Norman A. Paradis

High-dose epinephrine improves outcome from pediatric cardiac arrest

STUDY OBJECTIVE Animal studies suggest that the standard dose of epinephrine (SDE) for treatment of cardiac arrest in human beings may be too low. We compared the outcome after SDE with that after high-dose epinephrine (HDE) in children with refractory cardiac arrest. DESIGN Prospective intervention versus historic control groups. TYPE OF PARTICIPANTS Two similar groups of 20 consecutive patients each (median ages, 2.5 and 3 years) with witnessed cardiac arrest who remained in arrest after at least two SDEs (0.01 mg/kg). INTERVENTIONS Treatment with an additional SDE versus HDE (0.2 mg/kg). MEASUREMENTS AND MAIN RESULTS The rates of return of spontaneous circulation and long-term survival were compared. Fourteen of the HDE group (70%) had return of spontaneous circulation, whereas none of the SDE group did (P less than .001). Eight children survived to discharge after HDE, and three were neurologically intact at follow-up. No significant toxicity from HDE was observed. CONCLUSION HDE provided a higher return of spontaneous circulation rate and a better long-term outcome than SDE in our series of pediatric cardiac arrest. HDE may warrant incorporation into standard resuscitation protocols at an early enough point to prevent irreversible brain injury.

Effect of epinephrine on end-tidal carbon dioxide monitoring during CPR

End-tidal carbon dioxide (ETCO2) has been shown to correlate with coronary perfusion pressure (CPP) during CPR and has been proposed as a useful noninvasive monitor of CPR efficacy. The effects of therapeutic epinephrine dosing on ETCO2 and CPP in six dogs were examined. Ventricular fibrillation was induced and left untreated for five minutes before CPR was initiated. After five minutes of CPR, epinephrine 0.045 mg/kg IV was administered. CPP and ETCO2 were compared immediately before and two minutes after epinephrine administration. There was a significant increase in CPP from 12.2 +/- 9.6 to 26.8 +/- 7.1 mm Hg (P = .006) after epinephrine. This was accompanied by a significant decrease in ETCO2 from 8.2 +/- 2.9 to 3.8 +/- 2.0 mm Hg (P = .01). These data indicate that after epinephrine administration, caution must be exercised in using ETCO2 as an indicator of CPP.

Effects of arterial and venous volume infusion on coronary perfusion pressures during canine CPR

Intraarterial (IA) volume infusion has been reported to be more effective than intravenous (IV) infusion in treating cardiac arrest due to exsanguination. A rapid IA infusion was felt to raise intraaortic pressure and improve coronary perfusion pressure (CPP). The purpose of this study was to determine if IA or IV volume infusion could augment the effect of epinephrine on CPP during CPR in the canine model. Nineteen mongrel dogs with a mean weight of 26.3 +/- 4.2 kg were anesthetized and mechanically ventilated. Thoracic aortic (Ao), right atrial (RA) and pulmonary artery catheters were placed for hemodynamic monitoring. Additional Ao and central venous catheters were placed for volume infusion. Ventricular fibrillation was induced and Thumper CPR was begun after 5 min (t = 5). At t = 10, all dogs received 45 micrograms/kg IV epinephrine. Six animals received epinephrine alone (EPI). Five dogs received EPI plus a 500 cc bolus of normal saline over 3 min intravenously (EPI/IV). Another group (n = 8) received EPI plus the same fluid bolus through the aortic catheter (EPI/IA). Resuscitation was attempted at t = 18 using a standard protocol. There was a significant increase in CPP over baseline in all groups. The changes in CPP from baseline induced by EPI, EPI/IV and EPI/IA were 20.6 +/- 3.7, 22.8 +/- 4.2 and 22.2 +/- 2.4 mmHg, respectively. Volume loading did not augment the effect of therapeutic EPI dosing. By increasing both preload and afterload, volume administration may in fact be detrimental during CPR.

Nuclear magnetic resonance spectroscopy study of human brain after cardiac resuscitation.

