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The New England Journal of Medicine | 2015

Therapeutic Hypothermia after Out-of-Hospital Cardiac Arrest in Children

Frank W. Moler; Faye S. Silverstein; Richard Holubkov; Beth S. Slomine; James R. Christensen; Vinay Nadkarni; Kathleen L. Meert; Brittan Browning; Victoria L. Pemberton; Kent Page; Seetha Shankaran; Jamie Hutchison; Christopher J. L. Newth; Kimberly Statler Bennett; John T. Berger; Alexis A. Topjian; Jose A. Pineda; Joshua Koch; Charles L. Schleien; Heidi J. Dalton; George Ofori-Amanfo; Denise M. Goodman; Ericka L. Fink; Patrick S. McQuillen; Jerry J. Zimmerman; Neal J. Thomas; Elise W. van der Jagt; Melissa B. Porter; Michael T. Meyer; Rick Harrison

BACKGROUND Therapeutic hypothermia is recommended for comatose adults after witnessed out-of-hospital cardiac arrest, but data about this intervention in children are limited. METHODS We conducted this trial of two targeted temperature interventions at 38 childrens hospitals involving children who remained unconscious after out-of-hospital cardiac arrest. Within 6 hours after the return of circulation, comatose patients who were older than 2 days and younger than 18 years of age were randomly assigned to therapeutic hypothermia (target temperature, 33.0°C) or therapeutic normothermia (target temperature, 36.8°C). The primary efficacy outcome, survival at 12 months after cardiac arrest with a Vineland Adaptive Behavior Scales, second edition (VABS-II), score of 70 or higher (on a scale from 20 to 160, with higher scores indicating better function), was evaluated among patients with a VABS-II score of at least 70 before cardiac arrest. RESULTS A total of 295 patients underwent randomization. Among the 260 patients with data that could be evaluated and who had a VABS-II score of at least 70 before cardiac arrest, there was no significant difference in the primary outcome between the hypothermia group and the normothermia group (20% vs. 12%; relative likelihood, 1.54; 95% confidence interval [CI], 0.86 to 2.76; P=0.14). Among all the patients with data that could be evaluated, the change in the VABS-II score from baseline to 12 months was not significantly different (P=0.13) and 1-year survival was similar (38% in the hypothermia group vs. 29% in the normothermia group; relative likelihood, 1.29; 95% CI, 0.93 to 1.79; P=0.13). The groups had similar incidences of infection and serious arrhythmias, as well as similar use of blood products and 28-day mortality. CONCLUSIONS In comatose children who survived out-of-hospital cardiac arrest, therapeutic hypothermia, as compared with therapeutic normothermia, did not confer a significant benefit in survival with a good functional outcome at 1 year. (Funded by the National Heart, Lung, and Blood Institute and others; THAPCA-OH ClinicalTrials.gov number, NCT00878644.).


Critical Care Medicine | 2010

The circulatory-respiratory determination of death in organ donation

James L. Bernat; Alexander Morgan Capron; Thomas P. Bleck; Sandralee Blosser; Susan L. Bratton; James F. Childress; Michael A. DeVita; Gerard Fulda; Cynthia J. Gries; Mudit Mathur; Thomas A. Nakagawa; Cynda Hylton Rushton; Sam D. Shemie; Douglas B. White

Objective:Death statutes permit physicians to declare death on the basis of irreversible cessation of circulatory–respiratory or brain functions. The growing practice of organ donation after circulatory determination of death now requires physicians to exercise greater specificity in circulatory–respiratory death determination. We studied circulatory–respiratory death determination to clarify its concept, practice, and application to innovative circulatory determination of death protocols. Results:It is ethically and legally appropriate to procure organs when permanent cessation (will not return) of circulation and respiration has occurred but before irreversible cessation (cannot return) has occurred because permanent cessation: 1) is an established medical practice standard for determining death; 2) is the meaning of “irreversible” in the Uniform Determination of Death Act; and 3) does not violate the “Dead Donor Rule.” Conclusions:The use of unmodified extracorporeal membrane oxygenation in the circulatory determination of death donor after death is declared should be abandoned because, by restoring brain circulation, it retroactively negates the previous death determination. Modifications of extracorporeal membrane oxygenation that avoid this problem by excluding brain circulation are contrived, invasive, and, if used, should require consent of surrogates. Heart donation in circulatory determination of death is acceptable if proper standards are followed to declare donor death after establishing the permanent cessation of circulation. Pending additional data on “auto-resuscitation,” we recommend that all circulatory determination of death programs should utilize the prevailing standard of 2 to 5 mins of demonstrated mechanical asystole before declaring death.


