Post hospital admission blood lactate measurements are associated with mortality but not neurologic morbidity in children with cerebral malaria.

BACKGROUND: In children with cerebral malaria (CM) admission blood lactate has previously guided intravenous fluid therapy and been validated as a prognostic biomarker associated with death. The usefulness of post-admission measurements of blood lactate in children with CM is less clear. The strength of association between blood lactate and neurological sequelae in CM survivors, as well as the optimal duration of post-admission measurements of blood lactate to identify children at higher risk of adverse outcomes is unknown. METHODS: A retrospective cohort study of 1674 Malawian children with CM hospitalized from 2000 to 2018 who had blood lactate measurements every 6 h for the first 24 h after admission was performed. The strength of association between admission lactate or values measured at any time point in the first 24 h post-admission and outcomes (mortality and neurological morbidity in survivors) was estimated. The duration of time after admission that lactate remained a valid prognostic biomarker was assessed. RESULTS: When lactate is analysed as a continuous variable, children with CM who have higher values at admission have a 1.05-fold higher odds (95% CI 0.99-1.11) of death compared to those with lower lactate values. Children with higher blood lactate at 6 h have 1.16-fold higher odds (95% CI 1.09-1.23) of death, compared to those with lower values. If lactate levels are dichotomized into hyperlactataemic (lactate > 5.0 mmol/L) or not, the strength of association between admission lactate and mortality increases (OR = 2.49, 95% CI 1.47-4.22). Blood lactate levels obtained after 18 h post-admission are not associated with outcomes. Similarly, the change in lactate concentrations through time during the first 24 h of hospital admission is not associated with outcomes. Blood lactate during hospitalization is not associated with adverse neurologic outcomes in CM survivors. CONCLUSIONS: In children with CM, blood lactate is associated with death but not neurologic morbidity in survivors. To comprehensively estimate prognosis, blood lactate in children with CM should be assessed at admission and for 18 h afterwards.

Noninvasive Neuromonitoring Modalities in Children Part I: Pupillometry, Near-Infrared Spectroscopy, and Transcranial Doppler Ultrasonography.

BACKGROUND: Noninvasive neuromonitoring in critically ill children includes multiple modalities that all intend to improve our understanding of acute and ongoing brain injury. METHODS: In this article, we review basic methods and devices, applications in clinical care and research, and explore potential future directions for three noninvasive neuromonitoring modalities in the pediatric intensive care unit: automated pupillometry, near-infrared spectroscopy, and transcranial Doppler ultrasonography. RESULTS: All three technologies are noninvasive, portable, and easily repeatable to allow for serial measurements and trending of data over time. However, a paucity of high-quality data supporting the clinical utility of any of these technologies in critically ill children is currently a major limitation to their widespread application in the pediatric intensive care unit. CONCLUSIONS: Future prospective multicenter work addressing major knowledge gaps is necessary to advance the field of pediatric noninvasive neuromonitoring.

Adherence to severe malaria treatment guidelines in children at a Ugandan regional hospital: a baseline assessment for a malaria treatment quality improvement project.

BACKGROUND: Malaria is one of the most common causes of hospital admission and death in children under the age of five. The World Health Organization (WHO) has issued guidelines for the identification and treatment of severe malaria. Evidence has shown that adherence to standardized malaria treatment protocols improves outcomes. As a baseline assessment in preparation for a malaria treatment quality improvement project, this study aimed to determine adherence to the WHO severe malaria treatment guidelines in children at a Ugandan Regional Referral Hospital. METHODS: A retrospective review was performed on a convenience sample of children discharged between June 2021 and March 2022 from the Mbale Regional Referral Hospital Paediatrics Ward with a diagnosis of severe malaria. Data were collected using a standardized case report form. Demographics, presenting symptoms, laboratory results, treatments, length of stay, and mortality were extracted. Comparison of treatments received to items recommended in the WHO guidelines was undertaken to determine adherence. RESULTS: 147 patients were included. The median age was 5 years (IQR 2-7 years), and 55% were male. The most common features of severe malaria were haemoglobinuria (49%), haemoglobin < 5 mg/dL (34%), and altered mentation (24%). Median hospital length of stay was 3 days (IQR 2-4 days), and the mortality rate was 27% (n = 40). Overall adherence to all aspects of the WHO severe malaria guidelines was achieved in 3% (n = 4) of patients. The most common areas of deficiency were not testing to confirm malaria diagnosis (34%) and inadequate administration of artesunate (82%). Fewer than the three recommended doses of artesunate occurred in 22% of patients. Additionally, a delay in the administration of the second dose occurred in 67% (n = 78) and in the third dose in 77% (n = 71) of patients. While the recommended time between doses is 12 h, the median interval between dose one and dose two was 15 h (12-20) and the median interval from dose two to dose three was 17 h (14-25). CONCLUSIONS: Current adherence to severe malaria treatment guidelines in children at this Ugandan regional referral hospital is poor, but this study has identified target areas for improvement.

