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OBJECTIVES: To examine cerebrovascular pressure reactivity index (PRx) in a large cohort of children with severe traumatic brain injury (sTBI) in association with physiologic variables and outcome. DESIGN: Retrospective observational cohort study. SETTING: Red Cross War Memorial Children's Hospital in Cape Town, South Africa. PATIENTS: Pediatric (≤ 14 yr old) sTBI patients with intracranial pressure (ICP) monitoring (postresuscitation Glasgow Coma Score [Glasgow Coma Scale (GCS)] of ≤ 8). MEASUREMENTS AND MAIN RESULTS: Data were analyzed from ICM+ files sampled at 100Hz. PRx (a mathematical indicator of pressure reactivity) was calculated as a moving correlation coefficient between ICP and mean arterial pressure (MAP) as previously described. Associations between PRx, age, GCS, ICP, MAP, and cerebral perfusion pressure (CPP) were examined with summary measures and correlation analysis using high-frequency data. Associations between PRx and mortality/outcome were examined with multivariable logistic regression analysis and the prognostic ability of PRx with receiver operating characteristic (ROCs) curves. The dataset included over 1.7 million minutes (28,634 hr) of MAP and ICP data in 196 children. The series mortality was 10.7% (21/196), and unfavorable outcome 29.6% (58/196). PRx had a moderate positive correlation with ICP (r = 0.44; p < 0.001), a moderate negative correlation with CPP (r = -0.43; p < 0.001), and a weak negative correlation with MAP (r = -0.21; p = 0.004). PRx was consistently higher in patients with poor outcome and had a strong, independent association with mortality (ROC area under the curve = 0.91). A PRx threshold of 0.25 showed the best predictive ability for mortality. CONCLUSIONS: This is the largest cohort of children with PRx analysis of cerebrovascular reactivity to date. PRx had a strong association with outcome that was independent of ICP, CPP, GCS, and age. The data suggest that impaired autoregulation is an independent factor associated with poor outcome and may be useful in directing clinical care.

Background Candida bloodstream infection (BSI) causes appreciable mortality in neonates and children. There are few studies describing the epidemiology of Candida BSI in children living in sub-Saharan Africa. Methods A retrospective descriptive study was conducted at three public sector hospitals in Cape Town, South Africa. Demographic and clinical details, antifungal management and patient outcome data were obtained by medical record review. Candidaspecies distribution and antifungal susceptibility testing results were obtained from the National Health Laboratory Service database. Results Of the 97 CandidaBSI episodes identified during the study period, 48/97 (49%) were Candida albicans (C. albicans), and 49/97 (51%) were non-C. albicans species. The overall incidence risk was 0.8 Candida BSI episodes per 1000 admissions at Red Cross War Memorial Children’s Hospital. Of the 77/97 (79%) Candida BSI episodes with available clinical information, the median age (interquartile range) at the time of BSI was 7 (1-25) months, 36/77 (47%) were associated with moderate or severe underweight-for-age and vasopressor therapy was administered to 22/77 (29%) study participants. Most of the Candida BSI episodes were healthcare-associated infections, 63/77 (82%). Fluconazole resistance was documented among 17%, 0% and 0% of C. parapsilosis, C. tropicalis and C. albicans isolates respectively. All Candida isolates tested were susceptible to amphotericin B and the echinocandins. The mortality rate within 30 days of Candida BSI diagnosis was 13/75 (17%). On multivariable analysis, factors associated with mortality within 30 days of Candida BSI diagnosis included vasopressor therapy requirement during Candida BSI, adjusted Odds ratio (aOR) 53 (95% confidence interval 2-1029); hepatic dysfunction, aOR 13 (95% CI 1-146); and concomitant bacterial BSI, aOR 10 (95% CI 2-60). Conclusion The study adds to the limited number of studies describing paediatric Candida BSI in sub-Saharan Africa. Non-C. Albicans BSI episodes occurred more frequently than C. albicans episodes, and vasopressor therapy requirement, hepatic dysfunction and concomitant bacterial BSI were associated with an increase in 30-day mortality.

