Tight Blood-Glucose Control without Early Parenteral Nutrition in the ICU.

BACKGROUND: Randomized, controlled trials have shown both benefit and harm from tight blood-glucose control in patients in the intensive care unit (ICU). Variation in the use of early parenteral nutrition and in insulin-induced severe hypoglycemia might explain this inconsistency. METHODS: We randomly assigned patients, on ICU admission, to liberal glucose control (insulin initiated only when the blood-glucose level was >215 mg per deciliter [>11.9 mmol per liter]) or to tight glucose control (blood-glucose level targeted with the use of the LOGIC-Insulin algorithm at 80 to 110 mg per deciliter [4.4 to 6.1 mmol per liter]); parenteral nutrition was withheld in both groups for 1 week. Protocol adherence was determined according to glucose metrics. The primary outcome was the length of time that ICU care was needed, calculated on the basis of time to discharge alive from the ICU, with death accounted for as a competing risk; 90-day mortality was the safety outcome. RESULTS: Of 9230 patients who underwent randomization, 4622 were assigned to liberal glucose control and 4608 to tight glucose control. The median morning blood-glucose level was 140 mg per deciliter (interquartile range, 122 to 161) with liberal glucose control and 107 mg per deciliter (interquartile range, 98 to 117) with tight glucose control. Severe hypoglycemia occurred in 31 patients (0.7%) in the liberal-control group and 47 patients (1.0%) in the tight-control group. The length of time that ICU care was needed was similar in the two groups (hazard ratio for earlier discharge alive with tight glucose control, 1.00; 95% confidence interval, 0.96 to 1.04; P = 0.94). Mortality at 90 days was also similar (10.1% with liberal glucose control and 10.5% with tight glucose control, P = 0.51). Analyses of eight prespecified secondary outcomes suggested that the incidence of new infections, the duration of respiratory and hemodynamic support, the time to discharge alive from the hospital, and mortality in the ICU and hospital were similar in the two groups, whereas severe acute kidney injury and cholestatic liver dysfunction appeared less prevalent with tight glucose control. CONCLUSIONS: In critically ill patients who were not receiving early parenteral nutrition, tight glucose control did not affect the length of time that ICU care was needed or mortality. (Funded by the Research Foundation-Flanders and others; TGC-Fast ClinicalTrials.gov number, NCT03665207.).

Intermittent intravenous paracetamol versus continuous morphine in infants undergoing cardiothoracic surgery: a multi-center randomized controlled trial.

BACKGROUND: To determine whether intermittent intravenous (IV) paracetamol as primary analgesic would significantly reduce morphine consumption in children aged 0-3 years after cardiac surgery with cardiopulmonary bypass. METHODS: Multi-center, randomized, double-blinded, controlled trial in four level-3 Pediatric Intensive Care Units (PICU) in the Netherlands and Belgium. Inclusion period; March 2016-July 2020. Children aged 0-3 years, undergoing cardiac surgery with cardiopulmonary bypass were eligible. Patients were randomized to continuous morphine or intermittent IV paracetamol as primary analgesic after a loading dose of 100 mcg/kg morphine was administered at the end of surgery. Rescue morphine was given if numeric rating scale (NRS) pain scores exceeded predetermined cutoff values. Primary outcome was median weight-adjusted cumulative morphine dose in mcg/kg in the first 48 h postoperative. For the comparison of the primary outcome between groups, the nonparametric Van Elteren test with stratification by center was used. For comparison of the proportion of patients with one or more NRS pain scores of 4 and higher between the two groups, a non-inferiority analysis was performed using a non-inferiority margin of 20%. RESULTS: In total, 828 were screened and finally 208 patients were included; parents of 315 patients did not give consent and 305 were excluded for various reasons. Fourteen of the enrolled 208 children were withdrawn from the study before start of study medication leaving 194 patients for final analysis. One hundred and two patients received intermittent IV paracetamol, 106 received continuous morphine. The median weight-adjusted cumulative morphine consumption in the first 48 h postoperative in the IV paracetamol group was 5 times lower (79%) than that in the morphine group (median, 145.0 (IQR, 115.0-432.5) mcg/kg vs 692.6 (IQR, 532.7-856.1) mcg/kg; P < 0.001). The rescue morphine consumption was similar between the groups (p = 0.38). Non-inferiority of IV paracetamol administration in terms of NRS pain scores was proven; difference in proportion - 3.1% (95% CI - 16.6-10.3%). CONCLUSIONS: In children aged 0-3 years undergoing cardiac surgery, use of intermittent IV paracetamol reduces the median weight-adjusted cumulative morphine consumption in the first 48 h after surgery by 79% with equal pain relief showing equipoise for IV paracetamol as primary analgesic. Trial Registration Clinicaltrials.gov, Identifier: NCT05853263; EudraCT Number: 2015-001835-20.

