Publications (19)74.32 Total impact
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Article: Noninvasive autoregulation monitoring in a swine model of pediatric cardiac arrest.
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ABSTRACT: Cerebrovascular autoregulation after resuscitation has not been well studied in an experimental model of pediatric cardiac arrest. Furthermore, developing noninvasive methods of monitoring autoregulation using near-infrared spectroscopy (NIRS) would be clinically useful in guiding neuroprotective hemodynamic management after pediatric cardiac arrest. We tested the hypotheses that the lower limit of autoregulation (LLA) would shift to a higher arterial blood pressure between 1 and 2 days of recovery after cardiac arrest and that the LLA would be detected by NIRS-derived indices of autoregulation in a swine model of pediatric cardiac arrest. We also tested the hypothesis that autoregulation with hypertension would be impaired after cardiac arrest. Data on LLA were obtained from neonatal piglets that had undergone hypoxic-asphyxic cardiac arrest and recovery for 1 day (n = 8) or 2 days (n = 8), or that had undergone sham surgery with 2 days of recovery (n = 8). Autoregulation with hypertension was examined in a separate cohort of piglets that underwent hypoxic-asphyxic cardiac arrest (n = 5) or sham surgery (n = 5) with 2 days of recovery. After the recovery period, piglets were reanesthetized, and autoregulation was monitored by standard laser-Doppler flowmetry and autoregulation indices derived from NIRS (the cerebral oximetry [COx] and hemoglobin volume [HVx] indices). The LLA was determined by decreasing blood pressure through inflation of a balloon catheter in the inferior vena cava. Autoregulation during hypertension was evaluated by inflation of an aortic balloon catheter. The LLAs were similar between sham-operated piglets and piglets that recovered for 1 or 2 days after arrest. The NIRS-derived indices accurately detected the LLA determined by laser-Doppler flowmetry. The area under the curve of the receiver operator characteristic curve for cerebral oximetry index was 0.91 at 1 day and 0.92 at 2 days after arrest. The area under the curve for hemoglobin volume index was 0.92 and 0.89 at the respective time points. During induced hypertension, the static rate of autoregulation, defined as the percentage change in cerebrovascular resistance divided by the percentage change in cerebral perfusion pressure, was not different between postarrest and sham-operated piglets. At 2 days recovery from arrest, piglets exhibited neurobehavioral deficits and histologic neuronal injury. In a swine model of pediatric hypoxic-asphyxic cardiac arrest with confirmed brain damage, the LLA did not differ 1 and 2 days after resuscitation. The NIRS-derived indices accurately detected the LLA in comparison with laser-Doppler flow measurements at those time points. Autoregulation remained functional during hypertension.Anesthesia and analgesia 02/2012; 114(4):825-36. · 3.08 Impact Factor -
Article: Cerebral blood flow and cerebrovascular autoregulation in a swine model of pediatric cardiac arrest and hypothermia.
