Phoebe H. Yager

Reduced Tissue Damage and Improved Recovery of Motor Function after Traumatic Brain Injury in Mice Deficient in Complement Component C4

Complement component C4 mediates C3-dependent tissue damage after systemic ischemia—reperfusion injury. Activation of C3 also contributes to the pathogenesis of experimental and human traumatic brain injury (TBI); however, few data exist regarding the specific pathways (classic, alternative, and lectin) involved. Using complement knockout mice and a controlled cortical impact (CCI) model, we tested the hypothesis that the classic pathway mediates secondary damage after TBI. After CCI, C4c and C3d immunostaining were detected in cortical vascular endothelial cells in wild-type (WT) mice; however, C4c and C3d immunostaining were also detected in C1q−1/− mice, and C3d immunostaining was detected in C4−/− mice. After CCI, WT and C1q−1/− mice had similar motor deficits, Morris water maze performance, and brain lesion size. Naive C4−/− and WT mice did not differ in baseline motor performance, but C4−/− mice had reduced postinjury motor deficits (days 1 to 7, P < 0.05) and decreased brain tissue damage (days 14 and 35, P < 0.05) versus WT. Reconstitution of C4−/− mice with human C4 (hC4) reversed their protection against postinjury motor deficits (P < 0.05 versus vehicle), but administration of hC4 did not impair postinjury motor performance (versus vehicle) in WT mice. The protective effects of C4−/− were functionally distinct from the classic pathway and terminal complement, as C1q−/− and C3−/− mice had postinjury tissue damage and motor dysfunction similar to WT. Thus, C4 contributes to motor deficits and brain tissue damage after CCI by mechanism(s) fundamentally different from those involved in experimental systemic ischemia-reperfusion injury.

Mannose binding lectin gene deficiency increases susceptibility to traumatic brain injury in mice

Mannose binding lectin (MBL) initiates complement activation and exacerbates tissue damage after systemic ischemia/reperfusion. We tested the hypothesis that MBL activates complement and worsens outcome using two levels of controlled cortical impact (CCI) in mice. After moderate CCI (0.6 mm depth), MBL immunostaining was detected on injured endothelial cells of wild-type (WT) mice and C3d was detected in MBL KO (deficient in MBL A/C) and WT mice, suggesting that MBL is dispensable for terminal complement activation after CCI. Brain neutrophils, edema, blood-brain barrier permeability, gross histopathology, and motor dysfunction were similar in injured MBL KO and WT mice. In mice subjected to mild CCI (0.2 mm), MBL KO mice had almost two-fold increased acute CA3 cell degeneration at 6 h (P<0.01 versus WT). Naive MBL KO mice had decreased brain volume but performed similar to WT mice in two distinct Morris water maze (MWM) paradigms. However, injured MBL KO mice had impaired performance in cued platform trials (P<0.05 versus WT), suggesting a transient nonspatial learning deficit in injured MBL KO mice. The data suggest that MBL deficiency increases susceptibility to CCI through C3-independent mechanisms and that MBL-deficient patients may be at increased risk of poor outcome after traumatic brain injury.

Advances in simulation for pediatric critical care and emergency medicine.

Purpose of review Routine integration of simulation into healthcare education and practice has gained momentum. Simulation is particularly important to acute and critical care pediatrics, as it offers alternative methods of training for high-risk and/or lower-frequency events in children. This review will discuss the recent advances in simulation education for pediatric critical care and emergency medicine and assess its potential for future growth through these subspecialties. Recent findings Research indicates that simulation with a high-fidelity manikin is more realistic than with a simple manikin. Multievent simulation centers, on-site suites and mobile units for in-situ training offer a variety of venues for training. High-fidelity simulation is now used to identify performance gaps, enhance educational curricula and assess core competencies. A landmark study demonstrated improvement in outcomes from in-hospital pediatric cardiopulmonary arrest following the introduction of a pediatric simulation-based mock code program. Summary High-fidelity simulation is emerging as a powerful tool for pediatric emergency medicine and critical care education through both individual and team-based training exercises. Programs can be tailored to meet specific institutional needs and budget limitations. As pediatric simulation-based programs evolve, further progress is anticipated in acute and critical care outcomes.

