Occult risk factor for the development of cerebral edema in children with diabetic ketoacidosis: possible role for stomach emptying.

The incidence of cerebral edema during therapy of diabetic ketoacidosis (DKA) in children remains unacceptably high-this suggests that current treatment may not be ideal and that important risk factors for the development of cerebral edema have not been recognized. We suggest that there are two major sources for an occult generation of osmole-free water in these patients: first, fluid with a low concentration of electrolytes that was retained in the lumen of the stomach when the patient arrived in hospital; second, infusion of glucose in water at a time when this solution can be converted into water with little glucose. In a retrospective chart review of 30 patients who were admitted with a diagnosis of DKA and a blood sugar > 900 mg/dL (50 mmol/L), there were clues to suggest that some of the retained fluid in the stomach was absorbed. To minimize the likelihood of creating a dangerous degree of cerebral edema in patients with DKA, it is important to define the likely composition of fluid retained in the stomach on admission, to look for signs of absorption of some of this fluid during therapy, and to be especially vigilant once fat-derived brain fuels have disappeared, because this is the time when glucose oxidation in the brain should increase markedly, generating osmole-free water.

Indicators of lean body mass catabolism: emphasis on the creatinine excretion rate.

BACKGROUND: The major stress response to critical illness leads to a catabolic state and loss of lean body mass. AIMS: To test whether an increased rate of creatinine excretion might provide unique and timely information to monitor cell catabolism; to relate this information to balances of cell constituents (nitrogen, potassium, phosphate and magnesium); to evaluate the effectiveness of nutritional therapy to reverse this catabolic process. DESIGN: Prospective observational study. METHODS: Children with severe traumatic brain injury admitted to the paediatric critical care units of The Hospital for Sick Children, Toronto, Canada and Hospital das Clínicas, Faculty of Medicine of Ribeirão Preto, University of São Paulo, Brazil were studied. Complete 24 h urine collections were obtained for measurement of creatinine excretion rate and daily balances of nitrogen, potassium, phosphate and magnesium. RESULTS: Seventeen patients were studied for 3-10 days. On Day 1, all had negative balances for protein and phosphate. Balances for these intracellular constituents became positive when protein intake was >/=1 g/kg/day and energy intake was >/=50% of estimated energy expenditure (P < 0.0001). Creatinine excretion rate was positively correlated with the urea appearance rate (r = 0.60; P < 0.0001), and negatively with protein balance (r = -0.45; P < 0.0001). Sepsis developed in four patients; before its clinical detection, there were negative balances for all intracellular markers and an abrupt rise in the excretion of creatinine. CONCLUSION: Negative balances of intracellular components and an increase in rate of creatinine excretion heralded the onset of catabolism.

Uncovering the basis of a severe degree of acidemia in a patient with diabetic ketoacidosis.

In this teaching exercise, the goal is to demonstrate how an application of principles of physiology can reveal the basis for a severe degree of acidaemia (pH 6.81, bicarbonate <3 mmol/l (P(HCO(3))), PCO(2) 8 mmHg), why it was tolerated for a long period of time, and the issues for its therapy in an 8-year-old female with diabetic ketoacidosis. The relatively low value for the anion gap in plasma (19 mEq/l) suggested that its cause was both a direct and an indirect loss of NaHCO(3). Professor McCance suggested that ileus due to hypokalaemia might cause this direct loss of NaHCO(3), and that an excessive excretion of ketoacid anions without NH(4)(+) in the urine accounted for the indirect loss of NaHCO(3). In addition, he suspected that another factor also contributing to the severity of the acidaemia was a low input of alkali. He was also able to explain why there was a 16-h delay before there was a rise in the P(HCO(3)) once therapy began. The missing links in this interesting story, including a possible basis for the hypokalaemia, emerge during the discussion between the medical team and Professor McCance.

A hyperglycaemic hyperosmolar state in a young child: diagnostic insights from a quantitative analysis.

This teaching exercise demonstrates how the application of principles of physiology can identify the cause of a severe degree of hyperglycaemia (plasma glucose concentration 80 mmol/l) in a very young patient with newly diagnosed diabetes mellitus, determine whether the patient has diabetic ketoacidosis, and highlight the potential risks for this patient on admission and during initial therapy. A consultation with Professor McCance was sought to determine whether this patient had an unusual degree of 'insulin resistance'. There were also uncertainties regarding the acid-base diagnosis. The patient did not appear to have an important degree of metabolic acidosis as judged from his pH of 7.39 and plasma bicarbonate concentration of 20 mmol/l in arterial blood; hence the diagnostic impression was that he had a hyperglycaemic hyperosmolar state. However, his plasma anion gap was significantly elevated, and remained so for 60 h, despite the administration of insulin. Issues in management concerning the basis for this severe degree of hyperglycaemia and how to minimize the risk of developing cerebral oedema are addressed. The missing links in this interesting story emerge during a discussion between the medical team and their mentor, Professor McCance.

