e101CHAPTER 136 Board Review Questions 4 A 16 year old female is undergoing multimodal neurologic monitoring post–cardiac arrest due to arrhythmia Which of the following statements is true regarding p[.]
CHAPTER 136 Board Review Questions A 16-year-old female is undergoing multimodal neurologic monitoring post–cardiac arrest due to arrhythmia Which of the following statements is true regarding post-resuscitation care? A Children having blood pressures greater than 95% for age and gender post-arrest is associated with worse outcomes B Mild hypothermia was associated with statistically significantly improved outcomes after in-hospital pediatric cardiac arrest C Myoclonic status epilepticus has 100% specificity for predicting which patients will progress to brain death D The most powerful predictor of outcome after pediatric cardiac arrest is serial neurologic examination Preferred response: D Rationale Prognostication of child outcomes after cardiac arrest is best performed using multiple modalities However, the neurological examination, unimpeded by pharmacological therapies, is the most accurate single modality, especially when assessed repeatedly You assume care of a previously well 1-month-old child who was admitted the prior evening after being resuscitated following an unwitnessed cardiac arrest at home The child is currently hypotensive, febrile, and has low central venous saturation (45%) In addition to treating with cold saline infusion to achieve normothermia, which of the following tests should be prioritized in examining the patient for an underlying, treatable predisposing condition? A Brain CT B Echocardiography C Lumbar puncture D Newborn screen Preferred response: B Rationale Cardiac arrest in infants under the age of months are mostly due to asphyxia; however, some infants may have undiagnosed cardiac conditions such as ductal-dependent congenital heart disease Thus, these infants may benefit from a 12-lead electrocardiogram and echocardiography to diagnose anatomic lesions and other cardiac anomalies that may inform interventions (e.g., prostaglandin E1 for ductal dependent lesion) Which of the following is true regarding optimal postresuscitation clinical care? A Both hypoxia and hyperoxia on initial arterial blood gas are associated with poor outcome B Hypotension after cardiac arrest should not be aggressively treated due to concern for cerebral edema and brain herniation C Persistent fever after cardiac arrest facilitates more favorable cerebral blood flow patterns after cardiac arrest D Use of hyperventilation and hyperosmolar therapy to reduce intracranial pressure in children with coma and cerebral edema following ROSC is associated with improved outcomes Preferred response: A Rationale A large study of children with arterial blood gas taken within hour upon PICU presentation found that those with hyperoxia (Pao2 300 mm Hg) and hypoxia (Pao2 ,60 mm Hg) were associated with PICU mortality after covariate adjustment These e101 findings may have relevance for postresuscitation care of children surviving cardiac arrest but have not been explored in prospective clinical trials A 4-month-old infant was diagnosed with bronchiolitis two days ago His respiratory distress worsened, and the mother drove the patient to the pediatrician’s office When she arrived, she found the infant blue and not breathing Cardiopulmonary resuscitation (CPR) was initiated by the pediatrician and EMS were able to obtain return of spontaneous circulation The following statement is true regarding prognosis and therapeutic plans: A Because high-quality CPR was performed by the pediatrician, the infant will have good neurological recovery B Certain antioxidant and blood promoting therapies improved blood flow and outcomes in animal models of cardiac arrest; however, no blood flow directed therapies have been evaluated in children C Oxygen saturation should be maintained at 99–100% to assure optimal cerebral oxygenation D Vasodilator therapies are associated with improved outcomes in adults and children after cardiac arrest Preferred response: B Rationale Oxidative stress occurs acutely after hypoxia-ischemia-reperfusion and influence cerebral blood flow causing hyperemia via the neurovascular bundle Antioxidants and flow promoting interventions (e.g., fluid bolus) blunted hyperemia and improved outcomes in a pediatric experimental asphyxia cardiac arrest model Which ICU-initiated therapy has been shown to improve neurologic outcomes for children surviving cardiac arrest? A Maintaining Pao2 between 100 to 200 mm Hg immediately postcardiopulmonary resuscitation B Targeted temperature management to 33°C for 72 hours C Therapies that maintain intracranial pressure ,20 mm Hg D To date, there are no proved therapies that improve neurologic outcomes in children who suffered cardiac