Randomised trial of epinephrine dose and flush volume in term newborn lambs

ObjectivesNeonatal resuscitation guidelines recommend 0.5–1 mL saline flush following 0.01–0.03 mg/kg of epinephrine via low umbilical venous catheter for persistent bradycardia despite effective positive pressure ventilation (PPV) and chest compressions (CC). We evaluated the effects of 1 mL vs 3 mL/kg flush volumes and 0.01 vs 0.03 mg/kg doses on return of spontaneous circulation (ROSC) and epinephrine pharmacokinetics in lambs with cardiac arrest.DesignForty term lambs in cardiac arrest were randomised to receive 0.01 or 0.03 mg/kg epinephrine followed by 1 mL or 3 mL/kg flush after effective PPV and CC. Epinephrine (with 1 mL flush) was repeated every 3 min until ROSC or until 20 min. Haemodynamics, blood gases and plasma epinephrine concentrations were monitored.ResultsTen lambs had ROSC before epinephrine administration and 2 died during instrumentation. Among 28 lambs that received epinephrine, 2/6 in 0.01 mg/kg-1 mL flush, 3/6 in 0.01 mg/kg-3 mL/kg flush, 5/7 in 0.03 mg/kg-1 mL flush and 9/9 in 0.03 mg/kg-3 mL/kg flush achieved ROSC (p=0.02). ROSC was five times faster with 0.03 mg/kg epinephrine compared with 0.01 mg/kg (adjusted HR (95% CI) 5.08 (1.7 to 15.25)) and three times faster with 3 mL/kg flush compared with 1 mL flush (3.5 (1.27 to 9.71)). Plasma epinephrine concentrations were higher with 0.01 mg/kg-3 mL/kg flush (adjusted geometric mean ratio 6.0 (1.4 to 25.7)), 0.03 mg/kg-1 mL flush (11.3 (2.1 to 60.3)) and 0.03 mg/kg-3 mL/kg flush (11.0 (2.2 to 55.3)) compared with 0.01 mg/kg-1 mL flush.Conclusions0.03 mg/kg epinephrine dose with 3 mL/kg flush volume is associated with the highest ROSC rate, increases peak plasma epinephrine concentrations and hastens time to ROSC. Clinical trials evaluating optimal epinephrine dose and flush volume are warranted.

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Abstract 170: Temperature Maintenance and Oxygen Use in Newborns at Birth: A Surveillance of Clinical Practice and Compliance with Neonatal Resuscitation Guidelines

Circulation ◽

10.1161/circ.130.suppl_2.170 ◽

2014 ◽

Vol 130 (suppl_2) ◽

Author(s):

Georg M Schmölzer ◽

Roxanne Pinson ◽

Marion Molesky ◽

Heather Chinnery ◽

Karen Foss ◽

...

Keyword(s):

Body Temperature ◽

Knowledge Transfer ◽

Oxygen Saturation ◽

Neonatal Resuscitation ◽

Positive Pressure ◽

Respiratory Therapists ◽

Vaginal Deliveries ◽

Resuscitation Guidelines ◽

The Right ◽

Continuous Positive Pressure

Background: Guidelines of neonatal resuscitation are revised regularly. Gaps in knowledge transfer commonly occur when the guidelines are communicated to the clinical practitioners. Maintaining body temperature and supporting oxygenation are main goals that clinical practitioners aim to achieve in assisting newborns during the feto-neonatal transition at birth. Objectives: In this study, we aim to examine the compliance to guidelines in neonatal resuscitation regarding the temperature maintenance and oxygen use in newborns at birth. Methods: From October to November 2013, a prospective questionnaire surveillance was conducted in all attended deliveries at all four hospitals in Edmonton, Alberta, Canada. All clinical practitioners (registered nurses, physicians and respiratory therapists) were requested to complete the questionnaires immediately after the attended delivery regarding temperature maintenance and oxygenation monitoring. Descriptive statistics were used with mean±SD (range) and % presented. Results: During the 14-days study period, data was obtained in 518 of 712 (73%) attended deliveries of newborns with gestational age 38.6±2.0 (23-42) weeks and birth weight 3324±589 (348-6168) g. Of these deliveries, 58% were normal vaginal deliveries and 29% were cesarean sections. There were 8.8% and 8.4% newborns who required positive pressure ventilation and continuous positive pressure, respectively. Radiant warmer heat was used in 81% (419/518) with 63% (266/419) turned to full power. Room temperature was 21.6±1.6 (17-31)°C. Body temperature at 30-60 min after birth was 36.8±0.5 (32.4-38.1)°C with hypothermia (<36.5°C) in 17%. Percutaneous oxygen saturation was measured in 15% newborns and 96% had sensors placed at the right wrist. At the initiation of resuscitation, 21% oxygen was used in 76% and the oxygen concentration was adjusted according to an oxygen saturation chart in 17%. In 70% of the cases, clinical practitioners commented that this chart was not helpful. Conclusions: Gaps in knowledge transfer contribute to non-compliance in the guidelines of neonatal resuscitation for temperature maintenance and oxygen use. Caution is needed to avoid hypothermia and hyperoxia in at-risk populations such as prematurity.