Hypothermia pediatric head injury trial: the value of a pretrial clinical evaluation phase.

BACKGROUND: The utility of a pretrial clinical evaluation or run-in phase prior to conducting trials of complex interventions such as hypothermia therapy following severe traumatic brain injury in children and adolescents has not been established. METHODS: The primary objective of this study was to prospectively evaluate the ability of investigators to adhere to the clinical protocols of care including the cooling and rewarming procedures as well as management guidelines in patients with severe traumatic brain injury (Glasgow Coma Scale

Hypotonic versus isotonic saline in hospitalised children: a systematic review.

BACKGROUND: The traditional recommendations which suggest that hypotonic intravenous (i.v.) maintenance fluids are the solutions of choice in paediatric patients have not been rigorously tested in clinical trials, and may not be appropriate for all children. AIMS: To systematically review the evidence from studies evaluating the safety of administering hypotonic versus isotonic i.v. maintenance fluids in hospitalised children. DATA SOURCES: Medline (1966-2006), Embase (1980-2006), the Cochrane Library, abstract proceedings, personal files, and reference lists. Studies that compared hypotonic to isotonic maintenance solutions in children were selected. Case reports and studies in neonates or patients with a pre-existing history of hyponatraemia were excluded. RESULTS: Six studies met the selection criteria. A meta-analysis combining these studies showed that hypotonic solutions significantly increased the risk of developing acute hyponatraemia (OR 17.22; 95% CI 8.67 to 34.2), and resulted in greater patient morbidity. CONCLUSIONS: The current practice of prescribing i.v. maintenance fluids in children is based on limited clinical experimental evidence from poorly and differently designed studies, where bias could possibly raise doubt about the results. They do not provide evidence for optimal fluid and electrolyte homoeostasis in hospitalised children. This systematic review indicates potential harm with hypotonic solutions in children, which can be anticipated and avoided with isotonic solutions. No single fluid rate or composition is ideal for all children. However, isotonic or near-isotonic solutions may be more physiological, and therefore a safer choice in the acute phase of illness and perioperative period.

Acute and fatal hyponatraemia after resection of a craniopharyngioma: a preventable tragedy.

Central diabetes insipidus developed for the first time in a 14-year-old female during the resection of a craniopharyngioma. The water diuresis persisted until a vasopressin analogue (dDAVP) was given. Professor McCance was asked to explain why hypernatraemia developed, to anticipate dangers that might develop in the salt and water area with therapy, and to provide insights into why this patient died, due to the subsequent development of hyponatraemia that caused a lethal rise in intracranial pressure. The team specifically wanted Professor McCance's opinions as to why a PNa of 124 mmol/l was uniquely dangerous for this patient, and this was a particularly challenging conundrum. Nevertheless, with the aid of a mini-experiment, a careful chart review, and creative thinking, he was able to offer a novel solution, and to suggest ways to prevent its occurrence in other patients.

Resource use and health outcomes of paediatric extracorporeal membrane oxygenation.

The use of extracorporeal membrane oxygenation can be rationalised by the assumption that non-zero survival after refractory cardiorespiratory failure represents improved outcome. Survivors may have cognitive and or functional morbidities, require complex ongoing care, and as a consequence consume considerable healthcare resources.

Anterior versus posterior treatment of stable thoracolumbar burst fractures without neurologic deficit: a prospective, randomized study.

OBJECTIVE: A prospective randomized study was conducted to determine whether there exist any differences in radiographic, clinical, or functional outcomes when individuals with stable burst fractures of the thoracolumbar junction without neurologic deficit are treated with either a posterior fusion with instrumentation or anterior reconstruction, fusion, and instrumentation. There exists relatively little literature evaluating the outcomes of individuals treated with anterior surgery, and no prospective randomized studies exist comparing the two treatment approaches. METHODS: From May 1995 to March 2001, a consecutive series of subjects with acute isolated burst fractures of the thoracolumbar junction (T10-L2) without neurologic deficit were randomized to receive either an anterior fusion with instrumentation or a posterior fusion with instrumentation. Radiographs including computed tomography (CT) were obtained. Radiographs were repeated at 2, 4, 6, 12, and 24 months. The CT scan was also repeated at 24 months. Hospital stay, cost, operating time, blood loss, complications, and patient-related functional outcomes were measured. RESULTS: Of 43 enrolled, 38 completed a minimum of 2-year follow-up (average: 43 months; range: 24-108 months). Eighteen received a posterior spine fusion and 20 an anterior approach. Hospital stay and operating time were similar. Blood loss was higher in the group treated anteriorly; however, the incidence of transfusion was the same. There were 17 "complications" including instrumentation removal for pain in 18 patients treated posteriorly, but only 3 minor complications in 3 patients treated anteriorly. Patient-related functional outcomes were similar for the two groups. CONCLUSIONS: Although patient outcomes are similar, anterior fusion and instrumentation for thoracolumbar burst fractures may present fewer complications or additional surgeries.

