Intranasal ketamine for procedural sedation in children: An open-label multicenter clinical trial.

INTRODUCTION: There are limited options for pain and distress management in children undergoing minor procedures, without the burden of an intravenous line insertion. Prior to this study, we conducted a dose-escalation study and identified 6 mg/kg as a potentially optimal initial dose of intranasal ketamine. OBJECTIVE: To assess the efficacy and safety of intranasal ketamine at a dose of 6 mg/kg for procedural sedation to repair lacerations with sutures in children in the emergency department. METHODS: We conducted a single-arm, open-label multicenter clinical trial for intranasal ketamine for laceration repair with sutures in children aged 1 to 12 years. A convenience sample of 30 patients received 6 mg/kg of intranasal ketamine for their procedural sedation. The primary outcome was the proportion (95% CI) of patients who achieved an effective procedural sedation. RESULTS: We recruited 30 patients from April 2018 to December 2019 in two pediatric emergency departments in Canada. Lacerations repaired were mostly facial in 21(70%) patients and longer than 2 cm in 20 (67%) patients. Sedation was effective in 18/30 (60% [95% CI 45, 80]) children and was suboptimal in 5 (17%) patients but procedure was completed in them with minimal difficulties. Sedation was poor in the remaining 7 (23%) patients, with 3 (10%) of them required additional sedative agents. No serious adverse events were reported. CONCLUSIONS: Using a single dose of 6 mg/kg of intranasal Ketamine for laceration repair led to successful sedation in 60% of patients according to our a priori definition. An additional 17% of patients were considered suboptimal, but their procedure was still completed with minimal difficulty. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov (NCT03053947).

Balanced Versus Unbalanced Fluid in Critically Ill Children: Systematic Review and Meta-Analysis.

OBJECTIVES: The ideal crystalloid fluid bolus therapy for fluid resuscitation in children remains unclear, but pediatric data are limited. Administration of 0.9% saline has been associated with hyperchloremic metabolic acidosis and acute kidney injury. The primary objective of this systematic review was to compare the effect of balanced versus unbalanced fluid bolus therapy on the mean change in serum bicarbonate or pH within 24 hours in critically ill children. DATA SOURCES: We searched MEDLINE including Epub Ahead of Print, In-Process & Other Non-Indexed Citations, Embase, CENTRAL Trials Registry of the Cochrane Collaboration, ClinicalTrials.gov, and World Health Organization International Clinical Trials Registry Platform. STUDY SELECTION: Using the Preferred Reporting Items for Systematic Review and Meta-analysis Protocols guidelines, we retrieved all controlled trials and observational cohort studies comparing balanced and unbalanced resuscitative fluids in critically ill children. The primary outcome was the change in serum bicarbonate or blood pH. Secondary outcomes included the prevalence of hyperchloremia, acute kidney injury, renal replacement therapy, and mortality. DATA EXTRACTION: Study screening, inclusion, data extraction, and risk of bias assessments were performed independently by two authors. DATA SYNTHESIS: Among 481 references identified, 13 met inclusion criteria. In the meta-analysis of three randomized controlled trials with a population of 162 patients, we found a greater mean change in serum bicarbonate level (pooled estimate 1.60 mmol/L; 95% CI, 0.04-3.16; p = 0.04) and pH level (pooled mean difference 0.03; 95% CI, 0.00-0.06; p = 0.03) after 4-12 hours of rehydration with balanced versus unbalanced fluids. No differences were found in chloride serum level, acute kidney injury, renal replacement therapy, or mortality. CONCLUSIONS: Our systematic review found some evidence of improvement in blood pH and bicarbonate values in critically ill children after 4-12 hours of fluid bolus therapy with balanced fluid compared with the unbalanced fluid. However, a randomized controlled trial is needed to establish whether these findings have an impact on clinical outcomes before recommendations can be generated.

Pediatric cannabis intoxication trends in the pre and post-legalization era.

