Ethnicity and Observed Oxygen Saturations, Fraction of Inspired Oxygen, and Clinical Outcomes: A Post Hoc Analysis of the Oxy-PICU Trial of Conservative Oxygenation.

OBJECTIVES: A conservative oxygenation strategy, targeting peripheral oxygen saturations (Spo2) between 88% and 92% in mechanically ventilated children in PICU, was associated with a shorter duration of organ support and greater survival compared with Spo2 greater than 94% in our recent Oxy-PICU trial. Spo2 monitors may overestimate arterial oxygen saturation (Sao2) in patients with higher levels of skin pigmentation compared with those with less skin pigmentation. We investigated if ethnicity was associated with changes in distributions of Spo2 and Fio2 and outcome. DESIGN: Post hoc analysis of a pragmatic, open-label, multicenter randomized controlled trial. SETTING: Fifteen PICUs across the United Kingdom and Scotland. PATIENTS: Children aged 38 weeks corrected gestational age to 15 years accepted to a participating PICU as an unplanned admission and receiving invasive mechanical ventilation with supplemental oxygen for abnormal gas exchange. METHODS: Hierarchical regression models for Spo2 and Fio2, and ordinal models for the primary trial outcome of a composite of the duration of organ support at 30 days and death, were used to examine the effects of ethnicity, accounting for baseline Spo2, Fio2, and mean airway pressure and trial allocation. MEASUREMENTS AND MAIN RESULTS: Ethnicity data were available for 1577 of 1986 eligible children, 1408 (89.3%) of which were White, Asian, or Black. Spo2 and Fio2 distributions did not vary according to Black or Asian ethnicity compared with White children. The trial primary outcome measure also did not vary significantly with ethnicity. The point estimate for the treatment effect of conservative oxygenation in Black children was 0.64 (95% CI, 0.33-1.25) compared with 0.84 (0.68-1.04) in the overall trial population. CONCLUSIONS: These data do not suggest that the association between improved outcomes and conservative oxygenation strategy in mechanically ventilated children in PICU is modified by ethnicity.

Protocol for a Randomized Controlled Trial to Evaluate a Permissive Blood Pressure Target Versus Usual Care in Critically Ill Children with Hypotension (PRESSURE).

OBJECTIVES: Management of hypotension is a fundamental part of pediatric critical care, with cardiovascular support in the form of fluids or vasoactive drugs offered to every hypotensive child. However, optimal blood pressure (BP) targets are unknown. The PRotocolised Evaluation of PermiSSive BP Targets Versus Usual CaRE (PRESSURE) trial aims to evaluate the clinical and cost-effectiveness of a permissive mean arterial pressure (MAP) target of greater than a fifth centile for age compared with usual care. DESIGN: Pragmatic, open, multicenter, parallel-group randomized control trial (RCT) with integrated economic evaluation. SETTING: Eighteen PICUs across the United Kingdom. PATIENTS: Infants and children older than 37 weeks corrected gestational age to 16 years accepted to a participating PICU, on mechanical ventilation and receiving vasoactive drugs for hypotension. INTERVENTIONS: Adjustment of hemodynamic support to achieve a permissive MAP target greater than fifth centile for age during invasive mechanical ventilation. MEASUREMENTS AND MAIN RESULTS: Randomization is 1:1 to a permissive MAP target or usual care, stratified by site and age group. Due to the emergency nature of the treatment, approaching patients for written informed consent will be deferred until after randomization. The primary clinical outcome is a composite of death and days of ventilatory support at 30 days. Baseline demographics and clinical status will be recorded as well as daily measures of BP and organ support, and discharge outcomes. This RCT received Health Research Authority approval (reference 289545), and a favorable ethical opinion from the East of England-Cambridge South Research Ethics Committee on May 10, 2021 (reference number 21/EE/0084). The trial is registered and has an International Standard RCT Number (reference 20609635). CONCLUSIONS: Trial findings will be disseminated in U.K. national and international conferences and in peer-reviewed journals.

International Consensus Criteria for Pediatric Sepsis and Septic Shock.