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ABSTRACT: Knowledge remains limited regarding cerebral blood flow autoregulation after cardiac arrest and during postresuscitation hypothermia. We determined the relationship of cerebral blood flow to cerebral perfusion pressure in a swine model of pediatric hypoxic-asphyxic cardiac arrest during normothermia and hypothermia and tested novel measures of autoregulation derived from near-infrared spectroscopy. Prospective, balanced animal study. Basic physiology laboratory at an academic institution. Eighty-four neonatal swine. Piglets underwent hypoxic-asphyxic cardiac arrest or sham surgery and recovered for 2 hrs with normothermia followed by 4 hrs of either moderate hypothermia or normothermia. In half of the groups, blood pressure was slowly decreased through inflation of a balloon catheter in the inferior vena cava to identify the lower limit of cerebral autoregulation at 6 hrs postresuscitation. In the remaining groups, blood pressure was gradually increased by inflation of a balloon catheter in the aorta to determine the autoregulatory response to hypertension. Measures of autoregulation obtained from standard laser-Doppler flowmetry and indices derived from near-infrared spectroscopy were compared. Laser-Doppler flux was lower in postarrest animals compared to sham-operated controls during the 2-hr normothermic period after resuscitation. During the subsequent 4-hr recovery, hypothermia decreased laser-Doppler flux in both the sham surgery and postarrest groups. Autoregulation was intact during hypertension in all groups. With arterial hypotension, postarrest, hypothermic piglets had a significant decrease in the perfusion pressure lower limit of autoregulation compared to postarrest, normothermic piglets. The near-infrared spectroscopy-derived measures of autoregulation accurately detected loss of autoregulation during hypotension. In a pediatric model of cardiac arrest and resuscitation, delayed induction of hypothermia decreased cerebral perfusion and decreased the lower limit of autoregulation. Metrics derived from noninvasive near-infrared spectroscopy accurately identified the lower limit of autoregulation during normothermia and hypothermia in piglets resuscitated from arrest.Critical care medicine 06/2011; 39(10):2337-45. · 6.37 Impact Factor -
Article: What does it take to get some peace and quiet in the pediatric intensive care unit?
Pediatric Critical Care Medicine 03/2011; 12(2):238-40. · 3.13 Impact Factor -
Article: Continuous monitoring of cerebrovascular pressure reactivity after traumatic brain injury in children.
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ABSTRACT: We hypothesized that pressure reactivity index (PRx) values indicating preserved cerebrovascular pressure autoregulation would be associated with survival in children with traumatic brain injury (TBI). This hypothesis was tested in a prospective, blinded, observational, pilot study. Twenty-one children admitted between May 2006 and September 2008 with severe TBI necessitating invasive intracranial pressure monitoring were enrolled in this study. The PRx was continuously monitored as a moving, linear correlation coefficient between low-frequency waves of intracranial and arterial blood pressures. Positive values of PRx approaching 1 indicate impaired cerebrovascular pressure reactivity, whereas negative PRx values or values close to 0 indicate preserved cerebrovascular pressure reactivity. Survival was the primary outcome and was compared with the average PRx value obtained during the intracranial pressure-monitoring period. PRx was associated with survival in this cohort; survivors (N = 15) had a mean PRx +/- SD of 0.08 +/- 0.19, and nonsurvivors (N = 6) had a mean PRx of 0.69 +/- 0.21 (P = .0009). In this sample, continuous PRx monitoring suggested impaired cerebrovascular pressure reactivity at low levels of cerebral perfusion pressure (CPP) and intact cerebrovascular pressure reactivity at higher levels of CPP. Intact cerebrovascular pressure reactivity quantified with the PRx is associated with survival after severe head trauma in children. The PRx is CPP dependent in children. The PRx may be useful for defining age-specific and possibly patient-specific optimal targets for CPP after TBI.PEDIATRICS 12/2009; 124(6):e1205-12. · 4.47 Impact Factor -
Article: Delays and errors in cardiopulmonary resuscitation and defibrillation by pediatric residents during simulated cardiopulmonary arrests.
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ABSTRACT: The quality of life support delivered during cardiopulmonary resuscitation affects outcomes. However, little data exist regarding the quality of resuscitation delivered to children and factors associated with adherence to American Heart Association (AHA) resuscitation guidelines. Pediatric residents from an academic, tertiary care hospital. Prospective, observational cohort study of residents trained in the AHA PALS 2000 guidelines managing a high-fidelity mannequin simulator programmed to develop pulseless ventricular tachycardia (PVT). Proportion of residents who: (1) started compressions in < or =1min from onset of PVT, (2) defibrillated in < or =3min and (3) factors associated with time to defibrillation. Seventy of eighty (88%) residents participated. Forty-six of seventy (66%) failed to start compressions within 1min of pulselessness and 23/70 (33%) never started compressions. Only 38/70 (54%) residents defibrillated the mannequin in < or =3min of onset of PVT. There was no significant difference in time elapsed between onset of PVT and defibrillation by level of post-graduate training. However, residents who had previously discharged a defibrillator on either a patient or a simulator compared to those who had not were 87% more likely to successfully defibrillate the mannequin at any point in time (hazard ratio 1.87, 95% CI: 1.08-3.21, p=0.02). Pediatric residents do not meet performance standards set by the AHA. Future curricula should focus training on identified defects including: (1) equal emphasis on "airway and breathing" and "circulation" and (2) hands-on training with using and discharging a defibrillator in order to improve safety and outcomes.Resuscitation 05/2009; 80(7):819-25. · 3.60 Impact Factor -
Article: The lower limit of cerebral blood flow autoregulation is increased with elevated intracranial pressure.