Catheter-associated deep vein thrombosis in children with severe traumatic brain injury: A single-center experience.

BACKGROUND: This study was performed to describe the single-center experience of deep vein thrombosis (DVT) in children with severe traumatic brain injury (sTBI) who were mechanically ventilated with a central line, and to identify potentially modifiable risk factors. It was hypothesized that children with DVT would have a longer duration of central venous line (CVL) and a higher use of hypertonic saline (HTS) compared to those without DVT. PROCEDURE/METHODS: This was a retrospective study of children (0-18 years) with sTBI, who were intubated, had a CVL, and a minimum intensive care unit (ICU) stay of 3 days. Children were analyzed by the presence or absence of DVT. HTS use was evaluated using milliliter per kilogram (ml/kg) of 3% equivalents. Univariable and multivariable logistic regression models were used to determine which factors were associated with DVT. RESULTS: Seventy-seven children met inclusion criteria, 23 (29.9%) had a DVT detected in an extremity. On univariable analysis, children with DVT identified in an extremity had prolonged CVL use (14 vs. 8.5 days, p = .021) and longer duration of mechanical ventilation (15 vs. 10 days, p = .013). HTS 3% equivalent ml/kg was not different between groups. On multivariable analysis, mechanical ventilation duration was associated with DVT detection in an extremity, whereas neither CVL duration nor HTS use had an association. CONCLUSIONS: There was a high incidence of extremity DVT detected in children with sTBI who received invasive mechanical ventilation and had a CVL. HTS administration was not associated with DVT detection in an extremity.

Organ Dysfunction Among Children Meeting Brain Death Criteria: Implications for Organ Donation.

OBJECTIVES: Over 70% of pediatric organ donors are declared deceased by brain death (BD) criteria. Patients with these devastating neurologic injuries often have accompanying multiple organ dysfunction. This study was performed to characterize organ dysfunction in children who met BD criteria and were able to donate their organs compared with those deemed medically ineligible. DESIGN: Retrospective cohort study. SETTING: PICU at a quaternary care children's hospital. PATIENTS: Patients with International Classification of Diseases , 9th Edition codes corresponding to BD between 2012 and 2018 were included. MEASUREMENTS AND MAIN RESULTS: Demographics, comorbidities, Pediatric Risk of Mortality (PRISM)-III, and injury mechanisms were derived from the medical record. Organ dysfunction was quantified by evaluating peak daily organ-specific variables. Fifty-eight patients, from newborn to 22 years old, were included with a median PRISM-III of 34 (interquartile range [IQR], 26-36), and all met criteria for multiple organ dysfunction syndrome (MODS). Thirty-four of 58 BD children (59%) donated at least one organ. Of the donors (not mutually exclusive proportions), 10 of 34 donated lungs, with a peak oxygenation index of 11 (IQR, 8-23); 24 of 34 donated their heart (with peak Vasoactive Inotrope Score 23 [IQR, 18-33]); 31 of 34 donated kidneys, of whom 16 of 31 (52%) had evidence of acute kidney injury; and 28 of 34 patients donated their liver, with peak alanine transferase (ALT) of 104 U/L (IQR, 44-268 U/L) and aspartate aminotransferase (AST) of 165 U/L (IQR, 94-434 U/L). Organ dysfunction was similar between heart and lung donors and respective medically ineligible nondonors. Those deemed medically ineligible to donate their liver had higher peak ALT 1,518 U/L (IQR, 986-1,748 U/L) ( p = 0.01) and AST 2,200 U/L (IQR, 1,453-2,405 U/L) ( p = 0.01) compared with liver donors. CONCLUSIONS: In our single-center experience, all children with BD had MODS, yet more than one-half were still able to donate organs. Future research should further evaluate transplant outcomes of dysfunctional organs prior to standardizing donation eligibility criteria.