Endovascular transatrial stenting of pulmonary vein stenosis after lung transplantation.

Pulmonary vein stenosis (PVS) and pulmonary vein occlusion (PVO) represent rare complications after lung transplantation (LTx), with limited therapeutic options and a high risk of graft loss. We present 2 cases of successful endovascular transatrial stenting following double LTx. A 60-year-old woman with chronic obstructive pulmonary disease who underwent double lobar LTx was diagnosed at postoperative day 72 with a high-grade PVS on the left side. A 22-year-old woman with idiopathic pulmonary arterial hypertension who underwent double LTx was diagnosed 9 days later with PVO of the left upper lobe vein. To avoid surgical reintervention, endovascular transatrial dilatation and stenting were performed successfully in both cases. Transatrial endovascular stenting of PVS or PVO after LTx seems an effective and safe treatment option that should be considered for these life-threatening complications and executed with care.

Long-term outcomes of acute kidney injury in children.

PURPOSE OF REVIEW: Acute kidney injury (AKI) affects up to 35% of all critically ill children and is associated with substantial short-term morbidity and mortality. However, the link between paediatric AKI and long-term adverse outcomes remains incompletely understood. This review highlights the most recent clinical data supporting the role of paediatric AKI as a risk factor for long-term kidney and cardiovascular consequences. In addition, it stresses the need for long-term surveillance of paediatric AKI survivors. RECENT FINDINGS: Recent large-scale studies have led to an increasing understanding that paediatric AKI is a significant risk factor for adverse outcomes such as hypertension, cardiovascular disease and chronic kidney disease (CKD) over time. These long-term sequelae of paediatric AKI are most often observed in vulnerable populations, such as critically ill children, paediatric cardiac surgery patients, children who suffer from severe infections and paediatric cancer patients. SUMMARY: A growing body of research has shown that paediatric AKI is associated with long-term adverse outcomes such as CKD, hypertension and cardiovascular disease. Although therapeutic pathways tailored to individual paediatric AKI patients are yet to be validated, we provide a framework to guide monitoring and prevention in children at the highest risk for developing long-term kidney dysfunction.

International survey of neuromonitoring and neurodevelopmental outcome in children and adults supported on extracorporeal membrane oxygenation in Europe.

BACKGROUND: Adverse neurological events during extracorporeal membrane oxygenation (ECMO) are common and may be associated with devastating consequences. Close monitoring, early identification and prompt intervention can mitigate early and late neurological morbidity. Neuromonitoring and neurocognitive/neurodevelopmental follow-up are critically important to optimize outcomes in both adults and children. OBJECTIVE: To assess current practice of neuromonitoring during ECMO and neurocognitive/neurodevelopmental follow-up after ECMO across Europe and to inform the development of neuromonitoring and follow-up guidelines. METHODS: The EuroELSO Neurological Monitoring and Outcome Working Group conducted an electronic, web-based, multi-institutional, multinational survey in Europe. RESULTS: Of the 211 European ECMO centres (including non-ELSO centres) identified and approached in 23 countries, 133 (63%) responded. Of these, 43% reported routine neuromonitoring during ECMO for all patients, 35% indicated selective use, and 22% practiced bedside clinical examination alone. The reported neuromonitoring modalities were NIRS (n = 88, 66.2%), electroencephalography (n = 52, 39.1%), transcranial Doppler (n = 38, 28.5%) and brain injury biomarkers (n = 33, 24.8%). Paediatric centres (67%) reported using cranial ultrasound, though the frequency of monitoring varied widely. Before hospital discharge following ECMO, 50 (37.6%) reported routine neurological assessment and 22 (16.5%) routinely performed neuroimaging with more paediatric centres offering neurological assessment (65%) as compared to adult centres (20%). Only 15 (11.2%) had a structured longitudinal follow-up pathway (defined followup at regular intervals), while 99 (74.4%) had no follow-up programme. The majority (n = 96, 72.2%) agreed that there should be a longitudinal structured follow-up for ECMO survivors. CONCLUSIONS: This survey demonstrated significant variability in the use of different neuromonitoring modalities during and after ECMO. The perceived importance of neuromonitoring and follow-up was noted to be very high with agreement for a longitudinal structured follow-up programme, particularly in paediatric patients. Scientific society endorsed guidelines and minimum standards should be developed to inform local protocols.

