Pediatric Critical Care Medicine

Critical Illness and Cardiac Dysfunction in Anthracycline-Exposed Pediatric Oncology Patients* Objectives: To determine if the presence of cardiac dysfunction in anthracycline-exposed pediatric oncology patients is associated with an increased frequency of PICU admission or mortality. Design: Retrospective parallel cohort study. Setting: PICU at an academic freestanding children's hospital. Subjects: Children with oncologic diagnoses who received anthracyclines between January 2006 and December 2014 and were admitted to the hospital within 1 year of completion of therapy. Interventions: None. Measurements and Main Results: Charts of 734 patients were reviewed and 545 were included in analysis. Anthracycline-exposed pediatric oncology patients with cardiac dysfunction were more likely to be admitted to the PICU than those without cardiac dysfunction (87% vs 37% rate of PICU admission). PICU admission was also associated with identified infection and higher cumulative anthracycline dose. Once admitted to the PICU, those anthracycline-exposed patients with cardiac dysfunction had significantly higher mortality (26% vs 6%) and longer length of stay (7 vs 2 d) than children without cardiac dysfunction. Patients with cardiac dysfunction were more likely to require mechanical ventilation (59% vs 18%), required more vasoactive medications for longer, and were more likely to develop fluid overload. Death within 1 year of ICU admission was associated with higher cumulative anthracycline dose. Conclusions: Children with cancer who received anthracyclines, especially at higher doses, and who develop cardiac dysfunction are at higher risk of critical illness, have higher rates of multiple organ dysfunction and higher rates of mortality than anthracycline-exposed patients without cardiac dysfunction.

Bleeding Scales Applicable to Critically Ill Children: A Systematic Review Objectives: To summarize current bleeding scales and their validation to assess applicability to bleeding in critically ill children. Data Sources: We conducted electronic searches of Ovid MEDLINE, Ovid EMBASE, Cochrane Library, and Web of Science Core Collection databases from database inception to 2017. Study Selection: Included studies contained a bleeding score, bleeding measurement tool, or clinical measurement of hemorrhage. Data Extraction: We identified 2,097 unique citations; 20 full-text articles were included in the final review. Data Synthesis: Of the 18 studies that included subjects (two others were expert consensus definitions), seven (39%) were pediatric-only, seven (39%) were adult-only, and four (22%) included both adults and children. Nine (50%) occurred with inpatients (two studies in critical care units), seven (39%) involved outpatients and two (11%) included both inpatients and outpatients. Thirty-nine percent of the scales were developed for those with idiopathic thrombocytopenic purpura and only two (12%) described critically ill patients. The majority (80%) included need for treatment (either RBC transfusion or surgical intervention). The majority (65%) did not report measures of reliability or validation to clinical outcomes. Conclusions: There is a lack of validated bleeding scales to adequately assess bleeding and outcomes in critically ill children. Validated scales of bleeding are necessary and urgently needed.

Ultrasound-Guided Femoral Arterial Cannulation in Neonates Undergoing Cardiac Surgery or Catheterization: Comparison of 0.014-Inch Floppy Versus 0.019-Inch Straight Guidewire Objectives: Percutaneous femoral artery cannulation can be technically challenging in small infants. Design: We designed a prospective randomized trial to compare the use of two different guidewires for femoral arterial cannulation in neonates undergoing cardiac surgery or catheterization. Settings: Cardiac ICU in a university hospital. Patients: One-hundred twenty-four children were enrolled in this prospective study, with 64 being randomized to the 0.019-inch straight guidewire group and 60 to the 0.014-inch floppy guidewire group. Interventions: Femoral artery cannulation. Measurements and Main Results: The study period was limited to 10 minutes at the first site of arterial puncture. The time to complete cannulation, number of successful cannulation on first attempt, number of attempts, and number of successful cannulations were compared. The number of successful cannulations and successful cannulations on first attempt were higher in 0.014-inch floppy guidewire group (p = 0.001; p = 0.002, respectively). The time to complete cannulation was significantly shorter, and the number of attempts was lower in 0.014-inch floppy guidewire group (p = 0.001). Among the neonates less than 2000g, the number of attempts and time to complete cannulation were significantly lower (p < 0.001), and number of successful cannulation on first attempt and number of successful cannulations were significantly higher (p < 0.028; p < 0.001, respectively) in the 0.014-inch floppy guidewire Conclusions: Using 0.014-inch floppy guidewire for femoral arterial cannulation in particularly very small neonates provides significant improvement in first attempt success, number of successful cannulations, number of attempts, time to complete cannulation.

