Suspected Cerebral Edema in Diabetic Ketoacidosis: Is There Still a Role for Head CT in Treatment Decisions?

OBJECTIVES: Neurologic deterioration associated with cerebral edema in diabetic ketoacidosis is typically sudden in onset, progresses rapidly, and requires emergent treatment. The utility of brain imaging by head CT in decisions to treat for cerebral edema has not been previously studied. The objective of this study was to describe the characteristics of pediatric patients with diabetic ketoacidosis who develop altered mental status and evaluate the role of head CT in this cohort. DESIGN: Retrospective analysis of clinical, biochemical, and radiologic data. SETTING: Tertiary care children's hospital (2004-2010). PATIENTS: Six hundred eighty-six admissions of patients (< 26 yr) with diabetic ketoacidosis. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Altered mental status was documented during 96 of 686 diabetic ketoacidosis admissions (14%). Compared with alert patients, those with altered mental status were younger (median, 12.0 vs 13.1 yr; p = 0.007) and more acidotic (pH, 7.04 vs 7.19; p < 0.001), with higher serum osmolality (328 vs 315 mOsm/kg; p < 0.001) and longer hospital length of stay (4.5 vs 3 d; p = 0.002). Head CT was performed during 60 of 96 diabetic ketoacidosis admissions with altered mental status (63%), 16 (27%) of which had abnormal results. Hyperosmolar therapy for cerebral edema was given during 23 of the 60 admissions (38%), during which 12 (52%) had normal head CT results, eight of these 12 (67%) after cerebral edema treatment and four (33%) before. Of the 11 admissions with abnormal head CT results that received hyperosmolar therapy, four head CT scan (36%) occurred after hyperosmolar treatment and seven (64%) before. For the 11 admissions with head CT before cerebral edema treatment, there was a median 2-hour delay between head CT and hyperosmolar therapy. CONCLUSIONS: In this single-center retrospective study, there was no evidence that decisions about treatment of patients with diabetic ketoacidosis and suspected cerebral edema were enhanced by head CT, and head CT may have led to a significant delay in hyperosmolar therapy.

Design and rationale of Heart and Lung Failure - Pediatric INsulin Titration Trial (HALF-PINT): A randomized clinical trial of tight glycemic control in hyperglycemic critically ill children.

OBJECTIVES: Test whether hyperglycemic critically ill children with cardiovascular and/or respiratory failure experience more ICU-free days when assigned to tight glycemic control with a normoglycemic versus hyperglycemic blood glucose target range. DESIGN: Multi-center randomized clinical trial. SETTING: Pediatric ICUs at 35 academic hospitals. PATIENTS: Children aged 2weeks to 17years receiving inotropic support and/or acute mechanical ventilation, excluding cardiac surgical patients. INTERVENTIONS: Patients receive intravenous insulin titrated to either 80-110mg/dL (4.4-6.1mmol/L) or 150-180mg/dL (8.3-10.0mmol/L). The intervention begins upon confirmed hyperglycemia and ends when the patient meets study-defined ICU discharge criteria or after 28days. Continuous glucose monitoring, a minimum glucose infusion, and an explicit insulin infusion algorithm are deployed to achieve the BG targets while minimizing hypoglycemia risk. MEASUREMENTS AND MAIN RESULTS: The primary outcome is ICU-free days (equivalent to 28-day hospital mortality-adjusted ICU length of stay). Secondary outcomes include 90-day hospital mortality, organ dysfunction scores, ventilator-free days, nosocomial infection rate, neurodevelopmental outcomes, and nursing workload. To detect an increase of 1.25 ICU-free days (corresponding to a 20% relative reduction in 28-day hospital mortality and a one-day reduction in ICU length of stay), 1414 patients are needed for 80% power using a two-sided 0.05 level test. CONCLUSIONS: This trial tests whether hyperglycemic critically ill children randomized to 80-110mg/dL benefit more than those randomized to 150-180mg/dL. This study implements validated bedside support tools including continuous glucose monitoring and a computerized algorithm to enhance patient safety and ensure reproducible bedside decision-making in achieving glycemic control.

Endocrinologic Diseases in Pediatric Cardiac Intensive Care.

OBJECTIVES: The objectives of this review are to discuss the pathophysiology, clinical impact and treatment of hyperglycemia, and disturbances in thyroid and adrenal function prior to and following cardiac surgery in children. DATA SOURCE: MEDLINE and PubMed. CONCLUSIONS: Disturbances in glucose metabolism and thyroid and adrenal function are common in critically ill children with cardiac disease and in particular in children undergoing cardiac surgery for complex congenital heart disease. An understanding of the pathophysiology, clinical impact and treatment of these disturbances is essential for the management of these at risk patients.

Pediatric Cardiac Intensive Care Society 2014 Consensus Statement: Pharmacotherapies in Cardiac Critical Care Hormone Replacement Therapy.