Interdisciplinary Development and Implementation of Communication Checklist for Postoperative Management of Pediatric Airway Patients

Objective. The authors describe their multidisciplinary experience in applying the Institute of Health Improvement methodology to develop a protocol and checklist to reduce communication error during transfer of care for postoperative pediatric surgical airway patients. Preliminary outcome data following implementation of the protocol and checklist are also presented. Study Design. Prospective study from July 1, 2009, to February 1, 2011. Setting. Tertiary care center. Subjects. One hundred twenty-six pediatric airway patients who required coordinated care between Massachusetts Eye and Ear Infirmary and Massachusetts General Hospital. Methods. Two sentinel events involving airway emergencies demonstrated a critical need for a standardized, comprehensive instrument that would ensure safe transfer of care. After development and implementation of the protocol and checklist, an initial pilot period on the first set of 9 pediatric airway patients was reassessed. Subsequent prospective 11-month follow-up data of 93 pediatric airway patients were collected and analyzed. Results. A multidisciplinary pediatric team developed and implemented a formalized, postoperative checklist and transfer protocol. After implementation of the checklist and transfer protocol, prospective analysis showed no adverse events from miscommunication during transfer of care over the subsequent 11-month period involving 93 pediatric airway patients. Conclusion. There has been very little written in the quality and safety patient literature about coordinating effective transfer of care between the pediatric surgical and medical subspecialty realms. After design and implementation of a simple, electronically based transfer-of-care checklist and protocol, the number of postsurgical pediatric airway information transfer and communication errors decreased significantly.

Nighttime telecommunication between remote staff intensivists and bedside personnel in a pediatric intensive care unit: a retrospective study.

Objective:To investigate the hypothesis that nighttime telemedicine can help staff intensivists remotely manage patients in a pediatric intensive care unit, preserve continuity of care, communicate with the bedside team, and provide reassurance to families in a unit where fellows provide nighttime, onsite care, with supervision by staff intensivists available by pager. Design:A retrospective review. Setting:A pediatric intensive care unit in an academic, tertiary medical center with telemedicine capability, including a mobile telemedicine cart in the pediatric intensive care unit and a home-based unit for each pediatric staff intensivist. Patients:Critically ill pediatric patients between 0 and 19 yrs, who were admitted to the pediatric intensive care unit between May 2010 and July 2011 and were managed via telemedicine. Interventions:Consecutive intake forms completed by staff intensivists following each telemedicine encounter were reviewed. Main Results:Fifty-six consecutive intake forms were evaluated for the study period. Connectivity was established in 95% of attempts. Audio and video qualities were excellent 94% and 85% of the time, respectively. The median call duration was 15 mins. The pediatric critical care fellow was present for 100% of calls, nurses 68%, and parents 66%. Reasons for initiating the call were “patient assessment” (98%), “team meeting” (25%), and/or parent update (40%). “Patient assessment,” “communication with multidisciplinary care team,” and “communication with a patient’s family” were the outcomes most often cited that would not have been possible via telephone. A change in medical management was noted following 32% of encounters. Conclusions:This study demonstrates that nighttime telecommunication linking staff intensivists on home-call with pediatric intensive care unit bedside care providers, patients, and their families is technologically feasible and may enhance team communication, provide reassurance to families, and impact patient management.

Case records of the Massachusetts General Hospital. Case 6-2014. A 35-day-old boy with fever, vomiting, mottled skin, and severe anemia.

Dr. Anna L. Cook (Pediatrics): A 35-day-old boy was admitted to the pediatric intensive care unit (ICU) of this hospital because of fever, vomiting, mottled skin, and severe anemia. The patient was born at another hospital, after an uncomplicated 37.5-week gestation, by cesarean section for breech presentation with a fraternal twin. His mother had received prenatal care, and prenatal screening tests for gonorrhea, chlamydia, syphilis, group B streptococcus, human immunodeficiency virus, and hepatitis B virus had been negative; screening for immunity to rubella virus was positive. Placental membranes had ruptured less than 24 hours before birth, and antibiotic drugs were administered before delivery. The 1-minute and 5-minute Apgar scores were both 9. The first hepatitis B immunization was administered to the patient before he was discharged. Two days before presentation, at a routine 1-month examination by his pediatrician, he was well, and the second hepatitis B immunization was administered. The day before admission, the patient’s mother noted increased fussiness, with pale and warm skin; one episode of vomiting occurred. On the morning of admission, tachycardia was noted and vomiting increased. On examination at the pediatrician’s office, the patient was pale, with mottled skin; the temperature was 38.6°C. He was referred immediately to the emergency department of a second hospital. On examination, the weight was 3.61 kg, the rectal temperature 38.0°C, the blood pressure 113/63 mm Hg, the pulse 172 beats per minute, the respiratory rate 64 breaths per minute, and the oxygen saturation 97% while he was breathing ambient air. He was pale, listless, and fussy, with mild suprasternal and intercostal retractions, without grunting or nasal flaring. The remainder of the examination was normal. A lumbar puncture was performed. Samples of the blood, urine, and cerebrospinal fluid were obtained for culture. Blood levels of electrolytes, glucose, calcium, magnesium, alkaline phosphatase, and alanine aminotransferase were normal, as were the results of renal-function tests; other test results are shown in Table 1. Urinalysis revealed dark red, cloudy urine, with a pH of 7.0, a specific gravity of 1.015, a large amount of blood, 100 mg per deciliter of protein, and trace leukocyte esterase by dipstick, as well as 0 to 5 red cells and white cells per highCase 6-2014: A 35-Day-Old Boy with Fever, Vomiting, Mottled Skin, and Severe Anemia

