Genetic alterations shaping tumor response to anti-EGFR therapies.

The Epidermal Growth Factor Receptor (EGFR) has been targeted through the development of selective tyrosine kinase inhibitors (TKIs) and monoclonal antibodies (mAb). These molecules have shown effectiveness in a subset of patients with specific genetic alterations (i.e. gain-of-function EGFR mutations or EGFR gene amplification) and have been approved for their use in non-small-cell lung cancer (NSCLC), colorectal cancer (CRC), pancreatic cancer and head and neck cancer. In addition, extensive research is being performed in many other tumour types hoping for a future approval. However, the majority of the patients show no benefit from these molecules due to primary mechanisms of resistance, already present before treatment or show disease progression upon the acquisition of drug resistance mechanisms during the treatment. At present, the majority of patients display resistance due to alterations in genes related to the EGFR signalling pathway that eventually circumvent EGFR inhibition and allow cancer progression. Thus, in this review article we focus on the molecular mechanisms underlying drug resistance via genetic alterations leading to resistance to all anti-EGFR drugs approved by the FDA and/or EMA. We also discuss novel approaches to surmount these chemoresistance modalities.

Bihemispheric Cerebral Oximetry Monitoring's Functionality in Suspected Cerebral Edema Diabetic Ketoacidosis With Therapeutic 3% Hyperosmolar Therapy in a Pediatric Emergency Department.

BACKGROUND: Suspected cerebral edema diabetic ketoacidosis (SCEDKA) is more common than perceived with symptoms including altered mentation, headache with vomiting, depressed Glasgow coma scale (GCS), abnormal motor or verbal responses, combativeness, and neurological depression. Suspected cerebral edema diabetic ketoacidosis has been associated with initial diabetic ketoacidosis (DKA) presentation and at start of DKA therapy.Cerebral oximetry (bihemispheric regional cerebral oxygen saturation [rcSO2] and cerebral blood volume index [CBVI]) can detect increased intracranial pressure (ICP)-induced altered bihemispheric cerebral physiology (rcSO2) (Crit Care Med 2006;34:2217-2223, J Pediatr 2013;163: 1111-1116, Curr Med Chem 2009;16:94-112, Diabetologia 1985;28:739-742, Pediatr Crit Care Med 2013;14:694-700). In pediatrics, rcSO2 of less than 60% or rcSO2 of greater than 85% reflects increased ICP and cerebral edema (Crit Care Med 2006;34:2217-2223, J Pediatr 2013;163: 1111-1116, Curr Med Chem 2009;16:94-112, Diabetologia 1985;28:739-742, Pediatr Crit Care Med 2013;14:694-700). Cerebral oximetry can detect increased ICP-induced altered bihemispheric cerebral physiology (rcSO2, CBVI) and cerebral physiological changes (rcSO2, CBVI changes) during therapeutic mechanical cerebral spinal fluid removal to decrease increased ICP (Crit Care Med 2006;34:2217-2223, J Pediatr 2013;163: 1111-1116, Curr Med Chem 2009;16:94-112, Diabetologia 1985;28:739-742, Pediatr Crit Care Med 2013;14:694-700).In the pediatric intensive care units, SCEDKA patients with nonbihemispheric cerebral oximetry showed an initial rcSO2 of greater than 90%. Bihemispheric rcSO2 with CBVI in SCEDKA patients has the potential to detect the abnormal cerebral physiology and disruptive autoregulation while detecting 3% hypertonic saline solution (HTS) effects on the SCEDKA altered cerebral physiology (rcSO2). PURPOSE: The purposes of this study were to analyze and compare 3% HTS effect on bihemispheric rcSO2 readings, neurological and biochemical parameters in SCEDKA with 3% HTS infusion to non-SCEDKA patients in pediatric emergency department (PED). METHODS: An observational retrospective comparative analysis study of bihemispheric rcSO2 readings, neurological and biochemical parameters in 2 groups of PED DKA patients were performed: PED DKA patients with SCEDKA +3% HTS infusions versus non-SCEDKA without 3% HTS infusions. RESULTS: From 2008 to 2013, of the 1899 PED DKA patients, 60 SCEDKA patients received 3% HTS (5 mL/kg via peripheral intravenous) infusion (median age of 5 years [range, 3.7-7 years]), with 42 new DKA insulin dependent diabetes mellitus onset. Suspected cerebral edema diabetic ketoacidosis patients had GCS of 11 (range, 11-12), with consistent SCEDKA signs and symptoms (severe headaches with vomiting, confusion, blurred vision, altered speech, lethargy, and combativeness). Suspected cerebral edema diabetic ketoacidosis patients' initial (0-5 minutes) left rcSO2 readings were 91.4% (range, 88.4%-94.1%) and right was 90.3% (range, 88.6%-94.1%) compared with non-SCEDKA patients' left rcSO2 readings of 73.2% (range, 69.7%-77.8%) and right of 73.2% (range, 67.6%-77%) (P < 0.0001). The rcSO2 monitoring time before 3% HTS infusion was 54.9 minutes (range, 48.3-66.8 minutes) with 3% HTS time effect change: pre-3% HTS (54.9 minutes [range, 48.3-66.8 minutes]). Before 3% HTS infusion, the left rcSO2 readings were 90.0% (range, 89%-95%) and right was 91% (range, 86%-95%). The 30 to 45 minutes post-3% HTS showed that left was 64% (range, 62%-69%) and right was 65.4% (range, 63%-70%) (P < 0.0001). rcSO2 Δ change for post-3% HTS (0-20 minutes) to pre-3% HTS was as follows: left, -26.58 (-29.5 to -23.7) (P < 0.0001); right, -25.2 (-27.7 to -22.6) (P < 0.0001). Post-3% HTS GCS (14,15) and biochemistry compared with pre-3% HTS infusions all improved (P < 0.001). CONCLUSIONS: In PED SCEDKA patients, the pre-3% HTS bihemispheric rcSO2 readings were greater than 90% and had lower GCS than non-SCEDKA patients. The post-3% HTS infusion rcSO2 readings showed within minutes a substantial reduction compared with non-SCEDKA patients, with no complications. Changes in rcSO2 readings after 3% HTS correlated with improved SCEDKA indicators (improved mental status, headache, and GCS) without any complications. We showed that cerebral oximetry in PED SCEDKA patients has shown an initial bihemispheric of greater than 90% readings signifying abnormal bihemispheric cerebral physiology. We also showed the cerebral oximetry's functionality in detecting 3% HTS therapeutic effects on SCEDKA's abnormal cerebral physiology and the beneficial therapeutic effects of 3% HTS infusion in SCEDKA patients. Using cerebral oximetry in pediatric DKA patients' initial cerebral assessment could have a significant impact in detecting SCEDKA patients. Further SCEDKA research using cerebral oximetry should be considered.