Critical Care Medicine | 2015

Management of the Potential Organ Donor in the ICU: Society of Critical Care Medicine/American College of Chest Physicians/Association of Organ Procurement Organizations Consensus Statement

Robert M. Kotloff; Sandralee Blosser; Gerard Fulda; Darren Malinoski; Vivek N. Ahya; Luis F. Angel; Matthew C. Byrnes; Michael A. DeVita; Thomas E. Grissom; Scott D. Halpern; Thomas A. Nakagawa; Peter G. Stock; Debra Sudan; Kenneth E. Wood; Sergio Anillo; Thomas P. Bleck; Elling E. Eidbo; Richard A. Fowler; Alexandra K. Glazier; Cynthia J. Gries; Richard Hasz; Daniel L. Herr; Akhtar Khan; David Landsberg; Daniel J. Lebovitz; Deborah J. Levine; Mudit Mathur; Priyumvada Naik; Claus U. Niemann; David R. Nunley

This document was developed through the collaborative efforts of the Society of Critical Care Medicine, the American College of Chest Physicians, and the Association of Organ Procurement Organizations. Under the auspices of these societies, a multidisciplinary, multi-institutional task force was convened, incorporating expertise in critical care medicine, organ donor management, and transplantation. Members of the task force were divided into 13 subcommittees, each focused on one of the following general or organ-specific areas: death determination using neurologic criteria, donation after circulatory death determination, authorization process, general contraindications to donation, hemodynamic management, endocrine dysfunction and hormone replacement therapy, pediatric donor management, cardiac donation, lung donation, liver donation, kidney donation, small bowel donation, and pancreas donation. Subcommittees were charged with generating a series of management-related questions related to their topic. For each question, subcommittees provided a summary of relevant literature and specific recommendations. The specific recommendations were approved by all members of the task force and then assembled into a complete document. Because the available literature was overwhelmingly comprised of observational studies and case series, representing low-quality evidence, a decision was made that the document would assume the form of a consensus statement rather than a formally graded guideline. The goal of this document is to provide critical care practitioners with essential information and practical recommendations related to management of the potential organ donor, based on the available literature and expert consensus.


Pediatrics | 2011

Clinical Report—Guidelines for the Determination of Brain Death in Infants and Children: An Update of the 1987 Task Force Recommendations

Thomas A. Nakagawa; Stephen Ashwal; Mudit Mathur; Mohan R. Mysore

OBJECTIVE: To review and revise the 1987 pediatric brain death guidelines. METHODS: Relevant literature was reviewed. Recommendations were developed using the GRADE system. CONCLUSIONS AND RECOMMENDATIONS: (1) Determination of brain death in term newborns, infants and children is a clinical diagnosis based on the absence of neurologic function with a known irreversible cause of coma. Because of insufficient data in the literature, recommendations for preterm infants less than 37 weeks gestational age are not included in this guideline. (2) Hypotension, hypothermia, and metabolic disturbances should be treated and corrected and medications that can interfere with the neurologic examination and apnea testing should be discontinued allowing for adequate clearance before proceeding with these evaluations. (3) Two examinations including apnea testing with each examination separated by an observation period are required. Examinations should be performed by different attending physicians. Apnea testing may be performed by the same physician. An observation period of 24 hours for term newborns (37 weeks gestational age) to 30 days of age, and 12 hours for infants and chi (> 30 days to 18 years) is recommended. The first examination determines the child has met the accepted neurologic examination criteria for brain death. The second examination confirms brain death based on an unchanged and irreversible condition. Assessment of neurologic function following cardiopulmonary resuscitation or other severe acute brain injuries should be deferred for 24 hours or longer if there are concerns or inconsistencies in the examination. (4) Apnea testing to support the diagnosis of brain death must be performed safely and requires documentation of an arterial Paco2 20 mm Hg above the baseline and ≥ 60 mm Hg with no respiratory effort during the testing period. If the apnea test cannot be safely completed, an ancillary study should be performed. (5) Ancillary studies (electroencephalogram and radionuclide cerebral blood flow) are not required to establish brain death and are not a substitute for the neurologic examination. Ancillary studies may be us d to assist the clinician in making the diagnosis of brain death (i) when components of the examination or apnea testing cannot be completed safely due to the underlying medical condition of the patient; (ii) if there is uncertainty about the results of the neurologic examination; (iii) if a medication effect may be present; or (iv) to reduce the inter-examination observation period. When ancillary studies are used, a second clinical examination and apnea test should be performed and components that can be completed must remain consistent with brain death. In this instance the observation interval may be shortened and the second neurologic examination and apnea test (or all components that are able to be completed safely) can be performed at any time thereafter. (6) Death is declared when the above criteria are fulfilled.