arrest Preferred response: D Rationale There are prospective randomized controlled trials in neonates to support hypothermia treatment However, there are no studies to support the use of hypothermia or any of the previously listed therapies to improve neurologic outcomes in children with pediatric cardiac arrest Which of the following brain regions can be most vulnerable to hypoxic-ischemic insults? A CA1 region of the hippocampus B Cerebral cortex layers I and II C Occipital lobe D Respiratory center in the brainstem Preferred response: A Rationale Certain neurons—such as those in the CA1 region of the hippocampus; cerebral cortex layers III and V; portions of the amygdaloid nucleus; the cerebellar Purkinje cells; and, in infants, periventricular white matter regions and some brainstem nuclei—have long been known to be especially vulnerable to hypoxemic- e102 S E C T I O N XV Pediatric Critical Care: Board Review Questions ischemic insults Five minutes of complete global brain ischemia produces cell death that begins to appear between 48 and 72 hours after the insult in these regions, without apparent histologic damage in other brain areas 10 Which of the following statements regarding global cerebral blood flow and metabolism in the early postresuscitation phase after cardiac arrest is correct? A Cerebral metabolic rate for oxygen (CMRO2) increases immediately following reperfusion B Cerebral blood flow (CBF) reactivity to Paco2 remains intact in patients with poor outcome C Delayed hyperemia is common in patients with good outcome D Net CBF increases to levels above normal and then decreases Preferred response: A Rationale The classic study by Snyder and colleagues on the early postresuscitation period in a dog model of global ischemia showed that after 15 minutes of global brain ischemia, CBF transiently increased to levels well above baseline Then, after 15 to 30 minutes, CBF progressively decreased to a level below normal for the remainder of the monitoring period (90 minutes) This pattern of “early transient postischemic hyperemia” and subsequent “delayed postischemic hypoperfusion” has been observed almost universally in global cerebral ischemia models including ventricular fibrillation (VF) and asphyxia arrest The levels of hyperemia and subsequent hypoperfusion vary in relation to the duration of the insult Although these phases of increased and decreased CBF characterize the net global effect, regional CBF is often inhomogeneous, particularly during postischemic hypoperfusion, when areas of decreased and increased perfusion may coexist Metabolism, as assessed with CMRO2, is reduced during the early postischemic period and then progressively recovers to a level that varies, depending on the model used and the duration of ischemia After global cerebral ischemia, nimodipine may increase CBF during the early postischemic hypoperfusion phase CMRO2 recovery is generally not increased by treatment Although nimodipine has been shown to be beneficial in patients after subarachnoid hemorrhage but not ischemic stroke, the testing of strategies targeting early postarrest hypoperfusion deserves further study Immediately after cardiac arrest accompanied by restoration of systemic hemodynamic stability, transient global brain hyperemia occurs and is followed by a period of patchy hypoperfusion The magnitude and duration of these alterations in flow appear to be related to the duration of the insult In patients with good outcomes, global CBF recovers over the subsequent 24 to 72 hours, and carbon dioxide reactivity remains intact Patients who not regain consciousness or progress to brain death have absolute or relative CBF with impaired CO2 reactivity Results from clinical studies of asphyxia arrest are scarce and somewhat conflicting with regard to prognostic implication of high or low values of postarrest CBF on the basis of a single measurement; however, loss of CO2 reactivity appears to be associated with poor outcome in all studies Beyda obtained serial measurements of postarrest xenon Xe 133 in a series of children who had asphyxia arrest from submersion accidents Children with good neurologic outcomes had slightly decreased CBF values at 12 hours that increased to normal during the subsequent 24 to 60 hours In these children, CBF reactivity to CO2 was intact Children with eventual vegetative outcome or brain death exhibited hyperemia with loss or attenuation of CO2 reactivity This hyperemia progressed to low or normal flow during the following 12 to 72 hours in children with vegetative outcome and progressed to low and then no flow with the development of brain death 11 Which of the following are the most common excitatory amino acid neurotransmitters in the human central nervous system and have a role in neuronal death after a hypoxic injury? A Aspartate and glutamate