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ABSTRACT: The cerebral perfusion pressure that denotes the lower limit of cerebral blood flow autoregulation (LLA) is generally considered to be equivalent for reductions in arterial blood pressure (ABP) or increases in intracranial pressure (ICP). However, the effect of decreasing ABP at different levels of ICP has not been well studied. Our objective in the present study was to determine if the LLA during arterial hypotension was invariant with ICP. Using continuous ventricular fluid infusion, anesthetized piglets were assigned to 1 of 3 groups: naïve ICP (n = 10), moderately elevated ICP (20 mm Hg; n = 11), or severely elevated ICP (40 mm Hg; n = 9). Gradual hypotension was induced by inflation of a balloon catheter in the inferior vena cava. The LLA was determined by monitoring cortical laser-Doppler flux. The naïve ICP group had an average CPP at the LLA (LLA(CPP)) of 29.8 mm Hg (95% CI: 26.5-33.0 mm Hg). However, the moderately elevated ICP group had a mean LLA(CPP) of 37.6 mm Hg (95% CI: 32.0-43.2 mm Hg), and the severely elevated ICP group had a mean LLA(CPP) of 51.4 mm Hg (95% CI: 41.2-61.7 mm Hg). The LLA significantly differed among groups, and the increase in LLA correlated with the increase in ICP. In this atraumatic, elevated ICP model in piglets, the LLA had a positive correlation with ICP, which suggests that compensating for an acute increase in ICP with an equal increase in ABP may not be sufficient to prevent cerebral ischemia.Anesthesia and analgesia 05/2009; 108(4):1278-83. · 3.08 Impact Factor -
Article: Cerebrovascular reactivity measured by near-infrared spectroscopy.
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ABSTRACT: The pressure reactivity index (PRx) describes cerebral vessel reactivity by correlation of slow waves of intracranial pressure (ICP) and arterial blood pressure. In theory, slow changes in the relative total hemoglobin (rTHb) measured by near-infrared spectroscopy are caused by the same blood volume changes that cause slow waves of ICP. Our objective was to develop a new index of vascular reactivity, the hemoglobin volume index (HVx), which is a low-frequency correlation of arterial blood pressure and rTHb measured with near-infrared spectroscopy. Gradual hypotension was induced in piglets while cortical laser-Doppler flux was monitored. ICP was monitored, and rTHb was measured continuously using reflectance near-infrared spectroscopy. The HVx was recorded as a moving linear correlation between slow waves (20 to 300 seconds) of arterial blood pressure and rTHb. Autoregulation curves were constructed by averaging values of the PRx or HVx in 5-mm Hg bins of cerebral perfusion pressure. The laser-Doppler flux-determined lower limit of autoregulation was 29.4+/-6.7 mm Hg (+/-SD). Coherence between rTHb and ICP was high at low frequencies. HVx was linearly correlated with PRx. The PRx and HVx both showed higher values below the lower limit of autoregulation and lower values above the lower limit of autoregulation. Areas under the receiver operator characteristic curves were 0.88 and 0.85 for the PRx and HVx, respectively. Coherence between the rTHb and ICP waveforms at the frequency of slow waves suggests that slow waves of ICP are related to blood volume changes. The HVx has potential for further development as a noninvasive alternative to the PRx.Stroke 04/2009; 40(5):1820-6. · 5.73 Impact Factor -
Article: A survey of anesthesiologists' knowledge of American Heart Association Pediatric Advanced Life Support Resuscitation Guidelines.
