Development of cerebral edema after brain injury carries a high risk for brain damage and death. The present study tests the ability of a noninvasive cerebral edema monitoring system that uses near-infrared spectroscopy (NIRS) with water as the chromophore of interest to detect brain edema following hypoxia. Ventilated piglets were exposed to hypoxia for 1 h, and then returned to normal oxygen levels for 4 h. An NIRS sensor was placed on the animal’s head at baseline, and changes in light attenuation were converted to changes in H2O. Cerebral water content and aquaporin-4 protein (AQP4) expression were measured. The system detected changes in NIRS–derived water signal as early as 2 h after hypoxia, and provided fivefold signal amplification, representing a 10% increase in brain water content and a sixfold increase in AQP4, 4 h after hypoxia. Changes in water signal correlated well with changes in cerebral water content (R=0.74) and AQP4 expression (R=0.97) in the piglet brain. The data show that NIRS can detect cerebral edema early in the injury process, thus providing an opportunity to initiate therapy at an earlier and more effective time-point after an insult than is available with current technology.

HomeCirculationVol. 132, No. 18_suppl_2Part 3: Ethical Issues Free AccessResearch ArticlePDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessResearch ArticlePDF/EPUBPart 3: Ethical Issues2015 American Heart Association Guidelines Update for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Mary E. Mancini, Douglas S. Diekema, Theresa A. Hoadley, Kelly D. Kadlec, Marygrace H. Leveille, Jane E. McGowan, Michele M. Munkwitz, Ashish R. Panchal, Michael R. Sayre and Elizabeth H. Sinz Mary E. ManciniMary E. Mancini Search for more papers by this author , Douglas S. DiekemaDouglas S. Diekema Search for more papers by this author , Theresa A. HoadleyTheresa A. Hoadley Search for more papers by this author , Kelly D. KadlecKelly D. Kadlec Search for more papers by this author , Marygrace H. LeveilleMarygrace H. Leveille Search for more papers by this author , Jane E. McGowanJane E. McGowan Search for more papers by this author , Michele M. MunkwitzMichele M. Munkwitz Search for more papers by this author , Ashish R. PanchalAshish R. Panchal Search for more papers by this author , Michael R. SayreMichael R. Sayre Search for more papers by this author and Elizabeth H. SinzElizabeth H. Sinz Search for more papers by this author Originally published3 Nov 2015https://doi.org/10.1161/CIR.0000000000000254Circulation. 2015;132:S383–S396The goals of resuscitation are to preserve life; restore health; relieve suffering; limit disability; and respect individuals’ decisions, rights, and privacy. Because cardiopulmonary resuscitation (CPR) efforts must be initiated immediately at the time of arrest, a rescuer may not know who the victim is, what that individual’s goals of care are, or if an advance directive exists. As a result, administration of CPR may be contrary to the individual’s desires or best interests.1–3 This Part of the 2015 American Heart Association (AHA) Guidelines Update for CPR and Emergency Cardiovascular Care provides updates to the 2010 AHA Guidelines4 for healthcare providers who are faced with the difficult decision to provide or withhold emergency cardiovascular care.Ethical PrinciplesEthical, legal, and cultural factors influence decisions about resuscitation. Ideally, these decisions are guided by science, patient or surrogate preferences, local policies and legal requirements, and established ethical principles.Principle of Respect for AutonomyRespect for autonomy is an important social value in medical ethics and law.5 This principle is based on society’s respect for a competent individual’s ability to make decisions about his or her own health care. Adults are presumed to have decision-making capability unless they are incapacitated or declared incompetent by a court of law. Informed decisions require that individuals receive and understand accurate information about their condition and prognosis as well as the nature, risks, benefits, and alternatives of any proposed interventions. Individuals must deliberate and choose among alternatives by linking their decisions to their values and personal goals of care.When physicians strive to understand patients’ goals of care, decisions can be made based on the likelihood that together they will achieve the patients’ goals of care. The following 3-step process may assist healthcare providers in ensuring each patient understands and makes informed decisions: (1) the patient receives and understands accurate information about his or her condition, prognosis, nature of any proposed interventions, alternatives, and risks and benefits; (2) the patient is asked to paraphrase the information to give providers the opportunity to assess the patient’s understanding and correct any misimpressions; and (3) the patient deliberates and chooses among alternatives and justifies his or her decisions.6When decision-making capacity is temporarily impaired by conditions such as active illness, treatment of these conditions may restore capacity. When an individual’s preferences are unknown or uncertain, it is ethically appropriate to treat emergency conditions until further information is available.Pediatric Decision MakingAs a general rule, minors are considered incompetent to provide legally binding consent about their health care. Parents or guardians are generally empowered to make healthcare decisions on the behalf of minors, and in most situations, parents are given wide latitude in terms of the decisions they make on behalf of their children. Ethically, however, a child should be involved in decision making at a level appropriate for the child’s maturity. Children under 14 years of age in Canada and under 18 years of age in the United States rarely possess the legal authority to consent to their health care except under specific legally defined situations (eg, emancipated minors; mature minors; minors who have specific health conditions, such as those with sexually transmitted diseases or in need of pregnancy-related care). However, as older children develop the capacity to make decisions, it is ethically appropriate to include them in discussions about their care and the treatments using language and explanations suitable for the child’s level of maturity and cognitive function.Withholding and Withdrawing CPR (Termination of Resuscitative Efforts) Related to Out-of-Hospital Cardiac ArrestCriteria for Not Starting CPRWhile the general rule is to provide emergency treatment to a victim of cardiac arrest, there are a few exceptions where withholding CPR would be considered appropriate:Situations where attempts to perform CPR would place the rescuer at risk of serious injury or mortal peril (eg, exposure to infectious diseases).Obvious clinical signs of irreversible death (eg, rigor mortis, dependent lividity, decapitation, transection, decomposition).A valid advance directive, a Physician Orders for Life-Sustaining Treatment (POLST) form7 (www.polst.org) indicating that resuscitation is not desired, or a valid Do Not Attempt Resuscitation (DNAR) order.Terminating Resuscitative Efforts in Neonatal, Pediatric, or Adult Out-of-Hospital Cardiac ArrestThe 2010 Guidelines contain a complete discussion of clinical decision rules for terminating resuscitative efforts.4 In 2015, the International Liaison Committee on Resuscitation (ILCOR) Neonatal Life Support Task Force and the Pediatric Life Support Task Force completed systematic reviews to examine whether the presence of certain prognostic factors in the newly born or in infants or children enabled prediction of good neurologic outcome (see “Part 12: Pediatric Advanced Life Support” and “Part 13: Neonatal Resuscitation”).In the absence of clinical decision rules for the neonate, infant, child, or adult out-of-hospital cardiac arrest (OHCA) victim, CPR and advanced life support protocols are used by responsible prehospital providers in consultation with medical direction in real-time or as the victim is transported to the most appropriate facility per local directives. The impact of the availability of advanced hospital-based interventions, including extracorporeal membrane oxygenation (ECMO) during refractory CPR and the use of targeted temperature management (TTM), is now being considered in the local evaluation for continuing resuscitation and transport in some emergency medical service systems.8–10Use of Extracorporeal CPR for Adults With OHCA—UpdatedThe use of extracorporeal CPR (ECPR) may allow providers additional time to treat reversible underlying causes of cardiac arrest (eg, acute coronary artery occlusion, pulmonary embolism, refractory ventricular fibrillation, profound hypothermia, cardiac injury, myocarditis, cardiomyopathy, congestive heart failure, drug intoxication) or serve as a bridge for left ventricular