INTRODUCTION: On April 13, 2017, a bill to legalize cannabis was introduced to the Canadian Parliament and presented to the public. On October 17, 2018, Canada legalized recreational cannabis use. We assessed intoxication severity, reflected by ICU admission rates, risk factors and other characteristics in children who presented to the emergency department (ED) with cannabis intoxication, before and after legalization. METHODS: A retrospective cohort study of children 0-18 years who presented to a pediatric ED between January 1, 2008 and December 31, 2019 with cannabis intoxication. The pre-legalization period was defined from January 1, 2008 to April 12, 2017 and the peri-post legalization period from April 13, 2017 to December 31, 2019. RESULTS: We identified 298 patients; 232 (77.8%) presented in the pre legalization period and 66 (22.1%) in the peri-post legalization period; median age: 15.9 years (range: 11 months-17.99 years). A higher proportion of children were admitted to the ICU in the peri-post legalization period (13.6% vs. 4.7%, respectively; p = .02). While the median monthly number of cannabis-related presentations did not differ between the time periods (2.1 [IQR:1.9-2.5] in the pre legalization period vs. 1.7 [IQR:1.0-3.0] in the peri-post legalization period; p = .69), the clinical severity did. The proportions of children with respiratory involvement (65.9% vs. 50.9%; p = .05) and altered mental status (28.8% vs. 14.2%; p < .01) were higher in the peri-post legalization period. The peri-post legalization period was characterized by more children younger than 12 years (12.1% vs. 3.0%; p = .04), unintentional exposures (14.4% vs, 2.8%; p = .002) and edibles ingestion (19.7% vs. 7.8%; p = .01). Edible ingestion was an independent predictor of ICU admission (adjusted OR: 4.1, 95%CI: 1.2-13.7, p = .02). CONCLUSIONS: The recreational cannabis legalization in Canada is associated with increased rates of severe intoxications in children. Edible ingestion is a strong predictor of ICU admission in the pediatric population.

Impact of balanced versus unbalanced fluid resuscitation on clinical outcomes in critically ill children: protocol for a systematic review and meta-analysis.

BACKGROUND: Isotonic crystalloid fluid bolus therapy is used in critically ill children to restore or maintain hemodynamic stability. However, the ideal choice of crystalloid remains to be determined. The most easily available and most frequently used crystalloid is 0.9% saline, an unbalanced crystalloid, that has been associated with hyperchloremic metabolic acidosis and acute kidney injury (AKI). Balanced fluids such as Ringer's lactate (RL) were developed to be closer to the composition of serum. However, they are more expensive and less readily available than 0.9% saline. Few trials have found RL to be associated with more favorable outcomes, but pediatric data is limited and inconsistent. The objective of the present systematic review is to review existing literature to determine the effect of balanced versus unbalanced fluid bolus therapy on metabolic acidosis in critically ill children. METHODS: Using the Preferred Reporting Items for Systematic Review and Meta-analysis Protocols (PRISMA-P) guidelines, we will conduct a systematic review to retrieve all controlled trials and observational studies comparing balanced and unbalanced resuscitative fluids in critically ill children from age 28 days to 18 years old in any resuscitation settings. Search strategy was developed in collaboration with an experienced clinical research librarian. The primary outcome is the incidence and/or time to resolution of metabolic acidosis. Secondary outcomes included the incidence of hyperchloremia, AKI, duration of renal replacement therapy, vasopressors, mechanical ventilation, total volume of rehydration needed per day, extracorporeal membrane oxygenation, and length of stay and mortality. Study screening, inclusion, data extraction, and assessment of risk of bias will be performed independently by two authors. We intend to perform a meta-analysis with studies that are compatible on the basis of population and outcomes. DISCUSSION: Isotonic crystalloid fluid bolus therapy is a ubiquitous treatment in resuscitation of critically ill pediatric patients and yet there is no clear recommendation to support the choice of balanced versus unbalanced fluid. The present review will summarize current available data in the literature and assess whether recommendations can be generated regarding the choice of crystalloids or otherwise identify knowledge gaps which will open the door to a large-scale randomized controlled trial (RCT).

Aspirin Dose and Prevention of Coronary Abnormalities in Kawasaki Disease.

BACKGROUND: Acetylsalicylic acid (ASA) is part of the recommended treatment of Kawasaki disease (KD). Controversies remain regarding the optimal dose of ASA to be used. We aimed to evaluate the noninferiority of ASA at an antiplatelet dose in acute KD in preventing coronary artery (CA) abnormalities. METHODS: This is a multicenter, retrospective, nonrandomized cohort study including children 0 to 10 years of age with acute KD between 2004 and 2015 from 5 institutions, of which 2 routinely use low-dose ASA (3-5 mg/kg per day) and 3 use high-dose ASA (80 mg/kg per day). Outcomes were CA abnormalities defined as a CA diameter with a z score ≥2.5. We assessed the risk difference of CA abnormalities according to ASA dose. All subjects received ASA and intravenous immunoglobulin within 10 days of fever onset. RESULTS: There were 1213 subjects included, 848 in the high-dose and 365 in the low-dose ASA group. There was no difference in the risk of CA abnormalities in the low-dose compared with the high-dose ASA group (22.2% vs 20.5%). The risk difference adjusted for potential confounders was 0.3% (95% confidence interval [CI]: -4.5% to 5.0%). The adjusted risk difference for CA abnormalities persisting at the 6-week follow-up was -1.9% (95% CI: -5.3% to 1.5%). The 95% CI of the risk difference of CA abnormalities adjusted for confounders was within the prespecified 5% margin considered to be noninferior. CONCLUSIONS: In conjunction with intravenous immunoglobulin, low-dose ASA in acute KD is not inferior to high-dose ASA for reducing the risk of CA abnormalities.