Postoperative Cerebral Oxygen Saturation in Children After Congenital Cardiac Surgery and Long-Term Total Intelligence Quotient: A Prospective Observational Study.

OBJECTIVES: During the early postoperative period, children with congenital heart disease can suffer from inadequate cerebral perfusion, with possible long-term neurocognitive consequences. Cerebral tissue oxygen saturation can be monitored noninvasively with near-infrared spectroscopy. In this prospective study, we hypothesized that reduced cerebral tissue oxygen saturation and increased intensity and duration of desaturation (defined as cerebral tissue oxygen saturation < 65%) during the early postoperative period, independently increase the probability of reduced total intelligence quotient, 2 years after admission to a PICU. DESIGN: Single-center, prospective study, performed between 2012 and 2015. SETTING: The PICU of the University Hospitals Leuven, Belgium. PATIENTS: The study included pediatric patients after surgery for congenital heart disease admitted to the PICU. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Postoperative cerebral perfusion was characterized with the mean cerebral tissue oxygen saturation and dose of desaturation of the first 12 and 24 hours of cerebral tissue oxygen saturation monitoring. The independent association of postoperative mean cerebral tissue oxygen saturation and dose of desaturation with total intelligence quotient at 2-year follow-up was evaluated with a Bayesian linear regression model adjusted for known confounders. According to a noninformative prior, reduced mean cerebral tissue oxygen saturation during the first 12 hours of monitoring results in a loss of intelligence quotient points at 2 years, with a 90% probability (posterior ß estimates [80% credible interval], 0.23 [0.04-0.41]). Similarly, increased dose of cerebral tissue oxygen saturation desaturation would result in a loss of intelligence quotient points at 2 years with a 90% probability (posterior ß estimates [80% credible interval], -0.009 [-0.016 to -0.001]). CONCLUSIONS: Increased dose of cerebral tissue oxygen saturation desaturation and reduced mean cerebral tissue oxygen saturation during the early postoperative period independently increase the probability of having a lower total intelligence quotient, 2 years after PICU admission.

Early versus Late Parenteral Nutrition in Critically Ill Children.

BACKGROUND: Recent trials have questioned the benefit of early parenteral nutrition in adults. The effect of early parenteral nutrition on clinical outcomes in critically ill children is unclear. METHODS: We conducted a multicenter, randomized, controlled trial involving 1440 critically ill children to investigate whether withholding parenteral nutrition for 1 week (i.e., providing late parenteral nutrition) in the pediatric intensive care unit (ICU) is clinically superior to providing early parenteral nutrition. Fluid loading was similar in the two groups. The two primary end points were new infection acquired during the ICU stay and the adjusted duration of ICU dependency, as assessed by the number of days in the ICU and as time to discharge alive from ICU. For the 723 patients receiving early parenteral nutrition, parenteral nutrition was initiated within 24 hours after ICU admission, whereas for the 717 patients receiving late parenteral nutrition, parenteral nutrition was not provided until the morning of the 8th day in the ICU. In both groups, enteral nutrition was attempted early and intravenous micronutrients were provided. RESULTS: Although mortality was similar in the two groups, the percentage of patients with a new infection was 10.7% in the group receiving late parenteral nutrition, as compared with 18.5% in the group receiving early parenteral nutrition (adjusted odds ratio, 0.48; 95% confidence interval [CI], 0.35 to 0.66). The mean (±SE) duration of ICU stay was 6.5±0.4 days in the group receiving late parenteral nutrition, as compared with 9.2±0.8 days in the group receiving early parenteral nutrition; there was also a higher likelihood of an earlier live discharge from the ICU at any time in the late-parenteral-nutrition group (adjusted hazard ratio, 1.23; 95% CI, 1.11 to 1.37). Late parenteral nutrition was associated with a shorter duration of mechanical ventilatory support than was early parenteral nutrition (P=0.001), as well as a smaller proportion of patients receiving renal-replacement therapy (P=0.04) and a shorter duration of hospital stay (P=0.001). Late parenteral nutrition was also associated with lower plasma levels of γ-glutamyltransferase and alkaline phosphatase than was early parenteral nutrition (P=0.001 and P=0.04, respectively), as well as higher levels of bilirubin (P=0.004) and C-reactive protein (P=0.006). CONCLUSIONS: In critically ill children, withholding parenteral nutrition for 1 week in the ICU was clinically superior to providing early parenteral nutrition. (Funded by the Flemish Agency for Innovation through Science and Technology and others; ClinicalTrials.gov number, NCT01536275.).