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27 ECG monitoring during NRP: A false sense of security?

Paediatrics & Child Health ◽

10.1093/pch/pxab061.021 ◽

2021 ◽

Vol 26 (Supplement_1) ◽

pp. e21-e21

Author(s):

Laurence Gariépy-Assal ◽

Ahmed Moussa ◽

Michael-Andrew Assaad

Keyword(s):

Controlled Trial ◽

Neonatal Resuscitation ◽

Pulseless Electrical Activity ◽

Positive Pressure ◽

Ecg Monitoring ◽

Chest Compressions ◽

Perinatal Medicine ◽

Epinephrine Administration ◽

Sense Of Security ◽

False Sense

Abstract Primary Subject area Neonatal-Perinatal Medicine Background During neonatal resuscitation, use of an electrocardiogram (ECG) provides a more reliable measurement of heart rate than auscultation or pulse oximetry. Having an ECG monitor may, however, provide a false sense of security in the unlikely scenario of a newborn with pulseless rhythms. This could delay critical resuscitative steps during neonatal resuscitation. Objectives The aim of this study is to evaluate whether the presence of ECG monitoring has an impact on the resuscitative steps of neonatal resuscitation providers. Design/Methods We conducted a prospective crossover randomized controlled trial, which took place at Sainte-Justine University Health Center in Montreal, Quebec, Canada. Residents, fellows, attending physicians, transport nurses, and respiratory therapists were recruited in teams of three. They participated in two simulation scenarios (pulseless electrical activity [PEA] with and without ECG monitoring). Teams were randomized to one of the scenarios and then crossed over. A debriefing session followed the two scenarios. All sessions were video-recorded. The primary outcome was the time to pulse check once the simulated mannequin was programmed to become pulseless. Secondary outcomes were the number of pulse checks, time to intubation, time to start of chest compressions, and time to administration of epinephrine. Results Preliminary results (n=5 groups, 10 scenarios) showed that the time to check the pulse once the mannequin was pulseless was longer when ECG electrodes were used (98.0 vs 55.6 sec, p = 0.07). There was a statistically significant decreased number of pulse checks with the ECG compared to without (2.4 vs 5.6, p = 0.004). Time to start of positive pressure ventilation (31.3 vs 27 sec), intubation (182.4 vs 179.2 sec), chest compressions (235.2 vs 227.6 sec), and epinephrine administration (340.8 vs 241.5 sec), were all increased in the presence ECG monitoring, but the difference between groups was not statistically significant. Conclusion ECG monitoring may alter the behaviour of individuals and delay recognition of a pulseless state, but preliminary data suggest that clinical endpoints are not affected.

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ASSESSMENT OF HEART RATE USING AUSCULTATION AND ELECTROCARDIOGRAPHY DURING NEONATAL RESUSCITATION IN A PORCINE MODEL OF ASPHYXIA

Paediatrics & Child Health ◽

10.1093/pch/pxy054.070 ◽

2018 ◽

Vol 23 (suppl_1) ◽

pp. e27-e27

Author(s):

Sparsh Patel ◽

Po-Yin Cheung ◽

Tze-Fun Lee ◽

Jannatul Mustofa ◽

Matteo Pasquin ◽

...

