How to use meropenem in pediatric patients undergoing CKRT? Integrated meropenem pharmacokinetic model for critically ill children.

Standard dosing could fail to achieve adequate systemic concentrations in ICU children or may lead to toxicity in children with acute kidney injury. The population pharmacokinetic analysis was used to simultaneously analyze all available data (plasma, prefilter, postfilter, effluent, and urine concentrations) and provide the pharmacokinetic characteristics of meropenem. The probability of target fT > MIC attainment, avoiding toxic levels, during the entire dosing interval was estimated by simulation of different intermittent and continuous infusions in the studied population. A total of 16 critically ill children treated with meropenem were included, with 7 of them undergoing continuous kidney replacement therapy (CKRT). Only 33% of children without CKRT achieved 90% of the time when the free drug concentration exceeded the minimum inhibitory concentration (%fT > MIC) for an MIC of 2 mg/L. In dose simulations, only continuous infusions (60-120 mg/kg in a 24-h infusion) reached the objective in patients <30 kg. In patients undergoing CKRT, the currently used schedule (40 mg/kg/12 h from day 2 in a short infusion of 30 min) was clearly insufficient in patients <30 kg. Keeping the dose to 40 mg/kg q8h without applying renal adjustment and extended infusions (40 mg/kg in 3- or 4-h infusion every 12 h) was sufficient to reach 90% fT > MIC (>2 mg/L) in patients >10 kg. In patients <10 kg, only continuous infusions reached the objective. In patients >30 kg, 60 mg/kg in a 24-h infusion is sufficient and avoids toxicity. This population model could help with an individualized dosing approach that needs to be adopted in critically ill pediatric patients. Critically ill patients subjected to or not to CKRT may benefit from the administration of meropenem in an extended or continuous infusion.

Early Enteral Nutrition and Gastrointestinal Complications in Pediatric Patients on Extracorporeal Membrane Oxygenation.

OBJECTIVES: To assess the safety of enteral nutrition (EN) in children on extracorporeal membrane oxygenation (ECMO). To describe nutritional status and the characteristics of the nutritional support in this population. METHODS: A retrospective single-center analysis (2006-2016) including children <18 years on ECMO. Demographic data, nutritional status, characteristics of nutritional support, and development of gastrointestinal (GI) complications were recorded. RESULTS: One hundred children, with a median age of 9.7 months (interquartile range [IQR] 3.9-63.1) were enrolled. Undernutrition was prevalent among children on ECMO (33.3%) mainly in patients <2 years (P = 0.042). Most patients (64%) received EN at some point during ECMO therapy. EN was administered in the first 48 hours after ECMO initiation (48HEN) to 60.3% of the children.Mortality rate in the Pediatric Intensive Care Unit was lower in patients who received EN as the initial artificial nutrition support (ANS) (37.7 vs 51%, P = 0.005) and in children on 48HEN (34% vs 50%, P = 0.04). In the logistic regression analysis, duration of ECMO support and low cardiac output indication were the only factors associated with mortality.Although most patients on ECMO (45%) developed digestive complications, they were mostly mild, being constipation the most prevalent. In the logistic regression analysis, EN was not associated with an increase in GI complications (P = 0.09). Only three patients developed intestinal ischemia (one without EN and two on EN). CONCLUSIONS: Undernutrition is prevalent among children on ECMO, mainly in infants <2 years. EN is not associated with severe gastrointestinal complications or higher mortality in these children.

Doppler ultrasound in the assessment of renal perfusion before and during continuous kidney replacement therapy in the pediatric intensive care unit.