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ABSTRACT: Determine anesthesiologists' knowledge of the 2005 American Heart Association (AHA) Pediatric Advanced Life Support (PALS) recommendations. After obtaining institutional review board approval, a survey was sent in February 2007 to members of the Society for Pediatric Anesthesia via a web-based survey tool, and re-sent to nonresponders five times over the following 7 months. Overall response rate was 51% (389/768 members). Eighty-five percent of respondents had pediatric anesthesia fellowships, 71% provided anesthesia primarily to children, 71% had been in practice >10 years, 29% had PALS or APLS training during the previous year, and 37% had a patient requiring chest compressions in the previous year. Overall, 89% of respondents knew the correct initial dose of epinephrine (adrenaline) for asystole, 44% knew subsequent management for asystole if initial epinephrine dose was ineffective, 49% knew defibrillation sequence to treat pulseless ventricular tachycardia (VT), and 73% knew the medication sequence to treat pulseless VT. Only those respondents who reported to be in practice for >10 years scored significantly (p<0.0001) better on all resuscitation treatment questions. Respondents who had PALS or APLS training in the previous year or previous 2 years scored significantly better on the defibrillation sequence for pulseless VT (p=0.001 and p=0.045, respectively), and the medication sequence for pulseless VT (p=0.0005 and p=0.011, respectively) when compared with those who had no previous training. Deficiencies exist in the knowledge of current AHA PALS guidelines among anesthesiologists. Formal resuscitation training programs should be considered in ongoing continuing medical education.Resuscitation 10/2008; 79(3):499-505. · 3.60 Impact Factor -
Article: Continuous measurement of autoregulation by spontaneous fluctuations in cerebral perfusion pressure: comparison of 3 methods.
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ABSTRACT: Clinical application of continuous autoregulation monitoring would benefit from a comparison of curves generated by online monitoring with standard autoregulation curves in animal models. We characterized the accuracy of 3 continuous monitors of autoregulation in a piglet model of hypotension. Piglets 5 to10 days old with intracranial pressure (ICP) at naïve or elevated (20 mm Hg) levels had gradual arterial hypotension induced by a balloon catheter in the inferior vena cava. Elevated ICP was maintained by a continuous infusion of artificial cerebrospinal fluid. Three indices of autoregulation were simultaneously and continuously calculated. A moving, linear Pearson's coefficient between spontaneous slow waves of cerebral perfusion pressure and slow waves of laser-Doppler flux or cortical oxygenation rendered the laser-Doppler index and cerebral-oximetry index, respectively. Similar correlation between slow waves of arterial blood pressure and ICP rendered the pressure-reactivity index. The lower limit of autoregulation was determined directly for each animal by plotting laser-Doppler cortical red blood cell flux as a function of cerebral perfusion pressure. Receiver-operator characteristics were determined for the 3 indices. The areas under the receiver-operator characteristics curves for discriminating the individual lower limit of autoregulation at low and high ICP were 0.89 and 0.85 for the laser-Doppler index, 0.89 and 0.84 for the cerebral-oximetry index, and 0.79 and 0.79 for the pressure-reactivity index. The pressure-reactivity index performed equally well at low and high ICPs. Continuous monitoring of autoregulation by spontaneous slow waves of cerebral perfusion pressure can accurately detect loss of autoregulation due to hypotension in piglets by all 3 modalities.Stroke 10/2008; 39(9):2531-7. · 5.73 Impact Factor -
Article: A dynamic association between cavopulmonary shunt pressure and cerebrovascular autoregulation in an infant with congenital heart disease and intracranial hemorrhage.