Importance: Sepsis is a leading cause of death among children worldwide. Current pediatric-specific criteria for sepsis were published in 2005 based on expert opinion. In 2016, the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3) defined sepsis as life-threatening organ dysfunction caused by a dysregulated host response to infection, but it excluded children. Objective: To update and evaluate criteria for sepsis and septic shock in children. Evidence Review: The Society of Critical Care Medicine (SCCM) convened a task force of 35 pediatric experts in critical care, emergency medicine, infectious diseases, general pediatrics, nursing, public health, and neonatology from 6 continents. Using evidence from an international survey, systematic review and meta-analysis, and a new organ dysfunction score developed based on more than 3 million electronic health record encounters from 10 sites on 4 continents, a modified Delphi consensus process was employed to develop criteria. Findings: Based on survey data, most pediatric clinicians used sepsis to refer to infection with life-threatening organ dysfunction, which differed from prior pediatric sepsis criteria that used systemic inflammatory response syndrome (SIRS) criteria, which have poor predictive properties, and included the redundant term, severe sepsis. The SCCM task force recommends that sepsis in children be identified by a Phoenix Sepsis Score of at least 2 points in children with suspected infection, which indicates potentially life-threatening dysfunction of the respiratory, cardiovascular, coagulation, and/or neurological systems. Children with a Phoenix Sepsis Score of at least 2 points had in-hospital mortality of 7.1% in higher-resource settings and 28.5% in lower-resource settings, more than 8 times that of children with suspected infection not meeting these criteria. Mortality was higher in children who had organ dysfunction in at least 1 of 4-respiratory, cardiovascular, coagulation, and/or neurological-organ systems that was not the primary site of infection. Septic shock was defined as children with sepsis who had cardiovascular dysfunction, indicated by at least 1 cardiovascular point in the Phoenix Sepsis Score, which included severe hypotension for age, blood lactate exceeding 5 mmol/L, or need for vasoactive medication. Children with septic shock had an in-hospital mortality rate of 10.8% and 33.5% in higher- and lower-resource settings, respectively. Conclusions and Relevance: The Phoenix sepsis criteria for sepsis and septic shock in children were derived and validated by the international SCCM Pediatric Sepsis Definition Task Force using a large international database and survey, systematic review and meta-analysis, and modified Delphi consensus approach. A Phoenix Sepsis Score of at least 2 identified potentially life-threatening organ dysfunction in children younger than 18 years with infection, and its use has the potential to improve clinical care, epidemiological assessment, and research in pediatric sepsis and septic shock around the world.

Development and Validation of the Phoenix Criteria for Pediatric Sepsis and Septic Shock.

Importance: The Society of Critical Care Medicine Pediatric Sepsis Definition Task Force sought to develop and validate new clinical criteria for pediatric sepsis and septic shock using measures of organ dysfunction through a data-driven approach. Objective: To derive and validate novel criteria for pediatric sepsis and septic shock across differently resourced settings. Design, Setting, and Participants: Multicenter, international, retrospective cohort study in 10 health systems in the US, Colombia, Bangladesh, China, and Kenya, 3 of which were used as external validation sites. Data were collected from emergency and inpatient encounters for children (aged <18 years) from 2010 to 2019: 3 049 699 in the development (including derivation and internal validation) set and 581 317 in the external validation set. Exposure: Stacked regression models to predict mortality in children with suspected infection were derived and validated using the best-performing organ dysfunction subscores from 8 existing scores. The final model was then translated into an integer-based score used to establish binary criteria for sepsis and septic shock. Main Outcomes and Measures: The primary outcome for all analyses was in-hospital mortality. Model- and integer-based score performance measures included the area under the precision recall curve (AUPRC; primary) and area under the receiver operating characteristic curve (AUROC; secondary). For binary criteria, primary performance measures were positive predictive value and sensitivity. Results: Among the 172 984 children with suspected infection in the first 24 hours (development set; 1.2% mortality), a 4-organ-system model performed best. The integer version of that model, the Phoenix Sepsis Score, had AUPRCs of 0.23 to 0.38 (95% CI range, 0.20-0.39) and AUROCs of 0.71 to 0.92 (95% CI range, 0.70-0.92) to predict mortality in the validation sets. Using a Phoenix Sepsis Score of 2 points or higher in children with suspected infection as criteria for sepsis and sepsis plus 1 or more cardiovascular point as criteria for septic shock resulted in a higher positive predictive value and higher or similar sensitivity compared with the 2005 International Pediatric Sepsis Consensus Conference (IPSCC) criteria across differently resourced settings. Conclusions and Relevance: The novel Phoenix sepsis criteria, which were derived and validated using data from higher- and lower-resource settings, had improved performance for the diagnosis of pediatric sepsis and septic shock compared with the existing IPSCC criteria.

