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BACKGROUND: Ketamine has been considered as an adjunct for children who do not reach their predefined target sedation depth. However, there is limited evidence regarding the use of ketamine as a prolonged infusion (i.e., >24 hours) in the pediatric intensive care unit (PICU). OBJECTIVE: We sought to evaluate the safety and effectiveness of continuous ketamine infusion for >24 hours in mechanically ventilated children. METHODS: We conducted a prospective cohort study in a tertiary PICU from January 2020 to December 2022. The primary outcome was the incidence of adverse events (AEs) after ketamine initiation. The secondary outcome included assessing the median proportion of time the patient spent on the Richmond Agitation-Sedation Scale (RASS) goal after ketamine infusion. Patients were also divided into two groups based on the sedative regimen, ketamine-based or non-ketamine-based, to assess the incidence of delirium. RESULTS: A total of 269 patients were enrolled: 73 in the ketamine group and 196 in the non-ketamine group. The median infusion rate of ketamine was 1.4 mg/kg/h. Delirium occurred in 16 (22%) patients with ketamine and 15 (7.6%) patients without ketamine (p = 0.006). After adjusting for covariates, logistic regression showed that delirium was associated with comorbidities (odds ratio [OR] 4.2), neurodevelopmental delay (OR 0.23), fentanyl use (OR 7.35), and ketamine use (OR 4.17). Thirty-one (42%) of the patients experienced at least one AE following ketamine infusion. Other AEs likely related to ketamine were hypertension (n = 4), hypersecretion (n = 14), tachycardia (n = 6), and nystagmus (n = 2). There were no significant changes in hemodynamic variables 24 h after the initiation of ketamine. Regarding the secondary outcomes, patients were at their goal RASS level for a median of 76% (range 68-80.5%) of the time in the 24 hours before ketamine initiation, compared with 84% (range 74.5-90%) of the time during the 24 h after ketamine initiation (p < 0.001). The infusion rate of ketamine did not significantly affect concomitant analgesic and sedative infusions. The ketamine group experienced a longer duration of mechanical ventilation and a longer length of stay in the PICU and hospital than the non-ketamine group. CONCLUSION: The use of ketamine infusion in PICU patients may be associated with an increased rate of adverse events, especially delirium. High-quality studies are needed before ketamine can be broadly recommended or adopted earlier in the sedation protocol.

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OBJECTIVE: To assess the current evidence for the efficacy of care bundles in reducing unplanned extubations (UEs) in critically ill children. DESIGN: Systematic review according to the Cochrane guidelines and meta-analysis using random-effects modelling. METHODS: We searched MEDLINE, EMBASE, CINAHL, Web of Science, Scopus, Cochrane and SciELO databases from inception until April 2021. We conducted a quality appraisal for each study using the Newcastle-Ottawa Scale and Standards for Quality Improvement Reporting Excellence (SQUIRE) V.2.0 checklist. MAIN OUTCOME: The primary outcome measure was UE rates per 100 intubation days. RESULTS: We screened 10 091 records and finally included 11 studies. Six studies were pre/post-intervention studies, and five were interrupted time-series studies. The methodological quality was 'good' in 70%, and the remaining as 'fair' (30%). The most frequently used implementation strategies were staff education (100%), root cause analysis (100%), and audit and feedback (82%). Key bundle care components comprised identification of high-risk patients, endotracheal tube care and sedation protocol. Not all studies fully completed the SQUIRE V.2.0 checklist. Meta-analysis revealed a reduction in UE rate following the introduction of care bundles (rate ratio: 0.40 (95% CI: 0.19 to 0.84); p=0.02), which equates to a 60% reduction in UE rates. CONCLUSIONS: We found that identifying high-risk patients, endotracheal tube care and protocol-directed sedation are core elements in care bundles for preventing UEs. However, there are several methodological gaps in the literature, including poor evaluation of adherence to bundle components. Future studies should address these gaps to strengthen their validity.