Case 6-2014

Dr. Anna L. Cook (Pediatrics): A 35-day-old boy was admitted to the pediatric intensive care unit (ICU) of this hospital because of fever, vomiting, mottled skin, and severe anemia. The patient was born at another hospital, after an uncomplicated 37.5-week gestation, by cesarean section for breech presentation with a fraternal twin. His mother had received prenatal care, and prenatal screening tests for gonorrhea, chlamydia, syphilis, group B streptococcus, human immunodeficiency virus, and hepatitis B virus had been negative; screening for immunity to rubella virus was positive. Placental membranes had ruptured less than 24 hours before birth, and antibiotic drugs were administered before delivery. The 1-minute and 5-minute Apgar scores were both 9. The first hepatitis B immunization was administered to the patient before he was discharged. Two days before presentation, at a routine 1-month examination by his pediatrician, he was well, and the second hepatitis B immunization was administered. The day before admission, the patient’s mother noted increased fussiness, with pale and warm skin; one episode of vomiting occurred. On the morning of admission, tachycardia was noted and vomiting increased. On examination at the pediatrician’s office, the patient was pale, with mottled skin; the temperature was 38.6°C. He was referred immediately to the emergency department of a second hospital. On examination, the weight was 3.61 kg, the rectal temperature 38.0°C, the blood pressure 113/63 mm Hg, the pulse 172 beats per minute, the respiratory rate 64 breaths per minute, and the oxygen saturation 97% while he was breathing ambient air. He was pale, listless, and fussy, with mild suprasternal and intercostal retractions, without grunting or nasal flaring. The remainder of the examination was normal. A lumbar puncture was performed. Samples of the blood, urine, and cerebrospinal fluid were obtained for culture. Blood levels of electrolytes, glucose, calcium, magnesium, alkaline phosphatase, and alanine aminotransferase were normal, as were the results of renal-function tests; other test results are shown in Table 1. Urinalysis revealed dark red, cloudy urine, with a pH of 7.0, a specific gravity of 1.015, a large amount of blood, 100 mg per deciliter of protein, and trace leukocyte esterase by dipstick, as well as 0 to 5 red cells and white cells per highCase 6-2014: A 35-Day-Old Boy with Fever, Vomiting, Mottled Skin, and Severe Anemia

Case records of the Massachusetts General Hospital. Case 31-2012. An 18-year-old man with blurred vision, dysarthria, and ataxia.