assist device implantation or cardiac transplant.2015 Evidence SummaryThe 2015 ILCOR systematic review evaluated the use of ECPR techniques (including ECMO or cardiopulmonary bypass) compared with manual CPR or mechanical CPR. One post hoc analysis of data from a prospective, observational cohort of 162 OHCA patients who did not achieve return of spontaneous circulation (ROSC) with more than 20 minutes of conventional CPR, including propensity score matching, showed that at 3-month follow-up ECPR was associated with a higher rate of neurologically intact survival than continued conventional CPR.11A single prospective, observational study that enrolled 454 patients with OHCA who were treated with ECPR if they did not achieve ROSC with more than 15 minutes of conventional CPR after hospital arrival demonstrated improved neurologic outcomes at 1-month and 6-month follow-ups.12Pediatric OHCA was not included in the 2015 ILCOR systematic review.2015 RecommendationALS 723—RevisedThere is insufficient evidence to recommend the routine use of ECPR for patients with cardiac arrest. In settings where it can be rapidly implemented, ECPR may be considered for select cardiac arrest patients for whom the suspected etiology of the cardiac arrest is potentially reversible during a limited period of mechanical cardiorespiratory support (Class IIb, LOE C-LD).Intra-arrest Prognostic Factors for Cardiac Arrest in Infants and Children—UpdatedThe ILCOR Pediatric Life Support Task Force reviewed the available evidence to determine if there were intra-arrest prognostic indicators that reliably predict survival with good neurologic outcome for OHCA.2015 Evidence SummaryFor infants and children with OHCA, age of less than 1 year,13,14 longer duration of cardiac arrest,15–17 and presentation with a nonshockable as opposed to a shockable rhythm13,14,16 are all predictors of poor patient outcome.2015 RecommendationPeds 814—NewMultiple variables should be used when attempting to prognosticate outcomes during cardiac arrest (Class I, LOE C-LD). Although there are factors associated with better or worse outcomes, no single factor that was studied predicts outcome with sufficient accuracy to recommend termination or continuation of CPR.Withholding and Withdrawing CPR (Termination of Resuscitative Efforts) Related to In-Hospital Cardiac ArrestLimitation of Interventions and Withdrawal of Life-Sustaining TherapiesThis topic was last reviewed in 2010. Since that time, the term limitation of interventions has replaced limitations of care.4 In the 2010 Guidelines, it was noted that not initiating resuscitation and discontinuing life-sustaining treatment of in-hospital cardiac arrest (IHCA) during or after resuscitation are ethically equivalent, and clinicians should not hesitate to withdraw support on ethical grounds when functional survival is highly unlikely.Criteria for Withholding and Discontinuing CPR in Newly Born Infant IHCAIn the 2010 Guidelines, the data regarding management of neonates born at the margins of viability or those with conditions that predict a high risk of mortality or morbidity were reviewed, and it was concluded that there was variation in attitudes and practice by region and availability of resources. Moreover, it was emphasized that parents desire a larger role in decisions related to initiation of resuscitation and continuation of support of severely compromised newborns. Guidelines were provided for when resuscitation is not indicated or when it is nearly always indicated. Under circumstances when the outcome remains unclear, the desires of the parents should be supported.4Use of a Prognostic Score in the Delivery Room for Preterm InfantsNRP 805—UpdatedThe 2015 ILCOR systematic review evaluated studies about prognostic scores applied to extremely preterm infants (below 25 weeks) compared with assessment of gestational age only.2015 Recommendation—UpdatedThe data regarding prognostic scores are challenging to evaluate because of the difficulty in distinguishing between outcomes that are driven by practice and current belief about survivability, decision making by parents, and actual physiologic limitations of prematurity.Antenatal assignment of prognosis for survival and/or disability of the neonate born extremely preterm has generally been made on the basis of gestational age alone. Scoring systems for including additional variables such as gender, use of maternal antenatal steroids, and multiplicity have been developed in an effort to improve prognostic accuracy. Indeed, it was suggested in the 2010 Guidelines that decisions regarding morbidity and risks of mortality may be augmented by the use of published tools based on data from specific populations.18There is no evidence to support the prospective use of any particular delivery room prognostic score presently described, over gestational age assessment alone, in preterm infants at less than 25 weeks of gestation. Importantly, no score has been shown to improve the clinician’s ability to estimate likelihood of survival through the first 18 to 22 months after birth. However, in individual cases, when counseling a family and constructing a prognosis for survival at gestations below 25 weeks, it is reasonable to consider variables such as perceived accuracy of gestational age assignment, the presence or absence of chorioamnionitis, and the level of care available for the location of delivery. It is also recognized that decisions about appropriateness of resuscitation below 25 weeks of gestation will be influenced by region-specific guidelines. In making this statement, a higher value was placed on the lack of evidence for a generalized prospective approach to changing important outcomes over improved retrospective accuracy and locally validated counseling policies. The most useful data for antenatal counseling provides outcome figures for infants alive at the onset of labor, not only for those born alive or admitted to a neonatal intensive care unit19–24 (Class IIb, LOE C-LD).Terminating Resuscitative Efforts in Late Preterm and Term InfantsNRP 896—UpdatedThe 2015 ILCOR systematic review examined whether outcome is changed by continuing resuscitative efforts in late preterm and term infants with an Apgar score of 0 after 10 minutes of adequate resuscitation.2015 Recommendation—UpdatedAn Apgar score of 0 at 10 minutes is a strong predictor of mortality and morbidity in late preterm and term infants. We suggest that, in infants with an Apgar score of 0 after 10 minutes of resuscitation, if the heart rate remains undetectable, it may be reasonable to stop assisted ventilation; however, the decision to continue or discontinue resuscitative efforts must be individualized. Variables to be considered may include whether the resuscitation was considered optimal; availability of advanced neonatal care, such as therapeutic hypothermia; specific circumstances before delivery (eg, known timing of the insult); and wishes expressed by the family23,25–29 (Class IIb, LOE C-LD). For further information, see “Part 13: Neonatal Resuscitation.”Terminating Resuscitative Efforts in Pediatric or Adult IHCAUse of ECPR in IHCAALS 723, Peds 407—UpdatedTo answer the question of whether outcome is changed by the use of ECPR for individuals in IHCA, the available evidence was reviewed by the ILCOR Advanced Life Support and Pediatric Task Forces.2015 Evidence SummaryThe 2015 ILCOR review process evaluated the use of ECPR techniques (including ECMO or cardiopulmonary bypass) compared with manual CPR or mechanical CPR for adult survival from IHCA in any setting. One propensity-matched, prospective, observational study that enrolled 172 patients with IHCA reported greater likelihood of ROSC and improved survival at hospital discharge, 30-day follow-up, and 1-year follow-up with the use of ECPR among patients who received more than 10 minutes of CPR. However, this study showed no difference in neurologic outcomes.30 A single propensity-matched, retrospective, observational study that enrolled 118 patients with IHCA who underwent more than 10 minutes of CPR and then ECPR after cardiac arrest of cardiac origin showed no survival or neurologic benefit over conventional CPR at the time of hospital discharge, 30-day follow-up, or 1-year follow-up.30–32 A single retrospective, observational study that enrolled 120 patients with witnessed IHCA who underwent more than 10 minutes of CPR reported a modest benefit over historical controls with the use of ECPR over continued conventional CPR in both survival and neurologic outcome at discharge and 6-month follow-up.32For infants and children in IHCA, the evidence comparing standard resuscitation with standard resuscitation plus ECMO was reviewed. Most studies were not robust, and there was little evidence of benefit overall; however, the outcome of some patients, such as those with underlying heart disease, may be improved.33–382015 Recommendations—NewThere is insufficient