ESPE/LWPES consensus statement on diabetic ketoacidosis in children and adolescents.

Diabetic ketoacidosis (DKA) is the leading cause of morbidity and mortality in children with type 1 diabetes mellitus (TIDM). Mortality is predominantly related to the occurrence of cerebral oedema; only a minority of deaths in DKA are attributed to other causes. Cerebral oedema occurs in about 0.3-1% of all episodes of DKA, and its aetiology, pathophysiology, and ideal method of treatment are poorly understood. There is debate as to whether physicians treating DKA can prevent or predict the occurrence of cerebral oedema, and the appropriate site(s) for children with DKA to be managed. There is agreement that prevention of DKA and reduction of its incidence should be a goal in managing children with diabetes.

How to select optimal maintenance intravenous fluid therapy.

Hyponatraemia is the commonest electrolyte abnormality in hospitalized patients. If the plasma sodium concentration (P(Na)) declines to approximately 120 mM in <48 h, brain cell swelling might result in herniation, with devastating consequences. The volume and/or the composition of fluids used for intravenous therapy often contribute to the development of acute hyponatraemia. Our hypothesis is that the traditional calculation of the daily loss of insensible water overestimates this parameter, leading to an excessive daily recommended requirement for water. We offer suggestions to minimize the risk of iatrogenic hyponatraemia.

Inhaled nitric oxide for acute hypoxemic respiratory failure in children and adults.

BACKGROUND: Acute hypoxemic respiratory failure affects all age groups and may result from a number of systemic diseases. It continues to be associated with high mortality and morbidity. Initial studies examining the effect of inhaled nitric oxide in respiratory failure demonstrated transient improvement in oxygenation but did not examine mortality or other significant morbidity outcomes. OBJECTIVES: To systematically examine randomized controlled trials addressing the effect of inhaled nitric oxide, compared with placebo inhaled gas, on mortality and morbidity in patients with acute hypoxemic respiratory failure. SEARCH STRATEGY: Randomized controlled trials were identified from electronic databases: The Cochrane Central Register of Controlled Trials (CENTRAL) (Issue 2, 2002;MEDLINE (January 1966-August 2002); EMBASE (1980-March 2001); CINAHL (1982-July 2002), as well as from bibliographies of retrieved articles. Relevant journals and conference proceedings were hand searched and authors published in this field were contacted for knowledge of unpublished ongoing trials. SELECTION CRITERIA: Randomized controlled trials comparing inhaled nitric oxide with maximal conventional therapy and inhaled placebo, in either children or adults with acute hypoxemic respiratory failure. DATA COLLECTION AND ANALYSIS: Qualitative assessment of each trial was made and analyses performed according to statistical methods in Review Manager MetaView 4.1. A sub-group analysis was performed to assess the impact of inhaled nitric oxide at varied doses. MAIN RESULTS: Five randomized controlled trials were evaluated, assessing 535 patients with acute hypoxemic respiratory failure (Age range not provided). Lack of data prevented assessment of all outcomes. There was no significant difference of nitric oxide on mortality in trials without cross-over (RR 0.98, 95%CI 0.66,1.44). Published evidence from one study demonstrated nitric oxide to transiently improve oxygenation in the first 72 hours of treatment. Limited data demonstrated no significant difference in ventilator-free days between treatment and placebo groups, and no specific dose of nitric oxide was significantly advantageous over another. Other clinical indicators of effectiveness, such as duration of hospital and intensive care stay, were inconsistently reported. There were no significant complications directly attributable to this treatment. REVIEWER'S CONCLUSIONS: Nitric oxide did not demonstrate any statistically significant effect on mortality and transiently improved oxygenation in patients with hypoxemic respiratory failure. Lack of data prevented assessment of other clinically relevant end points. If further trials comparing inhaled nitric oxide with an inhaled placebo are to proceed, they should be stratified for primary disease, assess the impact of other combined treatment modalities for respiratory failure, and must specifically evaluate clinically relevant outcomes, before any benefit of inhaled nitric oxide for respiratory failure can be excluded.

Importance of timing of risk factors for cerebral oedema during therapy for diabetic ketoacidosis.