The New England Journal of Medicine | 2017

Therapeutic Hypothermia after In-Hospital Cardiac Arrest in Children

Frank W. Moler; Faye S. Silverstein; Richard Holubkov; Beth S. Slomine; James R. Christensen; Vinay Nadkarni; Kathleen L. Meert; Brittan Browning; Victoria L. Pemberton; Kent Page; M. R. Gildea; Barnaby R. Scholefield; Seetha Shankaran; Jamie Hutchison; John T. Berger; George Ofori-Amanfo; Christopher J. L. Newth; Alexis A. Topjian; Kimberly Statler Bennett; Joshua Koch; Nga Pham; N. K. Chanani; Jose A. Pineda; Rick Harrison; Heidi J. Dalton; J. Alten; Charles L. Schleien; Denise M. Goodman; Jerry J. Zimmerman; Utpal Bhalala

Background Targeted temperature management is recommended for comatose adults and children after out‐of‐hospital cardiac arrest; however, data on temperature management after in‐hospital cardiac arrest are limited. Methods In a trial conducted at 37 childrens hospitals, we compared two temperature interventions in children who had had in‐hospital cardiac arrest. Within 6 hours after the return of circulation, comatose children older than 48 hours and younger than 18 years of age were randomly assigned to therapeutic hypothermia (target temperature, 33.0°C) or therapeutic normothermia (target temperature, 36.8°C). The primary efficacy outcome, survival at 12 months after cardiac arrest with a score of 70 or higher on the Vineland Adaptive Behavior Scales, second edition (VABS‐II, on which scores range from 20 to 160, with higher scores indicating better function), was evaluated among patients who had had a VABS‐II score of at least 70 before the cardiac arrest. Results The trial was terminated because of futility after 329 patients had undergone randomization. Among the 257 patients who had a VABS‐II score of at least 70 before cardiac arrest and who could be evaluated, the rate of the primary efficacy outcome did not differ significantly between the hypothermia group and the normothermia group (36% [48 of 133 patients] and 39% [48 of 124 patients], respectively; relative risk, 0.92; 95% confidence interval [CI], 0.67 to 1.27; P=0.63). Among 317 patients who could be evaluated for change in neurobehavioral function, the change in VABS‐II score from baseline to 12 months did not differ significantly between the groups (P=0.70). Among 327 patients who could be evaluated for 1‐year survival, the rate of 1‐year survival did not differ significantly between the hypothermia group and the normothermia group (49% [81 of 166 patients] and 46% [74 of 161 patients], respectively; relative risk, 1.07; 95% CI, 0.85 to 1.34; P=0.56). The incidences of blood‐product use, infection, and serious adverse events, as well as 28‐day mortality, did not differ significantly between groups. Conclusions Among comatose children who survived in‐hospital cardiac arrest, therapeutic hypothermia, as compared with therapeutic normothermia, did not confer a significant benefit in survival with a favorable functional outcome at 1 year. (Funded by the National Heart, Lung, and Blood Institute; THAPCA‐IH ClinicalTrials.gov number, NCT00880087.)


Critical Care Medicine | 2011

Guidelines for the determination of brain death in infants and children: An update of the 1987 Task Force recommendations

Thomas A. Nakagawa; Stephen Ashwal; Mudit Mathur; Mohan R. Mysore; Derek Andrew Bruce; Edward E. Conway; Susan Duthie; Shannon E. G. Hamrick; Rick Harrison; Andrea M. Kline; Daniel J. Lebovitz; Maureen A. Madden; Vicki L. Montgomery; Jeffrey M. Perlman; Nancy Rollins; Sam D. Shemie; Amit Vohra; Jacqueline A. Williams-Phillips