BACKGROUND: This study aimed to assess observer variability and describe renal resistive index (RRI) and pulsatility index (PI) before and after onset of continuous kidney replacement therapy (CKRT). A secondary objective was to correlate Doppler ultrasound findings with those from direct measurement of renal blood flow (RBF). METHODS: This is a prospective observational study in hemodynamically stable Maryland piglets with and without acute kidney injury (AKI) and in hemodynamically unstable critically ill children requiring CKRT. Doppler-based RRI and PI were assessed for each subject. Measurements were made by two different operators (pediatric intensivists) before and after CKRT onset. RESULTS: Observer variability assessment in the measurement of RRI and PI rendered a moderate correlation for both RRI (ICC 0.65, IQR 0.51-0.76) and PI (ICC 0.63, IQR 0.47-0.75). RRI and PI showed no correlation with RBF or urine output. Baseline RRI and PI were normal in control piglets [RRI 0.68 (SD 0.02), PI 1.25 (SD 0.09)] and those with AKI [RRI 0.68 (SD 0.03), PI 1.20 (SD 0.13)]. Baseline RRI and PI were elevated in critically ill children (RRI 0.85, PI 2.0). PI and RRI did not change with CKRT in any study group. CONCLUSIONS: Observer variability between inexperienced pediatric intensivists was comparable with that between senior and junior operators. Doppler-based calculations did not correlate with invasive measurements of RBF. RRI and PI were normal in hemodynamically stable piglets with and without AKI. RRI and PI were high in hemodynamically unstable patients requiring CKRT. RRI and PI did not change after CKRT onset, despite changes in hemodynamic status. A higher resolution version of the Graphical abstract is available as Supplementary information.

Hemodynamic impact of the connection to continuous renal replacement therapy in critically ill children.

BACKGROUND: Continuous renal replacement therapy (CRRT) is the treatment of choice for critically ill children with acute kidney injury. Hypotension after starting CRRT is frequent but very few studies have analyzed its incidence and clinical relevance. METHODS: A prospective, observational study was performed including critically ill children treated with CRRT between 2010 and 2014. Hemodynamic data and connection characteristics were collected before, during, and 60 min after CRRT circuit connection. Hypotension with the connection was defined as a decrease in > 20% of the mean arterial pressure from baseline or when intravenous fluid resuscitation or an increase in vasopressors was required. RESULTS: One hundred sixty-one connections in 36 children (median age 18.8 months) were analyzed. Twenty-eight patients (77.8%) were in the postoperative period of cardiac surgery, 94% had mechanical ventilation, and 86.1% had vasopressors. The heparinized circuit priming solution was discarded in 8.7% and infused to the patient in 18% of the connections. The circuit was re-primed in the remaining 73.3% using albumin (79.3%), red blood cells (4.5%), or another crystalloid solution without heparin (16.2%). Hypotension occurred in 49.7% of the connections a median of 5 min after the beginning of the therapy. Fluid resuscitation was required in 38.5% and the dose of vasopressors was increased in 12.4% of the connections. There was no relationship between hypotension and age or weight. Re-priming the circuit with albumin reduced the incidence of hypotension from 71.4 to 44.6% (p = 0.004). CONCLUSIONS: Hypotension after the connection to CRRT is very frequent in critically ill children. Re-priming the circuit with albumin could improve hemodynamics during connection.

Differences in hospital length of stay between neonates exposed to buprenorphine versus methadone in utero: A retrospective chart review.

INTRODUCTION: Neonatal abstinence syndrome is a growing concern in neonatal intensive care units in rural and remote settings. METHODS: A retrospective chart review was conducted of 180 mother-infant dyads born with in utero exposure to buprenorphine (n=60), methadone (n=60) or to other opioids (n=60) to determine neonatal length of stay in hospital, number of days on morphine, day of life of initiation of morphine and the need for phenobarbital. RESULTS: The length of stay in hospital for neonates was 5.8 days shorter (95% confidence interval [CI] 6.1 to 8.5 days) for buprenorphine exposure in utero compared to methadone (P=0.001). For neonates requiring treatment for Neonatal abstinence syndrome, those with in utero exposure to buprenorphine required 6.1 fewer days (95% CI 2.5 to 9.7) of treatment with morphine then those exposed to methadone (P<0.0005). There were no statistically significant differences in day of life of initiation of morphine therapy for each of the study groups. The proportion of neonates requiring adjuvant therapy with phenobarbital was statistically significantly higher in neonates exposed to methadone in utero than either buprenorphine or illicit opioids (P<0.0005). CONCLUSIONS: Retrospective data suggest that neonates with in utero exposure to buprenorphine experience a shorter length of stay in hospital, fewer days of treatment with morphine for neonatal abstinence syndrome, and less use of phenobarbital than neonates exposed in utero to methadone. This suggests that Ontario provincial guidelines should be updated to recommend buprenorphine as first line for replacement therapy in pregnancy.