Double-lung versus heart-lung transplantation for precapillary pulmonary arterial hypertension: a 24-year single-center retrospective study.

Transplant type for end-stage pulmonary vascular disease remains debatable. We compared recipient outcome after heart-lung (HLT) versus double-lung (DLT) transplantation. Single-center analysis (38 HLT-30 DLT; 1991-2014) for different causes of precapillary pulmonary hypertension (PH): idiopathic (22); heritable (two); drug-induced (nine); hepato-portal (one); connective tissue disease (four); congenital heart disease (CHD) (24); chronic thromboembolic PH (six). HLT decreased from 91.7% [1991-1995] to 21.4% [2010-2014]. Re-intervention for bleeding was higher after HLT; (P = 0.06) while primary graft dysfunction grades 2 and 3 occurred more after DLT; (P < 0.0001). Graft survival at 90 days, 1, 5, 10, and 15 years was 93%, 83%, 70%, 47%, and 35% for DLT vs. 82%, 74%, 61%, 48%, and 30% for HLT, respectively (log-rank P = 0.89). Graft survival improved over time: 100%, 93%, 87%, 72%, and 72% in [2010-2014] vs. 75%, 58%, 42%, 33%, and 33% in [1991-1995], respectively; P = 0.03. No difference in chronic lung allograft dysfunction (CLAD)-free survival was observed: 80% & 28% for DLT vs. 75% & 28% for HLT after 5 and 10 years, respectively; P = 0.49. Primary graft dysfunction in PH patients was lower after HLT compared to DLT. Nonetheless, overall graft and CLAD-free survival were comparable and improved over time with growing experience. DLT remains our preferred procedure for all forms of precapillary PH, except in patients with complex CHD.

Leukocyte telomere length in paediatric critical illness: effect of early parenteral nutrition.

BACKGROUND: Children who have suffered from critical illnesses that required treatment in a paediatric intensive care unit (PICU) have long-term physical and neurodevelopmental impairments. The mechanisms underlying this legacy remain largely unknown. In patients suffering from chronic diseases hallmarked by inflammation and oxidative stress, poor long-term outcome has been associated with shorter telomeres. Shortened telomeres have also been reported to result from excessive food consumption and/or unhealthy nutrition. We investigated whether critically ill children admitted to the PICU have shorter-than-normal telomeres, and whether early parenteral nutrition (PN) independently affects telomere length when adjusting for known determinants of telomere length. METHODS: Telomere length was quantified in leukocyte DNA from 342 healthy children and from 1148 patients who had been enrolled in the multicenter, randomised controlled trial (RCT), PEPaNIC. These patients were randomly allocated to initiation of PN within 24 h (early PN) or to withholding PN for one week in PICU (late PN). The impact of early PN versus late PN on the change in telomere length from the first to last PICU-day was investigated with multivariable linear regression analyses. RESULTS: Leukocyte telomeres were 6% shorter than normal upon PICU admission (median 1.625 (IQR 1.446-1.825) telomere/single-copy-gene ratio (T/S) units vs. 1.727 (1.547-1.915) T/S-units in healthy children (P < 0.0001)). Adjusted for potential baseline determinants and leukocyte composition, early PN was associated with telomere shortening during PICU stay as compared with late PN (estimate early versus late PN -0.021 T/S-units, 95% CI -0.038; 0.004, P = 0.01). Other independent determinants of telomere length identified in this model were age, gender, baseline telomere length and fraction of neutrophils in the sample from which the DNA was extracted. Telomere shortening with early PN was independent of post-randomisation factors affected by early PN, including longer length of PICU stay, larger amounts of insulin and higher risk of infection. CONCLUSIONS: Shorter than normal leukocyte telomeres are present in critically ill children admitted to the PICU. Early initiation of PN further shortened telomeres, an effect that was independent of other determinants. Whether such telomere-shortening predisposes to long-term consequences of paediatric critical illness should be further investigated in a prospective follow-up study. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01536275 . Registered on 16 February 2012.

Near-Infrared Cerebral Oximetry to Predict Outcome After Pediatric Cardiac Surgery: A Prospective Observational Study.