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AIM: Studies assessing the association between admission time to paediatric intensive care unit (PICU) and mortality are sparse with conflicting results. We aimed to evaluate the impact of time of admission on PICU mortality within 48 h after admission. METHODS: This was a single-centre prospective cohort. We collected data from all consecutive children aged 1 month to 16 years over 10 years. RESULTS: We included a total of 1368 admissions, with a PICU mortality of 6.6%. Compared with daytime admissions, the overall mortality rate (5.3% vs. 8.5%, P = 0.026) and the mortality within 48 h after admission were higher for those admitted during night-time (2% vs. 4.2%, P = 0.021). There were no differences between mortality rates and the day of admission (weekend admissions vs. weekday admissions). The adjusted odds of death within 48 h after admission was 2.5 (95% confidence interval = 1.22-5.24, P = 0.012) for patients admitted at night-time. A secondary analysis assessing trends in mortality rates during admission showed that the last 5 years of study were more responsible for the chances of death within 48 h (odds ratio = 7.6, 95% confidence interval = 1.91-30.17, P = 0.0039). CONCLUSION: Admission to the PICU during night shifts was strongly associated with death compared to daytime admissions. A time analysis of the moment of admission is necessary as a metric of quality of care to identify the interruption or improvement in the continuity of care. Further studies are needed to assess the modified contributing factors.

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It is unknown if the requirement for high dose of vasopressor (HDV) represents a poor outcome in pediatric septic shock. This is a retrospective observational analysis with data obtained from a single center. We evaluated the association between the use of HDV and survival in these patients. A total of 62 children (38 survivors and 24 nonsurvivors) were assessed. The dose of vasopressor (hazard ratio 2.06) and oliguria (hazard ratio 3.17) was independently associated with mortality. The peak of vasopressor was the best prognostic predictor. A cutoff of 1.3 µg/kg/min was associated with mortality with a sensitivity of 75% and specificity of 89%. Vasopressor administration higher than 1.3 µg/kg/min was associated with increased mortality in children with septic shock.

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PURPOSE: Although several studies assess unplanned extubation (UE) in children, few have addressed determinants of UE and factors associated with reintubation in a case-controlled manner. We aimed to identify the risk factors and outcomes associated with UE in a pediatric intensive care unit. METHODS: Cases of UE were randomly matched with control patients at a ratio of 1:4 for age, severity of illness, and admission diagnosis. For cases and controls, we also collected data associated with UE events, reintubation, and outcomes. RESULTS: We analyzed 94 UE patients (0.75 UE per 100 intubation days) and found no differences in demographics between the 2 groups. Logistic regression revealed that patient agitation (odds ratio [OR]: 2.44; 95% confidence interval [CI]: 1.28-4.65), continuous sedation infusion (OR: 3.27; 95% CI: 1.70-6.29), night shifts (OR: 9.16; 95% CI: 4.25-19.72), in-charge nurse experience <2 years (OR: 2.38; 95% CI: 1.13-4.99), and oxygenation index (OI) >5 (OR: 76.9; 95% CI: 16.79-352.47) were associated with UE. Risk factors for reintubation after UE included prior level of sedation (COMFORT score < 27; OR: 7.93; 95% CI: 2.30-27.29), copious secretion (OR: 11.88; 95% CI: 2.20-64.05), and OI > 5 (OR: 9.32; 95% CI: 2.45-35.48). CONCLUSIONS: This case-control study showed that both patient- and nurse-associated risk factors were related to UE. Risk factors associated with reintubation included lower levels of consciousness, copious secretions, and higher OI. Further evidence-based studies, including a larger sample size, are warranted to identify predisposing factors in UEs.