Description of spatiotemporal patterns of infectious salmon anemia virus (ISAV) detections in marine Atlantic Salmon farms in Newfoundland and Labrador.

OBJECTIVE: The objectives of this study were to describe spatiotemporal patterns of infectious salmon anemia virus (ISAV) detections in marine salmonid production sites in the province of Newfoundland and Labrador in Canada. METHODS: Infectious salmon anemia virus surveillance data between 2012 and 2020 from the province of Newfoundland and Labrador were used. Data comprised a total of 94 sampling events from 20 Atlantic Salmon Salmo salar production sites in which ISAV was detected. Using linear regression models, factors influencing time to detection (days from stocking to first ISAV detection) and time to depopulation (days from first detection to production site depopulation) were investigated. RESULT: Based on 28 unique cases, site-level annual incidence risk of ISAV detection ranged from 3% to 29%. The proportion of ISAV detection by PCR in fish samples ranged from 2% to 45% annually. Overall, ISAV variants from the European clade were more common than variants from the North American clade. The type of ISAV clade, detections of ISAV in nearest production sites based on seaway distances, and year of infectious salmon anemia cases were not associated with time to first ISAV detection. Time to depopulation for sites infected with the ISAV-HPRΔ variant was not associated with ISAV North American or European clades. CONCLUSION: Our results contribute to the further understanding of the changing dynamics of infectious salmon anemia detections in Newfoundland and Labrador since its first detection in 2012 and will likely assist in the design of improved disease surveillance and control programs in the province.

Mechanisms of Transcranial Doppler Ultrasound phenotypes in paediatric cerebral malaria remain elusive.

BACKGROUND: Cerebral malaria (CM) results in significant paediatric death and neurodisability in sub-Saharan Africa. Several different alterations to typical Transcranial Doppler Ultrasound (TCD) flow velocities and waveforms in CM have been described, but mechanistic contributors to these abnormalities are unknown. If identified, targeted, TCD-guided adjunctive therapy in CM may improve outcomes. METHODS: This was a prospective, observational study of children 6 months to 12 years with CM in Blantyre, Malawi recruited between January 2018 and June 2021. Medical history, physical examination, laboratory analysis, electroencephalogram, and magnetic resonance imaging were undertaken on presentation. Admission TCD results determined phenotypic grouping following a priori definitions. Evaluation of the relationship between haemodynamic, metabolic, or intracranial perturbations that lead to these observed phenotypes in other diseases was undertaken. Neurological outcomes at hospital discharge were evaluated using the Paediatric Cerebral Performance Categorization (PCPC) score. RESULTS: One hundred seventy-four patients were enrolled. Seven (4%) had a normal TCD examination, 57 (33%) met criteria for hyperaemia, 50 (29%) for low flow, 14 (8%) for microvascular obstruction, 11 (6%) for vasospasm, and 35 (20%) for isolated posterior circulation high flow. A lower cardiac index (CI) and higher systemic vascular resistive index (SVRI) were present in those with low flow than other groups (p < 0.003), though these values are normal for age (CI 4.4 [3.7,5] l/min/m2, SVRI 1552 [1197,1961] dscm-5m2). Other parameters were largely not significantly different between phenotypes. Overall, 118 children (68%) had a good neurological outcome. Twenty-three (13%) died, and 33 (19%) had neurological deficits. Outcomes were best for participants with hyperaemia and isolated posterior high flow (PCPC 1-2 in 77 and 89% respectively). Participants with low flow had the least likelihood of a good outcome (PCPC 1-2 in 42%) (p < 0.001). Cerebral autoregulation was significantly better in children with good outcome (transient hyperemic response ratio (THRR) 1.12 [1.04,1.2]) compared to a poor outcome (THRR 1.05 [0.98,1.02], p = 0.05). CONCLUSIONS: Common pathophysiological mechanisms leading to TCD phenotypes in non-malarial illness are not causative in children with CM. Alternative mechanistic contributors, including mechanical factors of the cerebrovasculature and biologically active regulators of vascular tone should be explored.

Peripheral IV Administration of Hypertonic Saline: Single-Center Retrospective PICU Study.

