, the median time‐weighted average glucose level was significantly lower in the lower‐target group (109 mg per deciliter [IQR, 102 to 118]; 6.1 mmol per liter [IQR, 5.7 to 6.6]) than in the higher‐target group (123 mg per deciliter [IQR, 108 to 142]; 6.8 mmol per liter [IQR, 6.0 to 7.9]; P<0.001). Patients in the lower‐target group also had higher rates of health care–associated infections than those in the higher‐target group (12 of 349 patients [3.4%] vs. 4 of 349 [1.1%], P=0.04), as well as higher rates of severe hypoglycemia, defined as a blood glucose level below 40 mg per deciliter (2.2 mmol per liter) (18 patients [5.2%] vs. 7 [2.0%], P=0.03). No significant differences were observed in mortality, severity of organ dysfunction, or the number of ventilator‐free days. Conclusions Critically ill children with hyperglycemia did not benefit from tight glycemic control targeted to a blood glucose level of 80 to 110 mg per deciliter, as compared with a level of 150 to 180 mg per deciliter. (Funded by the National Heart, Lung, and Blood Institute and others; HALF‐PINT ClinicalTrials.gov number, NCT01565941.)

Continuous non-invasive end-tidal CO2 monitoring in pediatric inpatients with diabetic ketoacidosis

Introduction:  Pediatric inpatients with diabetic ketoacidosis (DKA) are routinely subjected to frequent blood draws in order to closely monitor degree of acidosis and response to therapy. The typical level of acidosis monitoring is less than ideal, however, because of the high cost and invasiveness of frequent blood labs. Previous studies have validated end‐tidal carbon dioxide (EtCO2) monitoring in the emergency department (ED) for varying periods of time. We extend these findings to the inpatient portion of the hospitalization during which the majority of blood tests are sent.

Value of continuous glucose monitoring for minimizing severe hypoglycemia during tight glycemic control.

Objective: Tight glycemic control can potentially reduce morbidity and mortality in the intensive care unit but increases the risk of hypoglycemia. The most effective means to avoid hypoglycemia is to obtain frequent blood glucose samples, but this increases the burden to nursing staff. The objective of this study was to assess the ability of a real-time continuous glucose monitor to reduce hypoglycemia (blood glucose <60 mg/dL [3.3 mmol/L]) during standard care or tight glycemic control effected with a proportional integral derivative insulin titration algorithm. Design: Real-time continuous glucose monitor profiles obtained from an ongoing prospective randomized trial of tight glycemic control were retrospectively analyzed to determine whether the continuous glucose measure had prevented instances of hypoglycemia. Setting: Cardiac intensive care unit. Patients: Children 3 yrs of age or younger undergoing cardiac surgery were studied. Interventions: Intravenous insulin infusion and rescue glucose guided by the real-time continuous glucose monitor and the proportional integral derivative algorithm in the tight glycemic control arm (n = 155; target glucose 80–110 mg/dL [4.4–6.1 mmol/L]) and the real-time continuous glucose monitor in the standard care arm (n = 156). Measurements and Main Results: No reduction in hypoglycemia was observed with real-time continuous glucose monitor alarms set at 60 mg/dL (3.3 mmol/L) (zero of 19 occurrences of blood glucose <60 mg/dL [3.3 mmol/L] detected); 18 of 40 subsequent incidences of hypoglycemia were detected after the alarm threshold was increased to 70 mg/dL (3.9 mmol/L). In the tight glycemic control arm, eight incidences were reduced in duration and an additional eight events were prevented with intravenous glucose. In the standard care arm, three of nine occurrences of hypoglycemia were detected with the duration reduced in all cases. On average, one to two false hypoglycemia alarms were observed in each patient. Conclusions: The real-time continuous glucose monitor in combination with proportional integral derivative control can reduce hypoglycemia during tight glycemic control. The real-time continuous glucose monitor can also reduce hypoglycemia during standard care. However, false alarms increase the overall nursing workload.

The correlation and level of agreement between end-tidal and blood gas pCO2 in children with respiratory distress: a retrospective analysis

BackgroundTo investigate the correlation and level of agreement between end-tidal carbon dioxide (EtCO2) and blood gas pCO2 in non-intubated children with moderate to severe respiratory distress.MethodsRetrospective study of patients admitted to an intermediate care unit (InCU) at a tertiary care center over a 20-month period with moderate to severe respiratory distress secondary to asthma, bronchiolitis, or pneumonia. Patients with venous pCO2 (vpCO2) and EtCO2 measurements within 10 minutes of each other were eligible for inclusion. Patients with cardiac disease, chronic pulmonary disease, poor tissue perfusion, or metabolic abnormalities were excluded.ResultsEighty EtCO2-vpCO2 paired values were available from 62 patients. The mean ± SD for EtCO2 and vpCO2 was 35.7 ± 10.1 mmHg and 39.4 ± 10.9 mmHg respectively. EtCO2 and vpCO2 values were highly correlated (r = 0.90, p < 0.0001). The correlations for asthma, bronchiolitis and pneumonia were 0.74 (p < 0.0001), 0.83 (p = 0.0002) and 0.98 (p < 0.0001) respectively. The mean bias ± SD between EtCO2 and vpCO2 was -3.68 ± 4.70 mmHg. The 95% level of agreement ranged from -12.88 to +5.53 mmHg. EtCO2 was found to be more accurate when vpCO2 was 35 mmHg or lower.ConclusionEtCO2 is correlated highly with vpCO2 in non-intubated pediatric patients with moderate to severe respiratory distress across respiratory illnesses. Although the level of agreement between the two methods precludes the overall replacement of blood gas evaluation, EtCO2 monitoring remains a useful, continuous, non-invasive measure in the management of non-intubated children with moderate to severe respiratory distress.