Keyword(s):

Heart Rate ◽

Cardiac Arrest ◽

Predictive Value ◽

Potential Benefit ◽

Porcine Model ◽

Neonatal Resuscitation ◽

Standard Of Care ◽

Ecg Monitoring ◽

Newborn Piglets ◽

Resuscitation Guidelines

Abstract BACKGROUND Recent neonatal resuscitation guidelines have suggested the potential benefit of introducing Electrocardiography (ECG) to monitor neonatal heart rate (HR) as standard of care for newborns receiving respiratory support in the delivery room due to advantages over auscultation. OBJECTIVES To assess effectiveness of HR detection using either ECG or auscultation. DESIGN/METHODS We reviewed recordings from our piglet neonatal resuscitations to compare an ECG with auscultation for assessing the detection of HR at cardiac arrest. Term newborn piglets (n=41) were anesthetized, intubated, instrumented, and exposed to 40-min normocapnic hypoxia followed by asphyxia, which was achieved by clamping the endotracheal tube until asystole. Asystole was confirmed by using Electrocardiography and auscultation. RESULTS The median (±IQR) duration of asphyxia was 318 (200–560)sec. In 41 piglets both auscultation and ECG HR were assessed. In 11 (27%) cases both auscultation and ECG correctly identified a bradycardic HR (mean (SD) 32(14)/min) at the beginning of chest compression. In 11 (27%) cases both auscultation and ECG correctly identified absent of any HR. However, in 19 (46%) cases auscultation did not detect a HR while ECG did detect a HR. Overall, the Positive Predictive Value was 37%, Negative Predictive Value was 100%, Sensitivity was 100%, and Specificity was 37% for the ECG to display accurate HR during asphyxia in newborn piglets. CONCLUSION Our data illustrates the need for caution in the routine use of ECG monitoring for all neonatal who might need advanced resuscitation in the deliver room.

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Neonatal resuscitation using a laryngeal mask airway: a randomised trial in Uganda

Archives of Disease in Childhood ◽

10.1136/archdischild-2017-312934 ◽

2017 ◽

Vol 103 (3) ◽

pp. 255-260 ◽

Cited By ~ 15

Author(s):

Nicolas J Pejovic ◽

Daniele Trevisanuto ◽

Clare Lubulwa ◽

Susanna Myrnerts Höök ◽

Francesco Cavallin ◽

...

Keyword(s):

Clinical Trial ◽

Laryngeal Mask Airway ◽

Low Income ◽

Spontaneous Breathing ◽

Randomised Trial ◽

Neonatal Resuscitation ◽

Face Mask ◽

Laryngeal Mask ◽

Positive Pressure ◽

Link Type

ObjectiveMortality rates from birth asphyxia in low-income countries remain high. Face mask ventilation (FMV) performed by midwives is the usual method of resuscitating neonates in such settings but may not always be effective. The i-gel is a cuffless laryngeal mask airway (LMA) that could enhance neonatal resuscitation performance. We aimed to compare LMA and face mask (FM) during neonatal resuscitation in a low-resource setting.SettingMulago National Referral Hospital, Kampala, Uganda.DesignThis prospective randomised clinical trial was conducted at the labour ward operating theatre. After a brief training on LMA and FM use, infants with a birth weight >2000 g and requiring positive pressure ventilation at birth were randomised to resuscitation by LMA or FM. Resuscitations were video recorded.Main outcome measuresTime to spontaneous breathing.ResultsForty-nine (24 in the LMA and 25 in the FM arm) out of 50 enrolled patients were analysed. Baseline characteristics were comparable between the two arms. Time to spontaneous breathing was shorter in LMA arm than in FM arm (mean 153 s (SD±59) vs 216 s (SD±92)). All resuscitations were effective in LMA arm, whereas 11 patients receiving FM were converted to LMA because response to FMV was unsatisfactory. There were no adverse effects.ConclusionA cuffless LMA was more effective than FM in reducing time to spontaneous breathing. LMA seems to be safe and effective in clinical practice after a short training programme. Its potential benefits on long-term outcomes need to be assessed in a larger trial.Clinical trial registryThis trial was registered in https://clinicaltrials.gov, with registration number NCT02042118.

