Transnasal Humidified Rapid Insufflation Ventilatory Exchange in children requiring emergent intubation (Kids THRIVE): a statistical analysis plan for a randomised controlled trial.

The placement of an endotracheal tube for children with acute or critical illness is a low-frequency and high-risk procedure, associated with high rates of first-attempt failure and adverse events, including hypoxaemia. To reduce the frequency of these adverse events, the provision of oxygen to the patient during the apnoeic phase of intubation has been proposed as a method to prolong the time available for the operator to insert the endotracheal tube, prior to the onset of hypoxaemia. However, there are limited data from randomised controlled trials to validate the efficacy of this technique in children. The technique known as transnasal humidified rapid insufflation ventilatory exchange (THRIVE) uses high oxygen flow rates (approximately 2 L/kg/min) delivered through nasal cannulae during apnoea. It has been shown to at least double the amount of time available for safe intubation in healthy children undergoing elective surgery. The technique and its application in real time have not previously been studied in acutely ill or injured children presenting to the emergency department or admitted to an intensive care unit. The Kids THRIVE trial is a multicentre, international, randomised controlled trial (RCT) in children less than 16 years old undergoing emergent intubation in either the intensive care unit or emergency department of participating hospitals. Participants will be randomised to receive either the THRIVE intervention or standard care (no apnoeic oxygenation) during their intubation. The primary objective of the trial is to determine if the use of THRIVE reduces the frequency of oxygen desaturation and increases the frequency of first-attempt success without hypoxaemia in emergent intubation of children compared with standard practice. The secondary objectives of the study are to assess the impact of the use of THRIVE on the rate of adverse events, length of mechanical ventilation and length of stay in intensive care. In this paper, we describe the detailed statistical analysis plan as an update of the previously published protocol.

Agreement Between Measured Weight and Fluid Balance in Mechanically Ventilated Children in Intensive Care.

OBJECTIVES: To investigate the agreement between change in body weight (BW) and fluid balance (FB), and the precision and safety of BW measurement in mechanically ventilated infants in intensive care. DESIGN: Prospective observational study. SETTING: Tertiary PICU. PATIENTS: Infants following cardiac surgery, at baseline, 24 hours, and 48 hours. INTERVENTIONS: BW and FB measurement at three time points. MEASUREMENTS AND MAIN RESULTS: Between May 2021 and September 2022, we studied 61 children. The median age was 8 days (interquartile range [IQR], 1.0-14.0 d). The median BW at baseline was 3,518 g (IQR, 3,134-3,928 g). Change in BW was -36 g (IQR, -145 to 105 g) and -97 g (IQR, -240 to -28 g) between baseline and 24 hours, and between 24 and 48 hours, respectively. Change in FB was -82 mL (IQR, -173 to 12 mL) and -107 mL (IQR, -226 to 103) between baseline and 24 hours, and between 24 and 48 hours, respectively. In Bland-Altman analyses, the mean bias between BW and FB at 24 and 48 hours was 54 g (95% CI, 12-97) and -43 g (95% CI, -108 to 23), respectively. This exceeded 1% of the median BW, and limits of agreement ranged from 7.6% to 15% of baseline BW. The precision of paired weight measurements, performed sequentially at each time interval, was high (median difference of ≤1% of BW at each time point). The median weight of connected devices ranged from 2.7% to 3% of BW. There were no episodes of tube or device dislodgments and no change in vasoactive therapies during weight measurements. CONCLUSIONS: There is moderate agreement between the changes in FB and BW, albeit greater than 1% of baseline BW, and the limits of this agreement are wide. Weighing mechanically ventilated infants in intensive care is a relatively safe and precise method for estimating change in fluid status. Device weight represents a relatively large proportion of BW.

Characteristics, management and changing incidence of children with empyema in a paediatric intensive care unit.

AIM: Paediatric intensive care unit (PICU) admissions for empyema increased following the 13-valent pneumococcal conjugate vaccine (PCV13). We describe the clinical characteristics, management and outcomes for children with empyema and compare incidence before and after PCV13. METHODS: Retrospective study of patients <18 years admitted to The Royal Children's Hospital Melbourne PICU with empyema between January 2016 and July 2019. We investigated the incidence of empyema during two time periods: 2007-2010 (pre-PCV13) and 2016-2019 (post-PCV13). RESULTS: Seventy-one children (1.9% of all PICU admissions) were admitted to PICU with empyema between 2016 and 2019. Sixty-one (86%) had unilateral disease, 11 (16%) presented with shock and 44 (62%) were ventilated. Streptococcus pneumoniae and group A Streptococcus were the most commonly identified pathogens. Forty-five (63%) were managed with video-assisted thoracoscopic surgery (VATS). There was a 31% reduction in empyema hospitalisations as a proportion of all hospitalisations (IRR 0.69, 95% CI 0.59-0.8), but a 2.8-fold increase in empyema PICU admissions as a proportion of all PICU admissions (95% CI 2.2-3.5, P < 0.001). For the PICU cohort, this was accompanied by reduction in PIM2 probability of death (median 1% vs. 1.9%, P = 0.02) and duration of intubation (median 69 h vs. 126.5 h, P = 0.045). CONCLUSIONS: In children with empyema in PICU 62% required ventilation, 16% had features of shock and 63% received VATS. Empyema admissions, as a proportion of all PICU admissions, increased in the era post-PCV13 compared to pre-PCV13 despite no increase in illness severity at admission.