Journal of cardiothoracic and vascular anesthesia 05/2008; 23(2):215-8. · 1.06 Impact Factor -
Article: Intensive care unit variables and outcome after pediatric traumatic brain injury: a retrospective study of survivors.
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ABSTRACT: Traumatic brain injury is a leading cause of death and disability in children. Hypotension has been associated with poor survival and outcome in children after traumatic brain injury, but the effect of acute hypertension is less certain. The objective was to obtain acute physiologic variables during the early hospitalization period in a cohort of children prospectively enrolled in another study. Retrospective chart reviews. University-affiliated pediatric rehabilitation center. Fifty-seven survivors, 5-17 yrs of age, admitted for rehabilitation between 1992 and 1995 after sustaining a traumatic brain injury. Standard of care. Outcomes were assessed at 1 yr postinjury through cognitive testing of the child and parent interview of the child's global functional skills. Cognitive outcome was measured using the Performance IQ from the Wechsler Intelligence Scale for Children, Third Edition. Overall functional outcome was assessed using the Disability Rating Scale. This study suggests that early markers of secondary injury after moderate to severe traumatic brain injury in children may be predictive of long-term outcome. This study reinforces the need for longer term, systematic, and more precise measurements of outcomes in children with traumatic brain injury and prospective studies to examine the predictive value of acute management variables on multiple types of outcomes after traumatic brain injury in children.Pediatric Critical Care Medicine 02/2008; 9(1):47-53. · 3.13 Impact Factor -
Article: Simulation of in-hospital pediatric medical emergencies and cardiopulmonary arrests: highlighting the importance of the first 5 minutes.
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ABSTRACT: Outcomes of in-hospital pediatric cardiopulmonary arrest are dismal. Recent data suggest that the quality of basic and advanced life support delivered to adults is low and contributes to poor outcomes, but few data regarding pediatric events have been reported. The objectives of this study were to (1) measure the median elapsed time to initiate important resuscitation maneuvers in simulated pediatric medical emergencies (ie, "mock codes") and (2) identify the types and frequency of errors committed during pediatric mock codes. A prospective, observational study was conducted of 34 consecutive hospital-based mock codes. A mannequin or computerized simulator was used to enact unannounced, simulated crisis situations involving children with respiratory distress or insufficiency, respiratory arrest, hemodynamic instability, and/or cardiopulmonary arrest. Assessment included time elapsed to initiation of specific resuscitation maneuvers and deviation from American Heart Association guidelines. Among the 34 mock codes, the median time to assessment of airway and breathing was 1.3 minutes, to administration of oxygen was 2.0 minutes, to assessment of circulation was 4.0 minutes, to arrival of any physician was 3.0 minutes, and to arrival of first member of code team was 6.0 minutes. Among cardiopulmonary arrest scenarios, elapsed time to initiation of compressions was 1.5 minutes and to request for defibrillator was 4.3 minutes. In 75% of mock codes, the team deviated from American Heart Association pediatric basic life support protocols, and in 100% of mock codes there was a communication error. Alarming delays and deviations occur in the major components of pediatric resuscitation. Future educational and organizational interventions should focus on improving the quality of care delivered during the first 5 minutes of resuscitation. Simulation of pediatric crises can identify targets for educational intervention to improve pediatric cardiopulmonary resuscitation and, ideally, outcomes.PEDIATRICS 02/2008; 121(1):e34-43. · 4.47 Impact Factor -
Article: Continuous time-domain analysis of cerebrovascular autoregulation using near-infrared spectroscopy.
