Jeffrey Perlman

2005 American Heart Association (AHA) guidelines for cardiopulmonary resuscitation (CPR) and emergency cardiovascular care (ECC) of pediatric and neonatal patients: Pediatric advanced life support

This publication presents the 2005 American Heart Association (AHA) guidelines for cardiopulmonary resuscitation (CPR) and emergency cardiovascular care (ECC) of the pediatric patient and the 2005 American Academy of Pediatrics/AHA guidelines for CPR and ECC of the neonate. The guidelines are based on the evidence evaluation from the 2005 International Consensus Conference on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations, hosted by the American Heart Association in Dallas, Texas, January 23–30, 2005. The “2005 AHA Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care” contain recommendations designed to improve survival from sudden cardiac arrest and acute life-threatening cardiopulmonary problems. The evidence evaluation process that was the basis for these guidelines was accomplished in collaboration with the International Liaison Committee on Resuscitation (ILCOR). The ILCOR process is described in more detail in the “International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations.” The recommendations in the “2005 AHA Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care” confirm the safety and effectiveness of many approaches, acknowledge that other approaches may not be optimal, and recommend new treatments that have undergone evidence evaluation. These new recommendations do not imply that care involving the use of earlier guidelines is unsafe. In addition, it is important to note that these guidelines will not apply to all rescuers and all victims in all situations. The leader of a resuscitation attempt may need to adapt application of the guidelines to unique circumstances. The following are the major pediatric advanced life support changes in the 2005 guidelines: There is further caution about the use of endotracheal tubes. Laryngeal mask airways are acceptable when used by experienced providers. Cuffed endotracheal tubes may be used in infants (except newborns) and children in in-hospital settings provided that cuff inflation pressure is kept <20 cm H2O. Confirmation of tube placement requires clinical assessment and assessment of exhaled carbon dioxide (CO2); esophageal detector devices may be considered for use in children weighing >20 kg who have a perfusing rhythm. Correct placement must be verified when the tube is inserted, during transport, and whenever the patient is moved. During CPR with an advanced airway in place, rescuers will no longer perform “cycles” of CPR. Instead, the rescuer performing chest compressions will perform them continuously at a rate of 100/minute without pauses for ventilation. The rescuer providing ventilation will deliver 8 to 10 breaths per minute (1 breath approximately every 6–8 seconds). Timing of 1 shock, CPR, and drug administration during pulseless arrest has changed and now is identical to that for advanced cardiac life support. Routine use of high-dose epinephrine is not recommended. Lidocaine is de-emphasized, but it can be used for treatment of ventricular fibrillation/pulseless ventricular tachycardia if amiodarone is not available. Induced hypothermia (32–34°C for 12–24 hours) may be considered if the child remains comatose after resuscitation. Indications for the use of inodilators are mentioned in the postresuscitation section. Termination of resuscitative efforts is discussed. It is noted that intact survival has been reported following prolonged resuscitation and absence of spontaneous circulation despite 2 doses of epinephrine. The following are the major neonatal resuscitation changes in the 2005 guidelines: Supplementary oxygen is recommended whenever positive-pressure ventilation is indicated for resuscitation; free-flow oxygen should be administered to infants who are breathing but have central cyanosis. Although the standard approach to resuscitation is to use 100% oxygen, it is reasonable to begin resuscitation with an oxygen concentration of less than 100% or to start with no supplementary oxygen (ie, start with room air). If the clinician begins resuscitation with room air, it is recommended that supplementary oxygen be available to use if there is no appreciable improvement within 90 seconds after birth. In situations where supplementary oxygen is not readily available, positive-pressure ventilation should be administered with room air. Current recommendations no longer advise routine intrapartum oropharyngeal and nasopharyngeal suctioning for infants born to mothers with meconium staining of amniotic fluid. Endotracheal suctioning for infants who are not vigorous should be performed immediately after birth. A self-inflating bag, a flow-inflating bag, or a T-piece (a valved mechanical device designed to regulate pressure and limit flow) can be used to ventilate a newborn. An increase in heart rate is the primary sign of improved ventilation during resuscitation. Exhaled CO2 detection is the recommended primary technique to confirm correct endotracheal tube placement when a prompt increase in heart rate does not occur after intubation. The recommended intravenous (IV) epinephrine dose is 0.01 to 0.03 mg/kg per dose. Higher IV doses are not recommended, and IV administration is the preferred route. Although access is being obtained, administration of a higher dose (up to 0.1 mg/kg) through the endotracheal tube may be considered. It is possible to identify conditions associated with high mortality and poor outcome in which withholding resuscitative efforts may be considered reasonable, particularly when there has been the opportunity for parental agreement. The following guidelines must be interpreted according to current regional outcomes: When gestation, birth weight, or congenital anomalies are associated with almost certain early death and when unacceptably high morbidity is likely among the rare survivors, resuscitation is not indicated. Examples are provided in the guidelines. In conditions associated with a high rate of survival and acceptable morbidity, resuscitation is nearly always indicated. In conditions associated with uncertain prognosis in which survival is borderline, the morbidity rate is relatively high, and the anticipated burden to the child is high, parental desires concerning initiation of resuscitation should be supported. Infants without signs of life (no heartbeat and no respiratory effort) after 10 minutes of resuscitation show either a high mortality rate or severe neurodevelopmental disability. After 10 minutes of continuous and adequate resuscitative efforts, discontinuation of resuscitation may be justified if there are no signs of life.