A pragmatic, open-label, randomized controlled trial of Plasma-Lyte-148 versus standard intravenous fluids in children receiving kidney transplants (PLUTO).

Acute electrolyte and acid-base imbalance is experienced by many children following kidney transplant. This is partly because doctors give very large volumes of artificial fluids to keep the new kidney working. When severe, fluid imbalance can lead to seizures, cerebral edema and death. In this pragmatic, open-label, randomized controlled trial, we randomly assigned (1:1) pediatric kidney transplant recipients to Plasma-Lyte-148 or standard of care perioperative intravenous fluids (predominantly 0.45% sodium chloride and 0.9% sodium chloride solutions). We then compared clinically significant electrolyte and acid-base abnormalities in the first 72 hours post-transplant. The primary outcome, acute hyponatremia, was experienced by 53% of 68 participants in the Plasma-Lyte-148 group and 58% of 69 participants in the standard fluids group (odds ratio 0·77 (0·34 - 1·75)). Five of 16 secondary outcomes differed with Plasma-Lyte-148: hypernatremia was significantly more frequent (odds ratio 3·5 (1·1 - 10·8)), significantly fewer changes to fluid prescriptions were made (rate ratio 0·52 (0·40-0·67)), and significantly fewer participants experienced hyperchloremia (odds ratio 0·17 (0·07 - 0·40)), acidosis (odds ratio 0·09 (0·04 - 0·22)) and hypomagnesemia (odds ratio 0·21 (0·08 - 0·50)). No other secondary outcomes differed between groups. Serious adverse events were reported in 9% of participants randomized to Plasma-Lyte-148 and 7% of participants randomized to standard fluids. Thus, perioperative Plasma-Lyte-148 did not change the proportion of children who experienced acute hyponatremia compared to standard fluids. However fewer fluid prescription changes were made with Plasma-Lyte-148, while hyperchloremia and acidosis were less common.

Conservative versus liberal oxygenation targets in critically ill children (Oxy-PICU): a UK multicentre, open, parallel-group, randomised clinical trial.

BACKGROUND: The optimal target for systemic oxygenation in critically ill children is unknown. Liberal oxygenation is widely practiced, but has been associated with harm in paediatric patients. We aimed to evaluate whether conservative oxygenation would reduce duration of organ support or incidence of death compared to standard care. METHODS: Oxy-PICU was a pragmatic, multicentre, open-label, randomised controlled trial in 15 UK paediatric intensive care units (PICUs). Children admitted as an emergency, who were older than 38 weeks corrected gestational age and younger than 16 years receiving invasive ventilation and supplemental oxygen were randomly allocated in a 1:1 ratio via a concealed, central, web-based randomisation system to conservative peripheral oxygen saturations ([SpO2] 88-92%) or liberal (SpO2 >94%) targets. The primary outcome was the duration of organ support at 30 days following random allocation, a rank-based endpoint with death either on or before day 30 as the worst outcome (a score equating to 31 days of organ support), with survivors assigned a score between 1 and 30 depending on the number of calendar days of organ support received. The primary effect estimate was the probabilistic index, a value greater than 0·5 indicating more than 50% probability that conservative oxygenation is superior to liberal oxygenation for a randomly selected patient. All participants in whom consent was available were included in the intention-to-treat analysis. The completed study was registered with the ISRCTN registry (ISRCTN92103439). FINDINGS: Between Sept 1, 2020, and May 15, 2022, 2040 children were randomly allocated to conservative or liberal oxygenation groups. Consent was available for 1872 (92%) of 2040 children. The conservative oxygenation group comprised 939 children (528 [57%] of 927 were female and 399 [43%] of 927 were male) and the liberal oxygenation group included 933 children (511 [56%] of 920 were female and 409 [45%] of 920 were male). Duration of organ support or death in the first 30 days was significantly lower in the conservative oxygenation group (probabilistic index 0·53, 95% CI 0·50-0·55; p=0·04 Wilcoxon rank-sum test, adjusted odds ratio 0·84 [95% CI 0·72-0·99]). Prespecified adverse events were reported in 24 (3%) of 939 patients in the conservative oxygenation group and 36 (4%) of 933 patients in the liberal oxygenation group. INTERPRETATION: Among invasively ventilated children who were admitted as an emergency to a PICU receiving supplemental oxygen, a conservative oxygenation target resulted in a small, but significant, greater probability of a better outcome in terms of duration of organ support at 30 days or death when compared with a liberal oxygenation target. Widespread adoption of a conservative oxygenation saturation target (SpO2 88-92%) could help improve outcomes and reduce costs for the sickest children admitted to PICUs. FUNDING: UK National Institute for Health and Care Research Health Technology Assessment Programme.