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ABSTRACT: Assessment of autoregulation in the time domain is a promising monitoring method for actively optimizating cerebral perfusion pressure (CPP) in critically ill patients. The ability to detect loss of autoregulatory vasoreactivity to spontaneous fluctuations in CPP was tested with a new time-domain method that used near-infrared spectroscopic measurements of tissue oxyhemoglobin saturation in an infant animal model. Piglets were made progressively hypotensive over 4 to 5 hours by inflation of a balloon catheter in the inferior vena cava, and the breakpoint of autoregulation was determined using laser-Doppler flowmetry. The cerebral oximetry index (COx) was determined as a moving linear correlation coefficient between CPP and INVOS cerebral oximeter waveforms during 300-second periods. A laser-Doppler derived time-domain analysis of spontaneous autoregulation with the same parameters (LDx) was also determined. An increase in the correlation coefficient between cerebral oximetry values and dynamic CPP fluctuations, indicative of a pressure-passive relationship, occurred when CPP was below the steady state autoregulatory breakpoint. This COx had 92% sensitivity (73% to 99%) and 63% specificity (48% to 76%) for detecting loss of autoregulation attributable to hypotension when COx was above a threshold of 0.36. The area under the receiver-operator characteristics curve for the COx was 0.89. COx correlated with LDx when values were sorted and averaged according to the CPP at which they were obtained (r=0.67). The COx is sensitive for loss of autoregulation attributable to hypotension and is a promising monitoring tool for determining optimal CPP for patients with acute brain injury.Stroke 11/2007; 38(10):2818-25. · 5.73 Impact Factor -
Article: Lightning, sudden cardiac death, simulation and an automated external defibrillator: the perfect storm.
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ABSTRACT: This is a report of an 11-year-old boy who had sudden cardiac death after a lightning strike while playing lacrosse at summer camp. The camp staff had performed weekly drills to prepare for various medical emergencies and quickly activated their "Emergency Activation System". The child received immediate cardiopulmonary resuscitation (CPR) and was defibrillated with an automated defibrillator (AED) within 3 min of becoming pulseless and was ultimately resuscitated after being defibrillated three times. A community ambulance with a defibrillator on board did not arrive until several minutes after the on-site team had achieved return of spontaneous circulation. In this report, we describe the clinical course of this patient; briefly review lightning injuries, other causes of sudden cardiac death in children and use of AEDs. Finally, we review how simulation has been used in this case and others as a mechanism to ensure preparedness for medical emergencies. This child is alive and well today because of these well-trained camp counselors. Their system of using simulation to maintain emergency readiness serves as an example for lay and professional medical providers alike.Resuscitation 10/2007; 74(3):567-71. · 3.60 Impact Factor -
Article: Pilot study to determine the hemodynamic safety and feasibility of magnesium sulfate infusion in children with severe traumatic brain injury.
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ABSTRACT: Magnesium sulfate is neuroprotective in preclinical models, but there are limited safety data regarding its clinical use for pediatric traumatic brain injury. We conducted a pilot study in children with severe traumatic brain injury to a) examine if magnesium sulfate decreases mean arterial pressure, decreases cerebral perfusion pressure, increases intracranial pressure, or adversely effects cardiac conduction; and b) determine the feasibility of a multiple-center trial of magnesium sulfate. Double-blinded, placebo-controlled, randomized pilot trial with repeated measurement of hemodynamic variables. Two pediatric trauma centers. Six children (3 months to 18 yrs) with severe traumatic brain injury. : Magnesium sulfate (50 mg/kg) bolus followed by (8.3 mg/kg/hr) infusion for 24 hr vs. equivolume placebo. We screened 96 patients with severe traumatic brain injury during 24 months; 20 were eligible for enrollment, six provided informed consent, four received magnesium sulfate, and two received placebo. Before and after study drug infusion, we repeatedly measured blood ionized magnesium concentration, mean arterial pressure, cerebral perfusion pressure, intracranial pressure, heart rate, and corrected QT interval. Mean age (7.9 yrs), mean highest Glasgow Coma Scale score (6), gender (33% boys), inflicted injury rate (17%), and case mortality rate (17%) did not differ between those enrolled and those not enrolled. Compared with baseline, magnesium sulfate did not change cerebral perfusion pressure, intracranial pressure, heart rate, or corrected QT interval. Mean arterial pressure was unchanged until the late phase of magnesium sulfate infusion, when mean arterial pressure rose (82 +/- 5 vs. 93 +/- 6 mm Hg, p < .05). Sixty-four percent of corrected QT interval determinations obtained in the first 6 days after injury exceeded 440 msecs; 12% were >600 msecs. In children with severe traumatic brain injury, magnesium sulfate administration did not decrease mean arterial pressure or cerebral perfusion pressure or adversely effect cardiac conduction. Our data suggest that enrollment of brain-injured children in a therapeutic trial remains challenging. These results provide information important for clinical trials of magnesium sulfate in children with severe traumatic brain injury.Pediatric Critical Care Medicine 02/2007; 8(1):1-9. · 3.13 Impact Factor -
Article: Acute cyanide poisoning.
