Cardiovascular Supportive Therapies for Neonates With Asphyxia — A Literature Review of Pre-clinical and Clinical Studies

Asphyxiated neonates often have hypotension, shock, and poor tissue perfusion. Various “inotropic” medications are used to provide cardiovascular support to improve the blood pressure and to treat shock. However, there is incomplete literature on the examination of hemodynamic effects of these medications in asphyxiated neonates, especially in the realm of clinical studies (mostly in late preterm or term populations). Although the extrapolation of findings from animal studies and other clinical populations such as children and adults require caution, it seems appropriate that findings from carefully conducted pre-clinical studies are important in answering some of the fundamental knowledge gaps. Based on a literature search, this review discusses the current available information, from both clinical studies and animal models of neonatal asphyxia, on common medications used to provide hemodynamic support including dopamine, dobutamine, epinephrine, milrinone, norepinephrine, vasopressin, levosimendan, and hydrocortisone

Neonatal resuscitation workshop for trainees in standardized medical residency training—a pilot practice in Shenzhen, China

BackgroundNeonatal resuscitation is an important skillset for clinicians attending deliveries. Accredited neonatal resuscitation training is not obligatory in most training centers of standardized medical residency programs before 2022 in China. We investigated the feasibility and effectiveness of neonatal resuscitation simulation training (neo-RST) in residents in Shenzhen, China.MethodsFour two-day neo-RST workshops were conducted in the University of Hong Kong-Shenzhen Hospital and Shenzhen Health Capacity Building and Continuing Education Center in 2020–2021. The workshops had Neonatal Resuscitation Program (NRP)® update, skill stations and simulation practice with debriefing. Each participant had the integrated skill station assessment (ISSA) at the end of workshop. Participants of workshops included residents of different disciplines and health care providers (HCPs) of neonatal and obstetrical departments. We compared demographic characteristics, neonatal resuscitation knowledge before training, ISSA overall and categorical scores on skill sets between residents and HCPs.ResultsIn 2020–2021, 4 neo-RST workshops were conducted with 48 residents and 48 HCPs. The residents group had less working experience, less prior experience in neo-RST and lower neonatal resuscitation knowledge scores than those of HCPs group. After the workshop, residents had higher overall ISSA score than that of HCPs group (90.2 ± 5.9 vs. 86.3 ± 6.6%, P = 0.003, respectively). There was no significant difference in the numbers of participants scored <80% in residents and HCPs group (3 [6.3%] vs. 7 [14.6%], respectively). Regarding the categorical scores, residents scored significantly higher in preparation, ventilation, crisis resource management and behavioral skills but lower in appropriate oxygen use, when compared with the HCPs.ConclusionNeo-RST for residents is feasible with promising short-term educational outcomes. Neo-RST could be implemented in standardized medical residency programs in China

Improved neonatal outcomes by multidisciplinary simulation—a contemporary practice in the demonstration area of China

BackgroundSimulation-based training improves neonatal resuscitation and decreases perinatal mortality in low- and middle-income countries. Interdisciplinary in-situ simulation may promote quality care in neonatal resuscitation. However, there is limited information regarding the effect of multidisciplinary in-situ simulation training (MIST) on neonatal outcomes. We aimed to investigate the impact of MIST on neonatal resuscitation in reducing the incidence of neonatal asphyxia and related morbidities.MethodsWeekly MIST on neonatal resuscitation has been conducted through neonatal and obstetrical collaboration at the University of Hong Kong-Shenzhen Hospital, China, since 2019. Each simulation was facilitated by two instructors and performed by three health care providers from obstetric and neonatal intensive care units, followed by a debriefing of the participants and several designated observers. The incidence of neonatal asphyxia, severe asphyxia, hypoxic-ischemic encephalopathy (HIE), and meconium aspiration syndrome (MAS) before (2017–2018) and after (2019–2020) the commencement of weekly MIST were analyzed.ResultsThere were 81 simulation cases including the resuscitation of preterm neonates of different gestational ages, perinatal distress, meconium-stained amniotic fluid, and congenital heart disease with 1,503 participant counts (225 active participants). The respective incidence of neonatal asphyxia, severe asphyxia, HIE, and MAS decreased significantly after MIST (0.64%, 0.06%, 0.01%, and 0.09% vs. 0.84%, 0.14%, 0.10%, and 0.19%, respectively, all P < 0.05).ConclusionsWeekly MIST on neonatal resuscitation decreased the incidence of neonatal asphyxia, severe asphyxia, HIE, and MAS. Implementation of regular resuscitation simulation training is feasible and may improve the quality of neonatal resuscitation with better neonatal outcomes in low- and middle-income countries

A Porcine Model of Neonatal Hypoxia-Asphyxia to Study Resuscitation Techniques in Newborn Infants