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Effect of a Larger Flush Volume on Bioavailability and Efficacy of Umbilical Venous Epinephrine during Neonatal Resuscitation in Ovine Asphyxial Arrest

Children ◽

10.3390/children8060464 ◽

2021 ◽

Vol 8 (6) ◽

pp. 464

Author(s):

Deepika Sankaran ◽

Payam Vali ◽

Praveen Chandrasekharan ◽

Peggy Chen ◽

Sylvia F. Gugino ◽

...

Keyword(s):

Perinatal Asphyxia ◽

Neonatal Resuscitation ◽

Cardiac Activity ◽

Venous Catheter ◽

Spontaneous Circulation ◽

Plasma Epinephrine ◽

Epinephrine Administration ◽

7Th Edition ◽

Near Term ◽

The Right

The 7th edition of the Textbook ofNeonatal Resuscitation recommends administration of epinephrine via an umbilical venous catheter (UVC) inserted 2–4 cm below the skin, followed by a 0.5-mL to 1-mL flush for severe bradycardia despite effective ventilation and chest compressions (CC). This volume of flush may not be adequate to push epinephrine to the right atrium in the absence of intrinsic cardiac activity during CC. The objective of our study was to evaluate the effect of 1-mL and 2.5-mL flush volumes after UVC epinephrine administration on the incidence and time to achieve return of spontaneous circulation (ROSC) in a near-term ovine model of perinatal asphyxia induced cardiac arrest. After 5 min of asystole, lambs were resuscitated per Neonatal Resuscitation Program (NRP) guidelines. During resuscitation, lambs received epinephrine through a UVC followed by 1-mL or 2.5-mL normal saline flush. Hemodynamics and plasma epinephrine concentrations were monitored. Three out of seven (43%) and 12/15 (80%) lambs achieved ROSC after the first dose of epinephrine with 1-mL and 2.5-mL flush respectively (p = 0.08). Median time to ROSC and cumulative epinephrine dose required were not different. Plasma epinephrine concentrations at 1 min after epinephrine administration were not different. From our pilot study, higher flush volume after first dose of epinephrine may be of benefit during neonatal resuscitation. More translational and clinical trials are needed.

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Epinephrine in Neonatal Resuscitation

Children ◽

10.3390/children6040051 ◽

2019 ◽

Vol 6 (4) ◽

pp. 51

Author(s):

Payam Vali ◽

Deepika Sankaran ◽

Munmun Rawat ◽

Sara Berkelhamer ◽

Satyan Lakshminrusimha

Keyword(s):

Clinical Trials ◽

Cardiac Arrest ◽

Animal Models ◽

Strong Evidence ◽

Neonatal Resuscitation ◽

Ovine Model ◽

Epinephrine Administration ◽

Liaison Committee ◽

Optimal Dosing ◽

Asphyxial Cardiac Arrest

Epinephrine is the only medication recommended by the International Liaison Committee on Resuscitation for use in newborn resuscitation. Strong evidence from large clinical trials is lacking owing to the infrequent use of epinephrine during neonatal resuscitation. Current recommendations are weak as they are extrapolated from animal models or pediatric and adult studies that do not adequately depict the transitioning circulation and fluid-filled lungs of the newborn in the delivery room. Many gaps in knowledge including the optimal dosing, best route and timing of epinephrine administration warrant further studies. Experiments on a well-established ovine model of perinatal asphyxial cardiac arrest closely mimicking the newborn infant provide important information that can guide future clinical trials.

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Impact of epinephrine administration frequency in out-of-hospital cardiac arrest patients: a retrospective analysis in a tertiary hospital setting

Journal of International Medical Research ◽

10.1177/0300060519860952 ◽

2019 ◽

Vol 47 (9) ◽

pp. 4272-4283

Author(s):

Mohammed A. Al-Mulhim ◽

Mohammed S. Alshahrani ◽

Laila Perlas Asonto ◽

Ahmad Abdulhady ◽

Talal M. Almutairi ◽

...