B Glycine and serotonin C Glutamate and glycine D Serotonin and dopamine Preferred response: A Rationale Glutamate and aspartate are the major excitatory amino acid neurotransmitters in the mammalian central nervous system, but both also have neurotoxic properties It has been shown in vitro that hypoxia-induced neuronal death is mediated by synaptic activity Inhibition of synaptic glutamate release or blockade of glutamate receptors prevented the hypoxic neuronal injury Glutamate is the major neurotransmitter in the selectively vulnerable zone and accumulates extracellularly in these regions after hypoxic or ischemic insults 12 Toxic oxygen radical species produced during postischemic reperfusion have been implicated as important contributors to reperfusion injury and delayed cell death The presence of which of the following is necessary for the production of hydroxyl radical from superoxide ion and hydrogen peroxide (Haber-Weiss/Fenton reaction)? A Calcium B Chloride C Iron D Magnesium Preferred response: C Rationale Toxic oxygen radical species of interest in reperfusion injury and delayed cell death after a hypoxic or ischemic event include superoxide anion, hydrogen peroxide, hydroxyl radical, and the reactive nitrogen species peroxynitrite Superoxide anion is produced by the electron transport chain during normal mitochondrial respiration Mitochondrial dysfunction, as may occur in conditions of ischemia, increases the generation of free radicals that may extend beyond the capacity of endogenous antioxidants, leading to oxidative stress Superoxide anion also can be produced as an enzymatic byproduct from the metabolism of arachidonic acid via the cyclooxygenase pathway to form prostaglandins This phenomenon occurs to a lesser extent via the lipoxygenase and cytochrome P-450 pathways Another source of superoxide anion are neutrophils via neutrophil-reduced nicotinamide adenine dinucleotide phosphate oxidase Xanthine oxidase (XO)-xanthine dehydrogenase (XD) is another potential oxygen radical source Energy depletion is associated with conversion of adenosine triphosphate to adenosine diphosphate and eventually hypoxanthine This ischemia- or CHAPTER 136 Board Review Questions anoxia-induced energy deprivation also causes conversion of XD to XO via calcium-activated proteases In the presence of hypoxanthine and oxygen, which become available during reperfusion, XO produces superoxide anion Auto-oxidation of circulating catecholamines or of neurotransmitter catecholamines may represent another potential source of oxygen radicals Another possible contributor to free radical generation is delocalized iron Iron is normally transported in the blood tightly bound to transferrin and stored inside the cell bound to ferritin In ischemic conditions with accompanying acidosis, however, iron may be displaced from its normal binding sites and can catalyze reactions that promote oxygen radical formation Most commonly implicated is the Haber-Weiss/Fenton reaction, whereby the potent hydroxyl radical is produced from superoxide anion and hydrogen peroxide in the presence of free iron Nitric oxide is another free radical that contributes to both nitrosative and oxidative stress 13 Which of the following worsens neuronal injury after a hypoxic insult? A Activation of nitric oxide synthase B Blockade of glutamate receptors C Induction of heat shock proteins D Upregulation of the bcl-2 gene Preferred response: A Rationale Nitric oxide is another free radical that contributes to both nitrosative and oxidative stress Nitric oxide increases during ischemia through N-methyl-D-aspartate receptor stimulation, mediated by the release of excitatory amino acids and subsequent calciummediated activation of neuronal nitric oxide synthase Nitric oxide, in the presence of superoxide, produces peroxynitrite Free radicals have also been associated directly with an increased release of excitatory amino acids and vice versa Not only they participate in each other’s release and formation, but they may act synergistically in causing tissue damage In response to the complex sequence of pathobiological events that evolve after brain injury, several endogenous neuroprotectants are produced, induced, or activated after ischemia, and their postulated or proved functions improve cell (specifically neuronal) survival in in vivo and in vitro models The heat shock proteins are one family of candidate neuroprotectants that are highly conserved among biological species and are induced in cells after a variety of stimuli Thermal stress is the classic example; however, any insult that damages protein structure, including ischemic and traumatic brain injury, can produce a heat shock protein response Another potential mechanism for endogenous neuroprotection is the up-regulation of genes that inhibit programmed cell