The Hospital for Sick Children; Toronto, ON, Canada The author has not disclosed any potential conflicts of interest. For information regarding this article, E-mail: [email protected]

The occurrence of acute hyponatremia associated with cerebral edema in hospitalized children has been increasingly recognized, with over 50 cases of neurological morbidity and mortality reported in the past decade. This condition most commonly occurs in previously healthy children where maintenance intravenous (IV) fluids have been prescribed in the form of hypotonic saline (e.g., 0.2 or 0.3 NaCl). In response to similar problems at The Hospital for Sick Children (six identified through hospital morbidity and mortality reviews and safety reports prior to fall 2007), an interdisciplinary clinician group from our institution developed a clinical practice guideline (CPG) to guide fluid and electrolyte administration for pediatric patients. This article reviews the evaluation of one patient safety improvement to change the prescribing practice for IV fluids in an acute care pediatric hospital, including the removal of the ability to prescribe hypotonic IV solutions with a sodium concentration of < 75 mmol/L. The evaluation of key components of the CPG included measuring practice and process changes pre- and post-implementation. The evaluation showed that the use of restricted IV fluids was significantly reduced across the organization. Success factors of this safety initiative included the CPG development, forcing functions, reminders, team engagement and support from the hospital leadership. A key learning was that a project leader with considerable dedicated time is required during the implementation to develop change concepts, organize and liaise with stakeholders and measure changes in practice. This project highlights the importance of active implementation for policy and guideline documents.

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.

The management of congenital diaphragmatic hernia (CDH) in the newborn infant has changed radically since the first successful outcomes were reported 60 years ago. Then it seemed a surgical problem with a surgical solution – do an operation, remove the intestines and solid viscera from the thoracic cavity, repair the defect and allow the lung to expand. CDH in that era was regarded as the quintessential neonatal surgical emergency. The expectation was that urgent surgery would result in improvement in lung function and oxygenation. That approach persisted up to the 1980s when it was realized that the problem was far more complex and involved both an abnormal pulmonary vascular bed as well as pulmonary hypoplasia. The use of systemically delivered pulmonary vasodilator therapy, principally tolazoline, became a focus of interest in the 1980s with small case reports and case series suggesting improved survival. In the 1990s, based on studies that showed worsening thoracic compliance and gas exchange following surgical repair, deferred surgery and pre-operative stabilization became the standard of care. At the same time extracorporeal membrane oxygenation (ECMO) was increasingly used either as part of pre-operative stabilization or as a rescue therapy after repair. Other centres chose to use high frequency oscillatory ventilation (HFOV). Despite all these innovations the survival in live born infants with CDH did not improve to more than 50% in large series published from high volume centres. However, in the past 10 years there has been an appreciable improvement in survival to the extent that many centres are now reporting survival rates of greater than 80%. Probably the biggest impact on this improvement has been the recognition of the role that ventilation induced lung injury plays in mortality and the need for ECMO rescue. This has ushered in an era of a lung protective or “gentle ventilation” strategy which has been widely adopted as a standard approach. While there have been these radical changes in postnatal management attempts have been made to improve outcome with prenatal interventions, starting with prenatal repair, which was abandoned because of preterm labour. More recently there has been increasing experience in the use of balloon occlusion of the trachea as a prenatal intervention strategy with patients being selected based on prenatal predictors of poor outcome. This approach can only be justified if those predictors can be validated and the outcomes (death or serious long term morbidity) can be shown to be better than those currently achievable, namely 80% survival in high volume CDH centres rather than the 50–60% survival frequently quoted in historical papers.

Vasopressin has been suggested as a useful vaso-active agent in the support of vasodilatory shock in adults; however, its effect in children is unclear. We hypothesized that low-dose vasopressin in this population, administered as an adjunctive vasoactive agent, would lead to more rapid reversal of vasodilatory shock when compared with placebo.

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 Clnicas, Faculty of Medicine of Ribeiro Preto, University of So 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 310 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.Conclusions: Negative balances of intracellular components and an increase in rate of creatinine excretion heralded the onset of catabolism.

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-HCO3), PCO2 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 NaHCO3. Professor McCance suggested that ileus due to hypokalaemia might cause this direct loss of NaHCO3, and that an excessive excretion of ketoacid anions without NH4+ in the urine accounted for the indirect loss of NaHCO3. 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 PHCO3 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.

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.