Newborn Mortality and Fresh Stillbirth Rates in Tanzania After Helping Babies Breathe Training

BACKGROUND: Early neonatal mortality has remained high and unchanged for many years in Tanzania, a resource-limited country. Helping Babies Breathe (HBB), a novel educational program using basic interventions to enhance delivery room stabilization/resuscitation, has been developed to reduce the number of these deaths. METHODS: Master trainers from the 3 major referral hospitals, 4 associated regional hospitals, and 1 district hospital were trained in the HBB program to serve as trainers for national dissemination. A before (n = 8124) and after (n = 78 500) design was used for implementation. The primary outcomes were a reduction in early neonatal deaths within 24 hours and rates of fresh stillbirths (FSB). RESULTS: Implementation was associated with a significant reduction in neonatal deaths (relative risk [RR] with training 0.53; 95% confidence interval [CI] 0.43–0.65; P ≤ .0001) and rates of FSB (RR with training 0.76; 95% CI 0.64–0.90; P = .001). The use of stimulation increased from 47% to 88% (RR 1.87; 95% CI 1.82–1.90; P ≤ .0001) and suctioning from 15% to 22% (RR 1.40; 95% CI 1.33–1.46; P ≤ .0001) whereas face mask ventilation decreased from 8.2% to 5.2% (RR 0.65; 95% CI 0.60–0.72; P ≤ .0001). CONCLUSIONS: HBB implementation was associated with a significant reduction in both early neonatal deaths within 24 hours and rates of FSB. HBB uses a basic intervention approach readily applicable at all deliveries. These findings should serve as a call to action for other resource-limited countries striving to meet Millennium Development Goal 4.

Reducing intrapartum-related neonatal deaths in low- and middle-income countries-what works?

Each year, 814,000 neonatal deaths and 1.02 million stillbirths result from intrapartum-related causes, such as intrauterine hypoxia. Almost all of these deaths are in low- and middle-income countries, where women frequently lack access to quality perinatal care and may delay care-seeking. Approximately 60 million annual births occur outside of health facilities, and most of these childbirths are without a skilled birth attendant. Conditions that increase the risk of intrauterine hypoxia--such as pre-eclampsia/eclampsia, obstructed labor, and low birth weight--are often more prevalent in low resource settings. Intrapartum-related neonatal deaths can be averted by a range of interventions that prevent intrapartum complications (eg, prevention and management of pre-eclampsia), detect and manage intrapartum problems (eg, monitoring progress of labor with access to emergency obstetrical care), and identify and assist the nonbreathing newborn (eg, stimulation and bag-mask ventilation). Simple, affordable, and effective approaches are available for low-resource settings, including community-based strategies to increase skilled birth attendance, partograph use by frontline health workers linked to emergency obstetrical care services, task shifting to increase access to Cesarean delivery, and simplified neonatal resuscitation training (Helping Babies Breathe(SM)). Coverage of effective interventions is low, however, and many opportunities are missed to provide quality care within existing health systems. In sub-Saharan Africa, recent health services assessments found only 15% of hospitals equipped to provide basic neonatal resuscitation. In the short term, intrapartum-related neonatal deaths can be substantially reduced by improving the quality of services for all childbirths that occur in health facilities, identifying and addressing the missed opportunities to provide effective interventions to those who seek facility-based care. For example, providing neonatal resuscitation for 90% of deliveries currently taking place in health facilities would save more than 93,000 newborn lives each year. Longer-term strategies must address the gaps in coverage of institutional delivery, skilled birth attendance, and quality by strengthening health systems, increasing demand for care, and improving community-based services. Both short- and long-term strategies to reduce intrapartum-related mortality should focus on reducing inequities in coverage and quality of obstetrical and perinatal care.

Oral contraceptive use and the risk of chlamydial and gonococcal infections.

Oral contraceptive users were compared with nonusers with respect to the rate of cervical infections by Chlamydia trachomatis and Neisseria gonorrhoeae. The comparison was adjusted for differences in demographic and behavioral characteristics between the two groups. The rates of infection among oral contraceptive users were increased by approximately 70% (statistically significant) for both pathogens. Cervical ectopy was implicated in the increased rate of chlamydia but not gonorrhea. Rates of gonorrheal infection differed significantly among oral contraceptive formulations; rates were higher for formulations containing more androgenic progestins.