Quality of life in home-ventilated children and their families.

HMV (home mechanical ventilation) in children has increased over the last years. The aim of the study was to assess perceived quality of life (QOL) of these children and their families as well as the problems they face in their daily life.We performed a multicentric cross-sectional study using a semi-structured interview about the impact of HMV on families and an evaluation questionnaire about perceived QOL by the patient and their families (pediatric quality of life questionnaire (PedsQL4.0)). We studied 41 subjects (mean age 8.2 years). Global scores in PedsQL questionnaire for subjects (median 61.4), and their parents (median 52.2) were below those of healthy children. 24.4% received medical follow-up at home and 71.8% attended school. Mothers were the main caregivers (75.6%), 48.8% of which were fully dedicated to the care of their child. 71.1% consider economic and healthcare resources insufficient. All families were satisfied with the care they provide to their children, even though it was considered emotionally overwhelming (65.9%). Marital conflict and neglect of siblings appeared in 42.1 and 36% of families, respectively. CONCLUSIONS: Perceived QOL by children with HMV and their families is lower than that of healthy children. Parents are happy to care for their children at home, even though it negatively affects family life. What is Known: • The use of home mechanical ventilation (HMV) in children has increased over the last years. • Normal family functioning is usually disrupted by HMV. What is New: • The aim of HMV is to provide a lifestyle similar to that of healthy children, but perceived quality of life by these patients and their parents is low. • Most of the families caring for children on HMV agree that support and resources provided by national health institutions is insufficient.

Evaluation of sublingual microcirculation in a paediatric intensive care unit: prospective observational study about its feasibility and utility.

BACKGROUND: Evaluation of the microcirculation in critically ill patients is usually done by means of indirect parameters. The aim of our study was to evaluate the functional state of the microcirculation by direct visualization of sublingual microcirculation using Sidestream Dark Field Imaging, to determine the correlation between these findings and other parameters that are commonly used in the clinical practice and to assess the applicability of the systematic use of this technique in critically ill children. METHODS: A prospective observational study was carried out in a Pediatric Intensive Care Unit (PICU) of a tertiary referral hospital. All patients admitted to the PICU during a three-month period were included in the study after obtaining the informed consent from the patient. Systematic evaluation of sublingual microcirculation was done in these patients (Total Vessel Density, Proportion of Perfused Vessels, Perfused Vessel Density, De Backer Score, Microvascular Flow Index, Heterogeneity Index) within the first day of admission (T1) and between the second and third day of admission (T2). Other clinical, hemodynamic, and biochemical parameters were measured and registered simultaneously. When the evaluation of the microcirculation was not feasible, the reason was registered. Descriptive analysis of our findings are expressed as means, medians, standard deviations and interquartile ranges. Mann-Whitney-Wilcoxon and Fisher tests were used to compare variables between patients with and without evaluation of the microcirculation. Pearson Correlation Coefficient (ρ) was used to evaluate the correlation between microcirculatory parameters and other clinical parameters. RESULTS: One hundred fine patients were included during the study period. Evaluation of the microcirculation was feasible in 18 patients (17.1%). 95.2% of them were intubated. The main reason for not evaluating microcirculation was the presence of respiratory difficulty or the absence of collaboration (95.1% on T1 and 68.9% on T2). Evaluated patients had a higher prevalence of intubation and ECMO at admission (72.2% vs. 14.9% and 16.6% vs. 1.1%, respectively), and longer median duration of mechanical ventilation (0 vs. 6.5 days), vasoactive drugs (0 vs. 3.5 days) and length of stay (3 vs. 16.5 days) than non-evaluated patients. There was a moderate correlation between microcirculatory parameters and systolic arterial pressure, central venous pressure, serum lactate and other biochemical parameters used for motoring critically ill children. CONCLUSIONS: Systematic evaluation of microcirculation in critically ill children is not feasible in the unstable critically ill patient, but it is feasible in stable critically ill children. Microcirculatory parameters show a moderate correlation with other parameters that are usually monitored in critically ill children.