Keyword(s):

Cardiac Arrest ◽

Retrospective Analysis ◽

Patient Survival ◽

Time Interval ◽

Ohca Patient ◽

Epinephrine Administration ◽

Significant Difference ◽

Epinephrine Dose ◽

The Impact ◽

Hospital Cardiac Arrest

Introduction Epinephrine is recommended for patients with out-of-hospital cardiac arrest (OHCA). However, whether epinephrine improves or adversely affects OHCA outcomes is controversial. Objectives This study aims to determine whether the frequency of epinephrine administration impacts OHCA patient survival. Methods We conducted a retrospective analysis of OHCA cases registered in the Emergency Department at King Fahd University Hospital, Saudi Arabia between 2005 and 2015. The primary outcomes were mortality and survival rates until discharge. The impact of epinephrine administration timing and frequency on patient survival was analyzed. Results Data from 300 OHCA cases were analyzed. Among them, 66.3% were men, and the overall mean age of 50.4 ± 20.6 years. The overall survival rate until hospital discharge was 12%. There was no statistically significant difference between in gender, age, or time interval to the first epinephrine dose in the survival and non-survival groups. Only the number of epinephrine doses was related to the survival outcome. Conclusion Non-survivors received significantly more epinephrine doses compared with survivors. However, a causal relationship between OHCA patient survival and epinephrine dose and time cannot be confirmed. Further studies are needed to investigate whether the long-term outcomes in OHCA patients are influenced by the timing and frequency of epinephrine administration.

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Epinephrine Versus Placebo During Resuscitation After Neonatal Hypoxic Cardiac Arrest: The Effect on ROSC and Markers of CNS Outcome Investigated in a Piglet Model

10.21203/rs.3.rs-638347/v1 ◽

2021 ◽

Author(s):

Hannah Brogaard Andersen ◽

Mads Andersen ◽

Ted Carl Andelius ◽

Mette Vestergård Pedersen ◽

Bo Løfgren ◽

...

Keyword(s):

Cardiac Arrest ◽

Neonatal Resuscitation ◽

Composite Endpoint ◽

Imaging Biomarkers ◽

Resonance Spectroscopy ◽

Short Term ◽

Term Survival ◽

Arterial Blood ◽

Resuscitation Guidelines ◽

Short Term Survival

Abstract Background: Epinephrine is an integral component of neonatal resuscitation guidelines, despite sparse evidence. The association between advanced cardiopulmonary resuscitation (CPR) and poor neurodevelopment is well known, and epinephrine may improve short-term survival but at the cost of poor neurologic outcome. Our objectives were to investigate the effect of epinephrine vs placebo in a piglet model of neonatal hypoxic cardiac arrest (CA) by: 1) return of spontaneous circulation (ROSC), 2) time-to-ROSC, 3) markers of CNS outcome by magnetic resonance spectroscopy and imaging (MRS/MRI), and 4) composite endpoint of death or severe CNS outcome. Methods: Twenty-five newborn piglets under 12 hours of age underwent hypoxia. Hypoxia was induced by clamping the endotracheal tube until CA (mean arterial blood pressure <20 mmHg and heart rate <60 bpm). CPR was commenced five minutes after CA. The animals were randomized to either CPR + intravenous epinephrine or CPR + placebo (saline). MRS/MRI was performed six hours after resuscitation. Results: ROSC was more frequent in animals subjected to epinephrine than placebo; RR = 2.31 (95 % CI: 1.09 to 5.77). We found no difference between groups in time-to-ROSC. Among survivors, we found no difference between groups in brain lactate/N-acetyl-aspartate ratios (Lac/NAA), N-acetyl-aspartate/creatine ratios (NAA/Cr), diffusion-weighted-signal, or oxygenation-dependent-signal. We found a tendency towards reduced risk of the composite endpoint of death or severe CNS outcome in animals resuscitated with epinephrine compared to placebo, RR = 0.7 (95 % CI: 0.37 to 1.19).Conclusions: Resuscitation with epinephrine compared to placebo improved ROSC frequency after neonatal hypoxic CA. Surviving animals after resuscitation with epinephrine compared to placebo showed no difference in MRS/MRI markers of brain damage. These results support that epinephrine improves short-term survival without increasing brain injury measured by early imaging biomarkers.