We used 31P nuclear magnetic resonance spectroscopy to study the cerebral metabolic function of eight patients with severe postischemic anoxic encephalopathy secondary to cardiac arrest. Spectroscopy was performed at 18 +/- 13 and 64 +/- 20 hours after resuscitation. Glasgow Coma Scale scores at the time of initial and repeat spectroscopy were 3.6 +/- 1.2 and 3.5 +/- 1.2, respectively. In those patients whose spectra were of adequate quality to monitor pH, all demonstrated tissue alkalosis in at least one brain region. The mean brain pH at initial spectroscopy was 7.14 +/- 0.09 and was significantly alkalotic when compared with age- and sex-matched normal controls (pH = 6.98 +/- 0.04, p less than 0.0001). Five of the eight patients showed at least one region of persistent alkalosis at repeat spectroscopy, whereas one patient demonstrated severe acidosis with a pH of 6.42. Spectra demonstrated marked metabolic heterogeneity, ranging from normal in appearance to complete obliteration of all high-energy phosphates with only inorganic phosphate remaining.

The effect of CO2 and non-CO2—generating buffers on cerebral acidosis after cardiac arrest: A 31P NMR study

There is controversy regarding the use of alkalinizing agents during reperfusion after cardiac arrest. The potential deleterious effects of sodium bicarbonate (bicarb) administration, including paradoxic cerebral acidosis, have led to the search for alternative agents. Tromethamine (tris) is a non-CO2-generating buffer that has been proposed for use during cardiopulmonary resuscitation. The purpose of this experiment was to compare the ability of tris with bicarb to correct brain pH (pH B) during reperfusion after a 12-minute cardiac arrest. Adult mongrel dogs were instrumented and placed in the bore of a Bruker Biospec 1.89 tesla superconducting magnet system. Ventricular fibrillation was induced; after 12 minutes, cardiopulmonary bypass was initiated and maintained for two hours with minimum flows of 80 mL/kg/min. Bicarb (n = 5) or tris (n = 5) were administered to correct arterial pH as rapidly as possible. 31P NMR spectra were obtained at baseline and throughout ischemia and reperfusion. The pH B was determined with the inorganic phosphate relative to the phosphocreatine resonance signal shift. Profile analysis indicates a difference between groups (P less than .02) related to an initial delay in pH B correction in the tris group. By 48 minutes of reperfusion, pH B did not differ between the groups. Moreover, there was no evidence of paradoxic cerebral acidosis in the bicarb group. Although tris corrects blood pH as quickly as bicarb, it is less effective in correcting pH B. Absence of paradoxic acidosis may be caused by efficient elimination of CO2 by cardiopulmonary bypass.

Cerebral lactate uptake during cardiopulmonary resuscitation in humans

Animal studies have shown cerebral lactate uptake under conditions of anoxia and ischemia. Cerebral lactate uptake in humans during cardiopulmonary resuscitation (CPR) has not been previously reported in the literature. Forty-five patients receiving CPR underwent simultaneous sampling through jugular venous bulb, right atrial, and central aortic catheterization. The mean net cerebral lactate uptake (central aortic minus jugular venous bulb) was 0.76 ± 1.86 and 0.80 ± 2.03 mM on initial measurement and 10 min later, respectively. Both measurements were statistically significant (p = 0.01) compared to normal controls who have net cerebral output of lactate of −0.18 ± 0.1 mM. Seventy-one percent of all patients had a cerebral uptake on initial sampling and this gradient persisted upon sampling 10 min later in 68% of the remaining 40 patients who did not have a return of spontaneous circulation. Among multiple variables measured, patients who exhibited a cerebral lactate uptake were 13.2 years younger (p = 0.004), received an additional 7.6 min of CPR (p = 0.05), and had a mean arterial lactate concentration of 4.8 mM higher (p = 0.005) than the nonuptake group. The pathophysiologic explanation of cerebral lactate uptake during CPR is multifactorial and includes utilization and/or diffusion.