A better understanding of the complex pathophysiology of traumatic brain injury (TBI) is needed to improve our current therapies. Cerebral microdialysis (CMD) is an advanced method to monitor the brain, but little is known about its parameters in children. Brain glycerol, one of the CMD variables, is an essential component of the phospholipid bilayer cell membrane and is considered a useful marker of tissue hypoxia in adults. This study examined the time course of glycerol and its associations in paediatric TBI. In this retrospective cohort study, we collected data on children ( 30% (p=0.01, p=0.04 and p=0.004). Absolute glycerol values had a weak but statistically significant association with intracranial pressure and brain oxygenation. We did not find an association with clinical outcome. This is the first study to provide data on brain interstitial glycerol in children. CMD glycerol, particularly an increase from baseline, is associated with other markers of injury and with a significant increase in lesion size on repeat head CT. As such, it may represent a useful monitorable marker for evolving injury in paediatric TBI.

OBJECTIVES To evaluate the performance of the Pediatric Index of Mortality 3 as mortality risk assessment model. DESIGN This prospective study included all admissions 30 days to 18 years old for 12 months during 2016 and 2017. Data gathered included the following: age and gender, diagnosis and reason for PICU admission, data specific for the Pediatric Index of Mortality 3 calculation, PICU outcomes (death or survival), and length of PICU stay. SETTING Nine units that care for children within tertiary or quaternary academic hospitals in South Africa. PATIENTS All admissions 30 days to 18 years old, excluding premature infants, children who died within 2 hours of admission, or children transferred to other PICUs, and those older than 18 years old. INTERVENTIONS None. MEASUREMENTS AND MAIN RESULTS There were 3,681 admissions of which 2,253 (61.3%) were male. The median age was 18 months (interquartile range, 6-59.5 mo). There were 354 deaths (9.6%). The Pediatric Index of Mortality 3 predicted 277.47 deaths (7.5%). The overall standardized mortality ratio was 1.28. The area under the receiver operating characteristic curve was 0.81 (95% CI 0.79-0.83). The Hosmer-Lemeshow goodness-of-fit test statistic was 174.4 (p < 0.001). Standardized mortality ratio for all age groups was greater than 1. Standardized mortality ratio for diagnostic subgroups was mostly greater than 1 except for those whose reason for PICU admission was classified as accident, toxin and envenomation, and metabolic which had an standardized mortality ratio less than 1. There were similar proportions of respiratory patients, but significantly greater proportions of neurologic and cardiac (including postoperative) patients in the Pediatric Index of Mortality 3 derivation cohort than the South African cohort. In contrast, the South African cohort contained a significantly greater proportion of miscellaneous (including injury/accident victims) and postoperative noncardiac patients. CONCLUSIONS The Pediatric Index of Mortality 3 discrimination between death and survival among South African units was good. Case-mix differences between these units and the Pediatric Index of Mortality 3 derivation cohort may partly explain the poor calibration. We need to recalibrate Pediatric Index of Mortality 3 to the local setting.

The international scope of critical neurologic insults in children is unknown. Our objective was to assess the prevalence and outcomes of children admitted to PICUs with acute neurologic insults. Prospective study. Multicenter (n = 107 PICUs) and multinational (23 countries, 79% in North America and Europe). Children 7 days to 17 years old admitted to the ICU with new traumatic brain injury, stroke, cardiac arrest, CNS infection or inflammation, status epilepticus, spinal cord injury, hydrocephalus, or brain mass. None. We evaluated the prevalence and outcomes of children with predetermined acute neurologic insults. Child and center characteristics were recorded. Unfavorable outcome was defined as change in pre-post insult Pediatric Cerebral Performance Category score greater than or equal to 2 or death at hospital discharge or 3 months, whichever came first. Screening data yielded overall prevalence of 16.2%. Of 924 children with acute neurologic insults, cardiac arrest (23%) and traumatic brain injury (19%) were the most common. All-cause mortality at hospital discharge was 12%. Cardiac arrest subjects had highest mortality (24%), and traumatic brain injury subjects had the most unfavorable outcomes (49%). The most common neurologic insult was infection/inflammation in South America, Asia, and the single African site but cardiac arrest in the remaining regions. Neurologic insults are a significant pediatric international health issue. They are frequent and contribute substantial morbidity and mortality. These data suggest a need for an increased focus on acute critical neurologic diseases in infants and children including additional research, enhanced availability of clinical resources, and the development of new therapies.