Determining the impact of body mass index on ultrasound accuracy for diagnosing appendicitis: Is it less useful in obese children?

BACKGROUND: Ultrasonography (US) is the preferred imaging for suspected pediatric appendicitis. We hypothesize that children with elevated Body-Mass-Index-for-age percentile (BMIP) may be more likely to have an inaccurate or equivocal (IE) US. METHODS: After IRB approval, a four-year review was performed on pediatric patients evaluated for appendicitis by US. The CDC BMIP Calculator was used. IE subgroups were analyzed together for comparison against the accurate group. RESULTS: 1059 patients were included: median age 11.3 years (IQR: 8.2, 14.6), 506 (47.8%) males. Median BMIP was 65.9 (IQR: 33.9, 89.6). US accurately diagnosed 857 (80.9%), incorrectly diagnosed 76 (7.2%), 126 (11.9%) were equivocal. Overall sensitivity was 0.85, specificity 0.96, PPV 0.93 and NPV 0.91. Obese children (BMIP ≥95%), had higher odds of IE US (OR: 1.86, 95% CI: 1.28, 2.70; p = 0.001). When analyzed by sex, risk increased in obese males (OR: 2.55, 95% CI:1.53, 4.24; p = 0.0003) but normalized in obese females (OR: 1.30, 95% CI:0.74, 2.28; p = 0.35). CONCLUSIONS: An elevated BMIP may increase difficulty in visualizing the appendix, resulting in inaccurate or equivocal findings. This risk is seen specifically in obese males. If US findings do not correlate with clinical assessment in obese children with abdominal pain, further evaluation may be warranted.

Assessing the Impact of 3% Hypertonic Saline Hyperosmolar Therapy on Intubated Children With Isolated Traumatic Brain Injury by Cerebral Oximetry in a Pediatric Emergency Setting.