evidence to recommend the routine use of ECPR for patients with cardiac arrest. In settings where it can be rapidly implemented, ECPR may be considered for select cardiac arrest patients for whom the suspected etiology of the cardiac arrest is potentially reversible during a limited period of mechanical cardiorespiratory support (Class IIb, LOE C-LD). ECPR may be considered for pediatric patients with cardiac diagnoses who have IHCA in settings with existing ECMO protocols, expertise, and equipment (Class IIb, LOE C-LD).In making these recommendations, the reviewers noted that the published series used rigorous inclusion criteria to select patients for ECPR, and this recommendation should apply to similar populations. ECMO is a resource-intensive and invasive therapy with potential for harm that must be balanced against the potential for benefit based on individual clinical situations.Terminating Cardiac Arrest Resuscitative Efforts in Pediatric IHCAPeds 814—UpdatedIn the 2010 Guidelines, it was noted that no predictors of pediatric (infant or child) resuscitative success or failure have been established. The 2015 ILCOR systematic review examined whether there were any intra-arrest prognostic indicators that reliably predicted survival with good neurologic outcome for IHCA in infants and children and updated several of the prior recommendations.2015 Evidence SummaryFor infants and children with IHCA, negative predictive factors include age of over 1 year39 and longer durations of cardiac arrest.39–42 The evidence is contradictory as to whether a nonshockable (as opposed to shockable) initial cardiac arrest rhythm is a negative predictive factor in the in-hospital setting.39,43,442015 Recommendation—UpdatedMultiple variables should be used when attempting to prognosticate outcomes during cardiac arrest (Class I, LOE C-LD). Although there are factors associated with better or worse outcomes, no single factor studied predicts outcome with sufficient accuracy to recommend termination or prolongation of CPR.Prognostication During CPRThe 2015 ILCOR ALS systematic review considered one intra-arrest modality, end-tidal CO2 (ETCO2) measurement, in prognosticating outcome from cardiac arrest in adults. This section focuses on whether a specific ETCO2 threshold can reliably predict ROSC and survival or inform a decision to terminate resuscitation efforts. For further information on the use of ETCO2, see “Part 7: Adult Advanced Cardiovascular Life Support.”2015 Evidence SummaryStudies on the predictive capacity of ETCO2 among intubated patients during cardiac arrest resuscitation are observational, and none have investigated survival with intact neurologic outcome. An ETCO2 less than 10 mm Hg immediately after intubation and 20 minutes after the initiation of resuscitation was associated with extremely poor chances for ROSC and survival in several observational studies.45–49 Although these results suggest that ETCO2 can be a valuable tool to predict futility during CPR, potential confounding reasons for a low ETCO2 and the relatively small numbers of patients in these studies suggest that the ETCO2 should not be used alone as an indication to terminate resuscitative efforts. However, the failure to achieve an ETCO2 greater than 10 mm Hg despite optimized resuscitation efforts may be a valuable component of a multimodal approach to deciding when to terminate resuscitation.There are no studies that assess the prognostic value of ETCO2 measurements sampled from a supraglottic airway or bag-mask device in predicting outcomes from a cardiac arrest.2015 RecommendationsALS 459—NewIn intubated patients, failure to achieve an ETCO2 of greater than 10 mm Hg by waveform capnography after 20 minutes of CPR may be considered as one component of a multimodal approach to decide when to end resuscitative efforts, but should not be used in isolation (Class IIb, LOE C-LD).The above recommendation is made with respect to ETCO2 in patients who are intubated, because the studies examined included only those who were intubated.In nonintubated patients, a specific ETCO2 cutoff value at any time during CPR should not be used as an indication to end resuscitative efforts (Class III: Harm, LOE C-EO).Prognostication After Cardiac ArrestPredicting Neurologic Outcome in Pediatric Patients After ROSCThere continues to be insufficient evidence to recommend or describe an approach to accurately predict the neurologic outcome of pediatric patients after cardiac arrest. Since the publication of the 2010 Guidelines, there have been an increasing number of publications associating a variety of findings with poor neurologic prognosis in these populations. Early and reliable prognostication of neurologic outcome in pediatric survivors of cardiac arrest is helpful for effective planning and family support and can inform decisions to continue or discontinue life-sustaining therapy.Postresuscitation Use of Electroencephalography for Prognosis in Pediatric Survivors of Cardiac Arrest—UpdatedThe 2015 ILCOR Pediatric Life Support Task Force examined the usefulness of electroencephalography (EEG) or evoked potential assessment to predict long-term good neurologic outcome in infants and children who have survived cardiac arrest.2015 Evidence SummaryObservational data from 2 small pediatric studies50,51 showed that a continuous and reactive tracing on EEG performed in the first 7 days after cardiac arrest was associated with a significantly higher likelihood of good neurologic outcome at hospital discharge, whereas an EEG demonstrating a discontinuous or isoelectric tracing was associated with a poorer neurologic outcome at hospital discharge.Predictive Factors After Cardiac Arrest in Pediatric PatientsPeds 822, Peds 813The 2015 systematic review examined whether there were factors that could assist with prognostication for pediatric patients who remained unconscious after cardiac arrest.2015 Evidence SummaryFour observational studies supported the use of pupillary reactivity at 12 to 24 hours after cardiac arrest in predicting survival to discharge,16,42,51,52 while 1 observational study found that reactive pupils 24 hours after cardiac arrest were associated with improved survival at 180 days with favorable neurologic outcome.53Several serum biomarkers of neurologic injury have been considered for their prognostic value. Two small observational studies found that lower neuron-specific enolase (NSE) and S-100B serum levels post-arrest were associated with improved survival to hospital discharge and improved survival with favorable neurologic outcome.53,54One observational study found that children with lower lactate levels in the first 12 hours after arrest had an improved survival to hospital discharge.552015 Recommendations—NewEEGs performed within the first 7 days after pediatric cardiac arrest may be considered in prognosticating neurologic outcome at the time of hospital discharge (Class IIb, LOE C-LD) but should not be used as the sole criterion.The reliability of any 1 variable for prognostication in children after cardiac arrest has not been established. Practitioners should consider multiple factors when predicting outcomes in infants and children who achieve ROSC after cardiac arrest (Class I, LOE C-LD).In situations where children have minimal prospects for recovery, we emphasize the use of multiple variables to inform treatment decisions. Given the greater neuroplasticity and potential for recovery in the developing brain, we place greater value on preserving opportunities for neonatal and pediatric recovery than on limiting therapy based on not-yet-validated prognostic tools. Accordingly, the decision to withdraw life-sustaining therapies is complex and continues to rest with the treating physician and family. Further research in this area is needed.Predicting Neurologic Outcomes in Adult Patients After Cardiac ArrestScientists and clinicians continue to attempt to identify clinical, electrographic, radiographic, and biomarker data, which may be able to prognosticate neurologic outcome in patients. The primary purpose in accurately correlating specific data with poor neurologic outcome is to allow clinicians and families to make informed, but often difficult, choices for a patient who remains comatose after cardiac arrest with subsequent ROSC. There is a growing body of data that correlates specific findings with poor neurologic outcome after cardiac arrest. To date, however, there is no one specific test that can predict with certainty a poor neurologic recovery in this patient population. In making decisions, particularly the decision of whether to continue or withdraw life-sustaining therapies, clinicians and families need the most accurate information possible; typically, this information is an aggregate of clinical, electrographic, radiographic, and laboratory (eg, biomarkers) findings (see “Part 8: Post–Cardiac Arrest Care”).Timing of Prognostication