Randomization to a Liberal Versus Conservative Oxygenation Target: Redox Responses in Critically Ill Children.

RATIONALE: Optimal systemic oxygenation targets in pediatric critical illness are unknown. A U-shaped relationship exists between blood oxygen levels and PICU mortality. Redox stress or iatrogenic injury from intensive treatments are potential mechanisms of harm from hyperoxia. OBJECTIVES: To measure biomarkers of oxidative status in children admitted to PICU and randomized to conservative (oxygen-hemoglobin saturation [Sp o2 ] 88-92%) versus liberal (Sp o2 > 94%) peripheral oxygenation targets. DESIGN: Mechanistic substudy nested within the Oxygen in PICU (Oxy-PICU) pilot randomized feasibility clinical trial ( ClinicalTrials.gov : NCT03040570). SETTING: Three U.K. mixed medical and surgical PICUs in university hospitals. PATIENTS: Seventy-five eligible patients randomized to the Oxy-PICU randomized feasibility clinical trial. INTERVENTIONS: Randomization to a conservative (Sp o2 88-92%) versus liberal (Sp o2 > 94%) peripheral oxygenation target. MEASUREMENTS AND MAIN RESULTS: Blood and urine samples were collected at two timepoints: less than 24 hours and up to 72 hours from randomization in trial participants (March 2017 to July 2017). Plasma was analyzed for markers of ischemic/oxidative response, namely thiobarbituric acid-reactive substances (TBARS; lipid peroxidation marker) and ischemia-modified albumin (protein oxidation marker). Total urinary nitrate/nitrite was measured as a marker of reactive oxygen and nitrogen species (RONS). Blood hypoxia-inducible factor (HIF)-1a messenger RNA (mRNA) expression (hypoxia response gene) was measured by reverse transcription- polymerase chain reaction. Total urinary nitrate/nitrite levels were greater in the liberal compared with conservative oxygenation group at 72 hours (median difference 32.6 µmol/mmol of creatinine [95% CI 13.7-93.6]; p < 0.002, Mann-Whitney test). HIF-1a mRNA expression was increased in the conservative group compared with liberal in less than 24-hour samples (6.0-fold [95% CI 1.3-24.0]; p = 0.032). There were no significant differences in TBARS or ischemia-modified albumin. CONCLUSIONS: On comparing liberal with conservative oxygenation targets, we show, first, significant redox response (increase in urinary markers of RONS), but no changes in markers of lipid or protein oxidation. We also show what appears to be an early hypoxic response (increase in HIF-1a gene expression) in subjects exposed to conservative rather than liberal oxygenation targets.

Chest physiotherapy for mechanically ventilated children: a survey of current UK practice.

OBJECTIVES: Chest physiotherapy is a treatment option for mechanically ventilated children. However, there is a lack of consensus regarding its value and informal discussions suggest variation in practice. This study describes chest physiotherapy practices for mechanically ventilated children in the UK and explores clinical decision making related to its delivery. DESIGN: Cross-sectional study, using an anonymous, electronic survey. PARTICIPANTS: Qualified physiotherapists working in UK NHS paediatric intensive care units (PICUs). RESULTS: The response rate was 61% (72/118), this included physiotherapists from 26/27 (96%) PICUs. All participants reported using manual hyperinflations and position changes 'always' or 'often'. Variation in practice was evident for some techniques, including Metaneb® and percussion. DNase (99%, 71/72) and hypertonic saline (90%, 65/72) were the most frequently used mucoactives: 91% (59/65) of physiotherapists reported only nebulising hypertonic saline and 69% (49/71) use both nebulised and instilled DNase. Use and delivery of N-acetylcysteine was inconsistent (nebulised only 55%, 26/47; instilled only 15%, 7/47; both 30%, 14/47). Chest physiotherapy was most commonly delivered with a nurse (67%, 48/72). Clinical decision making processes were comparable between physiotherapists and encompassed three main elements: individual patient assessment, involvement of the multidisciplinary team, and risk versus benefit analysis. CONCLUSIONS: A range of chest physiotherapy treatments and adjuncts were used with ventilated children. Variation was apparent and may be due to individual preferences of those training staff or local policies. Pragmatic, interventional studies are required to determine best practice. Further exploration is necessary to understand the variation in practice and intricacies of decision making.