C-spine injury and mandibular fractures: lifesaver broken in two spots.

BACKGROUND: Trauma is a leading cause of injury and mortality and may involve mandibular fractures and cervical spine injuries. Manipulation of the spine during trauma protocols and operative treatment has the potential to cause serious spinal cord injuries. The purpose of this study was to identify risk factors associated with cervical spine injury (CSI) in patients with mandibular fractures. METHODS: The National Trauma Databank (2007-2010) was used to identify patients with mandibular fractures. RESULTS: A total of 59,028 patients were identified and separated into adult and pediatric cohorts. There were 50,711 adults (86%) and 8317 children (14%). There were statistically significant lower rates of associated CSI in pediatric patients than adults (3.5% versus 7.3%, P < 0.01). Predictors of associated CSI in mandible fractures for both adults and children were older age, lower Glasgow Coma Scale, thoracic injuries, firearm or motor vehicle accident mechanisms, and symphyseal fractures. In the pediatric cohort, body, ramus, and subcondylar fractures were significantly associated with CSI. In adults, female gender, and upper extremity, abdominopelvic, and head injuries were also significantly associated with CSI. CONCLUSIONS: Multiple mandibular fractures were inversely correlated with CSI. One possibility is that energy dissipation in the mandible with multiple fractures is protective of the C-spine leading to fewer fractures. Children and adults had different associations in the pattern of mandible fractures concomitant with CSI. This has implications in management, imaging, and workup of trauma patients.

Comparative Outcomes and Quality Analysis of Inverted-T and Pure Vertical Scar Techniques in Superomedial Pedicle Reduction Mammaplasty.

INTRODUCTION: Multiple techniques exist for reduction mammoplasty, but no singular consensus exists as to which method is the most effective in providing an aesthetically pleasing breast. We reviewed our institution's reduction mammoplasty experience over a 2-year period to evaluate aesthetic and surgical outcomes comparing superiorly based pedicles with skin excisions resulting in either an inverted T or vertical scar. METHODS: An IRB-approved retrospective review of our institution's surgical database identified patient characteristics and outcomes of all breast reductions performed over a 2-year period (n = 104). A subgroup analysis of patients with complete preoperative and postoperative photographs (n = 56) evaluated postoperative aesthetics on a scale of 1 to 5 (1, poor; 5, excellent). RESULTS: Techniques included a superomedial pedicle with an inverted T-pattern skin excision (n = 81) and pure vertical reduction (n = 23). There was no significant difference in complications between techniques. Common patient risk factors (age, body mass index [BMI], and smoking status) did not correlate with postoperative complications. In the photograph analysis subgroup, inverted T scar pattern reductions had a significantly better scar quality score (3.5 vs 3.2, P < 0.05). In analysis of all subjects, volume of tissue resected was a significant factor in determining overall aesthetic score, with resections of less than 1300 g being significantly associated with an overall aesthetic score of 4 or higher. Logistic regression demonstrated patient age younger than 40 years was a significant contributor to aesthetic score of 4 or higher (P < 0.05). DISCUSSION: We reviewed our institution's experience with 2 common breast reduction techniques. Better scarring was associated with inverted T scar pattern versus vertical pattern. Additionally, rather than pedicle type or skin excision pattern, patient age and weight of tissue resected were the most important contributors to an aesthetically optimal outcome. This study suggests that a single superlative technique does not exist. Rather, inherent patient characteristics are most important in provision of the best aesthetic outcome.

Constipation in the Critically Ill Child: Frequency and Related Factors.