in Post–Cardiac Arrest AdultsALS 450, ALS 713In 2010, it was noted that there are no clinical neurologic signs, electrophysiologic studies, biomarkers, or imaging modalities that can reliably predict death or poor neurologic outcome (eg, Cerebral Performance Category of 3, 4, or 5) within the first 24 hours after cardiac arrest in patients treated with or without TTM. In 1 registry study,56 it was noted that 63% of patients who survived an IHCA were given a DNAR status, and 43% had medical interventions actively withdrawn. These patients were often young and had no terminal illnesses but experienced death after withdrawal of life support in a time frame that was inadequate to allow thorough examination. This tendency to withdraw interventions prematurely in patients after cardiac arrest may have contributed to a selection bias in the current literature on prognostic testing. As the data are continuing to evolve, it is important to consider the potential for premature withdrawal of life support (see “Part 8: Post–Cardiac Arrest Care”).Sedatives or neuromuscular blockers received during TTM may be metabolized more slowly in patients after cardiac arrest, and injured brains may be more sensitive to the depressant effects of many drugs than normal brains. Residual sedation or paralysis can confound accurate clinical examinations.2015 Recommendations—UpdatedThe earliest time for prognostication in patients treated with TTM using clinical examination where sedation or paralysis could be a confounder may be 72 hours after return to normothermia (Class IIb, LOE C-EO).We recommend the earliest time to prognosticate a poor neurologic outcome in patients not treated with TTM using clinical examination is 72 hours after cardiac arrest (Class I, LOE B-NR). This time can be even longer after cardiac arrest if the residual effect of sedation or paralysis confounds the clinical examination (Class IIa, LOE C-LD).Operationally, the timing for prognostication is typically 4.5 to 5 days after ROSC for patients treated with TTM. This approach minimizes the possibility of obtaining false-positive (ie, erroneously pessimistic) results because of drug-induced depression of neurologic function. In making this recommendation, it is recognized that in some instances, withdrawal of life support may occur appropriately before 72 hours because of underlying terminal disease, brain herniation, or other clearly nonsurvivable situations.Prognostic Testing in Adult Patients After Cardiac ArrestALS 713, ALS 450The 2015 systematic evidence reviews examined numerous studies on the diagnostic accuracy of a wide range of tests for patients who did or did not receive TTM therapy.The 2010 Guidelines recommended clinical examination, electrophysiologic measurements, imagining studies, and blood or cerebrospinal fluid markers of brain injury to estimate the prognosis for neurologic impairment in adult patients who remain comatose after cardiac arrest.4 Updated guidelines for prognostication have been proposed by other international organizations57 as well as the AHA in this 2015 Guidelines Update; for further information, see “Part 8: Post–Cardiac Arrest Care.”This topic continues to be an area of active research. The use of TTM has demonstrated the potential to improve the neurologic outcome in certain adult patients after cardiac arrest who might otherwise have a poor neurologic outcome. Although the data and literature are becoming more robust on this particular topic, there are few differences in the types of tests used in those who are and are not treated with TTM as relates to prognosticating neurologic outcome.2015 Evidence Summary—NewFor a full description of the evidence reviewed for each assessment of neurologic function and prognosis for adults who have had cardiac arrest, refer to “Part 8: Post–Cardiac Arrest Care.”2015 Recommendations: Clinical Examination Findings—NewIn comatose patients who are not treated with TTM, the absence of pupillary reflex to light at 72 hours or more after cardiac arrest is a reasonable exam f

Trisomy 22 is the third most common autosomal trisomy occurring in about 0.4% of all clinically recognized pregnancies. Complete non‐mosaic trisomy 22 is extremely rare in live births. Most affected children die before one year of age. To date, only 29 liveborn cases have been reported and none has carried an additional genetic lesion. In this report, we describe the clinical presentation, cytogenetic, and cytogenomic findings in a liveborn female with complete non‐mosaic trisomy 22 as well as a paternally inherited, balanced reciprocal chromosomal rearrangement t(4;6)(q33;q23.3). The proband manifested features commonly seen in individuals with non‐mosaic trisomy 22 such as intrauterine growth retardation (IUGR), single umbilical artery, cranial abnormalities, short neck, cleft lip and palate, dysmorphic ears, hypoplastic nipples, digital malformation, congenital heart defects, dysplastic kidneys, and genital anomalies. In addition, she had lobar holoprosencephaly, aqueductal stenosis, and limb and eye problems that have not been associated with complete trisomy 22 in previous reports. She died at 35 days of age of complex heart disease and renal failure. We are hereby expanding the cytogenetic and clinical spectrum of this rare chromosome disorder. Clinical features of liveborn children with non‐mosaic trisomy 22 are reviewed and compared to those in our proband. The impact of genomic content in relation to the survival of trisomies in humans is also discussed. © 2014 Wiley Periodicals, Inc.

For almost 25 years, the Neonatal Resuscitation Program of the American Academy of Pediatrics has provided educational tools that are used in the United States and throughout the world to teach neonatal resuscitation. Over that time period, the guidelines for resuscitation have been increasingly evidence-based and a formal system has been established to determine which steps should be updated on the basis of available information. The most recent update occurred in 2010. This article describes the evidence review process and the specific evidence that lead to a number of significant changes in practice that were included in the 2010 guidelines.

Objective Advanced life support (ALS) guidelines are widely adopted for healthcare provider training with recommendations for retraining every two years or longer. This systematic review studies the retention of adult ALS knowledge and skills following completion of an ALS course in healthcare providers. Methods We retrieved original articles using Medline, CINAHL, Cochrane Library, and PubMed, and reviewed reference citations to identify additional studies. We extracted data from included articles using a structured approach and organized outcomes by evaluation method, and knowledge and skills retention. Results Among 336 articles retrieved, 11 papers were included. Most studies used multiple-choice questionnaires to evaluate knowledge retention and cardiac arrest simulation or other skills tests to evaluate skills retention. All studies reported variable rates of knowledge or skills deterioration over time, from 6 weeks to 2 years after training. Two studies noted retention of knowledge at 18 months and up to 2 years, and one reported skills retention at 3 months. Clinical experience, either prior to or after the courses, has a positive impact on retention of knowledge and skills. Conclusion There is a lack of large well-designed studies examining the retention of adult ALS knowledge and skills in healthcare providers. The available evidence suggests that ALS knowledge and skills decay by 6 months to 1 year after training and that skills decay faster than knowledge. Additional studies are needed to help provide evidence-based recommendations for assessment of current knowledge and skills and need for refresher training to maximize maintenance of ALS competency.

The objective of this study is to investigate the relationship between glycemic status and severe retinopathy of prematurity (ROP). This is a retrospective cohort study of 114 infants <1000 g admitted to a level IV neonatal intensive care unit within 48 h of life. A cumulative, time-weighted glucose level (TWGL) derived from plotting glucose values over time was included in logistic regression analysis to identify predictors for severe ROP. Infants had 26.6±2 weeks gestational age and had a birth weight of 782±136 g. TWGL during first 10 and 30 days of life were greater in the severe ROP group (P<0.01). Unlike single events of glucose levels ⩾150 mg dl−1, 10 days TWGL ⩾100 mg dl−1 (odds ratio (OR) 5.2, P<0.02) and 30 days TWGL ⩾118 mg dl−1 (OR 5.7, P<0.02) were predictors for severe ROP (univariate). Multivariate regression confirmed 30 days TWGL ⩾118 mg dl−1 (OR 9.4 to 10) and gram-positive sepsis (OR 4.1 to 5) as predictors for severe ROP (P<0.05). High overall glycemic status is associated with the development of severe ROP.