BACKGROUND: Intubated pediatric patients with isolated traumatic brain injury (TBI) are a diagnostic challenge for early detection of altered cerebral physiology instigated by trauma-induced increased intracranial pressure (ICP) while preventing secondary neuronal damage (secondary insult detection) and assessing the effects of increased ICP therapeutic interventions (3% hypertonic saline [HTS]). Invasive brain tissue oxygen monitoring is guiding new intensive care unit TBI management but is not pediatric emergency department (PED) readily accessible. Objective measurements on pediatric isolated TBI-altered bihemispheric cerebral physiology and treatment effects of 3% HTS are currently lacking. Cerebral oximetry can assess increased ICP-induced abnormal bihemispheric cerebral physiology by measuring regional tissue oxygenation (rcSO2) and cerebral blood volume index (CBVI) and the mechanical cerebrospinal fluid removal effects on the increased ICP-induced abnormal bihemispheric cerebral physiology.In the PED intubated patients with isolated TBI, assessing the 3% HTS therapeutic response is solely by vital signs and limited clinical assessment skills. Objective measurements of the 3% HTS hyperosmolar effects on the PED isolated TBI patients' altered bihemispheric cerebral physiology are lacking. We believe that bihemispheric rcSO2 and CBVI could elucidate similar data on 3% HTS impact and influence in the intubated isolated TBI patients. OBJECTIVE: This study aimed to analyze the effects of 3% HTS on bihemispheric rcSO2 and CBVI in intubated patients with isolated TBI. METHODS: An observational, retrospective analysis of bihemispheric rcSO2 and CBVI readings in intubated pediatric patients with isolated TBI receiving 3% HTS infusions, was performed. RESULTS: From 2010 to 2017, 207 intubated patients with isolated TBI received 3% HTS infusions (median age, 2.9 [1.1-6.9 years]; preintubation Glasgow Coma Scale score, 7 [6-8]). The results were as follows: initial pre-3% HTS, 43% (39.5% to 47.5%; left) and 38% (35% to 42%; right) for rcSO2 < 60%, and 8 (-28 to 21; left) and -15 (-34 to 22; right) for CBVI; post-3% HTS, 68.5% (59.3% to 76%, P < 0.0001; left) and 62.5% (56.0% to 74.8%, P < 0.0001; right) for rcSO2 < 60%, and 12 (-7 to 24, P = 0.04; left) and 14 (-21 to 22, P < 0.0001; right) for CBVI; initial pre-3% HTS, 90% (83% to 91%; left) and 87% (82% to 92%; right) for rcSO2 > 80%, and 16.5 (6 to 33, P < 0.0001; left) and 16.8 (-2.5 to 27.5, P = 0.005; right) for CBVI; and post-3% HTS, 69% (62% to 72.5%, P < 0.0001; left) and 63% (59% to 72%, P < 0.0001; right) for rcSO2 > 80%, and 16.5 (6 to 33, P < 0.0001; left) and 16.8 (-2.5 to 27.5, P = 0.005; right) for CBVI. The following results for cerebral pathology pre-3% HTS were as follows: epidural: 85% (58% to 88.5%) for left rcSO2 and -9.25 (-34 to 19) for left CBVI, and 85.5% (57.5% to 89%) for right rcSO2 and -12.5 (-21 to 27) for CBVI; subdural: 45% (38% to 54%) for left rcSO2 and -9.5 (-25 to 19) for left CBVI, and 40% (33% to 49%) for right rcSO2 and -15 (-30.5 to 5) for CBVI. The following results for cerebral pathology post-3% HTS were as follows: epidural: 66% (58% to 69%, P = 0.03) for left rcSO2 and 15 (-1 to 21, P = 0.0004) for left CBVI, and 63% (52% to 72%, P = 0.009) for right rcSO2, and 15.5 (-22 to 24, P = 0.02) for CBVI; subdural: 63% (56% to 72%, P < 0.0001) for left rcSO2 and 9 (-20 to 22, P < 0.0001) for left CBVI, and 62.5% (48% to 73%, P < 0.0001) for right rcSO2, and 3 (-26 to 22, P < 0.0001) for CBVI. Overall, heart rate showed no significant change. Three percent HTS effect on interhemispheric rcSO2 difference >10 showed rcSO2 < 60%, and subdural hematomas had the greatest reduction (P < 0.001). The greatest positive changes occurred in bihemispheric or one-hemispheric rcSO2 < 60% with an interhemispheric discordance rcSO2 > 10 and required the greatest number of 3% HTS infusions. For 3% HTS 15% rcSO2 change time effect, all patients achieved positive change with subdural hematomas and hemispheric rcSO2 readings <60% with the shortest achievement time of 1.2 minutes (0.59-1.75; P < 0.001). CONCLUSIONS: In intubated pediatric patients with isolated TBI who received 3% HTS infusions, bihemispheric rcSO2 and CBVI readings immediately detected and trended the 3% HTS effects on the trauma-induced cerebral pathophysiology. The 3% HTS infusion produced a significant improvement in rcSO2 and CBVI readings and a reduction in interhemispheric rcSO2 discordance differences. In patients with bihemispheric or one-hemispheric rcSO2 readings <60% with or without an interhemispheric discordance, rcSO2 > 10 demonstrated the greatest significant positive delta change and required the greatest numbers of 3% HTS infusions. Overall, 3% HTS produced a significant positive 15% change within 2.1 minutes of infusion, whereas heart rate showed no significant change. During trauma neuroresuscitation, especially in intubated isolated TBI patients requiring 3% HTS, cerebral oximetry has shown its functionality as a rapid adjunct neurological, therapeutic assessment tool and should be considered in the initial emergency department pediatric trauma neurological assessment and neuroresuscitation regimen.