OBJECTIVE: To analyze the incidence and factors associated with constipation in critically ill children. STUDY DESIGN: We performed a prospective observational study that included children admitted to the pediatric intensive care unit for more than 3 days. Constipation was defined as more than 3 days without a bowel movement. Relationships between constipation and demographic data; clinical severity score; use of mechanical ventilation, use of vasoconstrictors, sedatives, and muscle relaxants; nutritional data; electrolyte disturbances; and clinical course were analyzed. RESULTS: Constipation developed in 46.7% of the 150 patients studied (mean age, 34.3 ± 7.1 months). It was most common in postoperative, older, and higher-body-weight patients, and in those with fecal continence (P < .01). Compared with patients without constipation, patients with constipation had higher severity scores and more frequently received midazolam, fentanyl, muscle relaxants, and inotropic support (P < .05). Patients with constipation also started nutrition later and with a lower volume of nutrition (P < .01). There were no between-group differences in mortality or length of pediatric intensive care unit stay. In multivariate analysis, independent factors associated with constipation were body weight (OR, 1.08; 95% CI, 1.03-1.13), Pediatric Index of Mortality 2 score (OR, 1.05; 95% CI, 1.02-1.09), admission after surgery (OR, 7.64; 95% CI, 2.56-22.81), and treatment with vasoconstrictors (OR, 10.28; 95% CI, 3.53-29.93). CONCLUSION: Constipation is common in critically ill children. Body weight, Pediatric Index of Mortality 2 clinical severity score, admission after surgery, and the need for vasoconstrictor therapy are major independent risk factors associated with constipation.

Chemoselective chromium(II)-catalyzed cross-coupling reactions of dichlorinated heteroaromatics with functionalized aryl grignard reagents.

Chromium(II) chloride catalyzes the chemoselective cross-coupling reaction of dichloropyridines with a range of functionalized (hetero)aromatic Grignard reagents at room temperature. Functional groups, such as esters and acetals, are well tolerated in this transformation. Previously challenging substrates, quinolines and isoquinolines, participate in the selective Cr-catalyzed cross-coupling in cyclopentyl methyl ether (CPME) as the solvent. The effective purging of Cr salts is demonstrated by using various solid supports.

Practical Iron- and Cobalt-Catalyzed Cross-Coupling Reactions between N-Heterocyclic Halides and Aryl or Heteroaryl Magnesium Reagents.

The reaction scope of iron- and cobalt-catalyzed cross-coupling reactions in the presence of isoquinoline (quinoline) in the solvent mixture tBuOMe/THF has been further investigated. Various 2-halogenated pyridine, pyrimidine, and triazine derivatives were arylated under these mild conditions in excellent yields. The presence of isoquinoline allows us to perform Fe-catalyzed cross-coupling reactions between 6-chloroquinoline and aryl magnesium reagents. Furthermore, it was found that the use of 10% N,N-dimethylquinoline-8-amine increases the yields of some Co-catalyzed cross-coupling reactions with chloropyridines bearing electron-withdrawing substituents.

Measurement of cardiac output in children by pressure-recording analytical method.

We evaluated two pressure-recording analytical method (PRAM) software versions (v.1 and v.2) to measure cardiac index (CI) in hemodynamically stable critically ill children and investigate factors that influence PRAM values. The working hypothesis was that PRAM CI measurements would stay within normal limits in hemodynamically stable patients. Ninety-five CI PRAM measurements were analyzed in 47 patients aged 1-168 months. Mean CI was 4.1 ± 1.4 L/min/m(2) (range 2.0-7.0). CI was outside limits defined as normal (3-5 L/min/m(2)) in 53.7% of measurements (47.8% with software v.1 and 69.2% with software v.2, p = 0.062). Moreover, 14.7% of measurements were below 2.5 L/min/m(2), and 13.6% were above 6 L/min/m(2). CI was significantly lower in patients with a clearly visible dicrotic notch than in those without (3.7 vs. 4.6 L/min/m(2), p = 0.004) and in children with a radial arterial catheter (3.5 L/min/m(2)) than in those with a brachial (4.4 L/min/m(2), p = 0.021) or femoral catheter (4.7 L/min/m(2), p = 0.005). By contrast, CI was significantly higher in children under 12 months (4.2 vs. 3.6 L/min/m(2), p = 0.034) and weighing under 10 kg (4.2 vs. 3.6 L/min/m(2), p = 0.026). No significant differences were observed between cardiac surgery patients and the rest of children. A high percentage of CI measurements registered by PRAM were outside normal limits in hemodynamically stable, critically ill children. CI measured by PRAM may be influenced by the age, weight, location of catheter, and presence of a dicrotic notch.