The following guidelines are an interpretation of the evidence presented in the 2010 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations 1). They apply primarily to newly born infants undergoing transition from intrauterine to extrauterine life, but the recommendations are also applicable to neonates who have completed perinatal transition and require resuscitation during the first few weeks to months following birth. Practitioners who resuscitate infants at birth or at any time during the initial hospital admission should consider following these guidelines. For the purposes of these guidelines, the terms newborn and neonate are intended to apply to any infant during the initial hospitalization. The term newly born is intended to apply specifically to an infant at the time of birth. Approximately 10% of newborns require some assistance to begin breathing at birth. Less than 1% require extensive resuscitative measures.2,3 Although the vast majority of newly born infants do not require intervention to make the transition from intrauterine to extrauterine life, because of the large total number of births, a sizable number will require some degree of resuscitation. Those newly born infants who do not require resuscitation can generally be identified by a rapid assessment of the following 3 characteristics: If the answer to all 3 of these questions is “yes,” the baby does not need resuscitation and should not be separated from the mother. The baby should be dried, placed skin-to-skin with the mother, and covered with dry linen to maintain temperature. Observation of breathing, activity, and color should be ongoing. If the answer to any of these assessment questions is “no,” the infant should receive one or more of the following 4 categories of action in …

HomeCirculationVol. 122, No. 16_suppl_2Part 11: Neonatal Resuscitation Free AccessResearch ArticlePDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessResearch ArticlePDF/EPUBPart 11: Neonatal Resuscitation2010 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations Jeffrey M. Perlman, Jonathan Wyllie, John Kattwinkel, Dianne L. Atkins, Leon Chameides, Jay P. Goldsmith, Ruth Guinsburg, Mary Fran Hazinski, Colin Morley, Sam Richmond, Wendy M. Simon, Nalini Singhal, Edgardo Szyld, Masanori Tamura, Sithembiso Velaphi, Neonatal Resuscitation Chapter Collaborators Khalid Aziz, David Boyle, Steven Byrne, Peter Davis, William A. Engle, Marilyn B. Escobedo, Maria Fernanda de Almeida, David Field, Judith Finn, Louis P. Halamek, Jane E. McGowan, Douglas D. McMillan, Lindsay Mildenhall, Rintaro Mori, Susan Niermeyer, Colm O'Donnell, Yacov Rabi, Steven A. Ringer, Jasmeet Soar, Benjamin J. Stenson, Enrique Udaeta, Dharmapuri Vidyasagar, Michael Watkinson, Gary M. Weiner and Myra H. Wyckoff Jeffrey M. PerlmanJeffrey M. Perlman *Co-chairs and equal first co-authors. Search for more papers by this author , Jonathan WyllieJonathan Wyllie *Co-chairs and equal first co-authors. Search for more papers by this author , John KattwinkelJohn Kattwinkel Search for more papers by this author , Dianne L. AtkinsDianne L. Atkins Search for more papers by this author , Leon ChameidesLeon Chameides Search for more papers by this author , Jay P. GoldsmithJay P. Goldsmith Search for more papers by this author , Ruth GuinsburgRuth Guinsburg Search for more papers by this author , Mary Fran HazinskiMary Fran Hazinski Search for more papers by this author , Colin MorleyColin Morley Search for more papers by this author , Sam RichmondSam Richmond Search for more papers by this author , Wendy M. SimonWendy M. Simon Search for more papers by this author , Nalini SinghalNalini Singhal Search for more papers by this author , Edgardo SzyldEdgardo Szyld Search for more papers by this author , Masanori TamuraMasanori Tamura Search for more papers by this author , Sithembiso VelaphiSithembiso Velaphi Search for more papers by this author , Neonatal Resuscitation Chapter Collaborators Search for more papers by this author , Khalid AzizKhalid Aziz Search for more papers by this author , David BoyleDavid Boyle Search for more papers by this author , Steven ByrneSteven Byrne Search for more papers by this author , Peter DavisPeter Davis Search for more papers by this author , William A. EngleWilliam A. Engle Search for more papers by this author , Marilyn B. EscobedoMarilyn B. Escobedo Search for more papers by this author , Maria Fernanda de AlmeidaMaria Fernanda de Almeida Search for more papers by this author , David FieldDavid Field Search for more papers by this author , Judith FinnJudith Finn Search for more papers by this author , Louis P. HalamekLouis P. Halamek Search for more papers by this author , Jane E. McGowanJane E. McGowan Search for more papers by this author , Douglas D. McMillanDouglas D. McMillan Search for more papers by this author , Lindsay MildenhallLindsay Mildenhall Search for more papers by this author , Rintaro MoriRintaro Mori Search for more papers by this author , Susan NiermeyerSusan Niermeyer Search for more papers by this author , Colm O'DonnellColm O'Donnell Search for more papers by this author , Yacov RabiYacov Rabi Search for more papers by this author , Steven A. RingerSteven A. Ringer Search for more papers by this author , Jasmeet SoarJasmeet Soar Search for more papers by this author , Benjamin J. StensonBenjamin J. Stenson Search for more papers by this author , Enrique UdaetaEnrique Udaeta Search for more papers by this author , Dharmapuri VidyasagarDharmapuri Vidyasagar Search for more papers by this author , Michael WatkinsonMichael Watkinson Search for more papers by this author , Gary M. WeinerGary M. Weiner Search for more papers by this author and Myra H. WyckoffMyra H. Wyckoff Search for more papers by this author Originally published19 Oct 2010https://doi.org/10.1161/CIRCULATIONAHA.110.971127Circulation. 2010;122:S516–S538Note From the Writing Group: Throughout this article, the reader will notice combinations of superscripted letters and numbers (eg, “Peripartum SuctioningNRP-011A, NRP-012A”). These callouts are hyperlinked to evidence-based worksheets, which were used in the development of this article. An appendix of worksheets, applicable to this article, is located at the end of the text. The worksheets are available in PDF format and are open access.Approximately 10% of newborns require some assistance to begin breathing at birth, and <1% require extensive resuscitation (LOE 41,2). Although the vast majority of newborn infants do not require intervention to make the transition from intrauterine to extrauterine life, the large number of births worldwide means that many infants require some assistance to achieve cardiorespiratory stability. Newborn infants who are born at term and are breathing or crying and have good tone must be dried and kept warm. These actions can be provided with the baby lying on the mother's chest and should not require separation of mother and baby.All others need to be assessed to determine their need for one or more of the following actions in sequence: Initial steps in stabilization (dry and provide warmth, position, assess the airway, stimulate to breathe)VentilationChest compressionsMedications or volume expansionProgression to the next step is initially based on simultaneous assessment of 2 vital characteristics: heart rate and respirations. Progression occurs only after successful completion of the preceding step. Approximately 30 seconds is allotted to complete each of the first 2 steps successfully, reevaluate, and decide whether to progress to the next (see Figure: Newborn Resuscitation Algorithm).Download figureDownload PowerPointFigure. Newborn Resuscitation Algorithm.Since publication of the 2005 International Consensus on CPR and ECC Science With Treatment Recommendations,3,4 several controversial neonatal resuscitation issues have been identified. The literature was researched and a consensus was reached on the assessment of oxygenation and role of supplementary oxygen, peripartum management of meconium, ventilation strategies, devices to confirm placement of an advanced airway (eg, tracheal tube or laryngeal mask airway), medications, maintenance of body temperature, postresuscitation management, and considerations for withholding and discontinuing resuscitation. Educational techniques for teaching, assessing, and maintaining resuscitation knowledge and skills and issues regarding the personnel needed at cesarean sections were also debated. The following are the major new recommendations: Progression to the next step following the initial evaluation is now defined by the simultaneous assessment of 2 vital