Tight Glycemic Control after Pediatric Cardiac Surgery in High-Risk Patient Populations: A Secondary Analysis of the Safe Pediatric Euglycemia after Cardiac Surgery Trial

Background— Our previous randomized, clinical trial showed that postoperative tight glycemic control (TGC) for children undergoing cardiac surgery did not reduce the rate of health care–associated infections compared with standard care (STD). Heterogeneity of treatment effect may exist within this population. Methods and Results— We performed a post hoc exploratory analysis of 980 children from birth to 36 months of age at the time of cardiac surgery who were randomized to postoperative TGC or STD in the intensive care unit. Significant interactions were observed between treatment group and both neonate (age ⩽30 days; P=0.03) and intraoperative glucocorticoid exposure (P=0.03) on the risk of infection. The rate and incidence of infections in subjects ⩽60 days old were significantly increased in the TGC compared with the STD group (rate: 13.5 versus 3.7 infections per 1000 cardiac intensive care unit days, P=0.01; incidence: 13% versus 4%, P=0.02), whereas infections among those >60 days of age were significantly reduced in the TGC compared with the STD group (rate: 5.0 versus 14.1 infections per 1000 cardiac intensive care unit days, P=0.02; incidence: 2% versus 5%, P=0.03); the interaction of treatment group by age subgroup was highly significant (P=0.001). Multivariable logistic regression controlling for the main effects revealed that previous cardiac surgery, chromosomal anomaly, and delayed sternal closure were independently associated with increased risk of infection. Conclusions— This exploratory analysis demonstrated that TGC may lower the risk of infection in children >60 days of age at the time of cardiac surgery compared with children receiving STD. Meta-analyses of past and ongoing clinical trials are necessary to confirm these findings before clinical practice is altered. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT00443599.Background— Our previous randomized, clinical trial showed that postoperative tight glycemic control (TGC) for children undergoing cardiac surgery did not reduce the rate of health care–associated infections compared with standard care (STD). Heterogeneity of treatment effect may exist within this population. Methods and Results— We performed a post hoc exploratory analysis of 980 children from birth to 36 months of age at the time of cardiac surgery who were randomized to postoperative TGC or STD in the intensive care unit. Significant interactions were observed between treatment group and both neonate (age ≤30 days; P =0.03) and intraoperative glucocorticoid exposure ( P =0.03) on the risk of infection. The rate and incidence of infections in subjects ≤60 days old were significantly increased in the TGC compared with the STD group (rate: 13.5 versus 3.7 infections per 1000 cardiac intensive care unit days, P =0.01; incidence: 13% versus 4%, P =0.02), whereas infections among those >60 days of age were significantly reduced in the TGC compared with the STD group (rate: 5.0 versus 14.1 infections per 1000 cardiac intensive care unit days, P =0.02; incidence: 2% versus 5%, P =0.03); the interaction of treatment group by age subgroup was highly significant ( P =0.001). Multivariable logistic regression controlling for the main effects revealed that previous cardiac surgery, chromosomal anomaly, and delayed sternal closure were independently associated with increased risk of infection. Conclusions— This exploratory analysis demonstrated that TGC may lower the risk of infection in children >60 days of age at the time of cardiac surgery compared with children receiving STD. Meta-analyses of past and ongoing clinical trials are necessary to confirm these findings before clinical practice is altered. Clinical Trial Registration— URL: . Unique identifier: [NCT00443599][1]. # CLINICAL PERSPECTIVE {#article-title-34} [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT00443599&atom=%2Fcirculationaha%2F129%2F22%2F2297.atom

Extreme stress hyperglycemia during acute illness in a pediatric emergency department.

