Erik Su

α-Synuclein levels are elevated in cerebrospinal fluid following traumatic brain injury in infants and children: the effect of therapeutic hypothermia.

α-Synuclein is one of the most abundant proteins in presynaptic terminals. Normal expression of α-synuclein is essential for neuronal survival and it prevents the initiation of apoptosis in neurons through covalent cross-linking of cytochrome c released from mitochondria. Exocytosis of α-synuclein occurs with neuronal mitochondrial dysfunction, making its detection in cerebrospinal fluid (CSF) of children after severe traumatic brain injury (TBI) a potentially important marker of injury. Experimental therapeutic hypothermia (TH) improves mitochondrial function and attenuates cell death, and therefore may also affect CSF α-synuclein concentrations. We assessed α-synuclein levels in CSF of 47 infants and children with severe TBI using a commercial ELISA for detection of monomeric protein. 23 patients were randomized to TH based on published protocols where cooling (32–33°C) was initiated within 6–24 h, maintained for 48 h, and then followed by slow rewarming. CSF samples were obtained continuously via an intraventricular catheter for 6 days after TBI. Control CSF (n = 9) was sampled from children receiving lumbar puncture for CSF analysis of infection that was proven negative. Associations of initial Glasgow Coma Scale (GCS) score, age, gender, treatment, mechanism of injury and Glasgow Outcome Scale (GOS) score with CSF α-synuclein were compared by multivariate regression analysis. CSF α-synuclein levels were elevated in TBI patients compared to controls (p = 0.0093), with a temporal profile showing an early, approximately 5-fold increase on days 1–3 followed by a delayed, >10-fold increase on days 4–6 versus control. α-Synuclein levels were higher in patients treated with normothermia versus hypothermia (p = 0.0033), in patients aged <4 years versus ≧4 years (p < 0.0001), in females versus males (p = 0.0007), in nonaccidental TBI versus accidental TBI victims (p = 0.0003), and in patients with global versus focal injury on computed tomography of the brain (p = 0.046). Comparisons of CSF α-synuclein levels with initial GCS and GOS scores were not statistically significant. Further studies are needed to evaluate the conformational status of α-synuclein in CSF, and whether TH affects α-synuclein aggregation.

Linezolid and Lactic Acidosis: A Role for Lactate Monitoring With Long-term Linezolid Use in Children

Linezolid administration has been associated with lactic acidosis in adults; however, the same phenomenon has not been reported in children. Mitochondrial protein synthesis inhibition is a demonstrated mechanism for toxicity, which therefore may manifest as lactic acidosis. Three cases of linezolid-associated lactic acidosis in children are reported to reinforce the need for pediatric caregivers to be vigilant of this potential side effect.

Severe Hypernatremia in a Hospitalized Child: Munchausen by Proxy

An 8-week-old infant presented to a referring institution with profuse diarrhea and infectious enteritis for 1 week. He was initially treated for suspected Salmonella spp. sepsis and meningitis, because the organism was found in the stool, but the childs illness progressed, manifested by paroxysmal profuse diarrhea and increased urine output. After several weeks, he suffered a sagittal venous thrombosis and intracranial hemorrhage. Subsequently the child was transferred to a tertiary center for intestinal evaluation. The patients diarrhea and excessive diuresis resolved, and his sodium normalized soon after transfer. Four days later, however, after his mother arrived, he immediately developed severe hypernatremia (serum sodium concentration [Na(+)] = 214 mEq/L), with resumption of diarrhea and excessive diuresis. A gastric aspirate during the crisis demonstrated an extremely high sodium content, [Na(+)] = 1416 mEq/L, consistent with salt intoxication. Surveillance of the mother revealed that she manipulated the indwelling nasogastric tube; confronted, she admitted to salt administration. This case describes one of the ways that Munchausen syndrome by proxy can manifest with profound neurologic sequelae, and highlights the need for close observation and swift intervention when sufficient cause is present.

Strain Echocardiography Parameters Correlate With Disease Severity in Children and Infants With Sepsis.

Objectives: In the progression of severe sepsis, sepsis-induced myocardial dysfunction contributes to severity of illness and ultimate mortality. Identification of sepsis-induced myocardial dysfunction causing depressed cardiac function during critical illness has implications for ongoing patient management. However, assessing pediatric cardiac function traditionally relies on echocardiographic qualitative assessment and measurement of left ventricular ejection fraction or fractional shortening. These metrics are often insensitive for detecting early or regional myocardial dysfunction. Strain echocardiography is a contemporary echocardiographic modality that may be more sensitive to perturbations in cardiac function. This investigation hypothesizes that strain echocardiography metrics correlate with severity of illness in pediatric sepsis despite normal fractional shortening. Design: Single-center retrospective observational study. Setting: Tertiary 36-bed medical/surgical PICU. Patients: Pediatric patients admitted with sepsis. Interventions: None. Measurements and Main Results: Twenty-three children with sepsis received an echocardiogram in the study period. Patients with sepsis demonstrated abnormal peak systolic longitudinal strain for age (mean = –0.13 ± 0.07; p < 0.01) and low normal peak systolic circumferential strain (mean = –0.17 ± 0.14; p = 0.02) compared with internal controls as well as previously published normal values. Depressed strain was demonstrated in the septic patients despite having normal fractional shortening (mean = 0.41; 95% CI, 0.38–0.43). On initial echocardiographic imaging, worsening peak systolic longitudinal strain was associated with increasing lactate (p = 0.04). Conclusions: Pediatric patients with sepsis demonstrate evidence of depressed strain echocardiography parameters not shown by fractional shortening that correlate with clinical indices of sepsis severity. Whether strain echocardiography could eventually assist in grading pediatric sepsis severity and affect management is an area for potential future investigation.