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ABSTRACT: Cyanide intoxication is an extremely rare event. We report a case of a teenager presenting with unresponsiveness, hemodynamic instability, and profound anion gap metabolic acidosis secondary to elevated lactate levels. It was later confirmed that he was a victim of cyanide poisoning. Individual case report. Pediatric intensive care unit of a tertiary care hospital. A 17-yr-old male presented with seizures, apnea, and cardiovascular collapse. His laboratory evaluation revealed extreme anion gap metabolic acidosis, elevated lactate levels, and absent arteriovenous saturation difference. The patient required inotropic support and external cardiac pacing for hemodynamic instability. Serial measurements of electrolytes and arterial and central venous blood gases were performed. When cyanide poisoning was suspected he received antidote therapy, administered initially with interval dosing and then as a continuous infusion. The antidote infusions were stopped because of a high level of resultant methemoglobinemia and the belief that all ingested cyanide had been cleared, given the time from exposure. The patient never recovered neurologic function, was declared brain dead, and became a tissue and organ donor. Cyanide poisoning is a rare and potentially fatal event. Prompt recognition of its possibility in a critically ill patient can lead to early intervention with antidote therapy and decrease the extent of morbidity and mortality.Pediatric Critical Care Medicine 02/2006; 7(1):79-82. · 3.13 Impact Factor -
Article: Nitration of the striatal Na,K-ATPase alpha3 isoform occurs in normal brain development but is not increased during hypoxia-ischemia in newborn piglets.
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ABSTRACT: Neonatal hypoxia-ischemia (HI) can result in significant sensorimotor abnormalities, including movement and posture disorders. These neurological impairments are believed to result from basal ganglia (striatum) damage, but the exact cause of this injury is not known. One mechanism involved in brain injury after HI is the generation of reactive oxygen species, which damage cellular macromolecules. We tested the hypothesis that inactivation of plasma membrane enzyme Na,K-ATPase during striatal neurodegeneration after HI emerges with peroxynitrite attack on the enzyme. In vitro, reaction of peroxynitrite (100-500 microM) with purified Na,K-ATPase produced nitration of the alpha (catalytic) and beta (transport) subunits, as quantified by immunoblots of the reaction products for nitrotyrosine. To evaluate for peroxynitrite damage to Na,K-ATPase in vivo, striatal plasma membrane fractions from 1-week-old piglets subjected to asphyxic cardiac arrest and recovery were also studied by immunoprecipitation. During the progression of striatal neurodegeneration and loss of enzyme function 3-24 h after arrest, nitration of the alpha3 (neuronal) isoform of Na,K-ATPase was not increased relative to sham control. Suprisingly, however, nitration of this alpha isoform occurs during normal brain development and peaks at 2 weeks of age. We conclude that Na,K-ATPase is a target of peroxynitrite, but that this mechanism is not responsible for enzyme inactivation after HI. Protein nitration may serve as marker of other normal, noninjurious cell processes in the developing brain.Neurochemical Research 01/2004; 28(12):1883-9. · 2.24 Impact Factor -
Article: Hypothermia for 24 hours after asphyxic cardiac arrest in piglets provides striatal neuroprotection that is sustained 10 days after rewarming.