OBJECTIVES: To determine the frequency and characteristics of complications of peripherally administered hypertonic saline (HTS) through assessment of infiltration and extravasation. DESIGN: Retrospective cross-sectional study. SETTING: Freestanding tertiary care pediatric hospital. PATIENTS: Children who received HTS through a peripheral IV catheter (PIVC). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We conducted a single-center retrospective review from January 2012 to 2019. A total of 526 patients with 1,020 unique administrations of HTS through a PIVC met inclusion criteria. The primary endpoint was PIVC failure due to infiltration or extravasation. The indication for the administration of HTS infusion was collected. Catheter data was captured, including the setting of catheter placement, anatomical location on the patient, gauge size, length of time from catheter insertion to HTS infusion, in situ duration of catheter lifespan, and removal rationale. The administration data for HTS was reviewed and included volume of administration, bolus versus continuous infusion, infusion rate, infusion duration, and vesicant medications administered through the PIVC. There were 843 bolus infusions of HTS and 172 continuous infusions. Of the bolus administrations, there were eight infiltrations (0.9%). The continuous infusion group had 13 infiltrations (7.6%). There were no extravasations in either group, and no patients required medical therapy or intervention by the wound care or plastic surgery teams. There was no significant morbidity attributed to HTS administration in either group. CONCLUSIONS: HTS administered through a PIVC infrequently infiltrates in critically ill pediatric patients. The infiltration rate was low when HTS is administered as a bolus but higher when given as a continuous infusion. However, no patient suffered an extravasation injury or long-term morbidity from any infiltration.

Descriptive epidemiology of variants of infectious salmon anaemia virus in four Atlantic salmon farms in Newfoundland and Labrador, Canada.

An incursion of infectious salmon anaemia virus (ISAV) was detected in 2020 in southern Newfoundland, Canada. This resulted in an outbreak affecting four marine farms stocking Atlantic salmon (Salmo salar L.) vaccinated against ISAV. This study provides the first description of epidemiologic characteristics of an ISAV outbreak in 2020 and 2021, and detected ISAV variants at the population level. Fish kidneys were screened for ISAV by real-time RT-PCR and non-negative samples were submitted for genotyping and further diagnostic testing. Nine distinct ISAV variants were identified: five European and three North American (NA) HPRΔ ISAV, and one NA-HPR0 ISAV variant. A notable finding was the concurrent detection of both an HPR0 and an HPRΔ ISAV variant in one individual fish. In two farms, both European and NA variants were simultaneously detected, while in the other two farms either NA or European variants were identified, but not both together. Generally, mortality increases followed rises in ISAV prevalence and cycle threshold values on RT-PCR decreased with time. Epidemiologic descriptions of ISAV outbreaks in Atlantic Canada contributes to the understanding of local disease dynamics and identification of changes thereof. Such insights are essential for the strengthening of disease management plans.

Optic nerve sheath diameter does not correlate with intracranial pressure in pediatric neurocritical care patients.

PURPOSE: Intracranial pressure (ICP) > 20 mmHg is associated with worse outcomes in children. The gold standard for monitoring ICP is invasive, has complications such as bleeding and infection, and may not be available in resource limited areas. Ultrasound of the optic nerve sheath diameter (ONSD) has been studied as a noninvasive way to evaluate for elevated ICP in adults. Its utility in pediatrics remains unclear. METHODS: A prospective study was performed in a pediatric intensive care unit in children ≤ 18 years old. ONSD ultrasound was performed using a 13-6 MHz linear probe with the patient's invasively measured ICP simultaneously recorded. Linear mixed effects models were used to evaluate the association between ONSD and ICP. RESULTS: One hundred thirty-six measurements were obtained from 16 patients. ONSD was not significantly associated with ICP (p = 0.51). A ROC curve assessing ONSD to determine elevated ICP > 20 mmHg had an area under the curve of 0.52 (95%CI = 0.32-0.72). There was no difference in measurements obtained between the left and right ONSD at the same time (p = 0.82). CONCLUSIONS: In conclusion, this study demonstrated no association between ONSD measurement and invasively monitored ICP in critically ill children.

Transcranial Doppler Ultrasound During Critical Illness in Children: Survey of Practices in Pediatric Neurocritical Care Centers.