Objective:To review and revise the 1987 pediatric brain death guidelines. Methods:Relevant literature was reviewed. Recommendations were developed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. Conclusions and Recommendations:1) Determination of brain death in term newborns, infants, and children is a clinical diagnosis based on the absence of neurologic function with a known irreversible cause of coma. Because of insufficient data in the literature, recommendations for preterm infants <37 wks gestational age are not included in this guideline. 2) Hypotension, hypothermia, and metabolic disturbances should be treated and corrected and medications that can interfere with the neurologic examination and apnea testing should be discontinued allowing for adequate clearance before proceeding with these evaluations. 3) Two examinations, including apnea testing with each examination separated by an observation period, are required. Examinations should be performed by different attending physicians. Apnea testing may be performed by the same physician. An observation period of 24 hrs for term newborns (37 wks gestational age) to 30 days of age and 12 hrs for infants and children (>30 days to 18 yrs) is recommended. The first examination determines the child has met the accepted neurologic examination criteria for brain death. The second examination confirms brain death based on an unchanged and irreversible condition. Assessment of neurologic function after cardiopulmonary resuscitation or other severe acute brain injuries should be deferred for ≥24 hrs if there are concerns or inconsistencies in the examination. 4) Apnea testing to support the diagnosis of brain death must be performed safely and requires documentation of an arterial Paco2 20 mm Hg above the baseline and ≥60 mm Hg with no respiratory effort during the testing period. If the apnea test cannot be safely completed, an ancillary study should be performed. 5) Ancillary studies (electroencephalogram and radionuclide cerebral blood flow) are not required to establish brain death and are not a substitute for the neurologic examination. Ancillary studies may be used to assist the clinician in making the diagnosis of brain death a) when components of the examination or apnea testing cannot be completed safely as a result of the underlying medical condition of the patient; b) if there is uncertainty about the results of the neurologic examination; c) if a medication effect may be present; or d) to reduce the interexamination observation period. When ancillary studies are used, a second clinical examination and apnea test should be performed and components that can be completed must remain consistent with brain death. In this instance, the observation interval may be shortened and the second neurologic examination and apnea test (or all components that are able to be completed safely) can be performed at any time thereafter. 6) Death is declared when these criteria are fulfilled.


Pediatrics | 2008

Variability in pediatric brain death determination and documentation in southern California.

Mudit Mathur; LuCyndi Petersen; Maria Stadtler; Colleen Rose; J. Chiaka Ejike; Floyd Petersen; Cynthia Tinsley; Stephen Ashwal

OBJECTIVES. Because the concept of brain death is difficult to define and to apply, we hypothesized that significant variability exists in pediatric brain death determination and documentation. METHODS. Children (0–18 years of age) for whom death was determined with neurologic criteria between January 2000 and December 2004, in southern California, were included. Medical charts were reviewed for documented performance of 14 specific elements derived from the 1987 brain death guidelines and confirmatory testing. RESULTS. A total of 51.2% of children (142 of 277 children) referred to OneLegacy became organ donors. Care locations varied, including PICUs (68%), adult ICUs (29%), and other (3%). One patient was <7 days, 6 were 7 days to 2 months, 22 were 2 months to 1 year, and 113 were >1 year of age. The number of brain death examinations performed was 0 (4 patients), 2 (122 patients), 3 (14 patients), or 4 (2 patients). Recommended intervals between examinations were followed for 18% of patients >1 year of age and for no younger patients. A mean of only 5.5 of 14 examination elements were completed by neurologists and pediatric intensivists and 5.8 by neurosurgeons. No apnea testing was recorded in 60% of cases, and inadequate Paco2 increase occurred in more than one half. Cerebral blood flow determination was performed as a confirmatory test 74% of the time (83 of 112 cases), compared with 26% (29 of 112 cases) for electroencephalography alone. CONCLUSIONS. Children suffering brain death are cared for in various locations by a diverse group of specialists. Clinical practice varies greatly from established guidelines, and documentation is incomplete for most patients. Physicians rely on cerebral blood flow measurements more than electroencephalography for confirmatory testing. Codifying clinical and testing criteria into a checklist could lend uniformity and enhance the quality and rigor of this crucial determination.


Pediatric Critical Care Medicine | 2005

Physician assistants as physician extenders in the pediatric intensive care unit setting-A 5-year experience.