OBJECTIVES: To assess whether near-infrared cerebral tissue oxygen saturation, measured with the FORESIGHT cerebral oximeter (CAS Medical Systems, Branford, CT) predicts PICU length of stay, duration of invasive mechanical ventilation, and mortality in critically ill children after pediatric cardiac surgery. DESIGN: Single-center prospective, observational study. SETTING: Twelve-bed PICU of a tertiary academic hospital. PATIENTS: Critically ill children and infants with congenital heart disease, younger than 12 years old, admitted to the PICU between October 2012 and November 2015. Children were monitored with the FORESIGHT cerebral oximeter from PICU admission until they were weaned off mechanical ventilation. Clinicians were blinded to cerebral tissue oxygen saturation data. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Primary outcome was the predictive value of the first 24 hours of postoperative cerebral tissue oxygen saturation for duration of PICU stay (median [95% CI], 4 d [3-8 d]) and duration of mechanical ventilation (median [95% CI], 111.3 hr (69.3-190.4 hr]). We calculated predictors on the first 24 hours of cerebral tissue oxygen saturation monitoring. The association of each individual cerebral tissue oxygen saturation predictor and of a combination of predictors were assessed using univariable and multivariable bootstrap analyses, adjusting for age, weight, gender, Pediatric Index of Mortality 2, Risk Adjustment in Congenital Heart Surgery 1, cyanotic heart defect, and time prior to cerebral tissue oxygen saturation monitoring. The most important risk factors associated with worst outcomes were an increased SD of a smoothed cerebral tissue oxygen saturation signal and an elevated cerebral tissue oxygen saturation desaturation score. CONCLUSIONS: Increased SD of a smoothed cerebral tissue oxygen saturation signal and increased depth and duration of desaturation below the 50% saturation threshold were associated with longer PICU and hospital stays and with longer duration of mechanical ventilation after pediatric cardiac surgery.

Early versus late parenteral nutrition in critically ill adults.

BACKGROUND: Controversy exists about the timing of the initiation of parenteral nutrition in critically ill adults in whom caloric targets cannot be met by enteral nutrition alone. METHODS: In this randomized, multicenter trial, we compared early initiation of parenteral nutrition (European guidelines) with late initiation (American and Canadian guidelines) in adults in the intensive care unit (ICU) to supplement insufficient enteral nutrition. In 2312 patients, parenteral nutrition was initiated within 48 hours after ICU admission (early-initiation group), whereas in 2328 patients, parenteral nutrition was not initiated before day 8 (late-initiation group). A protocol for the early initiation of enteral nutrition was applied to both groups, and insulin was infused to achieve normoglycemia. RESULTS: Patients in the late-initiation group had a relative increase of 6.3% in the likelihood of being discharged alive earlier from the ICU (hazard ratio, 1.06; 95% confidence interval [CI], 1.00 to 1.13; P=0.04) and from the hospital (hazard ratio, 1.06; 95% CI, 1.00 to 1.13; P=0.04), without evidence of decreased functional status at hospital discharge. Rates of death in the ICU and in the hospital and rates of survival at 90 days were similar in the two groups. Patients in the late-initiation group, as compared with the early-initiation group, had fewer ICU infections (22.8% vs. 26.2%, P=0.008) and a lower incidence of cholestasis (P<0.001). The late-initiation group had a relative reduction of 9.7% in the proportion of patients requiring more than 2 days of mechanical ventilation (P=0.006), a median reduction of 3 days in the duration of renal-replacement therapy (P=0.008), and a mean reduction in health care costs of €1,110 (about $1,600) (P=0.04). CONCLUSIONS: Late initiation of parenteral nutrition was associated with faster recovery and fewer complications, as compared with early initiation. (Funded by the Methusalem program of the Flemish government and others; EPaNIC ClinicalTrials.gov number, NCT00512122.).

Successful clinical transplantation of hearts donated after circulatory death using direct procurement followed by hypothermic oxygenated perfusion: A report of the first 3 cases.

Transplantation of hearts donated after circulatory death (DCD) is emerging. Currently applied techniques (thoraco-abdominal normothermic regional perfusion and direct procurement followed by normothermic machine perfusion) face financial, ethical, and logistical challenges. We report the first three clinical cases of successful direct procurement followed by hypothermic oxygenated perfusion (DP-HOPE) with good 30-day outcome. DP-HOPE is a promising strategy to improve and simplify DCD heart procurement and preservation.

Management of Bleeding and Hemolysis During Percutaneous Microaxial Flow Pump Support: A Practical Approach.