OBJECTIVES: The scope of transcranial Doppler ultrasound in the practice of pediatric neurocritical care is unknown. We have surveyed pediatric neurocritical care centers on their use of transcranial Doppler and analyzed clinical management practices. DESIGN: Electronic-mail recruitment with survey of expert centers using web-based questionnaire. SETTING: Survey of 43 hospitals (31 United States, 12 international) belonging to the Pediatric Neurocritical Care Research Group. PATIENTS: None. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A 67% (29/43) hospital-response rate. Of these centers, 27 reported using transcranial Doppler in the PICU; two hospitals opted out due to lack of transcranial Doppler availability/use. The most common diagnoses for using transcranial Doppler in clinical care were intracranial/subarachnoid hemorrhage (20 hospitals), arterial ischemic stroke (14 hospitals), and traumatic brain injury (10 hospitals). Clinical studies were carried out and interpreted by credentialed individuals in 93% (25/27) and 78% (21/27) of the centers, respectively. A written protocol for performance of transcranial Doppler in the PICU was available in 30% (8/27 hospitals); of these, two of eight hospitals routinely performed correlation studies to validate results. In 74% of the centers (20/27), transcranial Doppler results were used to guide clinical care: that is, when to obtain a neuroimaging study (18 hospitals); how to manipulate cerebral perfusion pressure with fluids/vasopressors (13 hospitals); and whether to perform a surgical intervention (six hospitals). Research studies were also commonly performed for a range of diagnoses. CONCLUSIONS: At least 27 pediatric neurocritical care centers use transcranial Doppler during clinical care. In the majority of centers, studies are performed and interpreted by credentialed personnel, and findings are used to guide clinical management. Further studies are needed to standardize these practices.

Survey of resources available to implement severe pediatric traumatic brain injury management guidelines in low and middle-income countries.

PURPOSE: Traumatic brain injury (TBI) is a leading cause of death and disability worldwide, with a disproportionately high burden in low-middle income countries. Guideline implementation has been associated with mortality reduction in high-income countries (HIC), but it is not known if hospitals in low and middle-income countries possess the resources to implement the pre-hospital TBI guidelines and the guidelines for the management of severe pediatric traumatic brain injury. METHOD: An anonymous online survey was undertaken by a range of health care professionals currently managing children with severe TBI in low to middle-income countries. A variety of international and national pediatric, intensive care, and neurological societies assisted in the survey distribution. Thirty-eight questions were included to evaluate patient care and the provider's perceptions of their resources available to implement the pre-hospital specific TBI and current pediatric severe TBI guidelines. RESULTS: Two hundred and forty-seven hospitals were represented from 68 countries. Fifty percent of LMIC hospitals that responded had the resources to implement 13 of 15 guidelines for the pediatric component of pre-hospital management for TBI and all baseline care recommendations. First tier therapies including the intracranial pressure (ICP) and cerebral perfusion pathways (CPP), however, demonstrated low capacity for uptake with 21.5% and 38.5% of surveyed hospitals possessing sufficient resources to follow the recommended pathways. CONCLUSION: Pediatric TBI ICP/CPP management guidelines require numerous resources not widely sourced in LMIC. The creation of international guidelines that outline recommendations of care for LMIC may benefit patient care and outcomes in these settings.

Non-invasive estimation of cerebral perfusion pressure using transcranial Doppler ultrasonography in children with severe traumatic brain injury.

OBJECTIVE: To identify if cerebral perfusion pressure (CPP) can be non-invasively estimated by either of two methods calculated using transcranial Doppler ultrasound (TCD) parameters. DESIGN: Retrospective review of previously prospectively gathered data. SETTING: Pediatric intensive care unit in a tertiary care referral hospital. PATIENTS: Twenty-three children with severe traumatic brain injury (TBI) and invasive intracranial pressure (ICP) monitoring in place. INTERVENTIONS: TCD evaluation of the middle cerebral arteries was performed daily. CPP at the time of the TCD examination was recorded. For method 1, estimated cerebral perfusion pressure (CPPe) was calculated as: CPPe = MAP × (diastolic flow (Vd)/mean flow (Vm)) + 14. For method 2, critical closing pressure (CrCP) was identified as the intercept point on the x-axis of the linear regression line of blood pressure and flow velocity parameters. CrCP/CPPe was then calculated as MAP-CrCP. MEASUREMENTS AND MAIN RESULTS: One hundred eight paired measurements were available. Using patient averaged data, correlation between CPP and CPPe was significant (r = 0.78, p = < 0.001). However, on Bland-Altman plots, bias was 3.7 mmHg with 95% limits of agreement of - 17 to + 25 for CPPe. Using patient averaged data, correlation between CPP and CrCP/CPPe was significant (r = 0.59, p = < 0.001), but again bias was high at 11 mmHg with wide 95% limits of agreement of - 15 to + 38 mmHg. CONCLUSIONS: CPPe and CrCP/CPPe do not have clinical value to estimate the absolute CPP in pediatric patients with TBI.