Background. Cardiac arrest is a potentially devastating event, associated with death or severe neurological complications in survivors. There is little evidence on paediatric cardiac arrest prevalence, characteristics and outcomes in South Africa (SA).Objective. To describe the characteristics, course and outcomes of children admitted to an SA paediatric intensive care unit (PICU) following cardiac arrest.Methods. Retrospective descriptive study of routinely collected data (January 2010 - December 2011).Results. Of 2 501 PICU admissions, 110 (4.4%) had preceding cardiac arrest. The median (interquartile range (IQR)) age of children was 7.2 (2.5 - 21.6) months. In-hospital arrests accounted for 80.6% of the events. The most common primary diagnostic categories were respiratory (29.1%), cardiovascular (21.4%) and gastrointestinal (21.4%). Twenty-four patients (23.3%) arrested during endotracheal intubation. Cardiopulmonary resuscitation (CPR) was applied for a median (IQR) of 10 (5 - 20) minutes. Duration of CPR for non-survivors and survivors was 17.5 (10 - 30) v. 10 (5 - 15) minutes (p=0.006). PICU mortality was 38.8%, with half of the deaths occurring within 24 hours of admission. The standardised mortality ratio was 0.7. The median (IQR) length of stay in the PICU and hospital was 3 (1 - 8) and 27 (9 -52) days, respectively. No independent predictors of mortality were identified. Thirty-nine surviving patients (76.5%) had normal neurological function or mild disability at follow-up after hospital discharge. Six (11.8%) survived with severe disability.Conclusion. Mortality was lower than predicted in children admitted to the PICU following cardiac arrest. The majority of survivors had good neurological outcomes.Keywords. Pediatric, cardiac arrest, cardiopulmonary resuscitation, pulseless electrical activity, ventricular tachycardia, pediatric intensive care unit, in-hospital cardiac arrest, out-of-hospital cardiac arrest

Objective Fluid resuscitation is integral to resuscitation guidelines and critical care. However, fluid overload (FO) yields increased morbidity. Methods Prospective observational study of Red Cross War Memorial Children's Hospital pediatric intensive care unit admissions (February to March 2013). FO % = (fluid in minus fluid out) [liters]/weight [kg] × 100%. Primary outcomes FO ≥ 10%, 28 day mortality. Results Median [interquartile range (IQR)] age: 9.5 (2.0-39.0) months, median (IQR) admission weight: 7.9 (3.6-13.7) kg. Median (IQR) FO with admission weight: 3.5 (2.1-4.9)%; three patients had FO ≥ 10%. The 28 day mortality was 10% (n = 10). Patients who died had higher mean (IQR) FO using admission weight [4.9 (2.9-9.3)% vs. 3.4 (1.9-4.8)%; p = 0.04]. Conclusions Low FO ≥ 10% prevalence with 28 day mortality 10%. Higher FO% with admission weight associated with mortality (p = 0.04). We advocate further investigation of FO% as a simple bedside tool.

To explore the relationship between lactate:pyruvate ratio, hyperlactataemia, metabolic acidosis, and morbidity. Prospective observational study in the paediatric intensive care unit (PICU) of a university hospital. Ninety-seven children after open cardiac surgery. Most children (94%) fell into low-moderate operative risk categories; observed PICU mortality was 1%. Blood was sampled on admission for acid-base analysis, lactate, and pyruvate. Metabolic acidosis was defined as standard bicarbonate lower than 22 mmol/l, raised lactate as higher than 2 mmol/l, and raised lactate:pyruvate ratio as higher than 20. Median cardiopulmonary bypass and aortic cross-clamp times were 80 and 46 min. Metabolic acidosis occurred in 74%, hyperlactataemia in 42%, and raised lactate:pyruvate ratio in 45% of children. In multivariate analysis lactate:pyruvate ratio increased by 6.4 in children receiving epinephrine infusion and by 0.4 per 10 min of aortic cross-clamp. Duration of inotropic support increased by 0.29 days, ventilatory support by 0.27 days, and PICU stay by 0.42 days, for each 1 mmol/l increase in lactate. Neither standard bicarbonate nor lactate:pyruvate ratio were independently associated with prolongation of PICU support. Elevated lactate:pyruvate ratio was common in children with mild metabolic acidosis and low PICU mortality. Hyperlactataemia, but not elevated lactate:pyruvate ratio or metabolic acidosis, was associated with prolongation of PICU support. Routine measurement of lactate:pyruvate ratio is not warranted for children in low-moderate operative risk categories.