Coronary Artery Dilatation in Viral Myocarditis Mimics Coronary Artery Findings in Kawasaki Disease.

Coronary artery (CA) dilatations are typical to Kawasaki disease (KD) in the pediatric population. CA involvement is a useful feature to help establish the diagnosis of KD. Since myocarditis is omnipresent in the acute phase of KD, we sought to investigate whether viral myocarditis may cause CA dilatation. This retrospective study reviewed 14 consecutive patients diagnosed with acute myocarditis at CHU Sainte-Justine, Montreal. KD diagnosis was excluded for all patients. All echocardiography studies were reviewed by an independent experienced echocardiographer for CA size and myocardial function parameters. CA involvement was classified under three categories: definite dilatation (Z-score ≥2.5 in one or more CA), occult dilatation (Z-score variation ≥2 points for the same CA on two different echocardiograms, but maximum Z-score always <2.5), and no dilatation otherwise. Demographics, laboratory values, microbial etiology testing, and diagnostic studies were collected from medical records. Mean age at presentation was 1.67 ± 3.22 years, where 11/14 (78 %) presented with acute and three with subacute myocarditis. Five (36 %) patients had normal CA measurements, six (43 %) had occult dilatation, and three (21 %) had definite dilatation. Maximal CA Z-score was within the first 8 days of presentation. Patients with viral myocarditis can present CA dilatation during the acute phase of the illness. This finding should be taken into account when KD diagnosis is being based on the CA involvement as the two illnesses may present with similar features.

Blood Transfusions After Pediatric Cardiac Operations: A North American Multicenter Prospective Study.

BACKGROUND: Red blood cell transfusion is an important supportive measure after pediatric cardiac operations. However, no clear hemoglobin threshold has been established. This study characterized anemia development and red blood cell transfusions in the pediatric intensive care unit (PICU) after cardiac operations. METHODS: A prospective, multicenter, 6-month cohort study on the management of anemia in critically ill pediatric patients was conducted in 30 North American PICUs. This observational study enrolled 977 consecutive children (aged <18 years) who stayed in the PICU for 48 hours or more. We analyzed a subgroup of postcardiac surgical patients from this study. RESULTS: Included were 175 cardiac patients, 56% of whom had cyanotic heart disease. The mean Pediatric Risk of Mortality (PRISM III) score was 6.4 ± 5.4. Fifty-four percent of children were anemic in the PICU (20% on admission, 34% during PICU stay). Most patients (79%) received at least one red blood cell transfusion in the PICU. Patients who received a transfusion had a significantly longer PICU stay (9.3 ± 6.3 vs 6.1 ± 5.4 days, p = 0.01). Pretransfusion hemoglobin was different in acyanotic and cyanotic patients (mean ± standard deviation: 11.1 ± 2.2 g/dL and 11.8 ± 2.1 g/dL, respectively). According to the attending physician, a low hemoglobin level was the primary indication for transfusion in only 17% of cases. CONCLUSIONS: Pediatric cardiac surgical patients are at high risk of receiving red blood cell transfusions. This study, which showed great variability in transfusion practices across North American PICUs, highlights the need for clearer transfusion guidelines in this specific population.

Rapidly progressive aortic aneurysmal dilation in a child with systemic lupus erythematosus: too early too severe.

About 10-20% of systemic lupus erythematosus cases occur in children, often with more severe features at onset and more active disease over time compared with adults. Cardiovascular complications are common in this population but thoracic aortic aneurysms rarely occur. Although the pathophysiology of this complication remains unclear, vasculitis seems to play an important role, leading to degeneration and fibrosis of the media and formation of the aneurysm. We report the case of a 9-year-old systemic lupus erythematosus patient with important renal involvement, who underwent aortic replacement surgery for the treatment of an aortic aneurysm. This case highlights the importance of monitoring the thoracic aorta in children with systemic lupus erythematosus and the need for the development of appropriate early management strategies for this serious complication.