Establishing intensivist-driven ultrasound at the PICU bedside--it's about time*.

Objective: To discuss pediatric intensivist–driven ultrasound and the exigent need for research and practice definitions pertaining to its implementation within pediatric critical care, specifically addressing issues in ultrasound-guided vascular access and intensivist-driven echocardiography. Conclusions: Intensivist-driven ultrasound improves procedure safety and reduces time to diagnosis in clinical ultrasound applications, as demonstrated primarily in adult patients. Translating these applications to the PICU requires thoughtful integration of the technology into practice and would best be informed by dedicated ultrasound research in critically ill children.

Ultrasound Guidance and Other Determinants of Successful Peripheral Artery Catheterization in Critically Ill Children.

Objective: Peripheral arterial catheterization is a common invasive procedure performed in critically ill children. However, the benefits of using ultrasound guidance for this procedure in critically ill children, especially when used by inexperienced trainees, are unclear. Our aims were to evaluate whether the use of ultrasound guidance for the placement of radial arterial catheters reduced time and improved success when compared with the palpation method and also to determine patient and trainee variables that influence procedure outcomes. Finally, we evaluated whether adoption of ultrasound guidance among trainees comes at the expense of learning landmark-based methods. Design: Prospective observational cohort. Setting: University affiliated PICU. Patients: A total of 208 procedures performed by 45 trainees in 192 unique patients (1 mo to 20 yr old) were observed. Intervention: Implementation of ultrasound curriculum. Measurements and Main Results: The main outcome measures were time and number of attempts required for the procedure. Compared with palpation method, ultrasound guidance was associated with reduced procedure time (8.1 ± 5.2 min compared with 16.5 ± 8.8 min; p < 0.001), reduced number of attempts (3.1 ± 2.6 attempts compared with 6.9 ± 4.2 attempts; p < 0.001), and improved first attempt success rate (28% compared with 11%; p = 0.001) even after adjusting for key confounders in multivariate random effects models. The factors most likely to interfere with peripheral arterial catheterization are patient age, patient systolic blood pressure, patient body mass index, degree of fluid overload, and trainee months in fellowship. The use of ultrasound guidance mitigates the influence of each of these factors. We found no evidence that the adoption of ultrasound guidance by trainees is associated with reduced proficiency in landmark-based methods. Conclusions: The use of ultrasound guidance by trainees for radial artery catheterization in critically ill children is associated with improved outcomes compared with the palpation method.

Intracranial monitoring and continuous data collection.

1. Stano P, Camporese A: Polymerase chain reaction–based rapid screening method is the real tool to prevent methicillin-resistant Staphylococcus aureus infections in intensive care unit. Crit Care Med 2012; 40:3113–3114 2. Flayhart D, Hindler JF, Bruckner DA, et al: Multicenter evaluation of BBL CHROMagar MRSA medium for direct detection of methicillin-resistant Staphylococcus aureus from surveillance cultures of the anterior nares. J Clin Microbiol 2005; 43:5536–5540 3. Chan JD, Dellit TH, Choudhuri JA, et al: Active surveillance cultures of methicillinresistant Staphylococcus aureus as a tool to predict methicillin-resistant S. aureus ventilator-associated pneumonia. Crit Care Med 2012; 40:1437–1442 4. Boyce JM, Havill NL: Comparison of BD GeneOhm methicillin-resistant Staphylococcus aureus (MRSA) PCR versus the CHROMagar MRSA assay for screening patients for the presence of MRSA strains. J Clin Microbiol 2008; 46:350–351