Risk Factors for Recurrent Acute Kidney Injury in Children Who Undergo Multiple Cardiac Surgeries: A Retrospective Analysis Objectives: Determine the risk factors for repeated episodes of acute kidney injury in children who undergo multiple cardiac surgical procedures. Design: Single-center retrospective chart review. Setting: Cardiac ICU at a quaternary pediatric care center. Patients: Birth to 18 years who underwent at least two cardiac surgical procedures with cardiopulmonary bypass. Interventions: None. Measurements and Main Results: One-hundred eighty patients underwent two cardiac surgical procedures and 89 underwent three. Acute kidney injury was defined by the Kidney Disease: Improving Global Outcomes serum creatinine criteria. Acute kidney injury frequency was 26% (n = 46) after surgery 1, 20% (n = 36) after surgery 2, and 24% (n = 21) after surgery 3, with most acute kidney injury occurring on postoperative days 1 and 2. The proportion of patients with severe acute kidney injury increased from surgery 1 to surgery 3. Patients with acute kidney injury had a significantly longer duration of ventilation and length of stay after each surgery. The odds of acute kidney injury after surgery 3 was 2.40 times greater if acute kidney injury was present after surgery 1 or 2 (95% CI, 1.26–4.56; p = 0.008) after adjusting for confounders. The time between surgeries was not significantly associated with acute kidney injury (p = 0.85). Conclusions: In a heterogeneous population of pediatric patients with congenital heart disease undergoing multiple cardiopulmonary bypass surgeries, odds of acute kidney injury after a third surgery was increased by the presence of acute kidney injury after prior procedures. Time between surgery did not play a role in increasing odds of acute kidney injury. Further studies in a larger multicenter investigation are necessary to confirm these findings.

Population Pharmacokinetics and Dosing of Milrinone After Patent Ductus Arteriosus Ligation in Preterm Infants Objectives: The postoperative course of patent ductus arteriosus ligation is often complicated by postligation cardiac syndrome, occurring in 10–45% of operated infants. Milrinone might prevent profound hemodynamic instability and improve the recovery of cardiac function in this setting. The present study aimed to describe the population pharmacokinetics of milrinone in premature neonates at risk of postligation cardiac syndrome and give dosing recommendations. Design: A prospective single group open-label pharmacokinetics study. Settings: Two tertiary care neonatal ICUs: Tallinn Children's Hospital and Tartu University Hospital, Estonia. Patients: Ten neonates with postmenstrual age of 24.6–30.1 weeks and postnatal age of 5–27 days undergoing patent ductus arteriosus ligation and at risk of postligation cardiac syndrome, based on echocardiographic assessment of left ventricular output of less than 200 mL/kg/min 1 hour after the surgery. Interventions: Milrinone at a dose of 0.73 μg/kg/min for 3 hours followed by 0.16 μg/kg/min for 21 hours. Four blood samples from each patient for milrinone plasma concentration measurements were collected. Measurements and Main Results: Concentration-time data of milrinone were analyzed with nonlinear mixed-effects modeling software (NONMEM Version 7.3 [ICON Development Solutions, Ellicott City, MD]). Probability of target attainment simulations gave a dosing schedule that maximally attains concentration targets of 150–250 μg/L. Milrinone pharmacokinetics was described by a one-compartmental linear model with allometric scaling to bodyweight and an age maturation function of glomerular filtration rate. Parameter estimates for a patient with the median weight were 0.350 (L/hr) for clearance and 0.329 (L) for volume of distribution. The best probability of target attainment was achieved with a loading dose of 0.50 μg/kg/min for 3 hours followed by 0.15 μg/kg/min (postmenstrual age < 27 wk) or 0.20 μg/kg/min (postmenstrual age ≥ 27 wk). Conclusions: Population pharmacokinetic modeling and simulations suggest a slow loading dose followed by maintenance infusion to reach therapeutic milrinone plasma concentrations within the timeframe of the postligation cardiac syndrome.

Mortality Rate-Dependent Variations in the Timing and Causes of Death in Extremely Preterm Infants Born at 23–24 Weeks' Gestation* Objectives: To determine mortality rate-dependent variations in the timing and causes of death, and to subsequently identify the clinical factors associated with decreased mortality in extremely preterm infants born at 23–24 weeks' gestation. Design: A retrospective cohort study. Setting: Korean Neonatal Network registry that includes all level greater than or equal to 3 neonatal ICUs in Korea. Patients: Eligible, actively treated infants born at 23–24 weeks' gestation (n = 574) from January 2014 to December 2016 were arbitrarily categorized based on institutional mortality rates of less than or equal to 50% (group I, n = 381) and greater than 50% (group II, n = 193). The primary outcome was mortality before discharge and the timing and causes of death according to the mortality rate. Interventions: None. Measurements and Main Results: The overall mortality rate was significantly lower in group I (40.7%) than in group II (79.3%). Regarding causes of death, mortalities due to cardiorespiratory, infectious, and gastrointestinal causes were significantly lower in group I than in group II. Mortality rates were significantly lower in group I, including all the subgroups that were categorized according to the timing of death, than in group II. The multivariate analyses showed that antenatal corticosteroid use, absence of oligohydramnios, birth weight, and body temperature at admission to the neonatal ICU were significantly associated with reduced mortality. Conclusions: The reduced mortality rate among the infants born at 23–24 weeks' gestation was attributable to decreased mortality ascribed to cardiorespiratory, infectious, and gastrointestinal causes, and it was associated with antenatal steroid use and body temperature at admission to the neonatal ICU.