Percutaneous ventricular assist devices (pVADs) are increasingly being used because of improved experience and availability. The Impella (Abiomed), a percutaneous microaxial, continuous-flow, short-term ventricular assist device, requires meticulous postimplantation management to avoid the 2 most frequent complications, namely, bleeding and hemolysis. A standardized approach to the prevention, detection, and treatment of these complications is mandatory to improve outcomes. The risk for hemolysis is mostly influenced by pump instability, resulting from patient- or device-related factors. Upfront echocardiographic assessment, frequent monitoring, and prompt intervention are essential. The precarious hemostatic balance during pVAD support results from the combination of a procoagulant state, due to critical illness and contact pathway activation, together with a variety of factors aggravating bleeding risk. Preventive strategies and appropriate management, adapted to the impact of the bleeding, are crucial. This review offers a guide to physicians to tackle these device-related complications in this critically ill pVAD-supported patient population.

Neurocognitive development of children 4 years after critical illness and treatment with tight glucose control: a randomized controlled trial.

CONTEXT: A large randomized controlled trial revealed that tight glucose control (TGC) to age-adjusted normoglycemia (50-80 mg/dL at age <1 year and 70-100 mg/dL at age 1-16 years) reduced intensive care morbidity and mortality compared with usual care (UC), but increased hypoglycemia (≤40 mg/dL) (25% vs 1%). OBJECTIVE: As both hyperglycemia and hypoglycemia may adversely affect the developing brain, long-term follow-up was required to exclude harm and validate short-term benefits of TGC. DESIGN, SETTING, AND PATIENTS: A prospective, randomized controlled trial of 700 patients aged 16 years or younger who were admitted to the pediatric intensive care unit (ICU) of the University Hospitals in Leuven, Belgium, between October 2004 and December 2007. Follow-up was scheduled after 3 years with infants assessed at 4 years old between August 2008 and January 2012. Assessment was performed blinded for treatment allocation, in-hospital (83%) or at home/school (17%). For comparison, 216 healthy siblings and unrelated children were tested. MAIN OUTCOME MEASURES: Intelligence (full-scale intelligence quotient [IQ]), as assessed with age-adjusted tests (Wechsler IQ scales). Further neurodevelopmental testing encompassed tests for visual-motor integration (Beery-Buktenica Developmental Test of Visual-Motor Integration); attention, motor coordination, and executive functions (Amsterdam Neuropsychological Tasks); memory (Children's Memory Scale); and behavior (Child Behavior Checklist). RESULTS: Sixteen percent of patients declined participation or could not be reached (n = 113), resulting in 569 patients being alive and testable at follow-up. At a median (interquartile range [IQR]) of 3.9 (3.8-4.1) years after randomization, TGC in the ICU did not affect full-scale IQ score (median [IQR], 88.0 [74.0-100.0] vs 88.5 [74.3-99.0] for UC; P = .73) and had not increased incidence of poor outcomes (death or severe disability precluding neurocognitive testing: 19% [68/349] vs 18% [63/351] with UC; risk-adjusted odds ratio, 0.93; 95% CI, 0.60-1.46; P = .72). Other scores for intelligence, visual-motor integration, and memory also did not differ between groups. Tight glucose control improved motor coordination (9% [95% CI, 0%-18%] to 20% [95% CI, 5%-35%] better, all P ≤ .03) and cognitive flexibility (19% [95% CI, 5%-33%] better, P = .02). Brief hypoglycemia evoked by TGC was not associated with worse neurocognitive outcome. CONCLUSION: At follow-up, children who had been treated with TGC during an ICU admission did not have a worse measure of intelligence than those who had received UC. TRIAL REGISTRATION: clinicaltrials.gov Identifier NCT00214916.

Heartmate 3 implantation in small patients: CT-guided chest diameter assessment.

In recent years, the Heartmate 3 (HM3) has largely replaced the use of other intracorporeal left ventricular assist devices in the adult field. Because the HM3 is larger than the Heartware Ventricular Assist Device, the general consensus was that for small patients, the Heartware Ventricular Assist Device was the most appropriate implantable device option. Our goal was to describe our experiences with the successful implantation of the HM3 in 2 children, aged 9 and 11. We report on the chest cavity dimensions, as measured on computed tomography, that can be used to assess the feasibility of HM3 implantation in small patients.

Persistent Markers of Kidney Injury in Children Who Developed Acute Kidney Injury After Pediatric Cardiac Surgery: A Prospective Cohort Study.