Prescription of Steroids in General Pediatric Intensive Care Patients-A Two-Center Retrospective Observational Study.

OBJECTIVES: Designing randomized trials to determine utility, dose, and timing of steroid administration in the management of critically unwell children may be difficult owing to a high proportion of patients who receive steroid as part of current care. We aimed to describe steroid use among all patients on two general PICUs. DESIGN: Retrospective observational study using a multilevel logistic regression model. SETTING: Two tertiary, general mixed medical and surgical PICUs. PATIENTS: All admissions between 2016 and 2019. All parenteral or enteral steroid prescriptions were identified, and steroid type, frequency, timing, and peak daily doses were recorded. The outcome measure was mortality prior to PICU discharge. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: There were 5,483 admissions during the study period, and 1,804 (33%) of these involved prescription of at least one steroid. Among patients prescribed steroids, the median peak daily dose when steroids were prescribed was 2.4 mg/kg/d prednisolone equivalent (interquartile range, 1.6-3.6), and the median time to peak steroid doses was 2 days (1-5 d). Administration of steroid was associated with increased risk-adjusted mortality odds ratio (OR) of 1.37 (95% CI, 1.04-1.79). Steroids were prescribed in 42.3% of admissions, in which the child did not survive to PICU discharge. Among children who were prescribed steroids, use of hydrocortisone (OR, 6.75; 95% CI, 3.79-12.27) and methylprednisolone (OR, 7.85; 95% CI, 4.21-14.56), or starting steroids later than 2 days after PICU admission were associated with an increased mortality (OR, 1.93; 95% CI, 1.15-3.25). CONCLUSIONS: Steroids are widely used in pediatric critical illness and nonsurvival associated with increased frequency of use. This association appears to be related to steroid class and timing of dose, both likely to reflect indication for steroid prescription. Prospective trials are required to estimate these complex risks and benefits, and study design will need to consider these patterns.

Using the TIDieR checklist to describe the intervention of the Sedation and Weaning in Children (SANDWICH) trial.

BACKGROUND: Published reports of complex interventions in randomized controlled trials often lack sufficient detail to allow trial replication and adoption into practice. AIM: The aim of this paper is to describe our experience of using the Template for Intervention Description and Replication (TIDieR) checklist in reporting a recent trial of sedation and ventilation weaning in critically ill children (the Sedation and Weaning in Children [SANDWICH] trial). METHODS: The TIDieR 12-point checklist has been used to detail and describe the specific SANDWICH trial intervention and methods of implementation. RESULTS/DISCUSSION: Overall, we found the checklist a useful tool to direct and ensure consistency of reporting of our complex intervention used in a multi-centre clinical trial. We experienced some minor limitations in classifying training materials and delivery mode into one item because of the overlapping nature of this component. CONCLUSION: Using the TIDieR checklist to report complex interventions tested in trials provides a structured, systematic way of describing necessary detail. This allows clinicians to understand the theory behind the intervention, how it should be delivered, and the resources required. RELEVANCE TO CLINICAL PRACTICE: The SANDWICH intervention had a significant beneficial effect on reducing time on ventilation for children. The detailed description of the team-based intervention will aid replication, implementation and monitoring of fidelity in other paediatric intensive care units.

The United Kingdom Paediatric Critical Care Society Study Group: The 20-Year Journey Toward Pragmatic, Randomized Clinical Trials.