Risk of Severe Intraventricular Hemorrhage in the First Week of Life in Preterm Infants Transported Before 72 Hours of Age* Objectives: Evaluate the risk of severe intraventricular hemorrhage, in the first week of life, in preterm infants undergoing early interhospital transport. Design: Retrospective cohort study. Setting: Tertiary neonatal centers of the Trent Perinatal Network in the United Kingdom. Patients: Preterm infants less than 32 weeks gestation, who were either born within and remained at the tertiary neonatal center (inborn), or were transferred (transported) between centers in the first 72 hours of life. Interventions: None. Measurements and Main Results: Multivariable logistic regression models adjusting for key confounders were used to calculate odds ratios for intraventricular hemorrhage with 95% CIs for comparison of inborn and transported infants. Cranial ultrasound findings on day 7 of life. Secondary analyses were performed for antenatal steroid course and gestational age subgroups. A total of 1,047 preterm infants were included in the main analysis. Transported infants (n = 391) had a significantly higher risk of severe (grade III/IV) intraventricular hemorrhage compared with inborns (n = 656) (9.7% vs 5.8%; adjusted odds ratio, 1.69; 95% CI, 1.04–2.76), especially for infants born at less than 28 weeks gestation (adjusted odds ratio, 1.83; 95% CI, 1.03–3.21). Transported infants were less likely to receive a full antenatal steroid course (47.8% vs 64.3%; p < 0.001). A full antenatal steroid course significantly decreased the risk of severe intraventricular hemorrhage irrespective of transport status (odds ratio, 0.33; 95% CI, 0.2–0.55). However, transported infants less than 28 weeks gestation remained significantly more likely to develop a severe intraventricular hemorrhage despite a full antenatal steroid course (adjusted odds ratio, 2.84; 95% CI, 1.08–7.47). Conclusions: Preterm infants transported in the first 72 hours of life have an increased risk of early-life severe intraventricular hemorrhage even when maternal antenatal steroids are given. The additional burden of postnatal transport could be an important component in the pathway to severe intraventricular hemorrhage. As timely in-utero transfer is not always possible, we need to focus research on improving the transport pathway to reduce this additional risk.

Decision-Making About Intracranial Pressure Monitor Placement in Children With Traumatic Brain Injury* Objectives: Little is known about how clinicians make the complex decision regarding whether to place an intracranial pressure monitor in children with traumatic brain injury. The objective of this study was to identify the decisional needs of multidisciplinary clinician stakeholders. Design: Semi-structured qualitative interviews with clinicians who regularly care for children with traumatic brain injury. Setting: One U.S. level I pediatric trauma center. Subjects: Twenty-eight clinicians including 17 ICU nurses, advanced practice providers, and physicians and 11 pediatric surgeons and neurosurgeons interviewed between August 2017 and February 2018. Interventions: None. Measurements and Main Results: Participants had a mean age of 43 years (range, 30–66 yr), mean experience of 10 years (range, 0–30 yr), were 46% female (13/28), and 96% white (27/28). A novel conceptual model emerged that related the difficulty of the decision about intracranial pressure monitor placement (y-axis) with the estimated outcome of the patient (x-axis). This model had a bimodal shape, with the most difficult decisions occurring for patients who 1) had a good opportunity for recovery but whose neurologic examination had not yet normalized or 2) had a low but uncertain likelihood of neurologically functional recovery. Emergent themes included gaps in medical knowledge and information available for decision-making, differences in perspective between clinical specialties, and ethical implications of decision-making about intracranial pressure monitoring. Experienced clinicians described less difficulty with decision-making overall. Conclusions: Children with severe traumatic brain injury near perceived transition points along a spectrum of potential for recovery present challenges for decision-making about intracranial pressure monitor placement. Clinician experience and specialty discipline further influence decision-making. These findings will contribute to the design of a multidisciplinary clinical decision support tool for intracranial pressure monitor placement in children with traumatic brain injury.

