A systematic review and meta-analysis of ketamine in pediatric status epilepticus.

OBJECTIVE: Status epilepticus (SE) is a common neurological medical emergency in the pediatric population, with 10%-40% of cases progressing to refractory SE (RSE), requiring treatment with anesthetic infusions. We present a systematic review and meta-analysis of the use of ketamine for the treatment of pediatric SE and its potential advantages over other anesthetic infusions. METHODS: This review follows the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement. Electronic databases, including PubMed, Cochrane Library, Ovid, Embase, and Google Scholar, were searched with the keywords "pediatrics," "status epilepticus," and "ketamine treatment." Randomized trials, prospective and retrospective cohort studies, and case reports were considered for inclusion. RESULTS: Eighteen publications met the initial inclusion criteria. The 18 publications comprise 11 case reports, one nonconclusive clinical trial, two case series, and four retrospective cohorts. After excluding the case reports because of reporting bias, only the six case series and cohorts were included in the final analysis. There were 172 patients in the six included studies. The weighted age was 9.93 (SD = 10.29) years. The weighted maximum dose was 7.44 (SD = 9.39) mg/kg/h. SE cessation was attained in 51% (95% confidence interval = 43-59) of cases with the addition of ketamine. The heterogeneity was I2 = 0%, t2 = 0, χ2 (5) = 3.39 (p = .64). SIGNIFICANCE: Pediatric RSE is difficult to treat, resulting in increased morbidity and mortality. Without strong recommendations and evidence regarding preferred agents, this review provides evidence that ketamine may be considered in managing SE in the pediatric population.

Peripheral vascular access as exclusive access mode in pediatric intensive care unit.

Introduction: The type of vascular access (central or peripheral) in pediatric critical care depends on several factors, including the duration of treatment, the properties of the medication (osmolarity or vesicant), and the need for central pressure monitoring. The utilization of peripheral intravascular catheters (PIVCs) has shown a notable increase in the number of patients being treated. Extended dwell or midline catheters are another peripheral access option in addition to PIVCs. However, there are currently no established guidelines on their placement. Objectives: The aim of this study is to estimate the duration of dwell time for PIVCs, analyze the specific parameters affecting it, and develop recommendations for switching to extended dwell and midline catheter placement as an alternative to peripheral access. Methods: The study enrolled patients aged 0-18 years admitted to the pediatric intensive care unit (PICU) for over 24 h and managed with peripheral access only over 2 years (2019-2021). Measurements and main results: A total of 484 patients met the specified criteria. Patients who had peripheral access exhibited a lower PRISM score and a shorter length of stay in the PICU, with mean values of 18 (SD: 8.5) and 9.5 (SD: 6.4) days, respectively, compared with patients who had central access with mean values of 8.9 (SD: 5.9) and 5.7 (SD: 3.6) days, respectively. The PIVC dwell time was found to be 50.1 h (SD: 65.3) and required an average of 1.6 insertion attempts. Patients with three or more insertions exhibited an increased odds ratio of 5.2 (95% CI: 3.1-8.5) for receiving an extended dwell or midline insertion. Increased dwell time was associated with female gender, 59.5 h (P < 0.001), first attempt insertion, 53.5 h (P < 0.001), use of 24 Ga bore, 56.3 h (P = 0.04), left-sided insertions, 54.9 (P = 0.07), less agitation, 54.8 h (P = 0.02), and less edema, 61.6 (P < 0.001). Decreased dwell time was associated with the use of vancomycin infusion at 24.2 h (P < 0.001) and blood transfusions at 29.3 h (P < 0.001). Conclusions: Extended catheters last longer than PIVCs in PICU patients. Extended catheter placement requires consideration of the length of treatment, as well as the overall body edema, the level of the patient's restlessness, and the need for vancomycin infusion or blood transfusions, as these factors reduce PIVC dwell time and expose the patients to painful insertions. For such cases, an extended dwell catheter may be a better option, even if the projected treatment time is less than 6 days.

Caring for Critically Ill Children With the ICU Liberation Bundle (ABCDEF): Results of the Pediatric Collaborative.