Hemispheric Cerebral Oximetry Monitoring During Pediatric Seizure Activity in a Pediatric Emergency Department.

BACKGROUND: Sustained neuronal activity during seizures causes cellular perturbations, alterations in cerebral physiology, and potentially neurological injury, a neurological emergency. With variable clinical manifestations of seizures, frequent failure of seizure recognition by providers in pediatric and developmentally challenged patients can increase seizure complications. Neuroresuscitation should include rapid cerebral physiology assessment for increased seizure recognition and optimal neurological outcomes. In neurological emergencies, cerebral oximetry has demonstrated its utility in altered cerebral physiology and a standard combat neurological assessment tool. During adult seizures, cerebral oximetry (regional cerebral oxygen saturation [rcSO2]) has been shown as a useful neurological assessment tool, but research is lacking in pediatric emergency department (PED) seizure patients. OBJECTIVE: The aim of this study was to identify trends in rcSO2 readings for patients presenting to the PED with seizure activity and in the postseizure state in order to evaluate usefulness of rcSO2 as a neurological assessment tool in pediatric seizure patients. METHODS: This was a PED observational case series comparing hemispheric rcSO2 readings in first-time clinically evident generalized and focal seizure patients to first-time postseizure patients with no PED seizures. RESULTS: Generalized or focal seizure (n = 185) hemispheric rcSO2 revealed significant differences compared with nonseizure and controls' rcSO2 readings (n = 115) (P < 0.0001). Generalized and focal seizure rcSO2's were either less than 60% or greater than 80% compared with nonseizure rcSO2 (P < 0.0001). Ipsilateral focal seizure rcSO2 correlated to seizure side (P < 0.0001) and was less than the contralateral rcSO2 (P < 0.0001), with interhemispheric rcSO2 discordance greater than 16 (P < 0.0001). Seizure to preseizure rcSO2 discordance was as follows: generalized 15.2, focal: left 19.8, right 20.3 (P < 0.0001). CONCLUSIONS: Hemispheric during-seizure rcSO2 readings significantly correlated with generalized and focal seizures and reflected altered cerebral physiology. Ipsilateral focal seizure rcSO2 readings correlated to the focal side with wide interhemispheric rcSO2 discordance. All postseizure rcSO2 readings returned to preseizure readings, showing altered cerebral physiology resolution. Overall, in generalized or focal seizure, rcSO2 readings were less than 60% or greater than 80%, and in focal seizure, interhemispheric rcSO2 discordance was greater than 10. During seizures, hemispheric rcSO2 readings demonstrated its potential pediatric seizure utility. Utilizing rcSO2 readings related to seizure activity could expedite pediatric and developmentally challenged patients' seizure recognition, cerebral assessment, and interventions especially in pharmacoresistant seizures.

Testing for Urinary Tract Infection in the Influenza/Respiratory Syncytial Virus-Positive Febrile Infant Aged 2 to 12 Months.