death The mammalian gene bcl-2, a proto-oncogene, can block apoptotic cell death and perhaps necrotic cell death as well bcl-2 is expressed in neurons surviving both focal and global ischemia and is reduced in degenerating neurons after cardiopulmonary arrest in rats Adenosine is an endogenous biochemical mediator that may serve a protective role after cerebral ischemia, particularly early after injury Adenosine is increased in brain tissue after experimental ischemia and in response to hypoxia, hypotension, and hypoglycemia The beneficial effects of adenosine after ischemia include improved regional blood flow, reduced local oxygen e103 demand, attenuation of both excitotoxicity and calcium accumulation, and antiinflammatory and rheologic effects Pioneering studies by Rothman and colleagues demonstrated in vitro that hypoxia-induced neuronal death is mediated by synaptic activity Inhibition of synaptic glutamate release or blockade of glutamate receptors prevented hypoxia-induced neuronal injury Glutamate is the major neurotransmitter in the selectively vulnerable zones and accumulates extracellularly at supraphysiologic levels in these regions after hypoxic or ischemic insults 14 Abnormal levels of which of the following in the cerebrospinal fluid (CSF) of victims of cardiopulmonary arrest are most predictive of poor outcome? A Aspartate B Glutamate C Glycine D S-100B Preferred response: D Rationale Adjunctive prognostic information can be derived from brainderived protein levels in serum or CSF High serum levels of neuron-specific enolase (NSE) in comatose patients at 24 and 48 hours after cardiopulmonary arrest predict poor neurologic outcome Martens and colleagues found that serum concentrations of the astrocyte-derived protein S-100B were superior to serum NSE (as well as CSF S-100B and NSE) in predicting which adult patients would regain consciousness after cardiac arrest A study used a multimodal approach, combining serum concentrations of NSE, the astrocyte-derived protein S-100B, and somatosensoryevoked potentials prospectively in 27 adult patients after cardiac arrest, and was able to predict all patients who did not regain consciousness Serum NSE is increased in children after cardiac arrest and peaks at 24 hours NSE and other biomarkers may be useful in determining responsiveness to therapeutic interventions; for example, it has been reported that decreasing serum NSE occurs mainly in hypothermic (versus normothermic) adults after cardiac arrest and is predictive of outcome Other biomarkers showing promise in case series are procalcitonin, alpha II-spectrin breakdown products, serum glial fibrillary acidic protein, and brain natriuretic peptide Chapter 66: Pediatric Stroke and Intracerebral Hemorrhage The best neuroimaging modality to diagnose childhood stroke is: A Cerebral catheter angiogram B Computerized tomography (CT) and computerized tomography angiography (CTA) C Cranial ultrasound D Magnetic resonance imaging (MRI) and magnetic resonance angiography (MRA) Preferred response: D Rationale Although head CT and brain MRI will both evaluate for acute hemorrhage, brain MRI will confirm acute ischemic stroke, rule out stroke mimics, and limit radiation exposure, and therefore is usually the best first-line study e104 S E C T I O N XV Pediatric Critical Care: Board Review Questions The most common cause of spontaneous intraparenchymal intracranial hemorrhage in childhood is: A Aneurysm B Arteriovenous malformation C Cerebral cavernous malformation D Coagulation abnormalities Preferred response: B Rationale Arteriovenous malformations (AVMs) account for approximately half of intraparenchymal intracranial hemorrhage in childhood Which of the following is not a risk factor for childhood arterial ischemic stroke? A Cerebral arteriopathy B Cyanotic congenital heart disease C Routine immunizations D Sickle cell disease Preferred response: C Rationale Cerebral arteriopathy is well associated with primary and recurrent stroke In the Vascular Effects of Infection in Pediatric Stroke (VIPS) study, definite or possible arteriopathy was present on vascular imaging in 46% of all patients, and in 55% of the subset of patients who were previously healthy, that is, had no previously known risk factors for stroke Stroke is a common complication of sickle cell disease (SCD), and without treatment, 11% of children will have a stroke by 20 years of age Cardioembolic stroke secondary to congenital and acquired cardiac disease accounts for almost one-third of AIS in children, with children with complex congenital heart disease (CHD) and right-to-left shunts at highest risk Among children with heart disease and stroke, one-quarter of strokes occurred in the setting of cardiac surgery or catheterization Routine immunizations may be protective against childhood AIS Chapter 