Pragmatic Randomized Trial of Corticosteroids and Inhaled Epinephrine for Bronchiolitis in Children in Intensive Care.

OBJECTIVE: To determine whether the combination of systemic corticosteroids and nebulized epinephrine, compared with standard care, reduces the duration of positive pressure support in children with bronchiolitis admitted to intensive care. STUDY DESIGN: We performed a pragmatic, multicenter, open-label, randomized trial between July 2013 and November 2019 in children younger than 18 months old with a clinical diagnosis of bronchiolitis. The intervention group received the equivalent of 13 mg/kg prednisolone over 3 days, then 1 mg/kg daily for 3 days, plus 0.05 mL/kg of nebulized 1% epinephrine made up to 6 ml with 0.9% saline via jet nebulizer and mask using oxygen at 12 l/min every 30 minutes for 5 doses, then 1-4 hourly for 3 days, then as required for 3 days. The primary outcome was clinician-managed duration of positive pressure support in intensive care defined as high-flow nasal-prong oxygen, nasopharyngeal continuous positive airway pressure, or mechanical ventilation. RESULTS: In total, 210 children received positive pressure support. In the corticosteroid-epinephrine group, 107 children received positive pressure support for a geometric mean of 26 (95% CI, 22-32) hours compared with 40 (95% CI 34-47) hours in 103 controls, adjusted ratio 0.66 (95% CI 0.51-0.84), P = .001. In the intervention group, 41 (38%) children experienced at least 1 adverse event, compared with 39 (38%) in the control group. CONCLUSIONS: In children with severe bronchiolitis, the duration of clinician-managed pressure support was reduced by regular treatment with systemic corticosteroids and inhaled epinephrine compared with standard care. CLINICAL TRIAL REGISTRATION: Australian Clinical Trials Research Network: ACTRN12613000316707.

Carboxyhemoglobin levels in children during extracorporeal membrane oxygenation support: a retrospective study.

INTRODUCTION: Hemolysis is a common complication of extracorporeal membrane oxygenation (ECMO). There are few data on whether carboxyhemoglobin (COHb), a potential marker of hemolysis, are elevated during ECMO support. METHODS: We conducted a single-center, retrospective study comparing peak COHb levels of children pre-, during, and post-ECMO from January 2017 to August 2020. RESULTS: There were 154 ECMO runs in 147 children (154 PICU admissions) included in the study. The median age was 3.5 (IQR 0.2, 39.2) months. Veno-arterial ECMO was the predominant mode: 146/154 (94.8%). Eighty-seven children (56.5%) underwent cardiac surgery. Peak COHb levels during ECMO were statistically significantly higher compared to pre ECMO (COHb 1.8% (IQR 1.4, 2.6) vs COHb 1.2% (IQR 0.7, 1.7), p < 0.001) and post ECMO (COHb 1.6% (IQR 1.3, 2.2), p = 0.009). Children with COHb ⩾2% were younger and had longer duration of ECMO support. Plasma hemoglobin weakly correlated with COHb level (r = 0.14; p = 0.04). CONCLUSIONS: Carboxyhemoglobin levels increased during ECMO support compared to the pre and post ECMO period. Younger age and longer ECMO duration were associated with COHb levels ⩾2%. Plasma hemoglobin weakly correlated with COHb level.

Outcomes of surgery for infective endocarditis in children: A 30-year experience.