characteristics: heart rate and respirations. Oximetry should be used for evaluation of oxygenation because assessment of color is unreliable.For babies born at term it is best to begin resuscitation with air rather than 100% oxygen.Administration of supplementary oxygen should be regulated by blending oxygen and air, and the concentration delivered should be guided by oximetry.The available evidence does not support or refute the routine endotracheal suctioning of infants born through meconium-stained amniotic fluid, even when the newborn is depressed.The chest compression-ventilation ratio should remain at 3:1 for neonates unless the arrest is known to be of cardiac etiology, in which case a higher ratio should be considered.Therapeutic hypothermia should be considered for infants born at term or near-term with evolving moderate to severe hypoxic-ischemic encephalopathy, with protocol and follow-up coordinated through a regional perinatal system.It is appropriate to consider discontinuing resuscitation if there has been no detectable heart rate for 10 minutes. Many factors contribute to the decision to continue beyond 10 minutes.Cord clamping should be delayed for at least 1 minute in babies who do not require resuscitation. Evidence is insufficient to recommend a time for clamping in those who require resuscitation.Initial Assessment and InterventionAssessment of Cardiorespiratory Transition and Need for ResuscitationNRP-001A, NRP-001B, NRP-014A, NRP-014BConsensus on ScienceA prompt increase in heart rate remains the most sensitive indicator of resuscitation efficacy (LOE 55). Of the clinical assessments, auscultation of the heart is the most accurate, with palpation of the umbilical cord less so. However, both are relatively insensitive (LOE 26 and LOE 47). Several studies have addressed the accuracy of pulse oximetry in measuring heart rate in the delivery room and have shown the feasibility of pulse oximetry during newborn resuscitation. However, none of these studies examined the impact of these measurements on resuscitation outcomes (LOE 47,8). Pulse oximetry (Spo2) and heart rate can be measured reliably after 90 seconds from birth with a pulse oximeter designed to reduce movement artifact and a neonatal probe (LOE 49,10). Preductal values, obtained from the right wrist or hand, are higher than postductal values.8,11 Applying the oximeter probe to the subject before connecting it to the instrument will produce reliable results more quickly (LOE 410).There is clear evidence that an increase in oxygenation and improvement in color may take many minutes to achieve, even in uncompromised babies. Furthermore, there is increasing evidence that exposure of the newly born to hyperoxia is detrimental to many organs at a cellular and functional level. For this reason color has been removed as an indicator of oxygenation or resuscitation efficacy. The oximeter can be used to adjust the increase in oxygenation to that of the uncompromised baby born at term.Treatment RecommendationsHeart rate should remain the primary vital sign by which to judge the need for and efficacy of resuscitation. Auscultation of the precordium should remain the primary means of assessing heart rate. There is a high likelihood of underestimating heart rate with palpation of the umbilical pulse, but this is preferable to other palpation locations.For babies who require ongoing resuscitation or respiratory support or both, the goal should be to use pulse oximetry. The sensor should be placed on the baby's right hand or wrist before connecting the probe to the instrument. Because of concerns about the ability to consistently obtain accurate measurements, pulse oximetry should be used in conjunction with and should not replace clinical assessment of heart rate during newborn resuscitation.Use of Supplementary OxygenNRP-013A, NRP-013B, NRP-014A, NRP-014BConsensus on ScienceIn term infants receiving resuscitation with intermittent positive-pressure ventilation, 100% oxygen conferred no advantage over air in the short term and resulted in increased time to first breath or cry or both (LOE 212,13). Meta-analyses of these studies showed a decrease in mortality with the group for whom resuscitation was initiated with air.14,15There is evidence in newborn animal models of asphyxia that exposure to high concentrations of oxygen at resuscitation does not confer any clinical advantage and is potentially harmful at the cellular level.16,17 Two animal models of hypoxia-ischemia and persistent bradycardia found that those resuscitated with room air rather than 100% oxygen developed untoward biochemical changes in the brain (LOE 518,19).In preterm infants at <32 weeks' gestation, if attempting to mimic the gradual rise in oxygen saturation of healthy term babies in the first 10 minutes after birth by titrating the concentration to the baby's saturation, initial use of air or 100% oxygen is more likely to result in hypoxemia or hyperoxemia, respectively, than initiation of resuscitation with 30% or 90% oxygen and titration to oxygen saturation (LOE 211,20). There is insufficient evidence in babies born at 32 to 37 weeks' gestation to define the appropriate oxygen administration strategy.Treatment RecommendationIn term infants receiving resuscitation at birth with positive-pressure ventilation, it is best to begin with air rather than 100% oxygen. If despite effective ventilation there is no increase in heart rate or if oxygenation (guided by oximetry) remains unacceptable, use of a higher concentration of oxygen should be considered.Because many preterm babies of <32 weeks' gestation will not reach target saturations in air, blended oxygen and air may be given judiciously and ideally guided by pulse oximetry. Both hyperoxemia and hypoxemia should be avoided. If a blend of oxygen and air is not available, resuscitation should be initiated with air.Peripartum SuctioningNRP-011A, NRP-012APeripartum suctioning was examined from 2 perspectives: (1) suctioning of the airway in depressed neonates born through clear amniotic fluid and (2) tracheal suctioning in depressed neonates born through meconium-stained amniotic fluid.Suctioning of the Upper AirwayConsensus on ScienceThere is no evidence to support or refute suctioning of the mouth and nose of depressed neonates at birth when the infant is born through clear amniotic fluid. In healthy neonates suctioning of the mouth and nose is associated with cardiorespiratory complications (LOE 121,22). In infants who are intubated, sedated, or paralyzed following resuscitation, endotracheal suctioning in the absence of secretions may result in a decrease in oxygenation, an increase in cerebral blood flow and intracranial pressure, and a decrease in compliance (LOE 523).Treatment RecommendationRoutine intrapartum oropharyngeal and nasopharyngeal suctioning for infants born with clear or meconium-stained amniotic fluid is no longer recommended.Tracheal SuctioningConsensus on ScienceDepressed infants born through meconium-stained amniotic fluid are at increased risk of developing meconium aspiration syndrome (LOE 424,25). Although these infants are at increased risk of developing meconium aspiration syndrome, the use of tracheal suctioning has not been associated with a reduction in the incidence of meconium aspiration syndrome or mortality (LOE 426; LOE 527). No randomized controlled studies have compared intubation and tracheal suctioning and no tracheal suctioning in depressed infants.Treatment RecommendationThe available evidence does not support or refute the routine endotracheal suctioning of depressed infants born through meconium-stained amniotic fluid.Ventilation StrategiesNRP-028A, NRP-028BVentilation strategies were examined from 4 perspectives: (1) characteristics of the initial assisted breaths and the role of positive end-expiratory pressure (PEEP), (2) continuous positive airway pressure (CPAP) during or following resuscitation, (3) devices to assist ventilation, and (4) strategies when resources are limited.Initial BreathsConsensus on ScienceBoth longer and shorter inspiratory times are in clinical use for initial ventilation in term infants, but there are no randomized controlled trials comparing these 2 approaches. In a small case series in term infants, a prolonged initial inflation of 5 seconds produced a 2-fold increase in functional residual capacity compared with historic controls (LOE 428). A single randomized controlled trial in preterm infants of a 10-second sustained inflation followed by nasal CPAP compared with face mask ventilation demonstrated decreased need for intubation in the first 72 hours, shorter