67: Central Nervous System Infections and Related Conditions A 6-day-old term infant presents to the emergency department (ED) with lethargy, poor feeding, and abnormal movements The patient arrives listless and is noted to have a temperature of 34°C (93.2°F) Additional vital signs include a heart rate of 185 beats per minute, respiratory rate 20 breaths per minute, Spo2 of 98% in room air, and blood pressure 55/26 mm Hg No abnormal movements are noted in the ED but the mother has a cell phone video of what appears to be left-sided clonic seizure activity lasting about 30 seconds prior to EMS arrival The patient has a flat anterior fontanelle and no obvious skin findings on exam Fluid resuscitation is given with slight improvement in the infant’s mental status, though now the patient is irritable and inconsolable A full sepsis evaluation is obtained including blood and urine cultures as well as a nontraumatic lumbar puncture with cerebrospinal fluid (CSF) examination and culture CSF reveals a white blood cell (WBC) count of 30 cells/mm3, red blood cell (RBC) count of 100 RBC/mm3, protein of 180 mg/dL and glucose of 60 mg/ dL The mother reports poor prenatal care but denies any infectious symptoms around the time of delivery and the patient was born via spontaneous vaginal delivery without complication In addition to empiric antibiotics with cefotaxime and ampicillin, what therapy is most appropriate at this time? A Acyclovir B Dexamethasone C Phenobarbital D Rifampin E Vancomycin Preferred response: A Rationale Herpes encephalitis must be considered in all septic infant workups, especially those with poor or no prenatal care An 11-year-old female is admitted to the pediatric intensive care unit for status epilepticus She has no history of epilepsy and had been in her usual state of health until about weeks prior to admission when she had a febrile, upper respiratory infection with a couple of episodes of nonbloody, nonbilious emesis lasting days About a week prior to admission, her parents report that her personality changed from a typically happy and pleasant child to one that was aloof and frequently irritable She also appeared to be hearing and seeing things that others could not She was taken to her pediatrician who referred her to a psychiatrist for evaluation One day prior to her psychiatry appointment she was brought to the emergency department following development of new generalized tonic-clonic seizure activity Her seizures were refractory to multiple doses of intravenous (IV) benzodiazepines as well as IV loading doses of levetiracetam and fosphenytoin, ultimately requiring intubation and placement on continuous infusion of midazolam and continuous electroencephalogram (EEG) monitoring Anti-NMDA receptor encephalitis is suspected as the etiology of her personality changes and status epilepticus In addition to cerebrospinal fluid (CSF) examination for antibodies against the NR1 subunit of the NMDA receptor, testing to evaluate for this condition must also be performed A Addison disease B Crohn disease C Cushing disease D Diabetes mellitus E Ovarian teratoma Preferred response: E Rationale Anti-NMDA receptor encephalitis is often associated with other medical conditions It was first described in women with ovarian teratomas CHAPTER 136 Board Review Questions A 6-year-old Hispanic male is admitted to the pediatric intensive care unit with a 2-day history of fever and worsening headaches History reveals a recent upper respiratory infection Initial exam shows delirium and papilledema He acutely develops tonic-clonic seizure activity requiring benzodiazepine administration and is endotracheally intubated An emergent head computed tomography shows no obvious intracranial lesions or hemorrhage A lumbar puncture demonstrates the following cerebral spinal fluid (CSF) findings: Laboratory study Value Units CSF glucose 30 mg/dL CSF leukocyte count and differential 1230 cells (80% neutrophils) /mm3 CSF red cell count /mm3 CSF protein 280 mg/dL Opening pressure 24 mm Hg CSF gram stain Numerous gram positive organisms in pairs Which of the following CSF findings is most commonly associated with development of seizure activity in this patient? A Elevated protein level B Low glucose level C Gram-positive organisms D Neutrophil predominance E Opening pressure 20 mm Hg Preferred response: C Rationale Risk factors for seizure development in acute bacterial meningitis include age less than years, pneumococcal etiology, altered mental status at admission, and CSF leukocyte count less than 1000 cells/mm3 A 13-year-old boy who resides in Tennessee recently returned from a fishing and swimming vacation to northeast Florida Five days prior to presentation, he began complaining of a strange taste in his mouth, sore throat, and headache He presented to the emergency department with