BACKGROUND: Infective endocarditis (IE) is rare in children. Limited data have been reported on long-term outcomes of children who undergo surgery for IE. METHODS: Data were retrospectively obtained from medical records for all children who underwent surgery for IE. RESULTS: Between 1987 and 2017, 138 children with IE required surgery (mean age, 8.3 ± 6.5 years). The majority of children (80.4% [111 out of 138]) had underlying cardiac structural anomalies. Prior heart surgery was performed in 50.7% of patients (70 out of 138), including 19.6% (27 out of 138) who had valve replacement. Operative mortality was 5.8% (8 out of 138). Mean follow-up time was 9.7 ± 7.6 years. Long-term survival at 5 and 25 years was 91.5% (95% confidence interval, 85.1%-95.2%) and 79.1% (95% confidence interval, 66.3%-87.5%), respectively. Risk factors associated with death were: age (hazard ratio [HR], 0.88; P = .015), prosthetic valve IE (HR, 3.86; P = .02), coagulase-negative staphylococci (HR, 4.52; P = .015), increased duration of preoperative antibiotic therapy (HR, 1.02; P = .009), shock (HR, 3.68; P = .028), and aortic valve replacement (HR, 3.22; P = .044). In patients with left-sided IE, risk factors independently associated with death were heart failure (HR, 18.8; P = .025) and vegetation size adjusted to body surface area (HR, 1.06; P = .008). Freedom from recurrent endocarditis was 94.7% (95% confidence interval, 87.7%-97.8%) at 25 years. CONCLUSIONS: Children undergoing surgery for IE had good long-term survival and recurrence of IE was uncommon. Surgery during the active phase of endocarditis did not increase risk of mortality or reoperation. In patients with left-sided IE, vegetation size adjusted for patient body surface area was identified as a risk factor for death, and a useful indicator of prognosis.

Haemodynamic response to fluid boluses in children after cardiac surgery: a technical report.

OBJECTIVE: To describe the haemodynamic response to fluid boluses (FB) in children after cardiac surgery. DESIGN: A prospective observational pilot study. SETTING: Single-centre, paediatric cardiac intensive care unit. PARTICIPANTS: Children after cardiac surgery. INTERVENTIONS: FB of 0.9% saline, 4% albumin or modified ultrafiltrate blood administered in less than 30 minutes. MAIN OUTCOME MEASURES: Heart rate, arterial blood pressure, central venous pressure, oesophageal temperature, and end-tidal carbon dioxide were measured continuously and reported minutely from 5 minutes before and 30 minutes after FB. A mean arterial pressure (MAP)-responsive episode was defined as a 10% increase in MAP from baseline. RESULTS: There were 21 FB recorded in 9 patients. Most patients (n = 8) weighed ≤ 6 kg, and three had univentricular circulation. Fourteen FB (67%) were 4% albumin and 15 (71%) were ≤ 7.5 mL/kg. There were nine MAP-responsive episodes (43%). Episodes of MAP responsiveness had a median MAP increment from baseline of 5 mmHg (interquartile range [IQR], 5-7) and 5 mmHg (IQR, 2-17) at 15 minutes and 30 minutes, respectively, significantly higher when compared with non-responsive episodes (median, 1 mmHg [IQR, -2 to 3]; and median, -1 mmHg [IQR, -3 to 1]; P < 0.01). In MAP-responsive episodes, median time to response was 6 minutes (IQR, 3-12) and seven episodes (78%) dissipated at a median of 2 minutes after response (IQR, 1-8). MAP response was not associated with fluid volume nor fluid composition. CONCLUSION: In this study, the haemodynamic response to FB in children is infrequent and unsustained. Larger studies are required to demonstrate the pattern of haemodynamic response of FB in critically ill children.

Fluid bolus therapy in critically ill children: a survey of practice among paediatric intensive care doctors in Australia and New Zealand.

OBJECTIVE: Fluid bolus therapy (FBT) is a widely used intervention in paediatric critical illness. The aim of this study was to describe the attitudes and practices towards FBT of paediatric intensive care doctors in Australia and New Zealand. DESIGN: An internet-based survey of paediatric intensive care doctors in Australia and New Zealand between 7 and 30 November 2016. SETTING: Paediatric intensive care units with greater than 400 admissions annually. PARTICIPANTS: Paediatric intensive care specialists and junior medical staff. MAIN OUTCOME MEASURES: Preferences for FBT and markers of fluid responsiveness. RESULTS: There were 106/175 respondents (61%); 0.9% saline and 4% albumin are used frequently or almost always by 86% and 57% of respondents respectively. The preferred volume and duration were 10 mL/kg in less than 10 minutes. The highest rated markers of fluid responsiveness were heart rate and blood pressure - rated as "good" or "very good" by 75% and 58% of respondents respectively. Central venous saturations and serum lactate were the highest rated biochemical markers. The most frequently expected magnitude of change for heart rate and blood pressure was 6-15% by 89% and 76% of respondents respectively. The preferred fluid composition for sepsis, trauma, traumatic brain injury and acute lung injury was 0.9% saline, and 4% albumin for post-operative cardiac surgery. CONCLUSIONS: Paediatric intensive care doctors prefer 0.9% saline and 4% albumin for FBT. Heart rate and blood pressure are the most preferred markers to assess fluid responsiveness. Preferences for FBT in specific conditions exist.