Continuous renal replacement therapy (CRRT) is thepreferred choice for blood purification and volumecontrol in critically ill children [1,2]. The reportedoverall survival rate for children requiring CRRTis 60% [3], and mortality in infants is comparable withthat of older children and adolescents [4].It is imperative in paediatric CRRT that equipmentbe adaptable to accommodate large variations in size(2–100kg). Until recently at the Hospital for SickChildren, CRRT was provided using the PRISMA

Background: The traditional recommendations which suggest that hypotonic intravenous (IV) 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 IV maintenance fluids in hospitalised children. Methods: 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 IV 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.

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 ≤8) treated with 24 h of hypothermia therapy. A secondary objective was to evaluate the ability of study research assistants to complete the study case report form using a procedures manual. The study was conducted at 18 sites in Canada, the United Kingdom and France prior to proceeding to a randomized controlled trial (RCT). After 2 patients were enrolled at each center, an independent clinical evaluation committee examined the process of care and the completeness of data collection. Centers were permitted to enroll patients in the RCT once they met pre-established adherence criteria. Results: Seventeen of the 18 centers completed the pretrial clinical evaluation phase demonstrating compliance with study procedures and proceeded to an RCT of hypothermia therapy. One center enrolled only 1 patient in the pretrial clinical evaluation phase due to small numbers of patients with traumatic brain injury, and therefore, did not proceed to the RCT. Three centers were required to enroll more than 2 patients in the pretrial clinical evaluation phase prior to proceeding to the RCT because of problems with adherence to the clinical protocols at two centers and the training of new study personnel at another center. Of the 39 patients enrolled during the pretrial clinical evaluation phase, 8 (20.5%) died and 22 (62.9%) had a good outcome defined as normal, mild or moderate disability assessed using the Pediatric Cerebral Performance Category score at 6 months following injury. Discussion: The pretrial clinical evaluation phase was useful to ensure compliance with complex hypothermia therapy and consensus-based clinical management guidelines of care successfully implemented across 17 of 18 centers. This study maneuver allowed us to complete a subsequent RCT in 225 children following severe traumatic brain injury.

Background: Congenital tracheal stenosis (CTS) may present as a life-threatening condition often requiring urgent surgical correction. We report our recent experience of 13 consecutive patients with CTS over the past 18 months.Method: Retrospective analysis of all patients with CTS admitted to our institution from January 2003 to June 2004.Results: Five of 13 patients (6 boys and 7 girls) were premature at birth. Mean age at repair was 3.8 months (range, 7 days to 9 months). Ten presented with cardiac arrests or "near-death" spells, 4 with copresenting pulmonary infection. Nine patients were local and 4 were national. Surgical repairs included slide tracheoplasty (n = 5), cartilage patch tracheoplasty (n 4), patch-and-slide tracheoplasty (n = 1), and balloon dilatation (n = 1). Preoperative computed tomographic imaging invariably underestimated the severity of pathology. Two patients with minimal symptoms were treated nonoperatively. Two patients required additional endobronchial stents for bronchomalacia. Cardiopulmonary bypass was used in 8 patients. There were 3 deaths, including 2 planned withdrawal of treatment. Two patients remained in hospital. The retraining patients were discharged from our hospital.Conclusions: Presentation of CTS can be precipitated by respiratory infection. Preoperative imaging often underestimates the caliber and length of pathology. The treatment options for patients with CTS including observation should be individualized. (c) 2005 Elsevier Inc. All rights reserved.

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.

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 usual way to decide why hyponatremia or hypernatremia has developed and to plan goals for its therapy is to analyze events in electrolyte-free water (EFW) terms. We shall demonstrate that an EFW balance does not supply this information. Rather, one must calculate mass balances for water and sodium plus potassium separately (a tonicity balance) to understand the basis for the change in natremia and the proper goals for its therapy. These points are illustrated with a clinical example.

OBJECTIVE: Asthma is the most common medical emergency in children. It is associated with significant morbidity and mortality rates and poses a tremendous societal burden worldwide. Management of the acute attack involves a stepwise approach that includes beta-agonist and steroid therapy, the mainstay of emergency treatment. Most patients will respond to this regime and can be discharged from the emergency department. Failure to respond to treatment necessitates hospital admission and sometimes admission to the intensive care unit (ICU). Management in the ICU involves intensification of pharmacologic therapy, including nonstandard therapies, in an attempt to avoid intubation and ventilation. When needed, mechanical ventilatory support can be rendered fairly safe with little morbidity if the likely cardiorespiratory physiologic derangements are appreciated and if appropriate ventilatory strategies are used. In the past two decades, the availability of newer potent medications and changes in approach to monitoring and ventilatory strategies have resulted in a decrease in ICU morbidity and mortality rates. Research endeavors are presently underway to further characterize the underlying mechanisms of the disease and are likely to lead to novel therapies. This article reviews the approach to management of acute severe asthma.