Dr. Patricia L. Musolino (Neurology): An 18-year-old man was transferred to this hospital because of blurred vision, dysarthria, and ataxia, which had reportedly progressed to coma. The patient had been well until 6 p.m. the evening before admission, when he had an abrupt onset of weakness, shaking and buckling of his legs, and clumsiness of his right hand. Approximately 20 minutes later, his speech became slurred; his parents transported him to the emergency department at another hospital. While in transit, the dysarthria worsened and the patient reported blurred vision. On arrival at the hospital 1 hour after the onset of symptoms, he required assistance getting into a wheelchair. He reported being off-balance and light-headed, with blurred vision and pain at the base of the right side of the skull. On examination, he was alert and oriented but slow to respond, and he intermittently laughed inappropriately. The vital signs were normal, and the oxygen saturation was 100% while he was breathing ambient air. On neurologic examination, the pupils and extraocular movements were reportedly normal, without nystagmus. The speech was slurred. The first cranial nerve was not tested; results of testing of the other cranial nerves were normal. The deep-tendon reflexes were 1+ and symmetric. Alternating movements of the hands were slow, with some lack of coordination; his performance on finger-to-nose testing was accurate. The white-cell count was 8600 per cubic millimeter, with 80% granulocytes, 14% lymphocytes, and 6% monocytes. The remainder of the complete blood count and the results of renaland liver-function tests were normal, as were the levels of electrolytes and glucose, measurements of arterial blood gases performed while the patient was breathing ambient air, and other test results. Screening of the blood for alcohol and the urine for toxins and drugs was negative. Computed tomography (CT) of the head was reportedly normal. The patient was admitted to the other hospital. A lumbar puncture was performed; tube 1 of the cerebrospinal fluid (CSF) appeared bloody, with gradual clearing. Reportedly, the white-cell count was 9 per cubic millimeter in tube 1 and 1 per cubic millimeter in tube 4, and the red-cell count was 10,000 per cubic millimeter in tube 1 and 54 per cubic millimeter in tube 4. The protein level was 58 mg per deciliter, and the glucose level 62 mg per deciliter (3.4 mmol per liter). No organisms were seen on Gram’s staining.

Potassium Abnormalities in a Pediatric Intensive Care Unit Frequency and Severity

Background: Potassium abnormalities are common in critically ill patients. We describe the spectrum of potassium abnormalities in our tertiary-level pediatric intensive care unit (PICU). Methods: Retrospective observational cohort of all the patients admitted to a single-center tertiary PICU over a 1-year period. Medical records and laboratory results were obtained through a central electronic data repository. Results: A total of 512 patients had a potassium measurement. Of a total of 4484 potassium measurements, one-third had abnormal values. Hypokalemia affected 40% of the admissions. Mild hypokalemia (3-3.4 mmol/L) affected 24% of the admissions. Moderate or severe hypokalemia (K <3.0 mmol/L) affected 16% of the admissions. Hyperkalemia affected 29% of the admissions. Mild hyperkalemia (5.1-6.0 mmol/L) affected 17% of the admissions. Moderate or severe hyperkalemia (>6.0 mmol/L) affected 12%. Hemolysis affected 2% of all the samples and 24% of hyperkalemic values. On univariate analysis, severity of hypokalemia was associated with mortality (odds ratio 2.2, P = .003). Conclusions: Mild potassium abnormalities are common in the PICU. Repeating hemolyzed hyperkalemic samples may be beneficial. Guidance in monitoring frequencies of potassium abnormalities in pediatric critical care is needed.

Dexmedetomidine Use in Pediatric Airway Reconstruction

Objective. Assess the postoperative use of dexmedetomidine (Precedex) in pediatric patients following airway reconstruction. Study Design. Historical cohort study. Setting. Tertiary medical center. Subjects and Methods. A retrospective review of 24 children undergoing laryngotracheal reconstruction (LTR) or laryngeal cleft repair (LCR) was conducted. Twelve children were treated with standard sedation protocols where dexmedetomidine was administered in lieu of propofol (Diprivan); 12 age-, gender-, and procedure-matched controls were selected. Subjects were divided into groups based on duration of postoperative intubation for cross-comparison; group 1 was intubated <24 hours, group 2 was intubated 2 to 6 days, and group 3 was intubated 7 days or longer. Baseline heart rate and blood pressure measurements were compared to hourly measurements for the first 6 hours following initiation of dexmedetomidine or mechanical ventilation in the control group. Number of supportive respiratory interventions, adverse events, self-extubations, premature termination of dexmedetomidine, amount of muscle relaxants, agents to treat withdrawal, and length of stay were evaluated. Results. Ten patients undergoing LTR and 2 patients undergoing LCR receiving dexmedetomidine were compared to 10 LTR and 2 LCR control patients. Overall, dexmedetomidine was well tolerated and without significant adverse effects, particularly in cases of short-term intubation or as a bridge to extubation. Conclusion. In cases requiring short-term intubation following airway reconstruction, dexmedetomidine may offer a safe alternative to propofol by providing readily reversible sedation during the periextubation period. Further studies are needed to determine the safety, efficacy, dosing, and potential complications of longer term dexmedetomidine administration in pediatric airway reconstruction.