OBJECTIVE: Infants 12 months or younger with influenza and respiratory syncytial virus (RSV) commonly present to the emergency department (ED) with fever. Previous publications have recommended that these patients have a urinalysis and urine culture performed. We aimed to assess the prevalence of urinary tract infection (UTI) in febrile RSV/influenza positive infants aged 2 to 12 months presenting to the ED. We also examined whether the 2011 American Academy of Pediatrics (AAP) UTI clinical practice guidelines could be used to identify patients at lower risk of UTI. METHODS: This was a retrospective chart review examining all infants aged 2 to 12 months with a documented fever of higher than 38°C who presented to our ED from 2009 to 2013 and tested positive for influenza and/or RSV. RESULTS: One thousand seven hundred twenty-four patients were found to meet our inclusion criteria. Of these, 98 were excluded because of known urinary tract anomaly or systemic antibiotic use in the 24 hours preceding evaluation. Of those patients remaining, 10 (0.62%) of 1626 had positive urine cultures (95% confidence interval, 0.3%-1.1%), and 8 (0.49%) of 1626 (95% confidence interval, 0.2%-0.97%) had positive urine cultures with positive urinalyses as defined in the 2011 AAP UTI clinical practice guidelines. All subjects with positive urine cultures as defined by the AAP had risk factors for UTI that placed their risk for UTI above 1%. CONCLUSIONS: Our population of 2- to 12-month-old febrile infants with positive influenza/RSV testing, who did not have risk factors to make their risk of UTI higher than 1%, may not have required evaluation with urinalysis or urine culture.

Implementing a Standardized Clinical Pathway Leads to Reduced Asthma Admissions and Health Care Costs.

INTRODUCTION: Asthma exacerbations are 1 of the leading causes of hospital admissions in children in the United States. High volumes in the emergency department can lead to delayed treatment. Several studies have shown that implementation of a standardized clinical pathway can improve adherence to evidence-based standards. The purpose of our quality improvement project was to develop a standardized pathway of care for children with asthma exacerbations to improve time to treatment and reduce admissions. METHODS: The team used process mapping to review the current process of care for patients with asthma exacerbations presenting to the Emergency Department. After identification of several barriers, the team used plan-do-study-act cycles to develop a standardized clinical pathway of care for children based on their respiratory clinical score. Further interventions occurred after data collection and analyzation through run charts. RESULTS: Implementation of a standardized clinical pathway for children with asthma presenting to the Emergency Department resulted in treatment with steroids in less than 60 minutes. Overall admissions were decreased from an average of 24% to 17% throughout the intervention period. We estimated cost savings for the institution at over $230,000 for the 2 years after implementation of the pathway. CONCLUSIONS: Using a multidisciplinary team approach to develop a standardized clinical pathway for a common childhood illness like asthma can result in reduced time to treatment and admissions.

Paediatric ED BiPAP continuous quality improvement programme with patient analysis: 2005-2013.

OBJECTIVE: In paediatric moderate-to-severe asthmatics, there is significant bronchospasm, airway obstruction, air trapping causing severe hyperinflation with more positive intraplural pressure preventing passive air movement. These effects cause an increased respiratory rate (RR), less airflow and shortened inspiratory breath time. In certain asthmatics, aerosols are ineffective due to their inadequate ventilation. Bilevel positive airway pressure (BiPAP) in acute paediatric asthmatics can be an effective treatment. BiPAP works by unloading fatigued inspiratory muscles, a direct bronchodilation effect, offsetting intrinsic PEEP and recruiting collapsed alveoli that reduces the patient's work of breathing and achieves their total lung capacity quicker. Unfortunately, paediatric emergency department (PED) BiPAP is underused and quality analysis is non-existent. A PED BiPAP Continuous Quality Improvement Program (CQIP) from 2005 to 2013 was evaluated using descriptive analytics for the primary outcomes of usage, safety, BiPAP settings, therapeutics and patient disposition. INTERVENTIONS: PED BiPAP CQIP descriptive analytics. SETTING: Academic PED. PARTICIPANTS: 1157 patients. INTERVENTIONS: A PED BiPAP CQIP from 2005 to 2013 for the usage, safety, BiPAP settings, therapeutic response parameters and patient disposition was evaluated using descriptive analytics. PRIMARY AND SECONDARY OUTCOMES: Safety, usage, compliance, therapeutic response parameters, BiPAP settings and patient disposition. RESULTS: 1157 patients had excellent compliance without complications. Only 6 (0.5%) BiPAP patients were intubated. BiPAP median settings: IPAP 18 (16,20) cm H2O range 12-28; EPAP 8 cmH2O (8,8) range 6-10; inspiratory-to-expiratory time (I:E) ratio 1.75 (1.5,1.75). Pediatric Asthma Severity score and RR decreased (p<0.001) while tidal volume increased (p<0.001). Patient disposition: 325 paediatric intensive care units (PICU), 832 wards, with 52 of these PED ward patients were discharged home with only 2 hours of PED BiPAP with no returning to the PED within 72 hours. CONCLUSIONS: BiPAP is a safe and effective therapeutic option for paediatric patients with asthma presenting to a PED or emergency department. This BiPAP CQIP showed significant patient compliance, no complications, improved therapeutics times, very low intubations and decreased PICU admissions. CQIP analysis demonstrated that using a higher IPAP, low EPAP with longer I:E optimises the patient's BiPAP settings and showed a significant improvement in PAS, RR and tidal volume. BiPAP should be considered as an early treatment in the PED severe or non-responsive moderate asthmatics.