duration of ventilatory support, and reduced bronchopulmonary dysplasia (LOE 129). Two other randomized controlled trials failed to show a benefit from delivery room application of a sustained initial inflation followed by nasal CPAP (LOE 130,31). Multiple variables among the 3 randomized controlled trials, including mode of intervention (nasopharyngeal tube versus face mask, T-piece versus self-inflating bag), as well as the use of CPAP in the delivery room make it difficult to determine the effect of the initial sustained inflation on establishing a functional residual capacity in very preterm infants.PressureThere is no evidence to support the use of inflation pressures higher than those that are necessary to achieve improvement in heart rate or chest expansion. This can usually be achieved in term infants with an inflation pressure of 30 cm H2O (LOE 428,32) and in preterm infants with pressures of 20 to 25 cm H2O (LOE 433). Occasionally higher pressures are required (LOE 434). In immature animals, ventilation at birth with high tidal volumes associated with the generation of high peak inflation pressures for a few minutes causes lung injury, impaired gas exchange, and reduced lung compliance (LOE 535).Positive End-Expiratory PressureThere is no evidence to support or refute the value of PEEP during resuscitation of term infants. In preterm infants 1 small study did not show a benefit from PEEP during initial stabilization in reducing the number of infants who required intubation in the delivery room (LOE 136). In studies of intubated immature animals the use of PEEP during initial stabilization after birth improved functional residual capacity, oxygenation, and lung compliance and reduced lung injury (LOE 537,38), but high levels of PEEP (8 to 12 cm H2O) may reduce pulmonary blood flow and increase the risk of pneumothorax (LOE 539,40).Treatment RecommendationTo establish initial lung inflation in apneic newborn infants, initiation of intermittent positive-pressure ventilation at birth can be accomplished with either shorter or longer inspiratory times. Initial peak inflating pressures necessary to achieve an increase in heart rate or movement of the chest are variable and unpredictable and should be individualized with each breath. If pressure is being monitored, an initial inflation pressure of 20 cm H2O may be effective in preterm babies, but a pressure of 30 to 40 cm H2O may be necessary in some term babies. If pressure is not being monitored, the minimal inflation required to achieve an increase in heart rate should be used. Providers should avoid creation of excessive chest wall movement during ventilation of preterm infants immediately after birth.Although measured peak inflation pressure does not correlate well with volume delivered in the context of changing respiratory mechanics, monitoring of inflation pressure may help provide consistent inflations and avoid unnecessarily high pressures. If positive-pressure ventilation is required, an initial inflation pressure of 20 to 25 cm H2O is adequate for most preterm infants. If prompt improvement in heart rate or chest movement is not obtained, then higher pressures to achieve effective ventilation may be needed. PEEP is likely to be beneficial during initial stabilization of apneic preterm infants who require positive-pressure ventilation and should be used if suitable equipment is available.Continuous Positive Airway PressureNRP-002A, NRP-002BConsensus on ScienceFor spontaneously breathing preterm infants at ≥25 weeks' gestation who have signs of respiratory distress, there is no significant difference between starting CPAP or intubation and mechanical ventilation in the delivery room when considering death or oxygen requirement at 36 weeks postmenstrual age. In spontaneously breathing infants at 25 to 28 weeks' gestation, CPAP compared with intubation reduced the rates of mechanical ventilation from 100% to 46% and surfactant use from 77% to 38% (LOE 141). In the same trial infants on CPAP had a significantly increased rate of pneumothorax (9% versus 3%) (LOE 141). There is no evidence to support or refute the use of CPAP in the term baby.For very preterm infants, a multifaceted intervention, including PEEP, giving a sustained inflation and starting CPAP in the delivery room reduces the need for intubation and rate of mechanical ventilation within 72 hours and reduces incidence of bronchopulmonary dysplasia compared with positive-pressure ventilation with a self-inflating bag via a face mask (LOE 129). When compared with historic controls, use of delivery room CPAP for very premature infants was associated with a decrease in the requirement for intubation, days on mechanical ventilation, and use of postnatal steroids (LOE 433), although a small underpowered feasibility trial of delivery room CPAP/PEEP versus no CPAP/PEEP did not show a significant difference in immediate outcomes (LOE 136).Treatment RecommendationSpontaneously breathing preterm infants who have respiratory distress may be supported with CPAP or intubation and mechanical ventilation. The most appropriate choice may be guided by local expertise and preferences.Assisted Ventilation DevicesNRP-015A, NRP-015B, NRP-015C, NRP-017A, NRP-017BConsensus on ScienceThere are no clinical studies in newborns requiring positive pressure during resuscitation to support or refute the superiority of the T-piece resuscitator over bag-mask ventilation in improving outcome. In mechanical models target inflation pressures are delivered more consistently when using T-piece resuscitators than with self-inflating bags or flow-inflating bags (LOE 542,43). In mechanical models PEEP is maintained more consistently with T-piece resuscitators compared with self-inflating bags or flow-inflating bags (LOE 544). In mechanical models the ability to deliver a sustained inflation is better with either a T-piece resuscitator or flow-inflating bag than with a self-inflating bag (LOE 542,45).Treatment RecommendationVentilation of the newborn can be performed effectively with a flow-inflating bag, a self-inflating bag, or a pressure-limited T-piece resuscitator.Laryngeal Mask AirwayNRP-017A, NRP-017BConsensus on ScienceIn 1 randomized controlled trial (LOE 146) providers had similar success providing effective ventilation with either the laryngeal mask airway or face mask among newborns in the delivery room. In 1 retrospective cohort study (LOE 247) and 3 large case series (LOE 448) effective ventilation was achieved quickly using a laryngeal mask airway in newborns weighing >2000 g or delivered at ≥34 weeks' gestation. In 1 randomized controlled trial (LOE 149) and 1 retrospective cohort study (LOE 250) providers had similar success providing effective ventilation using either the laryngeal mask airway or endotracheal tube among newborns in the delivery room. Although a single cohort study (LOE 250) suggests that newborns resuscitated with a laryngeal mask may require less respiratory support after initial resuscitation, this conclusion is subject to significant selection bias. In multiple small case reports effective ventilation was achieved with a laryngeal mask airway when both face mask ventilation and endotracheal intubation were unsuccessful. There is limited evidence to evaluate the effectiveness of the laryngeal mask airway for newborns weighing <2000 g, delivered at <34 weeks' gestation, in the setting of meconium-stained amniotic fluid, during chest compressions, or for administration of emergency intratracheal medications.Treatment RecommendationThe laryngeal mask airway should be considered during resuscitation of the newborn if face mask ventilation is unsuccessful and tracheal intubation is unsuccessful or not feasible. The laryngeal mask airway may be considered as an alternative to a face mask for positive-pressure ventilation among newborns weighing >2000 g or delivered at ≥34 weeks' gestation. There is limited evidence, however, to evaluate its use for newborns weighing <2000 g or delivered at <34 weeks' gestation. The laryngeal mask airway may be considered as an alternative to endotracheal intubation as a secondary airway for resuscitation among newborns weighing >2000 g or delivered at ≥34 weeks' gestation. The laryngeal mask airway has not been evaluated in the setting of meconium-stained amniotic fluid, during chest compressions, or for administration of emergency intratracheal medications.Upper Airway Interface DevicesNRP-003A, NRP-003BConsensus on ScienceWithin classes of interfaces, reports conflict about the ability to maintain a seal with an anatomically shaped mask compared with a soft round mask (LOE 