Adrenaline, terlipressin, and corticoids versus adrenaline in the treatment of experimental pediatric asphyxial cardiac arrest.

OBJECTIVE: To analyze if treatment with adrenaline (epinephrine) plus terlipressin plus corticoids achieves higher return of spontaneous circulation than adrenaline in an experimental infant animal model of asphyxial cardiac arrest. DESIGN: Prospective randomized animal study. SETTING: Experimental department in a University Hospital. SUBJECTS: Forty-nine piglets were studied. INTERVENTIONS: Cardiac arrest was induced by at least 10 minutes of removal of mechanical ventilation and was followed by manual external chest compressions and mechanical ventilation. After 3 minutes of resuscitation, piglets that did not achieve return of spontaneous circulation were randomized to two groups: adrenaline 0.02 mg kg every 3 minutes (20 animals) and adrenaline 0.02 mg kg every 3 minutes plus terlipressin 20 µg kg every 6 minutes plus hydrocortisone 30 mg kg one dose (22 animals). Resuscitation was discontinued when return of spontaneous circulation was achieved or after 24 minutes. MEASUREMENT AND MAIN RESULTS: Return of spontaneous circulation was achieved in 14 piglets (28.5%), 14.2% with only cardiac massage and ventilation. Return of spontaneous circulation was achieved in 25% of piglets treated with adrenaline and in 9.1% of those treated with adrenaline plus terlipressin plus hydrocortisone (p = 0.167). Return of spontaneous circulation was achieved in 45.4% of animals with pulseless electric activity, 20% with asystole, and 0% with ventricular fibrillation (p = 0.037). Shorter duration of cardiac arrest, higher mean blood pressure and EtCO2 and lower PaCO2 before resuscitation, and higher mean blood pressure during resuscitation were associated with higher return of spontaneous circulation. CONCLUSIONS: Treatment with adrenaline plus terlipressin plus corticoids does not achieve higher return of spontaneous circulation than that with adrenaline in an infant animal model of asphyxial cardiac arrest.

Postoperative neutrophil gelatinase-associated lipocalin predicts acute kidney injury after pediatric cardiac surgery*.

OBJECTIVE: We investigated the temporal pattern and predictive value of neutrophil gelatinase-associated lipocalin for early identification of acute kidney injury in children undergoing cardiac surgery. DESIGN: Prospective observational cohort study. SETTING: One PICU in a tertiary medical center in Madrid, Spain. PATIENTS: One hundred six children older than 15 days and younger than 16 years undergoing surgery for congenital cardiac lesions. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Urine samples were obtained before and at intervals after surgery. Acute kidney injury was defined according to pediatric Risk, Injury, Failure, Loss, and End-stage kidney disease criteria. The temporal pattern of both urine neutrophil gelatinase-associated lipocalin absolute concentration elevation and normalized to urine creatinine concentration was correlated with the development of acute kidney injury and other clinical outcomes. We evaluated the predictive ability of both urine neutrophil gelatinase-associated lipocalin and urine neutrophil gelatinase-associated lipocalin/creatinine by area under the curve, when added to a clinical predictive model. Data from 106 pediatric patients were analyzed. Acute kidney injury occurred in 42 patients (39.6%). Urine neutrophil gelatinase-associated lipocalin significantly increased in patients with acute kidney injury at 1, 3, and 15 hours postoperatively. Urine neutrophil gelatinase-associated lipocalin and urine neutrophil gelatinase-associated lipocalin/creatinine correlated with surgical variables and clinical outcomes. Acute kidney injury prediction improved when urine neutrophil gelatinase-associated lipocalin was added to a clinical model (area under the curve increased at 1 hr from 0.85 to 0.91 and at 3 hr to 0.92). Neither the urine neutrophil gelatinase-associated lipocalin nor the urine neutrophil gelatinase-associated lipocalin/creatinine values were significantly different between patients with prerenal and sustained acute kidney injury. CONCLUSIONS: Urine neutrophil gelatinase-associated lipocalin is a predictive biomarker for acute kidney injury after pediatric cardiac surgery, and it may permit earlier intervention that improves outcome of acute kidney injury. Urine neutrophil gelatinase-associated lipocalin normalized to urine creatinine improves the prediction of acute kidney injury severity but offers no advantage in acute kidney injury diagnosis.

