Intramuscular versus intravenous epinephrine administration in a pediatric porcine model of cardiopulmonary resuscitation.

Background: American Heart Association Pediatric Life Support guidelines recommend epinephrine administration via intravenous (IV) or intraosseous (IO) route, with endotracheal (ET) administration admissible in the absence of IV/IO access. Establishing IV/IO/ET access can take several minutes and may require proficient skills and/or specific equipment, which may not be readily available in all situations. Alternatively, intramuscular (IM) epinephrine could be administered immediately. At present, there is limited data on the use of IM epinephrine in pediatric resuscitation. Aim: To compare IM with IV epinephrine in a pediatric porcine model of asphyxia-induced cardiac arrest. We hypothesized that in a pediatric animal model of cardiac arrest, IM epinephrine would result in a similar time to achieve return of spontaneous circulation (ROSC) to IV epinephrine. Methods: Twenty pediatric piglets (5-10 days old) were anesthetized and asphyxiated by clamping the endotracheal tube. Piglets were randomized to IM or IV epinephrine with bradycardic or asystolic cardiac arrest (n = 5/group) and were resuscitated. Time to ROSC was recorded; blood plasma was collected throughout resuscitation for measurement of epinephrine concentration; heart rate, arterial blood pressure, carotid blood flow, cardiac function, and cerebral oxygenation were continuously recorded throughout the experiment. Results: Time to ROSC and the number of piglets that achieved ROSC were comparable between IM and IV epinephrine groups with either bradycardic or asystolic cardiac arrest. Conclusions: In a pediatric piglet model of bradycardic and asystolic cardiac arrest, administration of IM epinephrine resulted in similar resuscitative outcomes to IV epinephrine. Although immediate IM epinephrine injection may provide a first-line treatment option until subsequent IV/IO access is established, large, randomized trials are needed to confirm our finding before it can be used during pediatric resuscitation.

Cardiopulmonary resuscitation with 3:1 Compression:Ventilation or continuous compression with asynchronized ventilation in infantile piglets.

BACKGROUND: To compare neonatal and pediatric resuscitation approaches to ventilation and chest compression by using either continuous chest compression with asynchronized ventilation (CCaV) or 3:1 Compression:Ventilation ration (3:1 C:V) during infant cardiopulmonary resuscitation. We hypothesized that 3:1 C:V compared to CCaV will reduce time to return of spontaneous circulation (ROSC) in infantile piglets with asphyxia-induced bradycardic cardiac arrest. METHODS: Twenty infantile piglets (5-10 days old) were anesthetized and asphyxiated by clamping the endotracheal tube. Piglets were randomized to 3:1 C:V or CCaV for resuscitation (n = 10/group). Heart rate, arterial blood pressure, carotid blood flow, cerebral oxygenation, and respiratory parameters were continuously recorded throughout the experiment. RESULTS: The median time (IQR) to ROSC among survivors was 157 (113-219) vs 421 (118-660) for 3:1 C:V and CCaV, respectively (p = 0.253). The duration of resuscitation with 3:1 C:V compared to CCaV was 206 (119-660) vs 660 (212-660)sec, respectively (p = 0.171). The number of piglets achieving ROSC with 3:1 C:V and CCaV were 7/10 and 6/10, respectively (p = 1.00). There was no difference in hemodynamic and respiratory parameters between groups. CONCLUSIONS: Time to ROSC and survival was not different between 3:1 C:V and CCaV in infantile piglets. Either approach appears reasonable during infantile cardiopulmonary resuscitation. IMPACT: Similar time to return of spontaneous circulation and survival with 3:1 C:V and CCaV in infant piglets equivalent to 28-day-old children. Either approach appears reasonable during infantile cardiopulmonary resuscitation. Lack of scientific data to provide recommendations on when to switch between neonatal to pediatric resuscitation guidelines. No difference in time to return of spontaneous circulation or survival between 3:1 C:V and CCaV in infantile piglets with asphyxia-induced bradycardic cardiac arrest. Both methods are viable options during infant cardiopulmonary resuscitation.

Comparison of positive pressure ventilation devices during compliance changes in a neonatal ovine model.