OBJECTIVES: Assess clinical outcomes following PICU Liberation ABCDEF Bundle utilization. DESIGN: Prospective, multicenter, cohort study. SETTING: Eight academic PICUs. PATIENTS: Children greater than 2 months with expected PICU stay greater than 2 days and need for mechanical ventilation (MV). INTERVENTIONS: ABCDEF Bundle implementation. MEASUREMENT AND MAIN RESULTS: Over an 11-month period (3-mo baseline, 8-mo implementation), Bundle utilization was measured for 622 patients totaling 5,017 PICU days. Risk of mortality was quantified for 532 patients (4,275 PICU days) for correlation between Bundle utilization and MV duration, PICU length of stay (LOS), delirium incidence, and mortality. Utilization was analyzed as subject-specific (entire PICU stay) and day-specific (single PICU day). Median overall subject-specific utilization increased from 50% during the 3-month baseline to 63.9% during the last four implementation months ( p < 0.001). Subject-specific utilization for elements A and C did not change; utilization improved for B (0-12.5%; p = 0.007), D (22.2-61.1%; p < 0.001), E (17.7-50%; p = 0.003), and F (50-79.2%; p = 0.001). We observed no association between Bundle utilization and MV duration, PICU LOS, or delirium incidence. In contrast, on adjusted analysis, every 10% increase in subject-specific utilization correlated with mortality odds ratio (OR) reduction of 34%, p < 0.001; every 10% increase in day-specific utilization correlated with a mortality OR reduction of 1.4% ( p = 0.006). CONCLUSIONS: ABCDEF Bundle is applicable to children. Although enhanced Bundle utilization correlated with decreased mortality, increased utilization did not correlate with duration of MV, PICU LOS, or delirium incidence. Additional research in the domains of comparative effectiveness, implementation science, and human factors engineering is required to understand this clinical inconsistency and optimize PICU Liberation concept integration into clinical practice.

Pediatric Chronic Critical Illness: Validation, Prevalence, and Impact in a Children's Hospital.

OBJECTIVES: Large populations of chronically critically ill patients test the critical care system's resource utilization ability. Defining and tracking this group is necessary for census predictions. DESIGN: Retrospective cohort analysis. SETTINGS: Tertiary academic center in United States. PATIENTS: Patients admitted to PICU or neonatal ICU. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Demographics and resource utilization variables were sampled in PICU, intermediate care unit, cardiovascular ICU, and neonatal ICU on 3 random days in 3 consecutive months. The attendings' perception of pediatric chronic critical illness was contrasted to Shapiro's definition of chronic critical care criteria. Each unit's active and maximal capacity census was computed: the occurrence rate of pediatric chronic critical illness was 34%, the prevalence was 44.5%, and the tolerance, or percentage pediatric chronic critical illness patients to all available beds, was 36.8%. The median length of stay for the nonpatients with pediatric critical care illness to patients with pediatric critical care illness was 9 versus 46 days (1/5.1). The attending's decision was 58 times more concordant with the criteria. Pediatric chronic critical illness bed occupancy was 40.6% in PICU, 97.2% in intermediate care unit, 47.8% in cardiovascular ICU, and 33.9% in neonatal ICU. CONCLUSIONS: Pediatric chronic critical illness patients occupied more than one third of the ICU beds and have five times longer stay. This mounting load needs to be uniformly defined, addressed at regional and national levels, and considered in the current pandemic planning.

Impact of Different Cardiopulmonary Bypass Strategies on Renal Injury After Pediatric Heart Surgery.