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Effect of prehospital intraosseous combined with in-hospital intravenous access in out-of-hospital cardiac arrest

10.22514/sv.2021.046 ◽

2021 ◽

Keyword(s):

Emergency Department ◽

Cardiac Arrest ◽

Primary Outcome ◽

Spontaneous Circulation ◽

Secondary Outcome ◽

Epinephrine Administration ◽

Significant Difference ◽

Study Population ◽

Epinephrine Dose ◽

Hospital Cardiac Arrest

Objective: Obtaining vascular access during out-of-hospital cardiac arrest (OHCA) is challenging. The aim of this study was to compare the effectiveness of prehospital intraosseous infusion (IO) combined with in-hospital intravenous (IV) (pre-IO + in-IV) access versus the simple IV (pre-IV + in-IV) access in adult OHCA patients who do not achieve prehospital return of spontaneous circulation (ROSC). Methods: This retrospective observational study included adults with OHCA of presumed cardiac etiology between October 1, 2017-October 1, 2020 at an academic emergency department in China. All of the OHCA patients included within the study had Emergency Medical Services cardiopulmonary resuscitation and received prehospital epinephrine administration, but did not achieve prehospital ROSC. The study population were classified as either pre-IO + in-IV or IV (pre-IV + in-IV) based on their epinephrine administration route. The prehospital epinephrine routes were the first and only attempted route. The primary outcome investigated was sustained ROSC following arrival at the emergency department. The secondary outcome considered was the time from dispatch to the first epinephrine dose. Results: Of 193 included adult OHCA subjects who did not have prehospital ROSC, 128 received IV access only. The 65 pre-IO + in-IV-treated patients received epinephrine faster compared to IV-treated patients in terms of the median time from dispatch to the first injection of epinephrine (14.5 vs. 16.0 min, P = 0.001). In the pre-IO + in-IV group, 34 of 65 patients (52.3%) achieved sustained ROSC compared with 65 of 128 (50.8%) patients in the IV group (χ2 = 0.031, P = 0.841). There was no significant difference in sustained ROSC (adjusted OR1.049, 95% CI: 0.425-2.591, P = 0.918) between the two groups. Conclusion: A similar sustained ROSC rate was achieved for both the pre-IO + in-IV access group and the simple IV access group. Our results suggested that an IV route should be established quickly for prehospital IO-treated OHCA patients who do not achieve prehospital ROSC.

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Comparison of intraosseous and intravenous epinephrine administration during resuscitation of asphyxiated newborn lambs

Archives of Disease in Childhood - Fetal and Neonatal Edition ◽

10.1136/archdischild-2021-322638 ◽

2021 ◽

pp. fetalneonatal-2021-322638

Author(s):

Calum T Roberts ◽

Sarah Klink ◽

Georg M Schmölzer ◽

Douglas A Blank ◽

Shiraz Badurdeen ◽

...

Keyword(s):

Blood Pressure ◽

Blood Flow ◽

Systemic Blood Pressure ◽

Spontaneous Circulation ◽

Positive Pressure ◽

Plasma Epinephrine ◽

Intraosseous Access ◽

Systemic Blood ◽

Epinephrine Administration ◽

Cord Clamping

ObjectiveIntraosseous access is recommended as a reasonable alternative for vascular access during newborn resuscitation if umbilical access is unavailable, but there are minimal reported data in newborns. We compared intraosseous with intravenous epinephrine administration during resuscitation of severely asphyxiated lambs at birth.MethodsNear-term lambs (139 days’ gestation) were instrumented antenatally for measurement of carotid and pulmonary blood flow and systemic blood pressure. Intrapartum asphyxia was induced by umbilical cord clamping until asystole. Resuscitation commenced with positive pressure ventilation followed by chest compressions and the lambs received either intraosseous or central intravenous epinephrine (10 μg/kg); epinephrine administration was repeated every 3 min until return of spontaneous circulation (ROSC). The lambs were maintained for 30 min after ROSC. Plasma epinephrine levels were measured before cord clamping, at end asphyxia, and at 3 and 15 min post-ROSC.ResultsROSC was successful in 7 of 9 intraosseous epinephrine lambs and in 10 of 12 intravenous epinephrine lambs. The time and number of epinephrine doses required to achieve ROSC were similar between the groups, as were the achieved plasma epinephrine levels. Lambs in both groups displayed a similar marked overshoot in systemic blood pressure and carotid blood flow after ROSC. Blood gas parameters improved more quickly in the intraosseous lambs in the first 3 min, but were otherwise similar over the 30 min after ROSC.ConclusionsIntraosseous epinephrine administration results in similar outcomes to intravenous epinephrine during resuscitation of asphyxiated newborn lambs. These findings support the inclusion of intraosseous access as a route for epinephrine administration in current guidelines.

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