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ABSTRACT: The neuroprotective effect of hypothermia instituted after resuscitation from asphyxic cardiac arrest has not been studied in immature brain, particularly in a large animal model with recovery periods greater than 4 d. Moreover, protection from severe hypoxia seen with 3 h of hypothermia was reported to be lost when hypothermic duration was extended to 24 h in unsedated piglets, in contrast to the neuroprotection reported by 72 h of intrauterine head cooling in fetal sheep. Piglets (5-7 postnatal days) were subjected to asphyxic cardiac arrest followed by 24 h of either hypothermia (34 degrees C) or normothermia (38.5-39 degrees C). Comparisons were made with normothermic and hypothermic surgical sham animals without asphyxia. All of these groups were sedated, paralyzed, and mechanically ventilated for the first 24 h to prevent shivering and possible depletion of glucose stores. Hypothermia per se did not cause remarkable structural abnormalities. Ischemic damage was evaluated in putamen at 1 d of recovery without rewarming and at 11 d (10 d +/- SD after rewarming). Ischemic cytopathology affected 60 +/- 12% of neurons in putamen of normothermic animals compared with 9 +/- 6% in hypothermic animals at 1 d of recovery without rewarming. At 11 d of recovery from hypoxia-ischemia, the density of viable neurons (neuron profiles/mm2) in putamen was markedly reduced in normothermic animals (81 +/- 40) compared with hypothermic animals (287 +/- 22), which was the same as in sham normothermic (271 +/- 21), sham hypothermic (288 +/- 46) and naïve animals (307 +/- 51). These data demonstrate that 24 h of hypothermia at 34 degrees C with sedation and muscle relaxation after asphyxic cardiac arrest prevents necrotic striatal neuronal cell death in immature brain before rewarming, and that the effect is sustained at 11 d after injury without deleterious side effects.Pediatric Research 09/2003; 54(2):253-62. · 2.70 Impact Factor -
Article: Noise, stress, and annoyance in a pediatric intensive care unit.
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ABSTRACT: To measure and describe hospital noise and determine whether noise can be correlated with nursing stress measured by questionnaire, salivary amylase, and heart rate. Cohort observational study. Tertiary care center pediatric intensive care unit. Registered nurses working in the unit. None. Eleven nurse volunteers were recruited. An audiogram, questionnaire data, salivary amylase, and heart rate were collected in a quiet room. Each nurse was observed for a 3-hr period during patient care. Heart rate and sound level were recorded continuously; saliva samples and stress/annoyance ratings were collected every 30 mins. Variables assessed as potential confounders were years of nursing experience, caffeine intake, patients' Pediatric Risk of Mortality Score, shift assignment, and room assignment. Data were analyzed by random effects multiple linear regression using Stata 6.0. The average daytime sound level was 61 dB(A), nighttime 59 dB(A). Higher average sound levels significantly predicted higher heart rates (p =.014). Other significant predictors of tachycardia were higher caffeine intake, less nursing experience, and daytime shift. Ninety percent of the variability in heart rate was explained by the regression equation. Amylase measurements showed a large variability and were not significantly affected by noise levels. Higher average sound levels were also predictive of greater subjective stress (p =.021) and annoyance (p =.016). In this small study, noise was shown to correlate with several measures of stress including tachycardia and annoyance ratings. Further studies of interventions to reduce noise are essential.Critical Care Medicine 02/2003; 31(1):113-9. · 6.33 Impact Factor
Top co-authors
Top Journals
- Pediatric Critical Care Medicine (4)
- Stroke (3)
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- PEDIATRICS (2)
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Institutions
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2006–2012
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Johns Hopkins University
- Department of Anesthesiology and Critical Care Medicine
Baltimore, MD, USA
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2008
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Johns Hopkins Medicine
- Department of Anesthesiology and Critical Care Medicine
Baltimore, MD, USA
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2007
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Children's National Medical Center
- Center for Genetic Medicine Research
Washington, D. C., DC, USA
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