BACKGROUND: The purpose of this study is to compare the incidence and severity of acute kidney injury (AKI) after open heart surgery in neonates and infants for two different cardiopulmonary bypass (CPB) strategies. METHODS: In all, 151 infants undergoing cardiac surgery were prospectively enrolled between June 2017 and June 2018 at two centers, one using conventional CPB (2.4 L · min-1 · m-2, 150 mL · kg-1 · min-1) with reduction of flow rates with moderate hypothermia and with a targeted hematocrit greater than 25% (center 1, n = 91), and the other using higher bypass flow rates (175 to 200 mL · kg-1 · min-1) and higher minimum hematocrit (greater than 32%) CPB (center 2, n = 60). The primary endpoint was the incidence of postoperative AKI as defined by Acute Kidney Injury Network criteria and risk factors associated with AKI. RESULTS: Preoperative characteristics and complexity of surgery were comparable between centers. The overall incidence of early postoperative AKI was 10.6% (16 of 151), with 15.4% (14 of 91) in center 1 and 3.3% (2 of 60) in center 2 (P = .02). Mean lowest flow rates on CPB were 78 mL · kg-1 · min-1 vs 118 mL · kg-1 · min-1 and mean highest hematocrit on separation from CPB were 33% vs 43% at center 1 and 2, respectively (P < .001). Center 1 used less packed red blood cells but more fresh frozen plasma than center 2 (P = .001). By multivariate analysis, only lower flows on CPB (78 vs 96 mL · kg-1 · min-1, P = .043) and lower hematocrit at the end of CPB (33% vs 37%, P = .007) were associated with AKI. CONCLUSIONS: In this contemporary comparative study, higher flow rates and higher hematocrit during cardiopulmonary bypass were associated with better preservation of renal function.

Pulmonary function in infants with swallowing dysfunction.

BACKGROUND: Swallowing dysfunction can lead to recurring aspiration and is frequently associated with chronic symptoms such as cough and wheezing in infants. Our objective was to describe the characteristics of infants with swallowing dysfunction, determine if pulmonary function abnormalities are detectable, and if they improve after therapy. METHODS: We studied 38 infants with a history of coughing and wheezing who had pulmonary function tests performed within two weeks of their diagnosis of swallowing dysfunction. The raised lung volume rapid thoracoabdominal compression technique was used. After 6 months of therapy, 17 of the infants repeated the tests. RESULTS: Initially, 25 had abnormal spirometry, 18 had abnormal plethysmography, and 15 demonstrated bronchodilator responsiveness. Six months later test were repeated for seventeen patients. Ten patients had continued abnormal spirometry, two patients remained normal, three patients' abnormal spirometry had normalized, and two patients' previously normal studies became abnormal. Eight of the 17 patients had continued abnormal plethysmography, six had continued normal plethysmography, and three patients' normal plethysmography became abnormal. After 6 months of treatment, eight patients demonstrated bronchodilator responsiveness, of which five continued to demonstrate bronchodilator responsiveness and three developed responsiveness. The remainder either continued to be non- bronchodilator responsive (two) or lost responsiveness (three.) The findings of the abnormal tests in most infants tested is complicated by frequent occurrence of other co-morbidities in this population, including gastroesophageal reflux in 23 and passive smoke exposure in 13 of the infants. CONCLUSIONS: The interpretation of lung function changes is complicated by the frequent association of swallowing dysfunction with gastroesophageal reflux and passive smoke exposure in this population. Six months of medical therapy for swallowing dysfunction/gastroesophageal reflux did not significantly improve pulmonary function in these infants. Long-term studies will be necessary to determine which of these changes persists into adulthood.

Differential Role of Rapamycin and Torin/KU63794 in Inflammatory Response of 264.7 RAW Macrophages Stimulated by CA-MRSA.

Background. Rapamycin suppresses the RAW264.7 macrophage mediated inflammatory response but in lower doses induces it. In the present study, we tested the suppression of the inflammatory response in the presence of mTOR 1 and 2 inhibitors, Torin and KU63794. Methods. RAW264.7 cells were stimulated for 18 hrs with 10(6) to 10(7) CFU/mL inocula of community-acquired- (CA-) MRSA isolate, USA400 strain MW2, in the presence of Vancomycin. Then, in sequential experiments, we added Torin, KU63794, and Rapamycin alone and in various combinations. Supernatants were collected and assayed for TNF, IL-1, IL-6, INF, and NO. Results. Rapamycin induces 10-20% of the inflammatory cascade at dose of 0.1 ng/mL and suppresses it by 60% at dose of 10 ng/mL. The induction is abolished in the presence of Torin KU63794. Torin and KU63794 are consistently suppressing cytokine production 50-60%. Conclusions. There is a differential response between Rapamycin (mTOR-1 inhibitor) and Torin KU63794 (mTOR 1 and 2 inhibitors). Torin and KU63794 exhibit a dose related suppression. Rapamycin exhibits a significant induction-suppression biphasic response. Knowledge of such response may allow manipulation of the septic inflammatory cascade for clinical advantages.