Transcranial Doppler ultrasound findings in children with moderate-to-severe traumatic brain injury following abusive head trauma.

PURPOSE: Abusive head trauma (AHT) is the leading cause of fatal head injuries for children under 2 years. The objective was to evaluate, using transcranial Doppler ultrasound (TCD), whether children with AHT have a similar neurovascular response to injury compared with children without AHT. METHODS: Retrospective sub-analysis of previously prospectively acquired data in a pediatric intensive care unit in a level 1 trauma hospital. TCD was performed daily until hospital day 8, discharge, or death. Neurologic outcome was assessed using the Glasgow Outcome Scale Extended (GOS-E Peds) at 1 month from initial injury. RESULTS: Sixty-nine children aged 1 day to 17 years with moderate-to-severe traumatic brain injury were enrolled. Fifteen children suffered AHT and 54 had no suspicion for AHT. Fifteen children with AHT underwent 80 serial TCD examinations; 54 children without AHT underwent 308 exams. After standardization for age and gender normative values, there was no statistically significant difference in mean cerebral blood flow velocity of the middle cerebral artery (VMCA) between children with and without AHT. There was no difference in the incidence of extreme cerebral blood flow velocity (CBFV, greater or less than 2 standard deviations from normative value) between groups. Within the AHT group, there were no statistically significant differences in VMCA between children with a favorable (GOS-E Peds 1-4) versus unfavorable neurologic outcome (GOS-E Peds 5-8). CONCLUSION: Children with AHT have no significant differences in VMCA or percentage of extreme CBFV in the middle cerebral artery compared to with those without AHT.

Remifentanil for Sedation of Children With Traumatic Brain Injury.

OBJECTIVE: To determine whether remifentanil would provide adequate sedation while allowing frequent and reproducible neurologic assessments in children admitted to the pediatric intensive care unit (PICU) with traumatic brain injury (TBI) during mechanical ventilation. DESIGN: Retrospective review. SETTING: Tertiary care PICU. PATIENTS: Thirty-eight patients over a 30-month period. MEASUREMENTS AND MAIN RESULTS: Median age was 9 years (interquartile range [IQR] 2.25-12 years). The median Glasgow Coma Scale (GCS) was 9 (IQR: 8-10). All patients were tracheally intubated and receiving mechanical ventilation. A continuous infusion of remifentanil was started at 0.1 µg/kg/min, and bolus doses of 0.25 to 1 µg/kg were administered every 3 to 5 minutes as needed to reach the desired sedation level. Infusions were stopped at least hourly to perform neurologic examinations. The median remifentanil dose was 0.25 µg/kg/min with an IQR of 0.1 and 0.6 µg/kg/min. The maximum dose for any patient in the cohort was 2 µg/kg/min. Median duration of therapy with remifentanil was 20 hours (IQR: 8-44 hours). Adequate sedation was achieved with sedation scores (State Behavioral Scale) meeting target levels with a median value of 100% of the time (IQR: 79%-100%). Neurologic examinations were able to be performed within a median of 9 minutes (IQR: 5-14 minutes) of pausing the infusion. No serious safety events occurred. In 68% of the patients, neurologic examinations remained reassuring during remifentanil infusion, and patients were extubated. The remaining patients were transitioned to traditional sedative agents for long-term management of their traumatic injuries once the neurologic status was deemed stable. CONCLUSION: This data suggest that remifentanil is a suitable sedative agent for use in children with TBI. It provides a rapid onset of sedation with recovery that permits reliable and reproducible clinical examination.

Cerebrovascular Physiology During Pediatric Extracorporeal Membrane Oxygenation: A Multicenter Study Using Transcranial Doppler Ultrasonography.