fever to 102.4°F, hallucinations, and ataxia He has a right sixth nerve palsy but is currently protecting his airway and is intermittently able to follow commands Acyclovir, intravenous immunoglobulin, and meningitic dose antibiotics fail to improve his encephalopathy On the seventh day of his admission to the pediatric ICU, he develops status epilepticus and requires endotracheal intubation Which of the following treatments should be instituted immediately? A Glycerol, metronidazole, and dexamethasone B High-dose acyclovir and dexamethasone C Intravenous and intrathecal amphotericin, azithromycin, fluconazole, rifampin, miltefosine, and dexamethasone D Plasmapheresis followed by high-dose corticosteroids and intrathecal methotrexate Preferred response: C Rationale Primary amebic meningoencephalitis (PAM) is a rare, often fatal disease most commonly caused by infection with Naegleria fowleri, e105 a thermophilic, free-living ameba found in freshwater environments In the United States, N fowleri is commonly found in warm freshwater environments in 15 southern-tier states (Arizona, Arkansas, California, Florida, Georgia, Louisiana, Mississippi, Missouri, Nevada, New Mexico, North Carolina, Oklahoma, South Carolina, Texas, and Virginia) Naegleria species typically cause PAM in children and healthy adults who have been swimming in infected water N fowleri enter through the olfactory neuroepithelium at the level of the cribriform plate and invade the submucosal nervous plexus Symptoms begin after a 3- to 7-day incubation period PAM presents in a manner similar to acute bacterial meningitis, but physicians often miss the diagnosis initially History is vital for making the diagnosis Recent exposure to diving, swimming, or splashing in warm freshwater should suggest the possibility of amebic meningoencephalitis Prompt examination of the cerebrospinal fluid for N fowleri is fundamental to establishing this diagnosis The onset of PAM is abrupt but nonspecific Patients may complain of sore throat, headache, nausea, vomiting, malaise, and fever Early findings may also include irritability, hallucinations, meningismus, cerebellar ataxia, and cranial nerve palsies, although focal neurologic defects are usually absent Alterations in taste and smell may occur, likely due to involvement of the olfactory nerve The diagnosis is made by examination of centrifuged CSF wet mounts for motile trophozoites However, failure to visualize these amebas does not exclude PAM The diagnosis is often missed when Naegleria organisms are mistaken for atypical leukocytes, specifically monocytes or lymphocytes Based on the treatment regimens used in the most recent survivors of PAM, the CDC currently recommends the following drug therapy in CNS infections caused by Naegleria fowleri as well as Balamuthia mandrillaris and Acanthamoeba species: (1) IV amphotericin B, (2) intrathecal amphotericin B, (3) azithromycin, (4) fluconazole, (5) rifampin, (6) miltefosine, and (7) dexamethasone Five days after a viral upper respiratory tract infection, a previously healthy 7-year-old boy is admitted to the intensive care unit with fever and encephalopathy After a computed tomography scan shows no space-occupying lesion or signs of elevated intracranial pressure, a lumbar puncture is performed, and it shows normal opening pressure, 20 WBC/hpf, 90 mg/ dL protein, and no organisms on Gram stain Herpesvirus PCR is negative T2-weighted magnetic resonance images show several large asymmetric lesions of high signal intensity in the deep cortical gray and subcortical white matter EEG demonstrates diffuse slowing but no epileptiform activity Which treatment is most likely to be beneficial in this case? A Acyclovir B Ceftriaxone C High-dose methylprednisolone D Metronidazole Preferred response: C Rationale This patient is presenting with signs and symptoms of acute disseminated encephalomyelitis (ADEM) ADEM is an immunemediated process that may result in a clinical picture similar to infectious meningitis or encephalitis MRI typically demonstrates large, bilateral, poorly demarcated lesions in white matter and deep cortical gray structures First-line treatment for ADEM includes high-dose corticosteroids, typically methylprednisolone, ... hypoxanthine This ischemia- or CHAPTER 136 Board Review Questions anoxia-induced energy deprivation also causes conversion of XD to XO via calcium-activated proteases In the presence of hypoxanthine... neutrophils via neutrophil-reduced nicotinamide adenine dinucleotide phosphate oxidase Xanthine oxidase (XO)-xanthine dehydrogenase (XD) is another potential oxygen radical source Energy depletion... treatment is most likely to be beneficial in this case? A Acyclovir B Ceftriaxone C High-dose methylprednisolone D Metronidazole Preferred response: C Rationale This patient is presenting with signs