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OBJECTIVES: Tracheal suctioning is a routine procedure in mechanically ventilated children, however, in severe head-injured patients it can result in potential deleterious increase in intracranial pressure. We aimed to assess the effect of tracheal lidocaine administration on intracranial pressure during tracheal suctioning. DESIGN: Prospective randomized controlled crossover study. SETTING: PICU of a tertiary hospital. PATIENTS: Eleven patients with severe head trauma (Glasgow Coma Scale score 4-8) INTERVENTIONS:: Lidocaine (1.5 mg/kg) or saline solution was endotracheally instilled before a standardized tracheal suctioning maneuver. Each patient received both treatments in a crossover design. Cerebral hemodynamic and systemic and ventilatory effects were assessed at four time points: in baseline (T0), within 2 minutes (T1), 5 minutes (T2), and 15 minutes after tracheal instillation (T3). The 2-minute time interval around tracheal suctioning was used to assess each treatment efficacy MEASUREMENTS AND MAIN RESULTS:: The time course of intracranial pressure was different throughout the study in both treatment groups, with a significant increase of intracranial pressure from 14.82 ± 3.48 to 23.27 ± 9.06 with lidocaine (p = 0.003) and from 14.73 ± 2.41 to 30.45 ± 13.14 with saline (p = 0.02). The mean variation in intracranial pressure immediately after tracheal suctioning was smaller with lidocaine instillation than saline (8.45 vs 15.72 mm Hg; p = 0.006). Patients treated with lidocaine returned to baseline intracranial pressure value at 5 minutes after tracheal suctioning whereas those receiving saline solution returned to baseline intracranial pressure value at 15 minutes. Although patients treated with lidocaine had no significant hemodynamic changes, patients receiving saline solution experienced a higher mean value of mean arterial pressure (99.36 vs 81.73 mm Hg; p = 0.004) at T1. CONCLUSIONS: This preliminary study showed that tracheal lidocaine instillation can attenuate increase in intracranial pressure induced by tracheal suctioning and favor a faster return to the intracranial pressure baseline levels without significant hemodynamic and ventilatory changes.

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OBJECTIVE: While studies have focused on early readmissions or readmissions during the same hospitalization in a pediatric intensive care unit, little is known about the children with recurrent admissions. We sought to assess the characteristics of patients readmitted within 1 year in a Brazilian pediatric intensive care unit. METHODS: This was a retrospective study carried out in a tertiary pediatric intensive care unit. The outcome was the maximum number of readmissions experienced by each child within any 365-day interval during a 5-year follow-up period. RESULTS: Of the 758 total eligible admissions, 75 patients (9.8%) were readmissions. Those patients accounted for 33% of all pediatric intensive care unit bed care days. Median time to readmission was 73 days for all readmissions. Logistic regression showed that complex chronic conditions (odds ratio 1.07), severe to moderate cognitive disability (odds ratio 1.08), and use of technology assistance (odds ratio 1.17) were associated with readmissions. Multiple admissions had a significantly prolonged duration of mechanical ventilation (8 vs. 6 days), longer length of pediatric intensive care unit (7 vs 4 days) and hospital stays (20 vs 9 days), and higher mortality rate (21.3% vs 5.1%) compared with index admissions. CONCLUSION: The rate of pediatric intensive care unit readmissions within 1 year was low; however, it was associated with a relevant number of bed care days and worse outcomes. A 30-day index of readmission may be inadequate to mirror the burden of pediatric intensive care unit readmissions. Patients with complex chronic conditions, poor functional status or technology assistance are at higher risk for readmissions. Future studies should address the impact of qualitative interventions on healthcare and recurrent admissions.