Cerebral oximetry with cerebral blood volume index in detecting pediatric stroke in a pediatric ED.

BACKGROUND: Despite pediatric stroke awareness and pediatric stroke activation systems, recognition and imaging delays along with activation inconsistency still occur. Reliable objective pediatric stroke detection tools are needed to improve detection and activations. Regional cerebral oxygen saturation (rcso2) with cerebral blood volume index (CBVI) can detect abnormal cerebral physiology. OBJECTIVE: To determine cerebral oximetry in detecting strokes in stroke alert and overall stroke patients. METHOD: Left rcso2, right rcso2, and rcso2 side differences for stroke, location, and types were analyzed. RESULTS: Compared with stroke alert (n = 25) and overall strokes (n = 52), rcso2 and CBVI were less than those in nonstrokes (n = 133; P < .0001). Rcso2 side differences in stroke alert and overall strokes were greater than in nonstrokes (P < .0001). Lower rcso2 and CBVI correlated with both groups' stroke location, left (P < .0001) and right rcso2 (P = .004). Rcso2 differences greater than 10 had a 100% positive predictive value for stroke. Both groups' rcso2 and CBVI side differences were consistent for stroke location and type (P < .0001). For both groups, left rcso2 and CBVI were greater than those of the right (P < .0001). Hemorrhagic strokes had lower bilateral rcso2 and CBVI than did ischemic strokes (P < .001). CONCLUSIONS: Cerebral oximetry and CBVI detected abnormal cerebral physiology, stroke location, and type (hemorrhagic or ischemic). Rcso2 side differences greater than 10 or rcso2 readings less than 50% had a 100% positive predictive value for stroke. Cerebral oximetry has shown potential as a detection tool for stroke location and type in a pediatric stroke alert and nonalert stroke patients. Using cerebral oximetry by the nonneurologist, we found that the patient's rcso2 side difference greater than 10 or one or both sides having less than 50% rcso2 readings suggests abnormal hemispheric pathology and expedites the patient's diagnosis, neuroresuscitation, and radiologic imaging.

Innovative Application of Cerebral rSO2 Monitoring During Shunt Tap in Pediatric Ventricular Malfunctioning Shunts.

OBJECTIVE: This study aimed to determine the reliability and potential application of cerebral regional tissue oxygenation (rSO2) monitoring in malfunctioning ventricular shunts during tap. METHODS: This is a prospective case series using convenience sample in subjects with confirmed malfunctioning shunt who had left and right cerebral rSO2 monitoring every 5 seconds before, during, and 1 hour after shunt tap. RESULTS: Ninety-four subjects had cerebral rSO2 monitoring. Sixty-three subjects had proximal malfunctions, and 31 subjects had distal shunt malfunctions. The intrasubject's cerebral rSO2 trend and variability at pretap, during, and posttap times were highly correlated. Overall, the average rSO2 is lower in pretap as compared with posttap. Left cerebral rSO2 had lower means and larger SD as compared with right cerebral rSO2. Left pretap and posttap cerebral rSO2 variability was significantly associated with the location of shunt malfunction regardless of pretap, during, or posttap periods (P < 0.001), whereas right rSO2 variability was not predictive for malfunction location. Left cerebral rSO2 variability showed utility for identifying the location of malfunction with area under the receiver operating characteristic curve equal to 0.8. CONCLUSIONS: Reliable cerebral rSO2 readings before, during, and after shunt tap were demonstrated. Left cerebral rSO2 changes from before to after shunt tap were more predictive for shunt malfunction location than right cerebral rSO2 changes. Observing cerebral rSO2 changes in relationship to shunt tap represents a potential surrogate in measuring cerebral pressures and blood flow changes after cerebral spinal fluid drainage. Significantly greater cerebral rSO2 changes occur for distal malfunction versus proximal malfunction after shunt tap, indicating its potential as an adjunct tool for detecting shunt malfunction type.