551,52). Delivery of positive-pressure ventilation via nasal prongs has been shown to be superior to delivery via a triangular face mask for outcomes of chest compressions and intubation (LOE 253). It is likely that differences in clinical outcomes that have been reported in several studies may be attributable to the targeted intervention (ie, CPAP versus intermittent positive-pressure ventilation) rather than the interface. Nasal prongs may be a more effective device than face masks for providing respiratory support after birth (LOE 253). There is insufficient evidence to support or refute the use of one type of mask over another for achieving clinical outcome, except that the Rendell-Baker style mask is suboptimal in achieving an adequate seal when used for newborns (LOE 554).Treatment RecommendationsNasal prongs are an alternative way of giving respiratory support. Whichever interface is used, providers should ensure that they are skilled in using the interface devices available at the institution. Different masks must be held in different ways to appropriately reduce leak.Exhaled Air VentilationNRP-004A, NRP-004BConsensus on ScienceMouth-to-mouth ventilation is less effective than a self-inflating bag or tube and mask in improving survival rates in newborns with birth asphyxia (LOE 355). Use of mouth-to-mask ventilation at 30 insufflations per minute is as effective as self-inflating bag-mask ventilation in increasing heart rate in the first 5 minutes after birth (LOE 256). Mask-to-tube ventilation may cause infection in newborn infants (LOE 557). Two studies (LOE 558,59) demonstrated that tube-to-mask ventilation can be easily taught and acceptable breaths delivered. However, tube-to-mask ventilation was more difficult to use (LOE 560; LOE 355).Treatment RecommendationBag-mask ventilation is preferable to mouth-to-mask ventilation or tube-to-mask ventilation during neonatal resuscitation, but one of the latter two should be used when bag-mask devices are not available. Precautions must be taken because mouth-to-mask and mouth tube–to-mask ventilation are less comfortable and more tiring than bag-mask ventilation for the newborn at birth and may be associated with increased risk of infection in the infant and healthcare provider.Monitoring During and After IntubationGas Monitoring DevicesMeasurement of Tidal VolumeNRP-005A, NRP-005B, NRP-005CConsensus of ScienceThere are no studies that compare clinical outcomes in newborns after resuscitation with or without monitoring of tidal volume. In preterm animal models the tidal volume used during initial ventilation after birth may alter subsequent lung function and induce inflammation, but other factors, including the use and level of PEEP, appear to interact with tidal volume in determining specific effects (LOE 561,62). It is unclear whether the absolute tidal volumes used affected outcomes. Studies in manikins and animals (LOE 563,64) suggest that providers cannot maintain constant pressures or assess delivered volume during manual ventilation. The position of the mask and degree of leak may be improved by the use of a volume monitor (LOE 565).Treatment RecommendationsVentilation during newborn resuscitation should aim to adequately inflate the lung while avoiding overinflation. There is insufficient evidence to recommend routine use of tidal volume monitoring in neonates receiving positive-pressure ventilation during resuscitation.Use of Exhaled CO2 Detectors to Confirm Tracheal Tube PlacementNRP-016AConsensus on ScienceStudies (LOE 266–68) suggest that detection of exhaled CO2 confirms tracheal intubation in neonates with cardiac output more rapidly and accurately than clinical assessment alone. False-negative readings have been reported during cardiac arrest (LOE 469) despite models suggesting efficacy (LOE 570). False-positive readings may occur with colorimetric devices contaminated with epinephrine (adrenaline), surfactant, and atropine (LOE 571). Neonatal studies have excluded infants who need extensive resuscitation. There is no comparative information to recommend any one method for detection of exhaled CO2 in the neonatal population.Treatment RecommendationDetection of exhaled CO2 in addition to clinical assessment is recommended as the most reliable method to confirm endotracheal placement in neonates with spontaneous circulation.Colorimetric CO2 Detection to Assess Ventilation in Nonintubated PatientsNRP-018A, NRP-018B, NRP-018CConsensus on ScienceThe use of colorimetric exhaled CO2 detectors during face mask ventilation of small numbers of preterm infants in the intensive care unit (LOE 472) and the delivery room (LOE 473) has been reported and may help identify airway obstruction. It is unclear whether the use of exhaled CO2 detectors during face mask ventilation confers additional benefit over clinical assessment alone. No risks attributed to the use of exhaled CO2 detectors have been identified. The use of exhaled CO2 detectors with other interfaces (eg, nasal airways, laryngeal masks) during positive-pressure ventilation in the delivery room has not been reported.Treatment RecommendationThere is insufficient evidence to recommend routine use of colorimetric exhaled CO2 detectors during mask ventilation of newborns in the deliv

Free iron chelation after hypoxia-ischemia can reduce free radical-induced damage to brain cell membranes and preserve electrical brain activity. We investigated whether chelation of free iron with deferoxamine (DFO) preserved cortical cell membrane activity of Na+,K+-ATPase and electrocortical brain activity (ECBA) of newborn lambs during early reperfusion after severe hypoxia-ischemia. Hypoxia was induced in 16 lambs by decreasing the fraction of inspired oxygen to 0.07 for 30 min, followed by a 5-min period of hypotension (mean arterial blood pressure <35 mm Hg). ECBA (in microvolts) was measured using a cerebral function monitor. Immediately after hypoxia and additional ischemia, eight lambs received DFO (2.5 mg/kg, i.v.), and seven lambs received a placebo (PLAC). Two lambs underwent sham operation. One hundred eighty minutes after completion of hypoxia and ischemia, the brains were obtained and frozen. Na+,K+-ATPase activity was measured in the P2 fraction of cortical tissue. Na+,K+-ATPase activity was 35.1 ± 7.4, 42.0 ± 7.6, and 40.7 ± 1.4 μmol inorganic phosphate/mg protein per hour in PLAC-treated, DFO-treated, and sham-operated lambs, respectively (p < 0.05: DFO versus PLAC). ECBA was 11.2 ± 6.1, 14.8 ± 4.8, and 17.5±.0.5 μV in PLAC-treated, DFO-treated, and sham-operated lambs, respectively (p = 0.06: DFO versus PLAC). Na+,K+-ATPase activity correlated with ECBA at 180 min of reperfusion (r = 0.85, p < 0.001). We conclude that Na+,K+-ATPase activity of cortical brain tissue was higher in DFO-treated lambs compared with PLAC-treated animals during the early reperfusion phase after severe hypoxia-ischemia, suggesting a reduction of free radical formation by DFO. Furthermore, a positive relationship was found between Na+,K+-ATPase activity and ECBA.

Calcium influx via the NMDA receptor has been proposed as a mechanism of hypoxia-induced neuronal injury. The present study tests the hypothesis that the increase of [Ca2+]i observed under hypoxic conditions is the result of an NMDA-mediated Ca2+ influx. Changes of [Ca2+]i, measured fluorometrically with Fura-2, were followed after activation of the NMDA receptor with NMDA and glutamate, in the presence of glycine, in cortical synaptosomes prepared from six normoxic and six hypoxic guinea pig fetuses. [Ca2+]i was significantly higher in hypoxic vs normoxic synaptosomes, at baseline and in the presence of glycine as well as following activation of the NMDA receptor. Increase in [Ca2+]i was not observed in a Ca2+ free medium and was significantly decreased by MK-801 and thapsigargin. These results demonstrate that hypoxia-induced modifications of the NMDA receptor ion-channel results in increased [Ca2+]i in hypoxic vs normoxic synaptosomes. This increased accumulation may be due to an initial influx of Ca2+ via the altered NMDA receptor with subsequent release of Ca2+ from intracellular stores. Increase in intracellular calcium may initiate several pathways of free radical generation including cyclooxygenase, lipoxygenase, xanthine oxidase and nitric oxide synthase, and lead to membrane lipid peroxidation resulting in neuronal cell damage.

Effect of Deferoxamine on Na + ,K + -ATPase Activity and Electrocortical Brain Activity after Hypoxia-Ischemia in Newborn Lambs

Effect of In Vitro Nitration on High Affinity Ca ++ -ATPase Activity in Cerebral Cortical Nuclei of Newborn Piglets