Objectives: Although mild stress hyperglycemia in pediatric illness is common, severe hyperglycemic responses (≥300 mg/dL [16.7 mmol/L]) to stress are unusual. We sought to determine the incidence and course of extreme stress hyperglycemia (ESH) in acute pediatric illness, including whether it is a marker of increased mortality or associated with subsequent development of diabetes mellitus (DM). Methods: We retrospectively reviewed a cohort of 55,120 consecutive visits over 6 years to a pediatric emergency department at which blood glucose concentrations were measured and report on visits with laboratory glucose 300 mg/dL (16.7 mmol/L) or greater without DM. Results: There were 72 cases of ESH (incidence of 0.13%). Median age was 8.8 years; 63% were male. The most common diagnoses were respiratory illness (49%), trauma (15%), and seizure (8%), and 65% of patients had received glucose-influencing interventions before evaluation. Eighty-five percent were ill appearing, 60% were admitted to the intensive care unit, and half had acidemic pH values. The overall mortality rate was 22%. Despite treatment of hyperglycemia in only 8 patients, glucose concentrations decreased to 150 mg/dL (8.3 mmol/L) or less within 48 hours in 67% and before discharge or death in 85% of patients. Preceding symptoms and concurrent laboratory results were helpful to exclude diabetes, and none of the surviving patients with follow-up available went on to develop type 1 or 2 DM. Conclusions: Although rare, ESH (≥300 mg/dL [16.7 mmol/L]) does occur in acute pediatric illness, in most cases is at least partially iatrogenic, and is a marker of severe illness and high mortality. Normoglycemia is typically restored quickly with treatment of the primary illness. No association was found with a subsequent diagnosis of DM.

Utility of immediate hemoglobin A1c in children with type I diabetes mellitus

Agus MSD, Alexander JL, Wolfsdorf JI. Utility of immediate hemoglobin A1c in children with type I diabetes mellitus.

Design and rationale of safe pediatric euglycemia After cardiac surgery: A randomized controlled trial of tight glycemic control After pediatric cardiac surgery

Objectives: To describe the design of a clinical trial testing the hypothesis that children randomized to tight glycemic control with intensive insulin therapy after cardiac surgery will have improved clinical outcomes compared to children randomized to conventional blood glucose management. Design: Two-center, randomized controlled trial. Setting: Cardiac ICUs at two large academic pediatric centers. Patients: Children from birth to those aged 36 months recovering in the cardiac ICU after surgery with cardiopulmonary bypass. Interventions: Subjects in the tight glycemic control (intervention) group receive an intravenous insulin infusion titrated to achieve normoglycemia (target blood glucose range of 80–110 mg/dL; 4.4–6.1 mmol/L). The intervention begins at admission to the cardiac ICU from the operating room and terminates when the patient is ready for discharge from the ICU. Continuous glucose monitoring is performed during insulin infusion to minimize the risks of hypoglycemia. The standard care group has no target blood glucose range. Measurements and Main Results: The primary outcome is the development of any nosocomial infection (bloodstream, urinary tract, and surgical site infection or nosocomial pneumonia). Secondary outcomes include mortality, measures of cardiorespiratory function and recovery, laboratory indices of nutritional balance, immunologic, endocrinologic, and neurologic function, cardiac ICU and hospital length of stay, and neurodevelopmental outcome at 1 and 3 yrs of age. A total of 980 subjects will be enrolled (490 in each treatment arm) for sufficient power to show a 50% reduction in the prevalence of the primary outcome. Conclusions: Pediatric cardiac surgery patients may recognize great benefit from tight glycemic control in the postoperative period, particularly with regard to reduction of nosocomial infections. The Safe Pediatric Euglycemia after Cardiac Surgery trial is designed to provide an unbiased answer to the question of whether this therapy is indeed beneficial and to define the associated risks of therapy.

Use of a continuous glucose sensor in an extracorporeal life support circuit.

Background: Standard care for infants on extracorporeal life support (ECLS) relies on intermittent measurement of blood glucose (BG); however, this can lead to significant changes in BG that go unrecognized for several hours. The present study was designed to assess performance and clinical applicability of a subcutaneous glucose sensor technology modified for use as a blood-contacting sensor within the ECLS circuit. Methods: Twelve children, aged 3 years or less, requiring ECLS support were studied. Three continuous glucose sensors (Medtronic MiniMed) were inserted into hubs placed in line with the ECLS circuit. Blood glucose was assessed with a laboratory analyzer (BG LAB; Bayer Rapidlab 860) approximately every 5 h (mean 4.9 ± 3.3 h) with more frequent samples obtained with a bedside monitor (HemoCue) as needed. Sensor current (I SIG) was transmitted to a laptop computer and retrospectively calibrated using BG LAB. Sensor performance was assessed by mean absolute relative difference (MARD), linear regression slope and intercept, and correlation, all with BG LAB as reference. Results: The BG LAB averaged 107.6 ± 36.4 mg/dl (mean ± standard deviation) ranging from 58 to 366 mg/dl. The MARD was 11.4%, with linear regression slope (0.86 ± 0.030) and intercept (9.0 ± 3.2 mg/dl) different from 1 and 0, respectively (p < .05), and correlation (r 2 = 0.76; p < .001). The system was not associated with any adverse events, and placement and removal into the hubs was easily accomplished. Instances in which more frequent BG values were obtained using a bedside HemoCue (BG HEMO) monitor showed the sensor to respond rapidly to changes. Conclusions: We conclude that continuous sensors can be adapted for use in an ECLS circuit with accuracy similar to or better than that achieved with the subcutaneous site. Continuous glucose monitoring in this population can rapidly detect changes in BG that would not otherwise be observed. Further studies will be needed to assess the benefit of continuous glucose monitoring in this population.