Background Acute kidney injury (AKI) after pediatric cardiac surgery is common. Longer-term outcomes and the incidence of chronic kidney disease after AKI are not well-known. Methods and Results All eligible children (aged <16 years) who had developed AKI following cardiac surgery at our tertiary referral hospital were prospectively invited for a formal kidney assessment ≈5 years after AKI, including measurements of estimated glomerular filtration rate, proteinuria, α1-microglobulin, blood pressure, and kidney ultrasound. Longer-term follow-up data on kidney function were collected at the latest available visit. Among 571 patients who underwent surgery, AKI occurred in 113 (19.7%) over a 4-year period. Fifteen of these (13.3%) died at a median of 31 days (interquartile range [IQR], 9-57) after surgery. A total of 66 patients participated in the kidney assessment at a median of 4.8 years (IQR, 3.9-5.7) after the index AKI episode. Thirty-nine patients (59.1%) had at least 1 marker of kidney injury, including estimated glomerular filtration rate <90 mL/min per 1.73 m2 in 9 (13.6%), proteinuria in 27 (40.9%), α1-microglobinuria in 5 (7.6%), hypertension in 13 (19.7%), and abnormalities on kidney ultrasound in 9 (13.6%). Stages 1 to 5 chronic kidney disease were present in 18 (27.3%) patients. Patients with CKD were more likely to have an associated syndrome (55.6% versus 20.8%, P=0.015). At 13.1 years (IQR, 11.2-14.0) follow-up, estimated glomerular filtration rate <90 mL/min per 1.73 m² was present in 18 of 49 patients (36.7%), suggesting an average estimated glomerular filtration rate decline rate of -1.81 mL/min per 1.73 m² per year. Conclusions Children who developed AKI after pediatric cardiac surgery showed persistent markers of kidney injury. As chronic kidney disease is a risk factor for cardiovascular comorbidity, long-term kidney follow-up in this population is warranted.

Pharmacokinetics of Antibiotics in Pediatric Intensive Care: Fostering Variability to Attain Precision Medicine.

Children show important developmental and maturational changes, which may contribute greatly to pharmacokinetic (PK) variability observed in pediatric patients. These PK alterations are further enhanced by disease-related, non-maturational factors. Specific to the intensive care setting, such factors include critical illness, inflammatory status, augmented renal clearance (ARC), as well as therapeutic interventions (e.g., extracorporeal organ support systems or whole-body hypothermia [WBH]). This narrative review illustrates the relevance of both maturational and non-maturational changes in absorption, distribution, metabolism, and excretion (ADME) applied to antibiotics. It hereby provides a focused assessment of the available literature on the impact of critical illness-in general, and in specific subpopulations (ARC, extracorporeal organ support systems, WBH)-on PK and potential underexposure in children and neonates. Overall, literature discussing antibiotic PK alterations in pediatric intensive care is scarce. Most studies describe antibiotics commonly monitored in clinical practice such as vancomycin and aminoglycosides. Because of the large PK variability, therapeutic drug monitoring, further extended to other antibiotics, and integration of model-informed precision dosing in clinical practice are suggested to optimise antibiotic dose and exposure in each newborn, infant, or child during intensive care.

Strategies to Prevent Acute Kidney Injury after Pediatric Cardiac Surgery: A Network Meta-Analysis.

BACKGROUND AND OBJECTIVES: AKI is a common complication after pediatric cardiac surgery and has been associated with higher morbidity and mortality. We aimed to compare the efficacy of available pharmacologic and nonpharmacologic strategies to prevent AKI after pediatric cardiac surgery. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: PubMed/MEDLINE, Embase, Cochrane Controlled Trials Register, and reference lists of relevant articles were searched for randomized controlled trials from inception until August 2020. Random effects traditional pairwise, Bayesian network meta-analyses, and trial sequential analyses were performed. RESULTS: Twenty randomized controlled trials including 2339 patients and 11 preventive strategies met the eligibility criteria. No overall significant differences were observed compared with control for corticosteroids, fenoldopam, hydroxyethyl starch, or remote ischemic preconditioning in traditional pairwise meta-analysis. In contrast, trial sequential analysis suggested a 80% relative risk reduction with dexmedetomidine and evidence of <57% relative risk reduction with remote ischemic preconditioning. Nonetheless, the network meta-analysis was unable to demonstrate any significant differences among the examined treatments, including also acetaminophen, aminophylline, levosimendan, milrinone, and normothermic cardiopulmonary bypass. Surface under the cumulative ranking curve probabilities showed that milrinone (76%) was most likely to result in the lowest risk of AKI, followed by dexmedetomidine (70%), levosimendan (70%), aminophylline (59%), normothermic cardiopulmonary bypass (57%), and remote ischemic preconditioning (55%), although all showing important overlap. CONCLUSIONS: Current evidence from randomized controlled trials does not support the efficacy of most strategies to prevent AKI in the pediatric population, apart from limited evidence for dexmedetomidine and remote ischemic preconditioning.