Two to three million newborn infants worldwide need extensive cardiopulmonary resuscitation (CPR), and approximately one million of these infants die annually worldwide. Therefore, resuscitation techniques require further refinement to provide better outcomes. To investigate the effectiveness of various interventions and to understand the pathophysiology and pharmacology of neonatal CPR, it is important to have animal models that reliably reproduce features observed in neonates who require resuscitation. Herein, we describe an experimental animal model in newborn piglets that simulates neonatal asphyxia and enables us to examine resuscitation interventions, reoxygenation, and recovery processes. The newborn piglet has several advantages including similar development to a human fetus at 36–38 week’s gestation, and comparable body systems and body size, allowing for surgical instrumentation, monitoring, and collection of biological samples. Furthermore, using this model of neonatal asphyxia, we are also able to describe an increasingly important clinical situation in the laboratory setting—pulseless electrical activity (PEA). Since the integration of electrocardiogram into the neonatal resuscitation guidelines, there has been an increased awareness of PEA in newborn infants. The animal model we describe can therefore serve as a valuable tool to bridge the knowledge gap and improve the outcome of asphyxiated newborns in the delivery room

Respiratory Function During Chest Compressions

Chest compression (CC) is an infrequent event (0.08%) in newborns delivered at near-term and term gestation, and occurs at a higher frequency (10%) in preterm deliveries. In addition, outcome studies of deliveries requiring resuscitation or chest compression have reported high rates of mortality and neurodevelopmental impairment in surviving children. A respiratory function monitor (RFM) can help guide a resuscitator during cardiopulmonary resuscitation (CPR) in a neonate and help assess the quality and efficacy of chest compression. Utilizing a non-invasive respiratory function monitor during chest compression may decrease high mortality rates in addition to having many distinct advantages, which will benefit both the newborn and the resuscitators. There are several different ways that a respiratory function monitor can assist a resuscitator during chest compression; these include confirming and ensuring adequate lung ventilation, analyzing the efficacy and quality of chest compression and exhaled CO2 monitoring

Attenuation of Acute Renal Injury After the Post-resuscitation Administration of Doxycycline in Surviving Newborn Piglets With Severe Hypoxia-Reoxygenation

Background: Asphyxiated neonates often have myocardial dysfunction and renal insufficiency. Previously we demonstrated that doxycycline improved cardio-renal function through matrix metalloproteinase (MMP)-2 inhibition in an acute swine model of neonatal hypoxia-reoxygenation. The prolonged cardio-renal protective effects of doxycycline in neonates still remained unknown. We therefore hypothesized that the protective effects of doxycycline persisted in surviving subjects.Methods: Newborn piglets were instrumented and subjected to 1 h of hypoxia followed by reoxygenation with 21–25% oxygen and observed for 4 days. Intravenous doxycycline (30 mg/kg) or normal saline (1 mL, saline-control group) was given at 5 min of reoxygenation (n = 8/group) in a randomized, blinded fashion. Sham-operated piglets (n = 5) received no hypoxia-reoxygenation. At 96 h after reoxygenation, the left ventricular function was assessed by Millar® catheter. Renal injury was investigated by measuring plasma creatinine, urinary N-acetyl-D-glucosaminidase activity, renal tissue lactate and MMP-2 activity.Results: Both hypoxia-reoxygenation groups had similar hypoxic stress with severe lactate acidosis, and hemodynamic recovery. Doxycycline-treated piglets had higher urine output with lower urine N-acetyl-D-glucosaminidase, plasma creatinine, and renal MMP-2 activity (vs. saline-controls; all p < 0.05). These markers were all negatively correlated with urine output.Conclusions: In newborn piglets surviving hypoxia-reoxygenation, we observed a weak but significant and persistent attenuation of renal injury and improved recovery with the post-resuscitation administration of doxycycline

Improved Carotid and Mesenteric Blood Flows with the Use of 21% Oxygen During Resuscitation of Newborn Piglets with Severe Asphyxia

peer reviewe

The Relationship Between Heart Rate and Left Ventricular Isovolumic Relaxation During Normoxia and Hypoxia-Asphyxia in Newborn Piglets

Background: Many asphyxiated neonates have cardiac complications including arrhythmia and contractile dysfunction. Little is known about the relationship between heart rate (HR) and diastolic function in asphyxiated neonates. We aimed to study the relationship between HR and left ventricular (LV) isovolumic relaxation (IVR) in neonates with asphyxia using a swine model.Methods: Term newborn piglets were anesthetized and acutely instrumented with the placement of Millar® catheter in the left ventricle. Hemodynamic parameters including HR, cardiac output, stroke volume, dP/dtmax and dP/dtmin, and IVR time constant (Tau) were continuously measured and recorded. Sixteen piglets were exposed to 50-minute normocapnic hypoxia followed by asphyxia (mean of 3.2 min) by clamping of the endotracheal tube. Sham-operated piglets (n = 11) had no hypoxia nor asphyxia. The relationship between HR and other hemodynamic parameters were analyzed using Pearson Product Moment correlation test.Results: Asphyxiated piglets had cardiogenic shock and metabolic acidosis (vs. sham-operated piglets). There were significant correlations between HR and diastolic function as shown by Tau at baseline (sham-operated: r = -0.68, p = 0.02; asphyxia: r = -0.55, p = 0.03) and during normoxia (53 min) of sham-operated piglets (r = -0.69, p = 0.02). HR and Tau was not correlated during hypoxia-asphyxia (HA) (r = -0.01, p = 0.97). Cardiac output was tightly correlated with stroke volume (p < 0.001) but not HR throughout the experimental period in both groups. There was no significant correlation between HR and other hemodynamic parameters during the experimental period in both groups.Conclusion: We observed an uncoupling between HR and IVR Tau of the neonatal heart during HA, which deserves further studies of the relationship between HR and LV diastolic function