Cerebral oximetry with blood volume index in asystolic pediatric cerebrospinal fluid malfunctioning shunt patients.

Pediatric cerebrospinal fluid shunt malfunctions can present with varying complaints. The primary cause is elevated intracranial pressure (ICP). Malfunctioning sites are the proximal or distal sites[1-4]. A rare presenting complaint is cardiac arrest. Immediate ICP reduction is the only reversible option for this type of cardiac arrest.

Cerebral oxygen saturation monitoring in pediatric altered mental status patients.

OBJECTIVES: A pilot study assessing the potential utility of cerebral oximetry (local cerebral oxygen saturation [rcSO2]) in children presenting to the emergency department (ED) with altered mental status (AMS) and no history of trauma. METHODS: Patients who presented to a tertiary pediatric ED with AMS were monitored with left and right cerebral near-infrared spectroscopy probes and the first 30 minutes of rcSO2 data was analyzed. Patients with a history of trauma were excluded. Patients with an abnormal head computed tomography (CT) (n = 146) were compared with those with a negative head CT (n = 45). RESULTS: Mean rcSO2 values were consistent during each time period studied (5, 10, 20, and 30 minutes). In this study population, rcSO2 less than 50% or greater than 80% and increased absolute difference between the left and right rcSO2 measurements were associated with an abnormal CT scan. A difference of 12.2% between the left and right rcSO2 values had a 100% positive predictive value for an abnormal head CT among our patients. Cumulative graphical plots of rcSO2 trends showed that values <50% were associated with subdural hematomas (SDH) and values >80% were associated with epidural hematomas (EDH). CONCLUSIONS: This study demonstrated that cerebral oximetry can noninvasively detect altered cerebral physiology among a selected patient population. The difference between the left and right rcSO2 readings most reliably identified those subjects with altered cerebral physiology. In the future, rcSO2 monitoring has the potential to be used as a screening tool to identify, localize, and characterize intracranial injuries among children with AMS without a history of trauma.

Cerebral oximetry and cerebral blood flow monitoring in 2 pediatric survivors with out-of-hospital cardiac arrest.

In pediatric out-of-hospital cardiac arrest (POHCA), cardiovascular monitoring tools have improved resuscitative endeavors and cardiovascular outcomes but with still poor neurologic outcomes. Regarding cardiac arrest in patients with congenital heart disease during surgery, the application of cerebral oximetry with blood volume index (BVI) during the resuscitation has shown significant results and prognostic significance. We present 2 POHCA patients who had cerebral oximetry with BVI monitoring during their arrest and postarrest phase in the emergency department and its potential prognostic aspect.Basic procedures include left and right cerebral oximetry with BVI monitoring at every 5-second interval during cardiac arrest, resuscitation, and postarrest in 2 POHCA patients in the pediatric emergency department.Regional cerebral tissue oxygen saturation (rSo2) with BVI readings in these 2 POHCA survivors demonstrated interesting cerebral physiology, blood flow, and potential prognostic outcome. In 1 patient, the reference range of cerebral rSo2 with positive blood flow during arrest and postarrest phases consistently occurred. This neurologic monitoring had its significance when the resuscitation effectiveness was used and end-tidal CO2 changes were lost. The other patient's cerebral rSo2 with simultaneous BVI readings and trending showed the effectiveness of the emergency medical services (EMS) resuscitation.Cerebral oximetry with cerebral blood flow index monitoring in these POHCA survivors demonstrates compelling periarrest and postarrest cerebral physiology information and prognostication. Cerebral oximetry with cerebral BVI monitoring during these arrest phases has potential as a neurologic monitor for the resuscitative intervention's effectiveness and its possible neurologic prognostic application in the pediatric OCHA patients.