BACKGROUND: To compare tidal volume (VT) delivery with compliance at 0.5 and 1.5 mL/cmH2O using four different ventilation (PPV) devices (i.e., self-inflating bag (SIB), T-Piece resuscitator, Next Step (a novel Neonatal Resuscitator), and Fabian ventilator (conventional neonatal ventilator) using a neonatal piglet model. DESIGN/METHODS: Randomized experimental animal study using 10 mixed-breed neonatal piglets (1-3 days; 1.8-2.4 kg). Piglets were anesthetized, intubated, instrumented, and randomized to receive positive pressure ventilation (PPV) for one minute with a SIB with or without a respiratory function monitor (RFM), T-Piece resuscitator with or without an RFM, Next Step, and Fabian Ventilator with both compliance levels. Compliance changes were achieved by placing a wrap around the piglets' chest and tightened it. Our primary outcome was targeted VT delivery of 5 mL/kg at 0.5 and 1.5 mL/cmH2O lung compliance. RESULTS: At 0.5 mL/cmH2O compliance, the mean(SD) expired VT with the Next Step was 5.1(0.2) mL/kg compared to the Fabian 4.8(0.5) mL/kg, SIB 8.9(3.6) mL/kg, SIB + RFM 4.5(1.8) mL/kg, T-Piece 7.4(4.3) mL/kg, and T-Piece+RFM 6.4(3.1) mL/kg. At 1.5 mL/cmH2O compliance, the mean(SD) expired VT with the Next Step was 5.2(0.6) mL/kg compared to the Fabian 4.4(0.7) mL/kg, SIB 12.1(5.3) mL/kg, SIB + RFM 9.4(3.9) mL/kg, T-Piece 8.6(1.5) mL/kg, and T-Piece+RFM 6.5 (1.6) mL/kg. CONCLUSION: The Next Step provides consistent VT during PPV, which is comparable to a mechanical ventilator. IMPACT: Current guidelines recommend fixed peak inflation pressure in resuscitation, linked to lung and brain injury. The Next Step Neonatal Resuscitator, a cost-effective device, offers volume-targeted positive pressure ventilation with consistent tidal volumes. With two different compliances, the Next Step Neonatal Resuscitator delivered a consistent tidal volume which was similar to a mechanical ventilator. The Next Step Neonatal Resuscitator outperformed self-inflating bags and T-Pieces in delivering targeted tidal volumes. The Next Step Neonatal Resuscitator could be an alternative ventilation device for neonatal resuscitation.

Cardiac Agents during Neonatal Cardiopulmonary Resuscitation.

BACKGROUND: Epinephrine (adrenaline) is currently the only cardiac agent recommended during neonatal resuscitation. The inability to predict which newborns are at risk of requiring resuscitative efforts at birth has prevented the collection of large, high-quality human data. SUMMARY: Information on the optimal dosage and route of epinephrine administration is extrapolated from neonatal animal studies and human adult and pediatric studies. Adult resuscitation guidelines have previously recommended vasopressin use; however, neonatal studies needed to create guidelines are lacking. A review of the literature demonstrates conflicting results regarding epinephrine efficacy through various routes of access as well as vasopressin during asystolic cardiac arrest in animal models. Vasopressin appears to improve hemodynamic and post-resuscitation outcomes compared to epinephrine in asystolic cardiac arrest animal models. KEY MESSAGES: The current neonatal resuscitation guidelines recommend epinephrine be primarily given via the intravenous or intraosseous route, with the endotracheal route as an alternative if these routes are not feasible or unsuccessful. The intravenous or intraosseous dose ranges between 0.01 and 0.03 mg/kg, which should be repeated every 3-5 min during chest compressions. However, the optimal dosing and route of administration of epinephrine remain unknown. There is evidence from adult and pediatric studies that vasopressin might be an alternative to epinephrine; however, the neonatal data are scarce.

Comparison of various vasopressin doses to epinephrine during cardiopulmonary resuscitation in asphyxiated neonatal piglets.

BACKGROUND: Current neonatal resuscitation guidelines recommend epinephrine for cardiac arrest. Vasopressin might be an alternative during asphyxial cardiac arrest. We aimed to compare vasopressin and epinephrine on incidence and time to return of spontaneous circulation (ROSC) in asphyxiated newborn piglets. DESIGN/METHODS: Newborn piglets (n = 8/group) were anesthetized, intubated, instrumented, and exposed to 30 min of normocapnic hypoxia, followed by asphyxia and asystolic cardiac arrest. Piglets were randomized to 0.2, 0.4, or 0.8IU/kg vasopressin, or 0.02 mg/kg epinephrine. Hemodynamic parameters were continuously measured. RESULTS: Median (IQR) time to ROSC was 172(103-418)s, 157(100-413)s, 122(93-289)s, and 276(117-480)s for 0.2, 0.4, 0.8IU/kg vasopressin, and 0.02 mg/kg epinephrine groups, respectively (p = 0.59). The number of piglets that achieved ROSC was 6(75%), 6(75%), 7(88%), and 5(63%) for 0.2, 0.4, 0.8IU/kg vasopressin, and 0.02 mg/kg epinephrine, respectively (p = 0.94). The epinephrine group had a 60% (3/5) rate of post-ROSC survival compared to 83% (5/6), 83% (5/6), and 57% (4/7) in the 0.2, 0.4, and 0.8IU/kg vasopressin groups, respectively (p = 0.61). CONCLUSION: Time to and incidence of ROSC were not different between all vasopressin dosages and epinephrine. However, non-significantly lower time to ROSC and higher post-ROSC survival in vasopressin groups warrant further investigation. IMPACT: Time to and incidence of ROSC were not statistically different between all vasopressin dosages and epinephrine. Non-significantly lower time to ROSC and higher post-ROSC survival in vasopressin-treated piglets. Overall poorer hemodynamic recovery following ROSC in epinephrine piglets compared to vasopressin groups. Human neonatal clinical trials examining the efficacy of vasopressin during asphyxial cardiac arrest will begin recruitment soon.