Factors associated with successful liberation from continuous renal replacement therapy in children and young adults: analysis of the worldwide exploration of renal replacement outcomes collaborative in Kidney Disease Registry.

PURPOSE: Continuous renal replacement therapy (CRRT) is used for supportive management of acute kidney injury (AKI) and disorders of fluid balance (FB). Little is known about the predictors of successful liberation in children and young adults. We aimed to identify the factors associated with successful CRRT liberation. METHODS: The Worldwide Exploration of Renal Replacement Outcomes Collaborative in Kidney Disease study is an international multicenter retrospective study (32 centers, 7 nations) conducted from 2015 to 2021 in children and young adults (aged 0-25 years) treated with CRRT for AKI or FB disorders. Patients with previous dialysis dependence, tandem extracorporeal membrane oxygenation use, died within the first 72 h of CRRT initiation, and those who never had liberation attempted were excluded. Patients were categorized based on first liberation attempt: reinstituted (resumption of any dialysis within 72 h) vs. success (no receipt of dialysis for ≥ 72 h). Multivariable logistic regression was used to identify factors associated with successful CRRT liberation. RESULTS: A total of 622 patients were included: 287 (46%) had CRRT reinstituted and 335 (54%) were successfully liberated. After adjusting for sepsis at admission and illness severity parameters, several factors were associated with successful liberation, including higher VIS (vasoactive-inotropic score) at CRRT initiation (odds ratio [OR] 1.35 [1.12-1.63]), higher PELOD-2 (pediatric logistic organ dysfunction-2) score at CRRT initiation (OR 1.71 [1.24-2.35]), higher urine output prior to CRRT initiation (OR 1.15 [1.001-1.32]), and shorter CRRT duration (OR 0.19 [0.12-0.28]). CONCLUSIONS: Inability to liberate from CRRT was common in this multinational retrospective study. Modifiable and non-modifiable factors were associated with successful liberation. These results may inform the design of future clinical trials to optimize likelihood of CRRT liberation success.

Major Adverse Kidney Events in Pediatric Continuous Kidney Replacement Therapy.

Importance: Continuous kidney replacement therapy (CKRT) is increasingly used in youths with critical illness, but little is known about longer-term outcomes, such as persistent kidney dysfunction, continued need for dialysis, or death. Objective: To characterize the incidence and risk factors, including liberation patterns, associated with major adverse kidney events 90 days after CKRT initiation (MAKE-90) in children, adolescents, and young adults. Design, Setting, and Participants: This international, multicenter cohort study was conducted among patients aged 0 to 25 years from The Worldwide Exploration of Renal Replacement Outcomes Collaborative in Kidney Disease (WE-ROCK) registry treated with CKRT for acute kidney injury or fluid overload from 2015 to 2021. Exclusion criteria were dialysis dependence, concurrent extracorporeal membrane oxygenation use, or receipt of CKRT for a different indication. Data were analyzed from May 2 to December 14, 2023. Exposure: Patient clinical characteristics and CKRT parameters were assessed. CKRT liberation was classified as successful, reinstituted, or not attempted. Successful liberation was defined as the first attempt at CKRT liberation resulting in 72 hours or more without return to dialysis within 28 days of CKRT initiation. Main Outcomes and Measures: MAKE-90, including death or persistent kidney dysfunction (dialysis dependence or ≥25% decline in estimated glomerular filtration rate from baseline), were assessed. Results: Among 969 patients treated with CKRT (529 males [54.6%]; median [IQR] age, 8.8 [1.7-15.0] years), 630 patients (65.0%) developed MAKE-90. On multivariable analysis, cardiac comorbidity (adjusted odds ratio [aOR], 1.60; 95% CI, 1.08-2.37), longer duration of intensive care unit admission before CKRT initiation (aOR for 6 days vs 1 day, 1.07; 95% CI, 1.02-1.13), and liberation pattern were associated with MAKE-90. In this analysis, patients who successfully liberated from CKRT within 28 days had lower odds of MAKE-90 compared with patients in whom liberation was attempted and failed (aOR, 0.32; 95% CI, 0.22-0.48) and patients without a liberation attempt (aOR, 0.02; 95% CI, 0.01-0.04). Conclusions and Relevance: In this study, MAKE-90 occurred in almost two-thirds of the population and patient-level risk factors associated with MAKE-90 included cardiac comorbidity, time to CKRT initiation, and liberation patterns. These findings highlight the high incidence of adverse outcomes in this population and suggest that future prospective studies are needed to better understand liberation patterns and practices.