Birth Asphyxia: A Major Cause of Early Neonatal Mortality in a Tanzanian Rural Hospital

OBJECTIVE: Early neonatal mortality within the first 24 hours contributes substantially to overall neonatal mortality rates. The definition of birth asphyxia (BA) is imprecise, and reliable cause-specific mortality data are limited; thus the estimated proportion of BA-related deaths globally remains questionable. The objective was to determine the presumed causes of neonatal death within the first 24 hours in a rural hospital in Northern Tanzania. METHODS: This is a prospective descriptive observational study conducted in the delivery room and adjacent neonatal area. Research assistants were trained to observe and record events related to labor, neonatal resuscitation, and 24-hour postnatal course. BA was defined as failure to initiate spontaneous respirations and/or 5-minute Apgar score <7, prematurity as gestational age <36 weeks, and low birth weight (LBW) as birth weight <3rd centile for gestational age. Data were analyzed with χ2 and Student’s t tests. RESULTS: Over 1 year, 4720 infants were born and evaluated. Of these, 256 were admitted to the neonatal area. Forty-nine infants died secondary to BA (61%), prematurity (18%), LBW (8%), infection (2%), congenital abnormalities (8%), and unclear reason (2%). The 5-minute Apgar score was ≥7 in 50% of the infants who died secondary to BA. CONCLUSIONS: Most cases of early neonatal mortality were related to BA, and prematurity and LBW are additional important considerations. Reducing perinatal mortality requires a multifaceted approach with attention to issues related to BA, potential complications of prematurity, and LBW. The 5-minute Apgar score is a poor surrogate of BA.

Static and Dynamic Roles of Extracellular Loops in G-Protein-Coupled Receptors: A Mechanism for Sequential Binding of Thyrotropin-Releasing Hormone to Its Receptor

Small ligands generally bind within the seven transmembrane-spanning helices of G-protein-coupled receptors, but their access to the binding pocket through the closely packed loops has not been elucidated. In this work, a model of the extracellular loops of the thyrotropin-releasing hormone (TRH) receptor (TRHR) was constructed, and molecular dynamics simulations and quasi-harmonic analysis have been performed to study the static and dynamic roles of the extracellular domain. The static analysis based on curvature and electrostatic potential on the surface of TRHR suggests the formation of an initial recognition site between TRH and the surface of its receptor. These results are supported by experimental evidence. A quasi-harmonic analysis of the vibrations of the extracellular loops suggest that the low-frequency motions of the loops will aid the ligand to access its transmembrane binding pocket. We suggest that all small ligands may bind sequentially to the transmembrane pocket by first interacting with the surface binding site and then may be guided into the transmembrane binding pocket by fluctuations in the extracellular loops.

Reducing Hypothermia in Preterm Infants Following Delivery

BACKGROUND: Moderate hypothermia (temperature <36°C) at birth is common in premature infants and is associated with increased mortality and morbidity. METHODS: A multidisciplinary practice plan was implemented to determine in premature infants <35 weeks old whether a multifaceted approach would reduce the number of inborn infants with an admitting axillary temperature <36°C by 20% without increasing exposure to a temperature >37.5°C. The plan included use of occlusive wrap a transwarmer mattress and cap for all infants and maintaining an operating room temperature between 21°C and 23°C. Data were obtained at baseline (n = 66), during phasing in (n = 102), and at full implementation (n = 193). RESULTS: Infant axillary temperature in the delivery room (DR) increased from 36.1°C ± 0.6°C to 36.2°C ± 0.6°C to 36.6°C ± 0.6°C (P < .001), and admitting temperature increased from 36.0°C ± 0.8°C to 36.3°C ± 0.6°C to 36.7°C ± 0.5°C at baseline, phasing in, and full implementation, respectively (P < .001). The number of infants with temperature <36°C decreased from 55% to 6.2% at baseline versus full implementation (P < .001), and intubation at 24 hours decreased from 39% to 17.6% (P = .005). There was no increase in the number of infants with a temperature >37.5°C over time. The use of occlusive wrap, mattress, and cap increased from 33% to 88% at baseline versus full implementation. Control charts showed significant improvement in DR ambient temperature at baseline versus full implementation. CONCLUSIONS: The practice plan was associated with a significant increase in DR and admitting axillary infant temperatures and a corresponding decrease in the number of infants with moderate hypothermia. There was an associated reduction in intubation at 24 hours. These positive findings reflect increased compliance with the practice plan.