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OBJECTIVES: Postextubation dysphagia is common and associated with worse outcomes in the PICU. Although there has been an increased participation of speech-language pathologists in its treatment, there is limited evidence to support speech-language pathologists as core PICU team member. We aimed to assess the impact of speech-language pathologists interventions on the treatment of postextubation dysphagia. DESIGN: A quasi-experimental prospective study. In the historical group (controls), patients received a standard care management for dysphagia whereas the intervention group was routinely treated by speech-language pathologists. SETTING: PICU of a tertiary hospital. PATIENTS: Children who were endotracheally intubated for a period greater than 24 hours with greater oral intake limitation as defined by a Functional Oral Intake Scale less than or equal to 3. INTERVENTION: Routine speech-language pathologist assessment. MEASUREMENTS AND MAIN RESULTS: A total of 74 patients were enrolled to receive intervention (January 2015 to December 2016) and 41 patients to the historical group (January 2014 to December 2014). There were no differences in the demographic and clinical characteristics. The historical group had both longer time to initiate oral intake (7 vs 4 d; p = 0.0002; hazard ratio, 2.33) and to reach full oral intake compared with intervention group (9 vs 13 d; p < 0.001; hazard ratio, 2.51). A total of 32 controls (78%) and 74 intervention patients (100%) were on total oral intake at discharge (p ≤ 0.001). Three of nine control patients were feeding tube dependent at hospital discharge. Also, controls had a longer length of hospital stay (25 vs 20 d) and a higher rate of reintubation when compared with those patients of intervention group (10% vs 2%). CONCLUSIONS: Incorporating speech-language pathologists in the routine management of postextubation dysphagia can result in faster functional improvement and favorable patient outcomes. Yet, further and larger studies in pediatric dysphagia are required to support the related interventions and strategies to guide clinical practice.

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PURPOSE: Reintubation following unplanned extubation (UE) is often required and associated with increased morbidity; however, knowledge of risk factors leading to reintubation and subsequent outcomes in children is still lacking. We sought to determine the incidence, risk factors, and outcomes related to reintubation after UEs. METHODS: All mechanically ventilated children were prospectively tracked for UEs over a 7-year period in a pediatric intensive care unit. For each UE event, data associated with reintubation within 24 hours and outcomes were collected. RESULTS: Of 757 intubated patients, 87 UE occurred out of 11 335 intubation days (0.76 UE/100 intubation days), with 57 (65%) requiring reintubation. Most of the UEs that did not require reintubation were already weaning ventilator settings prior to UE (73%). Univariate analysis showed that younger children (<1 year) required reintubation more frequently after an UE. Patients experiencing UE during weaning experienced significantly fewer reintubations, whereas 90% of patients with full mechanical ventilation support required reintubation. Logistic regression revealed that requirement of full ventilator support (odds ratio: 37.5) and a COMFORT score <26 (odds ratio: 5.5) were associated with UE failure. There were no differences between reintubated and nonreintubated patients regarding the length of hospital stay, ventilator-associated pneumonia rate, need for tracheostomy, and mortality. Cardiovascular and respiratory complications were seen in 33% of the reintubations. CONCLUSION: The rate of reintubation is high in children experiencing UE. Requirement of full ventilator support and a COMFORT score <26 are associated with reintubation. Prospective research is required to better understand the reintubation decisions and needs.

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BACKGROUND AND AIMS: Although iatrogenic withdrawal syndrome (IWS) has been recognized in patients exposed to opioids and benzodiazepines, very few studies have used a validated tool for diagnosis and assessment of IWS in critically ill children. We sought to determine IWS rate, risk factors, and outcomes of IWS patients. METHODS: Prospective observational study conducted in a pediatric intensive care unit. A total of 137 patients (31 with IWS and 106 with no IWS) received a continuous infusion of fentanyl and midazolam for 3 or more days. The Sophia Observation withdrawal Symptoms scale was repeatedly applied when children were weaned off sedation/analgesia. RESULTS: The overall incidence of IWS was 22.6%. Of the 31 IWS patients, 6 showed IWS with less than 5 days sedation or analgesia. Logistic regression showed that the median peak dose of midazolam was associated with IWS development (odds ratio 1.4). Receiver-operating curve showed a cut-off value of 0.35 mg/kg/h for midazolam peak dose (sensitivity 96.7%, specificity 51%, positive predictive value 36.6%, and negative predictive value 98.2%), with area under the curve of 0.80. IWS patients had a longer time on mechanical ventilation, prolonged pediatric intensive care unit, and hospital stays, and required prolonged period to have drugs discontinued. CONCLUSIONS: Although length of sedation/analgesia for at least5 days has been widely proposed for monitoring IWS, our data suggest that initiating monitoring after 3 sedation days is highly recommended. In addition, patients requiring infusion rates of midazolam above 0.35 mg/kg/h should be considered at high risk for IWS.

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