OBJECTIVES: To explore changes to expected, age-related transcranial Doppler ultrasound variables during pediatric extracorporeal membrane oxygenation. DESIGN: Prospective, observational, multicenter study. SETTING: Tertiary care PICUs. PATIENTS: Children 1 day to 18 years old requiring veno arterial extracorporeal membrane oxygenation. METHODS: Participants underwent daily transcranial Doppler ultrasound measurement of bilateral middle cerebral artery flow velocities. Acute neurologic injury was diagnosed if seizures, cerebral hemorrhage, or diffuse cerebral ischemia was detected. MEASUREMENTS AND MAIN RESULTS: Fifty-two children were enrolled and analyzed. In the 44 children without acute neurologic injury, there was a significant reduction in systolic flow velocity and mean flow velocity compared with predicted values over time (F [8, 434] = 60.44; p ≤ 0.0001, and F [8, 434] = 17.61; p ≤ 0.0001). Middle cerebral artery systolic flow velocity was lower than predicted on extracorporeal membrane oxygenation days 1-5, and mean flow velocity was lower than predicted on extracorporeal membrane oxygenation days 1-3. In the six infants less than 90 days old suffering diffuse cerebral ischemia, middle cerebral artery systolic flow velocity, mean flow velocity, and diastolic flow velocity from extracorporeal membrane oxygenation days 1-9 were not significantly different when compared with children of similar age in the cohort that did not suffer acute neurologic injury (systolic flow velocity F [8, 52] = 0.6659; p = 0.07 and diastolic flow velocity F [8, 52] = 1.4; p = 0.21 and mean flow velocity F [8, 52] = 1.93; p = 0.07). Pulsatility index was higher in these infants over time than children of similar age in the cohort on extracorporeal membrane oxygenation that did not suffer acute neurologic injury (F [8, 52] = 3.1; p = 0.006). No patient in the study experienced cerebral hemorrhage. CONCLUSIONS: Flow velocities in the middle cerebral arteries of children requiring extracorporeal membrane oxygenation are significantly lower than published normative values for critically ill, mechanically ventilated, sedated children. Significant differences in measured systolic flow velocity, diastolic flow velocity, and mean flow velocity were not identified in children suffering ischemic injury compared with those who did not. However, increased pulsatility index may be a marker for ischemic injury in young infants on extracorporeal membrane oxygenation.

Factors Associated With Poor Outcome in Pediatric Near-Hanging Injuries.

BACKGROUND: Hanging injury is the most common method of suicide among children 5 to 11 years of age and near-hangings commonly occur. Adult studies in near-hanging injury have shown that need for cardiopulmonary resuscitation, initial blood gas, and poor mental status are associated with poor prognosis. The literature for similar factors in children is lacking. OBJECTIVES: This retrospective, single-center study was performed to identify the clinical factors associated with neurologic outcome in children after near-hanging. METHODS: Inclusion criteria included <18 years of age and a diagnosis of near-hanging or strangulation. All physician documentation was reviewed, and incidences of respiratory complications, seizure, and multiorgan failure were noted. Pediatric cerebral performance category score was based on information at discharge and was defined as favorable (score of 1-4) or unfavorable (score of 5-6). Comparisons were made between outcome groups and suspected clinical factors. RESULTS: The median age was 11.5 years with a median initial Glasgow Coma Scale (GCS) score of 10. Of all patients, 25% had a prehospital cardiac arrest, and 51% were admitted to the intensive care unit. Patients with unfavorable outcomes had a lower initial pH (6.9 vs. 7.3) and initial GCS score (3T vs. 14). Patients with an unfavorable outcome had significantly higher rates of intensive care unit admission, respiratory complications, anoxic brain injury, and multiorgan failure. No patient who presented with an initial GCS score of 3T and prehospital cardiac arrest had a favorable neurologic outcome. CONCLUSIONS: This is the largest single-center study of children with near-hanging injury. An initial GCS score of 3T and prehospital cardiac arrest was uniformly associated with poor neurologic outcome.

Transcranial Doppler Ultrasonography Provides Insights into Neurovascular Changes in Children with Cerebral Malaria.