Over the past two decades, pediatric intensive care research networks have been formed across North America, Europe, Asia, and Australia/New Zealand. The U.K. Paediatric Critical Care Society Study Group (PCCS-SG) has over a 20-year tradition of fostering collaborative research, leading to the design and successful conduct of randomized clinical trials (RCTs). To date, the PCCS-SG network has delivered 13 different multicenter RCTs, covering a spectrum of study designs, methodologies, and scale. Lessons from the early years have led PCCS-SG to now focus on the entire process needed for developing an RCT, starting from robust preparatory steps such as surveys, data analysis, and feasibility work through to a definitive RCT. Pilot RCTs have been an important part of this process as well. Facilitators of successful research have included the presence of a national registry to facilitate efficient data collection; close partnerships with established Clinical Trials Units to bring together clinicians, methodologists, statisticians, and trial managers; greater involvement of transport teams to recruit patients early in trials of time-sensitive interventions; and the funded infrastructure of clinical research staff within the National Health Service to integrate research within the clinical service. The informal nature of PCCS-SG has encouraged buy-in from clinicians. Greater international collaboration and development of embedded trial platforms to speed up the generation and dissemination of trial findings are two key future strategic goals for the PCCS-SG research network.

Commentary on the First-Line Support for Assistance in Breathing in Children Trials on Noninvasive Respiratory Support: Taking a Closer Look.

Noninvasive respiratory support modalities such as high-flow nasal cannula (HFNC) therapy and continuous positive airway pressure (CPAP) are used frequently in pediatric critical care to support acutely ill children with respiratory failure (step-up management) and children following extubation (step-down management). Although there are several observational studies and database analyses comparing the efficacy of HFNC and CPAP, and a few small randomized clinical trials (RCTs), until recently, there were no large RCTs comparing the two modalities in a mixed group of critically ill children. In the first half of 2022, results from the First-Line Support for Assistance in Breathing in Children (FIRST-ABC) trials were published; these comprised a master protocol of two trials: one in acutely ill children (step-up RCT) and one in extubated children (step-down RCT). Each of these pragmatic trials randomized 600 children to either HFNC or CPAP when the treating clinician decided that noninvasive respiratory support beyond standard oxygen therapy was required. The primary outcome was time to liberation from all forms of respiratory support (invasive and noninvasive), excluding supplemental oxygen. The FIRST-ABC trials represent a significant advance in the field of noninvasive respiratory support, which has traditionally been evidence-poor and associated with considerable variability in clinical practice. In this article, we provide an overview of how the FIRST-ABC trials were conceived and conducted, our view on the results, and how the trial findings have changed our clinical practice.

Factors to be Considered in Advancing Pediatric Critical Care Across the World.

This article reviews the many factors that have to be taken into account as we consider the advancement of pediatric critical care (PCC) in multiple settings across the world. The extent of PCC and the range of patients who are cared for in this environment are considered. Along with a review of the ongoing treatment and technology advances in the PCC setting, the structures and systems required to support these services are also considered. Finally the question of how PCC can be made sustainable in a volatile world with the impacts of global crises such as climate change is addressed.

Evaluation of blood pressure trajectories and outcome in critically ill children with initial hypertension on admission to Paediatric Intensive Care.

OBJECTIVE: Hypertension on paediatric intensive care (PICU) is associated with adverse outcomes. Management is complex; hypertension often represents a physiological adaptive response and exposure to hypertension could lead to altered pressure-flow autoregulation. International treatment consensus is to avoid rapid blood pressure (BP) reduction. Our aim was to examine if the rate and magnitude of BP reduction in hypertensive patients was correlated with harm. PATIENTS AND METHODS: We performed a single centre, retrospective, observational study in a quaternary PICU analysing the first 24 h post admission high resolution BP profiles of children with admission BP above the 95th centile. Individual BP profiles were analysed regarding both time spent and magnitude below a threshold; 75% of the admission BP in the first 24 h. Outcomes were organ support-free days at day 28, change in serum creatinine and PICU mortality. MAIN FINDINGS: Of 3069 admissions in a 36-month period (2016-2018), 21.7% had initial hypertension on admission to PICU. A total of 3,259,111 BP measurements (99.4% invasive) were available. Pre-existing hypertension was documented in 4.9% of patients. Both time spent and magnitude below threshold BP was poorly correlated with duration of required organ support and risk of death after adjusting for PIM score, pre-existing hypertension and raised intracranial pressure. We did find an association with a rise in serum creatinine on both uni- and multivariable analysis. CONCLUSIONS: The risk of harm due to early and significant reduction of raised blood pressure in critically ill children appears to be limited.