To develop explicit criteria for patient admission in order to optimize utilization of PICU facilities in the face of increasing demand outstripping resources.Multidisciplinary PICU in a university-affiliated referral hospital in Cape Town, South Africa.Retrospective description of policy development and implementationAll patients referred to the Paediatric Intensive Care Unit of the Red Cross War Memorial Children's Hospital.Development and application of admission policy.In consultation with clinicians at the hospital, principles for utilization of PICU resources were established and then translated into specific policies for prioritization of admission of particular groups of patients. The hospital team developed and implemented: criteria for intensive care admission; prioritization for certain categories of patients (including those scheduled for elective surgery); processes for refusing intensive care admission to other categories of patients; and processes to review implementation. These criteria and procedures were made explicit to clinicians, administrators, and managers and eventually agreed to by them. It was challenging to obtain "buy-in" from all potential stakeholders in the process and also to implement such policies under conditions of high stress.Development and implementation of explicit policies for utilization of PICU resources provide a "reasonable" process for fair and equitable utilization of scarce resources. The factors that have to be considered while developing these policies may extend beyond the priorities of individual patients. Implementation is still fraught with problems. Development of explicit admission policies that consider the needs of individual patients and also the longer term development of healthcare services may enable the retention of small but essential services.

Aims: To describe acid–base derangements in children following open cardiac surgery on cardiopulmonary bypass (CPB), using the Fencl–Stewart strong ion approach. Methods: Prospective observational study set in the paediatric intensive care unit (PICU) of a university children's hospital. Arterial blood gas parameters, serum electrolytes, strong ion difference, strong ion gap (SIG), and partitioned base excess (BE) were measured and calculated on admission to PICU. Results: A total of 97 children, median age 57 months (range 0.03–166), median weight 14 kg (range 2.1–50), were studied. Median CPB time was 80 minutes (range 17–232). Predicted mortality was 2% and there was a single non-survivor. These children showed mild metabolic acidosis (median standard bicarbonate 20.1 mmol/l, BE –5.1 mEq/l) characterised by hyperchloraemia (median corrected Cl 113 mmol/l), and hypoalbuminaemia (median albumin 30 g/l), but no significant excess unmeasured anions or cations (median SIG 0.7 mEq/l). The major determinants of the net BE were the chloride and albumin components (chloride effect –4.8 mEq/l, albumin effect +3.4 mEq/l). Metabolic acidosis occurred in 72 children (74%) but was not associated with increased morbidity. Hyperchloraemia was a causative factor in 53 children (74%) with metabolic acidosis. Three (4%) hyperchloraemic children required adrenaline for inotropic support, compared to eight children (28%) without hyperchloraemia. Hypoalbuminaemia was associated with longer duration of inotropic support and PICU stay. Conclusions: In these children with low mortality following open cardiac surgery, hypoalbuminaemia and hyperchloraemia were the predominant acid–base abnormalities. Hyperchloraemia was associated with reduced requirement for adrenaline therapy. It is suggested that hyperchloraemic metabolic acidosis is a benign phenomenon that should not prompt escalation of haemodynamic support. By contrast, hypoalbuminaemia, an alkalinising force, was associated with prolonged requirement for intensive care.

In Reply .— We welcome the comments of Hatherill et al, because they agree with our main contention,1 ie, that the current practice of administering hypotonic maintenance parenteral fluid therapy to children can lead to dangerous hyponatremia and is in need of change. Where we differ, however, is in how we propose to change it. Hatherill et al suggest reducing the volume of maintenance fluid rather than using isotonic saline.2 Although it is true that fluid restriction will prevent hyponatremia, we are concerned that this practice could cause harm by perpetuating a state of subclinical volume depletion. Volume depletion is common in children who are unable to take enteral fluids, and it can be difficult to assess on clinical grounds.3 Using 0.9% NaCl is the most physiologic …