OBJECTIVE: To evaluate neurovascular changes in pediatric patients with cerebral malaria. STUDY DESIGN: African children with cerebral malaria were enrolled and underwent daily transcranial Doppler ultrasound (TCD) examinations through hospital day 8, discharge, or death. Neurologic outcomes were assessed 2 weeks after enrollment. RESULTS: In total, 160 children with cerebral malaria and 155 comparison patients were included. In patients with cerebral malaria, TCD flow changes characterized as hyperemia were seen in 42 (26%), low flow in 46 (28%), microvascular obstruction in 35 (22%), cerebral vasospasm in 21 (13%), and isolated posterior hyperemia in 7 (4%). Most had a single neurovascular phenotype observed throughout participation. Among comparison patients, 76% had normal TCD findings (P < .001). Impaired autoregulation was present in 80% of cases (transient hyperemic response ratio 1.01 ± 0.03) but improved through day 4 (1.1 ± 0.02, P = .014). Overall mortality was 24% (n = 39). Neurologic deficits were evident in 21% of survivors. Children meeting criteria for vasospasm were most likely to survive with sequelae, and children meeting criteria for low flow were most likely to die. Autoregulation was better in children with a normal neurologic outcome (1.09, 95% CI 1.06-1.12) than in others (0.98, 95% CI 0.95-1) (P ≤ .001). CONCLUSIONS: Several distinct changes in TCD measurements were identified in children with cerebral malaria that permitted phenotypic grouping. Groups had distinct associations with neurologic outcomes. Validation of pathogenic mechanisms associated with each phenotype may aid in developing TCD as a portable, easy-to-use tool to help guide targeted adjunctive therapy in cerebral malaria aimed at causative mechanisms of injury on an individual level.

Relationships between cerebral flow velocities and neurodevelopmental outcomes in children with moderate to severe traumatic brain injury.

PURPOSE: This study aimed to determine relationships between cerebral blood flow and neurodevelopmental outcomes in children with moderate to severe traumatic brain injury (TBI). METHODS: Children with TBI, a Glasgow Coma Score of 8-12, and abnormal brain imaging were enrolled prospectively. Cerebral blood flow velocity (CBFV) was assessed within 24 h of trauma and daily thereafter through death, discharge, or hospital day 8, whichever came first. Twelve months from injury, participants completed neurodevelopmental testing. RESULTS: Sixty-nine patients were enrolled. Low flow velocities (< 2 SD below age/gender normal) were found in 6% (n = 4). No patient with a single low CBFV measurement had a good neurologic outcome (Pediatric Glasgow Outcome Scale (GOS-E Peds) ≤ 4)). Normal flow velocities (± 2 SD around age/gender normal) were seen in 43% of participants (n = 30). High flow velocities (> 2 SD above age and gender normal with a Lindegaard ratio (LR) < 3) were identified in 23% of children (n = 16), and vasospasm (> 2 SD above age/gender normal with LR ≥ 3) was identified in 28% (n = 19). Children with good outcomes based on GOS-E Peds scoring were more likely to have had normal flow velocity than other flow patterns. No other differences in neurodevelopmental outcomes were noted. CONCLUSIONS: Individual patient responses to TBI in terms of CBFV alterations were heterogeneous. Low flow was uniformly associated with a poor outcome. Patients with good outcomes were more likely to have normal flow. This suggests CBFV may serve as a prognostic indicator in children with TBI. Future studies are needed to determine if aberrant CBFVs are also a therapeutic target.

Cerebral Blood Flow Following Hybrid Stage I Palliation in Infants with Hypoplastic Left Heart Syndrome.

Hypoplastic left heart syndrome (HLHS) palliation may result in altered cerebral blood flow with subsequent neurodevelopmental implications. The purpose of the study was to assess blood flow in the middle cerebral artery (MCA) and investigate the relationship with early neurodevelopmental outcomes in infants with HLHS after hybrid stage I. Transcranial Doppler (TCD) was performed to obtain peak systolic, end-diastolic, and mean velocities, as well as pulsatility index of the MCA in infants with HLHS (n = 18) at baseline and at 2, 4, and 6 months of age. Developmental assessment was performed at 6 months of age. Results of TCD and development were compared to healthy control subjects (n = 6) and normative data. Overall, peak systolic velocity (p = 0.0031), end-diastolic velocity (p < 0.0001), and mean velocity (p < 0.0001) were significantly lower and pulsatility index (p = 0.0011) significantly higher in the HLHS group compared to the control group. A significant increase in change over time was noted for peak systolic velocity (p < 0.0016) and mean velocity (p < 0.0046). There was no significant correlation between TCD variables and development scores. TCD values in 5-6 months old infants with HLHS who undergo hybrid stage I palliation had consistently lower blood flow velocities than control infants; however, pulsatility index was slightly higher. No correlation between TCD measurements and measures of cognitive, language, and motor skills were noted.