Role of IV Immunoglobulin in Indian Children With Guillain-Barré Syndrome* Objectives: To evaluate the outcome of Indian children with Guillain-Barré syndrome who received IV immunoglobulin compared with those who did not receive any specific therapy. Design: Single center, prospective cross-sectional study. Setting: Tertiary care neurology teaching hospital. Patients: Children (≤ 18 yr old) with Guillain-Barré syndrome were included from a prospectively maintained Guillain-Barré syndrome registry from January 2008 to April 2017. Children were classified into acute inflammatory demyelinating polyradiculoneuropathy, acute motor axonal neuropathy, acute motor-sensory axonal neuropathy, and inexcitable motor nerves based on nerve conduction study. Interventions: Out of 138 pediatric Guillain-Barré syndrome, 50 received IV immunoglobulin and another 50 age and peak disability matched controls (who did not receive IV immunoglobulin or plasmapheresis) were selected from the same registry for comparison. Measurements and Main Results: Outcome at 3 and 6 months was defined on the basis of a 0–10 Clinical Grading Scale into complete (Clinical Grading Scale < 3), partial (Clinical Grading Scale 3–5), and poor (Clinical Grading Scale > 5) recovery. The primary outcome was proportion of patients with complete recovery at 3 and 6 months in IV immunoglobulin and non-IV immunoglobulin groups. Secondary outcomes included in-hospital deaths, duration of mechanical ventilation, and hospital stay. Subgroup analysis was done in acute motor axonal neuropathy and acute inflammatory demyelinating polyradiculoneuropathy groups. The baseline characteristics were similar except for shorter duration of illness and higher proportion of facial palsy in IV immunoglobulin group. Hospital deaths, duration of mechanical ventilation, hospital stay, and outcome at 3 and 6 months were not different between the two groups. Children with acute motor axonal neuropathy had better recovery at 6 months on IV immunoglobulin (58.3% vs 11.1%; p = 0.03), but not those with acute inflammatory demyelinating polyradiculoneuropathy (58.3% vs 72.2%; p = 0.22). In nonambulatory Guillain-Barré syndrome children, complete recovery at 6 months was similar in IV immunoglobulin and non-IV immunoglobulin group (57.4% vs 57.1%; p = 0.98). Conclusions: In Indian children with Guillain-Barré syndrome, the outcome at 6 months in IV immunoglobulin treated group was similar to non-IV immunoglobulin group. Children with acute motor axonal neuropathy responded better to IV immunoglobulin.

Inter-Rater Reliability Between Critical Care Nurses Performing a Pediatric Modification to the Glasgow Coma Scale* Objectives: Estimate the inter-rater reliability of critical care nurses performing a pediatric modification of the Glasgow Coma Scale in a contemporary PICU. Design: Prospective observation study. Setting: Large academic PICU. Patients/Subjects: All 274 nurses with permanent assignments in the PICU were eligible to participate. A subset of 18 nurses were selected as study registered nurses. All PICU patients were eligible to participate. Interventions: None. Measurements and Main Results: PICU nurses were educated and demonstrated proficiency on a pediatric modification of the Glasgow Coma Scale we created to make it more applicable to a diverse PICU population that included patients who are sedated, mechanically ventilated, and/or have developmental disabilities. Each study registered nurse observed a sample of nurses perform the Glasgow Coma Scale, and they independently scored the Glasgow Coma Scale. Patients were categorized as having developmental disabilities if their preillness Pediatric Cerebral Performance Category score was greater than or equal to 3. Fleiss' Kappa (κ), intraclass correlation coefficient, and percent agreement assessed inter-rater reliability for each Glasgow Coma Scale component (eye, verbal, motor) and age-specific scale (≥ 2 and < 2-yr-old). The overall percent agreement between study registered nurses and nurses was 89% for the eye, 91% for the verbal, and 79% for the motor responses. Inter-rater reliability ranged from good (intraclass correlation coefficient = 0.75) to excellent (intraclass correlation coefficient = 0.96) for testable patients. Agreement on the motor response was significantly lower for children with developmental disabilities (< 2 yr: 59% vs 95%; p = 0.0012 and ≥ 2 yr: 55% vs 91%; p = 0.0012). Agreement was significantly worse for intermediate range Glasgow Coma Scale motor responses compared with responses at the extremes (e.g., motor responses 2, 3, 4 vs 1, 5, 6; p < 0.05). Conclusions: A pediatric modification of the Glasgow Coma Scale performed by trained PICU nurses has excellent inter-rater reliability, although reliability was reduced in patients with developmental disabilities and for intermediate range Glasgow Coma Scale responses. Further research is needed to determine the effectiveness of this Glasgow Coma Scale modification to detect clinical deterioration.

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182

6948891480

alsfakia@gmail.com