Point-of-care ultrasound in pediatric anesthesiology and critical care medicine

Ultrasound has increasingly become a clinical asset in the hands of the anesthesiologist and intensivist who cares for children. Though many applications for ultrasound parallel adult modalities, children as always are not simply small adults and benefit from the application of ultrasound to their management in various ways. Body composition and size are important factors that affect ultrasound performance in the child, as are the pathologies that may uniquely afflict children and aspects of procedures unique to this patient population. Ultrasound simplifies vascular access and other procedures by visualizing structures smaller than those in adults. Maturation of the thoracic cage presents challenges for the clinician performing pulmonary ultrasound though a greater proportion of the thorax can be seen. Moreover, ultrasound may provide unique solutions to sizing the airway and assessing it for cricothyroidotomy. Though cardiac ultrasound and neurosonology have historically been performed by well-developed diagnostic imaging services, emerging literature stresses the utility of clinician ultrasound in screening for pathology and providing serial observations for monitoring clinical status. Use of ultrasound is growing in clinical areas where time and diagnostic accuracy are crucial. Implementation of ultrasound at the bedside will require institutional support of education and credentialing. It is only natural that the pediatric anesthesiologist and intensivist will lead the incorporation of ultrasound in the future practice of these specialties.RésuméL’échographie est devenue de plus en plus un outil clinique dans les mains des anesthésiologistes et des intensivistes qui prennent soin d’enfants. Bien que de nombreuses applications échographiques suivent le modèle des modalités pour adultes, les enfants ne sont pas simplement de petits adultes et bénéficient d’applications échographiques propres à la gestion de leur situation. La composition et la taille de leur corps sont des facteurs importants qui affectent la performance de l’échographie, de même que les maladies des enfants ainsi que les procédures qui sont uniques à cette population. L’échographie simplifie l’accès vasculaire et d’autres procédures en visualisant des structures qui sont plus petites que celle des adultes. La maturation de la cage thoracique présente des défis pour le clinicien effectuant une échographie pulmonaire bien qu’il puisse voir une plus grande proportion du thorax. De plus, l’échographie peut fournir des réponses uniques aux dimensions des voies respiratoires et à leur évaluation en vue d’une cricothyroïdotomie. Historiquement, les échographies cardiaques et neurologiques ont été réalisées par des services d’imagerie diagnostique bien développés, mais des publications de plus en plus nombreuses soulignent la pertinence de la pratique de l’échographie par des cliniciens pour dépister des troubles et fournir des observations répétées dans le cadre d’une surveillance clinique. L’utilisation de l’échographie est en progression dans des domaines cliniques où le temps et l’exactitude diagnostique sont essentiels. La mise en œuvre de l’échographie au point d’intervention nécessitera un soutien institutionnel en matière de formation et de reconnaissance des compétences. Il est tout à fait naturel que les anesthésiologistes et Intensivistes pédiatriques soient à la tête de l’incorporation de l’échographie dans la pratique future de ces spécialités.

Return of Viable Cardiac Function after Sonographic Cardiac Standstill in Pediatric Cardiac Arrest

Abstract Sonographic cardiac standstill during adult cardiac arrest is associated with failure to get return to spontaneous circulation. This report documents 3 children whose cardiac function returned after standstill with extracorporeal membranous oxygenation. Sonographic cardiac standstill may not predict cardiac death in children.

1302: CLINICIAN ULTRASOUND SCREENING FOR CATHETER-ASSOCIATED THROMBOSIS IN CRITICALLY ILL CHILDREN

www.ccmjournal.org Critical Care Medicine • Volume 46 • Number 1 (Supplement) Learning Objectives: Vascular catheter associated thrombosis (CAT) is an iatrogenic hazard to patient safety in the ICU as a source for ischemic and embolic vessel disease. This is particularly significant for the young patient, due to vessel obstruction from adult-sized catheters, sizedependent anticoagulant dosing, and projected life-years affected by CAT or its sequelae. Despite the crucial importance of durable vascular access in the critically ill child, an organized approach for screening for CAT in children and infants with central venous access is nonexistent. Methods: This is an IRB-approved pilot study examining the prospective use of ultrasound (US) by pediatric intensive care unit (PICU) practitioners in early identification of symptomatic CAT at a medical and surgical PICU. Patients < 18 years receiving central venous catheters in vessels, without previous thrombotic disease, were approached by the study team for consent. Enrolled patients received US examinations daily when safe. A simplified 4 image US protocol that could be completed in less than 15 min. was implemented, and thrombosis was defined as evidence of vessel noncompressibility in a region demonstrating a paucity of Doppler-detectable blood flow. Results: 25 catheters (14 CVC, 11 PICC) have been examined in 22 patients ranging from < 1 month to 16 years. 11 (44%) of the catheters demonstrated thrombosis confirmed by radiologist secondary read. 7 (28%) of the thrombi caused obstructive symptoms and the other four were asymptomatic. 10 of 11 thrombi were detected with CUS before other indicators of CAT were recognized. 2 patients identified with CAT by clinicians were negative according to a full diagnostic US (DUS). No patients with confirmed CAT were missed using CUS. This yielded a sensitivity of 1.00 and specificity of 0.86 (PPV 0.85, NPV 1.00) and suggests the modality is useful for screening. 3 patients identified with CAT using CUS did not demonstrate thrombosis using DUS, however the presence of CAT was confirmed by radiologist interpretation of the CUS images. The frequency of CAT in this population (44%) is higher than that reported in retrospective studies published to date (2–18%), and suggests that CAT can be readily missed in the ICU. Conclusions: CAT is detectable by clinicians with excellent screening accuracy using available PICU US equipment. Ongoing development and optimization of ICU US protocols for CAT screening is warranted to reduce the burden of thromboembolic disease in the critically ill patient.