Neonatal Outcome Following Cord Clamping After Onset of Spontaneous Respiration

BACKGROUND AND OBJECTIVE: Evolving data indicate that cord clamping (CC) beyond 30 to 60 seconds after birth is of benefit for all infants. Recent experimental data demonstrated that ventilation before CC improved cardiovascular stability by increasing pulmonary blood flow. The objective was to describe the relationship between time to CC, onset of spontaneous respirations (SR), and 24-hour neonatal outcome. METHODS: In a rural Tanzanian hospital, trained research assistants, working in shifts, have observed every delivery (November 2009–February 2013) and recorded data including time interval from birth to SR and CC, fetal heart rate, perinatal characteristics and outcome (normal, death, admission). RESULTS: Of 15 563 infants born, 12 780 (84.3%) initiated SR at 10.8 ± 16.7 seconds, and CC occurred at 63 ± 45 seconds after birth. Outcomes included 12 730 (99.7%) normal, 31 deaths, and 19 admitted; 11 967 were of birth weight (BW) ≥2500 g and 813 <2500 g. By logistic modeling, the risk of death/admission was consistently higher if CC occurred before SR. Infants of BW <2500 g were more likely to die or be admitted. The risk of death/admission decreased by 20% for every 10-second delay in CC after SR; this risk declined at the same rate in both BW groups. CONCLUSIONS: Healthy self-breathing neonates are more likely to die or be admitted if CC occurs before or immediately after onset of SR. These clinical observations support the experimental findings of a smoother cardiovascular transition when CC is performed after initiation of ventilation.

The 3:1 is superior to a 15:2 ratio in a newborn manikin model in terms of quality of chest compressions and number of ventilations

Background Most cases of delivery room cardiopulmonary arrest result from an asphyxial process. Experimental evidence supports an important role for ventilation during asphyxial arrest. The optimal compression: ventilation (CV) ratio remains unclear and recommendations for newborns have varied from 3:1, 5:1 and 15:2. Objective Compare 3:1, 5:1 and 15: 2 CV ratios using the two-thumb technique in relationship to depth of compressions, decay of compression depth over time, compression rates and breaths delivered. Methods Thirty-two subjects, physicians and neonatal nurses, participated with compressions performed on a manikin. Evaluations included 2 min of compressions using 3:1, 5:1 and 15:2 CV ratios. Results Compression depth was comparable between groups. By paired analysis per subject, the depth was only greater for 3:1 versus 15:2 (ie, 0.91±2.2 mm) (p=0.01) and greater for women than men. Comparing the initial and second minute of compressions, no decay in compression depth for 3:1 ratio was noted, however significant decay was observed for 5:1 and 15:2 ratios (p<0.05). The compression rates were least and ventilations breaths were highest for 3:1 as opposed to the other ratios (p<0.05). Conclusions Providers using a 3:1 versus 15:2 achieve a greater depth of compressions over 2 min with a greater difference noted in women. More consistent compression depth over time was achieved with 3:1 as opposed to the other ratios. Thus, the 3:1 ratio is appropriate for newly born infants requiring resuscitation.

Randomized Trial of Volume Infusion During Resuscitation of Asphyxiated Neonatal Piglets

Despite its use, there is little evidence to support volume infusion (VI) during neonatal cardiopulmonary resuscitation (CPR). This study compares 5% albumin (ALB), normal saline (NS), and no VI (SHAM) on development of pulmonary edema and restoration of mean arterial pressure (MAP) during resuscitation of asphyxiated piglets. Mechanically ventilated swine (n = 37, age: 8 ± 4 d, weight: 2.2 ± 0.7 kg) were progressively asphyxiated until pH <7.0, Paco2 >100 mm Hg, heart rate (HR) <100 bpm, and MAP <20 mm Hg. After 5 min of ventilatory resuscitation, piglets were randomized blindly to ALB, NS, or SHAM infusion. Animals were recovered for 2 h before euthanasia and lung tissue sampled for wet-to-dry weight ratio (W/D) as a marker of pulmonary edema. SHAM MAP was similar to VI during resuscitation. At 2 h post-resuscitation, MAP of SHAM (48 ± 13 mm Hg) and ALB (43 ± 19 mm Hg) was higher than NS (29 ± 10 mm Hg; p = 0.003 and 0.023, respectively). After resuscitation, SHAM piglets had less pulmonary edema (W/D: 5.84 ± 0.12 versus 5.98 ± 0.19; p = 0.03) and better dynamic compliance (Cd) compared with ALB or NS (Cd: 1.43 ± 0.69 versus 0.97 ± 0.37 mL/cm H2O, p = 0.018). VI during resuscitation did not improve MAP, and acute recovery of MAP was poorer with NS compared with ALB. VI was associated with increased pulmonary edema. In the absence of hypovolemia, VI during neonatal resuscitation is not beneficial.