Supplementation of vitamins, trace elements and electrolytes in the PEPaNIC Randomised Controlled Trial: Composition and preparation of the prescription.

BACKGROUND AND AIMS: Following the results of the paediatric early versus late parenteral nutrition in critical illness (PEPaNIC) multicentre, randomised, controlled trial, the new ESPGHAN/ESPEN/ESPR/CSPEN and ESPNIC guidelines recommend to consider withholding parenteral macronutrients for 1 week, while providing micronutrients, in critically ill children if enteral nutrition is insufficient. Critically ill children are suspected to be vulnerable to micronutrient deficiencies due to inadequate enteral nutrition, increased body's demands and excessive losses. Hitherto, micronutrient requirements in PICU are estimated based on recommended daily intakes for healthy children and expert opinion. We aimed to provide an overview of the current practice of micronutrient administration and practical considerations in the three participating centres of the PEPaNIC study, and compare these therapies with the recommendations in the new ESPGHAN/ESPEN/ESPR/CSPEN guidelines. METHODS: We describe the current composition and preparation of the prescribed parenteral micronutrients (consisting of vitamins, trace elements and electrolytes) in the three centres (Leuven, Rotterdam and Edmonton) that participated in the PEPaNIC RCT, and compare this per micronutrient with the ESPGHAN/ESPEN/ESPR/CSPEN guidelines recommendations. RESULTS: The three centres use a different micronutrient supplementation protocol during the first week of critical illness in children, with substantial differences regarding the amounts administered. Leuven administers commercial vitamins, trace elements and electrolytes in separate infusions both in 4 h. Rotterdam provides commercial vitamins and trace elements simultaneously via 8-h infusion and electrolytes continuously over 24 h. Lastly, Edmonton administers commercial vitamins and institutionally prepared trace elements solutions in 1 h and electrolytes on demand. Comparison with the ESPGHAN/ESPEN/ESPR/CSPEN guidelines yields in differences between the recommendations and the administered amounts, which are most substantial for vitamins. CONCLUSION: The practice of intravenous micronutrient administration differs substantially between the three PEPaNIC centres and in comparison with the current guideline recommendations. This deviation is at least partially explained by the inability to provide all recommended amounts with the currently available commercial products and by the lack of strong evidence supporting these recommendations.

Intensive insulin therapy for patients in paediatric intensive care: a prospective, randomised controlled study.

BACKGROUND: Critically ill infants and children often develop hyperglycaemia, which is associated with adverse outcome; however, whether lowering blood glucose concentrations to age-adjusted normal fasting values improves outcome is unknown. We investigated the effect of targeting age-adjusted normoglycaemia with insulin infusion in critically ill infants and children on outcome. METHODS: In a prospective, randomised controlled study, we enrolled 700 critically ill patients, 317 infants (aged <1 year) and 383 children (aged >or=1 year), who were admitted to the paediatric intensive care unit (PICU) of the University Hospital of Leuven, Belgium. Patients were randomly assigned by blinded envelopes to target blood glucose concentrations of 2.8-4.4 mmol/L in infants and 3.9-5.6 mmol/L in children with insulin infusion throughout PICU stay (intensive group [n=349]), or to insulin infusion only to prevent blood glucose from exceeding 11.9 mmol/L (conventional group [n=351]). Patients and laboratory staff were blinded to treatment allocation. Primary endpoints were duration of PICU stay and inflammation. Analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00214916. FINDINGS: Mean blood glucose concentrations were lower in the intensive group than in the conventional group (infants: 4.8 [SD 1.2] mmol/L vs 6.4 [1.2] mmol/L, p<0.0001; children: 5.3 [1.1] mmol/L vs 8.2 [3.3] mmol/L, p<0.0001). Hypoglycaemia (defined as blood glucose median) stay in PICU was 132 (38%) in the intensive group versus 165 (47%) in the conventional group (p=0.013). Nine (3%) patients died in the intensively treated group versus 20 (6%) in the conventional group (p=0.038). INTERPRETATION: Targeting of blood glucose concentrations to age-adjusted normal fasting concentrations improved short-term outcome of patients in PICU. The effect on long-term survival, morbidity, and neurocognitive development needs to be investigated. FUNDING: Research Foundation (Belgium); Research Fund of the University of Leuven (Belgium) and the EU Information Society Technologies Integrated project "CLINICIP"; and Institute for Science and Technology (Belgium).