OBJECTIVE: To provide an overview of the current literature on the use of hormone replacement therapies in pediatric cardiac critical care. DATA SOURCES: PubMed, EMBASE, and the Cochrane Library were searched using keywords relevant to the hormonal therapy, with no limits on language but restricting the search to children 0-18 years old. STUDY SELECTION: All clinical studies believed to have relevance were considered. Where studies in children were sparse, additional evidence was sought from adult studies. DATA EXTRACTION: All relevant studies were reviewed, and the most relevant data were incorporated in this review. DATA SYNTHESIS: All authors of this review contributed to the appraisal of the data extracted. Challenges and revisions by the authors were conducted by group e-mail debate. CONCLUSIONS: Glycemic control: although it is likely that some children could benefit, the routine use of tight glycemic control cannot be recommended in children after cardiac surgery. Thyroid hormone replacement: routine use of thyroid hormone replacement to normalize levels after cardiac surgery cannot be recommended on current evidence. Until further evidence from adequately powered studies is available, therapeutic decisions should be based on individual patient circumstances. Corticosteroids: 1) cardiopulmonary bypass: although studies seem to favor steroid administration during surgery with cardiopulmonary bypass, a large randomized controlled trial is required before strong recommendations can be made; 2) refractory hypotension: the evidence for the use of steroid replacement in refractory hypotension is poor, and no firm recommendations can be made; and 3) abnormal adrenal function after cardiac surgery: there is inadequate evidence on which to make recommendations on the use of corticosteroid replacement in children with critical illness-related corticosteroid insufficiency in children following cardiac surgery.

Tight Glycemic Control in the Pediatric Intensive Care Unit.

Hyperglycemia is a common complication in critically ill, nondiabetic children. Four large pediatric randomized controlled trials of tight glycemic control (TGC) have been conducted to date with contradicting results. This review will highlight the design and outcomes of these trials and other relevant studies to provide an overview of the advantages and disadvantages of TGC for different populations at risk of hyperglycemia along with future directions for research.

The relationship between TSH and systemic inflammation in extremely preterm newborns.

Elevated thyrotropin (TSH) levels in critically ill extremely premature infants have been attributed to transient hypothyroidism of prematurity or non-thyroidal illness syndrome. We evaluated the hypothesis that relatively high TSH levels in the first 2 postnatal weeks follow recovery from systemic inflammation, similar to non-thyroidal illness syndrome. The study was conducted in 14 Neonatal Intensive Care Units and approved by each individual Institutional Review Board. We measured the concentrations of TSH and 25 inflammation-related proteins in blood spots obtained on postnatal days 1, 7, and 14. We then evaluated the temporal relationships between hyperthyrotropinemia (HTT), defined as a TSH concentration in the highest quartile for gestational age and postnatal day, and elevated levels of inflammation-related proteins. 880 newborns less than 28 weeks of gestation were included. Elevated concentrations of inflammation-related proteins during the first or second week did not precede day-14 HTT. Systemic inflammation on day 7 was associated with day-14 HTT only if inflammation persisted through the end of the 2 week period. HTT frequently accompanied elevated concentrations of inflammation-related proteins on the same day. The hypothesis that HTT follows recovery from severe illness, defined as preceding systemic inflammation, is weakly supported by our study. Our findings more prominently support the hypothesis that TSH conveys information about concomitant inflammation in the extremely premature newborn.

Are preterm newborns who have relative hyperthyrotropinemia at increased risk of brain damage?

BACKGROUND: We sought to disentangle the contributions of hyperthyrotropinemia (an indicator of thyroid dysfunction) (HTT) and intermittent or sustained systemic inflammation (ISSI) to structural and functional indicators of brain damage. METHODS: We measured the concentrations of thyroid-stimulating hormone (TSH) on day 14 and of 25 inflammation-related proteins in blood collected during the first 2 postnatal weeks from 786 infants born before the 28th week of gestation who were not considered to have hypothyroidism. We defined hyperthyrotropinemia (HTT) as a TSH concentration in the highest quartile for gestational age on postnatal day 14 and ISSI was defined as a concentration in the top quartile for gestational age of a specific inflammation-related protein on 2 separate days a week apart during the first 2 postnatal weeks. We first assessed the risk of brain damage indicators by comparing 1) neonates who had HTT to those without (regardless of ISSI) and 2) neonates with HTT only, ISSI only, or HTT+ISSI to those who were exposed to neither HTT nor ISSI. RESULTS: In univariable models that compared those with HTT to those without, HTT was not significantly associated with any indicator of brain damage. In models that compared HTT only, ISSI only, and HTT+ISSI to those with neither, children with ISSI only or with HTT+ISSI were at significantly higher risk of ventriculomegaly [odds ratios (ORs) 2-6], whereas those with HTT only were at significantly reduced risk of a hypoechoic lesion (ORs 0.2-0.4). Children with HTT only had a higher risk of quadriparesis and those with ISSI alone had a higher risk of hemiparesis (ORs 1.6-2.4). Elevated risk of a very low mental development score was associated with both ISSI only and HTT+ISSI, whereas a very low motor development score and microcephaly were associated with HTT+ISSI. CONCLUSIONS: The association of HTT with increased or decreased risk of indicators of brain damage depends on the presence or absence of ISSI.

Measuring and reporting glycemic control in clinical trials: building a path to consensus.

Clinical trials over time have used a variety of approaches for both measuring tight glycemic control and reporting results. The review by Finfer and colleagues in this issue of Critical Care is a step toward consensus within the research community to standardize the way blood glucose is measured and reported in clinical trials. The authors propose using specific measures of central tendency and dispersion for reporting glucose, advocate the use of blood gas analyzers and elimination of point-of-care glucose monitors in the intensive care unit, and comment on performance of continuous glucose monitors. As we await the release of updated rules from the International Standards Organization and process the new rules from the Clinical Laboratory and Standards Institute to regulate glucose monitoring, these recommendations should trigger many more conversations within the field as we strive for uniformity. However, we need to be cautious in prematurely proposing and adopting standards of care that fail to account for newer technology and data in this rapidly growing area of research.