Mudit Mathur; Angeli Rampersad; Kathleen Howard; Gilbert M. Goldman

Objective: To describe the scope of practice and complementary role of physician assistants as physician extenders in the pediatric intensive care unit. Design: Descriptive report of a 5-yr experience using a physician assistant-resident staffing model in comparison to the traditional resident-only coverage. Setting: Six-bed pediatric intensive care unit at a tertiary care center subject to longstanding New York Hospital Code 405 restrictions on resident work hours. Interventions: Orientation, training, credentialing, and evaluation of physician assistants. Measurements and Main Results: New Accreditation Council for Graduate Medical Education regulations based on the longstanding New York Hospital Code 405 limit the number of resident hours worked per week. Our hospital employs physician assistants as physician extenders in the pediatric intensive care unit to enable regulatory compliance. Physician assistants were oriented for a period of 6 months to 1 yr to develop skill competencies, observe and learn pediatric intensive care unit practices and procedures, and complete credentialing to perform traditionally physician, nursing, and respiratory therapist functions. Physician assistants were then assigned to an independent but supervised patient care role similar to that of a resident physician. The impact of the physician assistant program was assessed by the attending physicians, and resident opinions were surveyed. Conclusions: Physician assistants play a complementary role as physician extenders in the pediatric intensive care unit, enabling compliance with New York state and Accreditation Council for Graduate Medical Education resident work hour regulations. Physician assistants perform similar tasks and activities as the pediatric intensive care unit residents and integrate well with them in enhancing bedside patient care. Over time, physician assistants provide additional direction to the residents by virtue of their familiarity with unit-specific policies and procedures and repetitive pediatric intensive care unit practice patterns. As multifunctional members of the health care team, they support nursing and respiratory therapy functions and improve the day-to-day functioning of the unit. The physician assistant serves as a key member of the pediatric intensive care unit transport team. Limitations observed include high job turnover rates among the physician assistants and confusion between their role as shift workers or professional employees.


Acta Clinica Belgica | 2007

Outcomes of children with abdominal compartment syndrome.

J. Chiaka Ejike; S. Humbert; Khaled Bahjri; Mudit Mathur

Abstract Introduction: Abdominal compartment syndrome (ACS) is a problem across all critical care scenarios and is associated with a high mortality. It has not been well described in pediatric populations. Objective: To describe the occurrence of ACS in a subset of critically ill pediatric patients and determine its effects on mortality and length of pediatric intensive care stay (PICU LOS). We also aimed to find predictors of mortality and development of ACS. Setting: 25 bed tertiary pediatric intensive care unit. Patients: Patients less than 50 kg on mechanical ventilation and a urethral catheter. Measurements: Intra-abdominal pressures (IAP) were monitored using the intra-vesical technique. ACS was defined as IAP of >12mmHg associated with new organ dysfunction or failure. Demographics, physiologic measures of organ dysfunction, PICU LOS and mortality were monitored. Main Results: 14 (4.7%) of 294 eligible patients had ACS. Mortality was 50% among those with ACS versus 8.2% without (p<.001). PICU LOS stay did not differ between groups. No difference in mortality or PICU LOS was seen in primary versus secondary ACS or in patients who underwent abdominal decompression compared to those without decompression. IAP and ACS were independent predictors of mortality (odds ratio 1.53, 95% CI, 1.17 – 1.99 and 9.09, 95% CI, 1.07 - 76.84) respectively. IAP and a PRISM score of ≥17 were predictive of developing ACS. Conclusions: ACS is a clinical problem that increases the risk of mortality in critically ill children. IAP and PRISM scores may help identify children likely to develop ACS.


Critical Care Medicine | 2008

What is the normal intra-abdominal pressure in critically ill children and how should we measure it?

J. Chiaka Ejike; Khaled Bahjri; Mudit Mathur

Introduction:The intravesical method has been validated and is considered the gold standard for indirect intra-abdominal pressure (IAP) measurements. In adults, a standard volume (25 mL) is instilled into the bladder to measure IAP. However, the optimal volume for accurate IAP measurements in children has not been well studied and using inappropriate volumes could give erroneous IAP readings. Objective:To determine the normal IAP in critically ill children and the optimal volume for IAP measurement by the intravesical method in this population. Design:Prospective observational study. Setting:Tertiary pediatric intensive care unit. Patients:Ninety-six mechanically ventilated children younger than 18 yrs of age with no clinical evidence of intra-abdominal hypertension. Measurements and Results:Graduated volumes of normal saline in increments of 3–50 mL were instilled in the bladder via a urethral catheter. IAP was recorded by using the AbViser device (WolfeTory Medical, Inc., Salt Lake City, UT) with each instillation. A pressure–volume curve was generated for every patient, and the minimum and mean optimal volumes were determined from this curve. Data were analyzed by stratification of patients according to weights 0–10 kg, >10–20 kg, and >20–50 kg. Descriptive statistics was used for statistical analysis. Normal IAP for critically ill children was 7 ± 3 and was similar in the different weight groups (p = .745). Although the mean optimal volume to measure accurate IAP was variable in the different weight groups, the minimum optimal volume was 3 mL irrespective of weight. Conclusions:Mean IAP in critically ill children is 7 ± 3 mm Hg. The minimum optimal volume needed to accurately measure IAP by the intravesical method in children is 3 mL. We recommend that 3 mL be the standard instillation volume for IAP measurement by the intravesical method in children. IAP >10 mm Hg should be considered elevated in children.

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Mohan R. Mysore

University of Nebraska Medical Center

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Alexis A. Topjian

Children's Hospital of Philadelphia

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