Cerebral oedema is the most common cause of mortality and morbidity during the first day of conventional treatment for diabetic ketoacidosis in paediatric patients. It is possible that therapy contributes to its development. Risk factors that predispose to cerebral oedema should lead to an expansion of the intracellular and/or the extracellular fluid compartment(s) of the brain because water normally accounts for close to 80% of brain weight. With respect to the intracellular fluid compartment, the driving force to cause cell swelling is a gain of effective osmoles in brain cells and/or a significant decline in the effective osmolality of the extracellular fluid compartment. Factors leading to an expansion of the intracerebral extracellular fluid volume can be predicted from Starling forces acting at the blood-brain barrier. Some of these risk factors have an early impact, while others have their major effects later during therapy for diabetic ketoacidosis. Based on a theoretical analysis, suggestions to modify current therapy for diabetic ketoacidosis in children are provided.

The American College of Nurse-Midwives Domestic Violence Education Project (DVEP).

OBJECTIVE: The American College of Nurse-Midwives implemented a 4-year Domestic Violence Education Project (DVEP) with the goal of educating all midwives in the USA to respond appropriately to abuse experienced by the women they serve. METHOD: A four-pronged set of objectives was used that included policy, basic preservice education, continuing education and activism/advocacy. RESULT: The success of this project is the sustainable impact on education of student midwives and a continued commitment to this issue. CONCLUSION: The full impact of the DVEP on practicing midwives may not be measurable for some time.

A method to estimate urinary electrolyte excretion in patients at risk for developing cerebral salt wasting.

OBJECT: Two major criteria are necessary to diagnose cerebral salt wasting (CSW): a cerebral lesion and a large urinary excretion of Na+ and Cl- at a time when the extracellular fluid (ECF) volume is contracted. Nevertheless, it is difficult for the physician to confirm from bedside observation that a patient has a contracted ECF volume. Hyponatremia, although frequently present, should not be a criterion for a diagnosis of salt wasting. A contracted ECF volume is unlikely if there are positive balances of Na+ and Cl-. The goal of this study was to assess the accuracy of calculating balances for Na+ plus K+ and of Cl- over 1 to 10 days in an intensive care unit (ICU) setting. METHODS: A prospective comparison of measured and estimated quantities of Na+ plus K+ and of Cl- excreted over 1 to 10 days in 10 children and 12 adults who had recently received a traumatic brain injury or undergone recent neurosurgery. Plasma concentrations of electrolytes were recorded at the beginning and end of the study period. The total volumes infused and excreted and the concentrations of Na+, K+, and Cl- in the infusate were obtained from each patient's ICU chart. The electrolytes in the patients' urine were measured and calculated. Correlations between measured and calculated values for excretions of Cl- and of Na+ plus K+ were excellent. CONCLUSIONS: Mass balances for Na+ plus K+ and for Cl- can be accurately estimated. These data provide information to support or refute a clinical diagnosis of CSW. The danger of relying on balances for these electrolytes measured within a single day to diagnose CSW is illustrated.

Mechanical circulatory support for the treatment of children with acute fulminant myocarditis.

BACKGROUND: Viral myocarditis may follow a rapidly progressive and fatal course in children. Mechanical circulatory support may be a life-saving measure by allowing an interval for return of native ventricular function in the majority of these patients or by providing a bridge to transplantation in the remainder. METHODS: A retrospective chart review of 15 children with viral myocarditis supported with extracorporeal membrane oxygenation (12 patients) or ventricular assist devices (3 patients) was performed. RESULTS: All patients had histories and clinical findings consistent with acute myocarditis. The median age was 4.6 years (range 1 day-13.6 years) with a median duration of mechanical circulatory support of 140 hours (range 48-400 hours). Myocardial biopsy tissue demonstrated inflammatory infiltrates or necrosis, or both, in 8 (67%) of the 12 patients who had biopsies. Overall survival was 12 (80%) of 15 patients, with 10 (83%) survivors of extracorporeal membrane oxygenation and 2 (67%) survivors of ventricular assist device support. Nine (60%) of the 15 patients were weaned from support, with 7 (78%) survivors; the remaining 6 patients were successfully bridged to transplantation, with 5 (83%) survivors. All survivors not undergoing transplantation are currently alive with normal ventricular function after a median follow-up of 1.1 years (range 0.9-5.3 years). CONCLUSION: Eighty-percent of the children who required mechanical circulatory support for acute myocarditis survived in this series. Recovery of native ventricular function to allow weaning from support can be anticipated in many of these patients with excellent prospects for eventual recovery of full myocardial function.

Extracorporeal life support in heart and lung transplantation.

Extracorporeal life support is a technology that is being increasingly used to support children with cardiac and respiratory failure who fail conventional measures. Both extracorporeal membrane oxygenation and ventricular assist devices have been used in cardiac failure with the opportunity to support patients who fail repair of congenital heart disease and in primary myocardial disease. Outcomes in the latter are superior to the surgical patients which has lead to increasing use of extracorporeal life support as a bridge to transplantation. Experience with membrane oxygenation as a support mode after lung transplantation is limited to adult series with similar outcomes.