Efficient chromium(II)-catalyzed cross-coupling reactions between Csp2 centers.

Low-toxicity chromium(II) chloride catalyzes at 25 °C within minutes the coupling reactions of various (hetero)arylmagnesium reagents with N-heterocyclic halides, aromatic halogenated ketones or imines, and alkenyl iodides. Remarkably, much lower amounts of homo-coupling side products are obtained compared to related iron, cobalt, or manganese cross-couplings.

Protocol for treatment of constipation with polyethylene glycol 3350 plus electrolytes in critically ill children.

INTRODUCTION AND OBJECTIVES: No studies have analysed the effectiveness of treatment for constipation in critically ill children. The aim of this study was to assess the implementation, efficacy and safety of a treatment protocol using polyethylene glycol 3350 with electrolytes (PEG 3350 + E) for constipation in critically ill children. METHODS: We conducted a single-centre prospective study in children admitted to the paediatric intensive care unit for a minimum of 72 h and who developed constipation. Children with previous gastrointestinal disorders or diseases were excluded. The patients were treated with rectal enemas or with the oral PEG 3350 + E protocol at the discretion of the treating physician. We compared clinical and demographic variables as well as adverse events (diarrhoea, abdominal distension and electrolyte imbalances). RESULTS: The sample included 56 patients with a mean age of 48.2 ±â€¯11.9 months, of who 55.4% were male. Forty-four patients (78.6%) were treated with PEG 3350 + E and 12 (21.4%) with rectal enemas. The proportion of patients that responded well to treatment was greater in the PEG 3350 + E group (79.5%) compared to the enema group (58.3%), but the difference was not statistically significant (P = .151). There were no significant differences between the groups in any of the adverse effects. Treatment with PEG 3350 + E was more effective in children aged less than 2 years (100%) compared to older children (100% vs 65.4%; P < .01), with no significant differences in the development of adverse events. CONCLUSIONS: The PEG 3350 + E treatment protocol for constipation in critically ill children was effective and associated with few adverse events, even in children aged less than 2 years.

Volumetric capnography and return of spontaneous circulation in an experimental model of pediatric asphyxial cardiac arrest.

A secondary analysis of a randomized study was performed to study the relationship between volumetric capnography (VCAP) and arterial CO2 partial pressure (PCO2) during cardiopulmonary resuscitation (CPR) and to analyze the ability of these parameters to predict the return of spontaneous circulation (ROSC) in a pediatric animal model of asphyxial cardiac arrest (CA). Asphyxial CA was induced by sedation, muscle relaxation and extubation. CPR was started 2 min after CA occurred. Airway management was performed with early endotracheal intubation or bag-mask ventilation, according to randomization group. CPR was continued until ROSC or 24 min of resuscitation. End-tidal carbon dioxide (EtCO2), CO2 production (VCO2), and EtCO2/VCO2/kg ratio were continuously recorded. Seventy-nine piglets were included, 26 (32.9%) of whom achieved ROSC. EtCO2 was the best predictor of ROSC (AUC 0.72, p < 0.01 and optimal cutoff point of 21.6 mmHg). No statistical differences were obtained regarding VCO2, VCO2/kg and EtCO2/VCO2/kg ratios. VCO2 and VCO2/kg showed an inverse correlation with PCO2, with a higher correlation coefficient as resuscitation progressed. EtCO2 also had an inverse correlation with PCO2 from minute 18 to 24 of resuscitation. Our findings suggest that EtCO2 is the best VCAP-derived parameter for predicting ROSC. EtCO2 and VCO2 showed an inverse correlation with PCO2. Therefore, these parameters are not adequate to measure ventilation during CPR.