Shake, rattle, and roll: an update on pediatric seizures.

Seizure is a common presenting complaint for patients in the pediatric emergency department (PED) setting. In some cases, protocols are in place on how to manage this group of patients, for example, a patient with a simple febrile seizure already back to baseline or a patient with known epilepsy already back to baseline. However, many scenarios present dilemmas for physicians in the PED, specifically patients with status epilepticus (SE). Unfortunately, there is not a national SE protocol, and hospital-specific guidelines may or may not exist. Current practices are constantly changing because new medications arise, and more information is gathered regarding existing medications and guidelines. Here we will review the basics about first-time afebrile seizures presenting to the PED and common treatments specific to seizure types. We will then review SE management basics and medical therapy, including both older and newer agents and their routes of administration for both the prehospital and the hospital setting.

Potentially fatal mistakes. Why pediatric dosing errors happen & how to avoid them.

Calls involving critically ill or injured children are some of the most stressful situations EMS providers encounter. Their anxiety can be exponentially compounded with the sudden realization that precise mathematical equations must be rapidly performed "in the moment," making a challenging situation even worse at a time when there is no room for error. To help avoid these potentially devastating mistakes, all providers need to be aware of their vulnerability to pediatric dosing errors, and organizations need to support personnel with the training and resources necessary to mitigate these risks as much as possible.

Emergency response planning and sudden cardiac arrests in high schools after automated external defibrillator legislation.

OBJECTIVE: To compare medical emergency response plan (MERP) and automated external defibrillator (AED) prevalence and define the incidence and outcomes of sudden cardiac arrest (SCA) in high schools before and after AED legislation. STUDY DESIGN: In 2011, Tennessee Secondary School Athletic Association member schools were surveyed regarding AED placement, MERPs, and on-campus SCAs within the last 5 years. Results were compared with a similar study conducted in 2006, prior to legislation requiring AEDs in schools. RESULTS: Of the schools solicited, 214 (54%, total enrollment 182 289 students) completed the survey. Compared with 2006, schools in the 2011 survey had a significantly higher prevalence of MERPs (84% vs 71%, P < .001), annual practice (56% vs 36%, P < .001), medical emergency communication systems (80% vs 62%, P < .001), and defibrillators (90% vs 47%, P < .001). No differences were noted in the prevalence of cardiopulmonary resuscitation training (20% vs 17%, P = .58) or full compliance with American Heart Association guidelines (11% vs 7%, P = .16). Twenty-two SCA victims were identified, yielding a 5-year incidence of 1 in 10 schools. CONCLUSIONS: After state legislation, schools demonstrated a significant increase in MERPs and on-campus defibrillators but rates of cardiopulmonary resuscitation training and overall compliance with guidelines remained low.

Sudden cardiac arrests, automated external defibrillators, and medical emergency response plans in Tennessee high schools.

OBJECTIVES: Schools are important public locations of sudden cardiac arrest (SCA), and the American Heart Association (AHA) recommends medical emergency response plans (MERPs), which may include an automated external defibrillator (AED) in schools. The objective of this study was to determine the incidence of SCA and the prevalence of AEDs and MERPs in Tennessee high schools. METHODS: Tennessee Secondary School Athletic Association member schools were surveyed regarding SCA on campus within 5 years, AED presence, and MERP characteristics. RESULTS: Of 378 schools, 257 (68%) completed the survey. There were 21 (5 student and 16 adult) SCAs on school grounds, yielding a 5-year incidence of 1 SCA per 12 high schools. An AED was present at 11 of 21 schools with SCA, and 6 SCA victims were treated with an AED shock. A linear increase in SCA frequency was noted with increasing school size (<500 students: 3.3% incidence, 500-1000: 6.5%, 1000-1500: 12.5%, ≥1500: 18.2%; P = 0.003). Of 257 schools, 71% had an MERP, 48% had an AED, and only 4% were fully compliant with AHA recommendations. Schools with a history of SCA were more likely to be compliant (19% vs. 3%, P = 0.011). CONCLUSIONS: The 5-year incidence of SCA in Tennessee high schools is 1 in 12, but increases to 1 in 7 for schools with more than 1000 students. Compliance with AHA guidelines for MERPs is poor, but improved in schools with recent SCA. Future recommendations should encourage the inclusion of AED placement in schools with more than 1000 students.