Dose-response relationship between aortic infusions of polymerized bovine hemoglobin and return of circulation in a canine model of ventricular fibrillation and advanced cardiac life support

OBJECTIVES Return of spontaneous circulation after cardiac arrest may be a function of vital organ perfusion. Selective aortic perfusion and oxygenation with oxygenated ultrapurified polymerized bovine hemoglobin improves vital organ perfusion and is an effective adjunct in the treatment of cardiac arrest. This study determined the dose-response relationship between intra-aortic oxygenated ultrapurified polymerized bovine hemoglobin and return of spontaneous circulation. DESIGN Randomized, interventional study, using a clinically relevant model of ventricular fibrillation with a prolonged arrest time and cardiopulmonary resuscitation based on external chest compression and aortic occlusion with oxygenated ultrapurified polymerized bovine hemoglobin infusion. SETTING University, resuscitation research laboratory. SUBJECTS Fasted, mongrel dogs (> 20 kg). INTERVENTIONS After alpha-chloralose anesthesia, blood gases and vital signs were normalized. Electrocardiogram, aortic arch, and intraesophageal pressures were measured continuously. A descending aortic occlusion-infusion balloon catheter was placed through the femoral artery. Ventricular fibrillation was induced and basic life support was begun after 10 mins. Interanimal differences in basic life support were minimized by standardization of the esophageal pulse pressure and aortic blood gases. At 13 mins, the aortic occlusion balloon was inflated and a dose of 10, 20, or 30 mL/kg of ultrapurified polymerized bovine hemoglobin was infused at 300 mL/min. Defibrillation was attempted at the end of the infusion. MEASUREMENTS AND MAIN RESULTS Only two of five animals given 10 mL/kg of ultrapurified polymerized bovine hemoglobin had return of spontaneous circulation, vs. four of five animals given 20 mL/kg, and all seven animals given 30 mL/kg. All resuscitated animals were alive at 1 hr after return of spontaneous circulation. CONCLUSIONS There is a dose-response relationship between the volume of oxygenated ultrapurified polymerized bovine hemoglobin administered by selective aortic perfusion and oxygenation and return of spontaneous circulation after prolonged cardiac arrest. This result supports the hypothesis that vital organ flow is causally related to improved outcome.

Aortic-Based Therapy for Cardiac Arrest

After the failure of electrical countershock, the successful treatment of cardiac arrest is a function of raising aortic pressure so as to improve vital organ perfusion. Pharmacologic pressor agents have until recently been the most direct means of increasing aortic pressure. We have now begun to reevaluate direct aortic techniques including occlusion, infusion, counter-pulsation, and combinations of these. Clinical studies have demonstrated that the aorta can be accessed quickly and reliably even under emergency conditions. Initial laboratory studies indicate that some nonpharmacologic aortic therapies hold promise as adjuncts to external chest compression, or even as stand-alone therapies. Considerable research will be needed to identify the most effective approach before clinical trials can be considered.

A swine model of pseudo-pulseless electrical activity induced by partial asphyxiation

BACKGROUND The incidence of pulseless electrical activity (PEA) as a presenting rhythm during cardiac arrest is increasing. The current animal models of PEA arrest, post-countershock or total asphyxiation, unreliably generate PEA for a specific time period. Neither of these models predictably generate pseudo-PEA. The purpose of this study was to create an animal model of pseudo-PEA that will allow for a prolonged time period in this arrest state for future research. METHODS In a laboratory setting, five ventilated swine on inhaled anesthesia and 100% oxygen with continuous EKG recordings were instrumented with central aortic and venous pressure-transducing catheters. Animals were then switched to intravenous anesthesia while being ventilated with a 16% oxygen/84% nitrogen mix. Continuous EKG, aortic and venous pressures were recorded to a computerized data collection program. Arterial blood gas samples were taken every 10min. Time until onset of pseudo-PEA, duration of pseudo-PEA, and cardiac rhythm during pseudo-PEA were recorded. RESULTS Mean time to onset of pseudo-PEA was 80.6+/-47.3min. Mean duration of pseudo-PEA was 18.6+/-6.2min. Mean arterial pH at pseudo-PEA onset was 7.20+/-0.05 with a mean associated base excess of -11.4+/--5.94. No significant differences were noted in other recorded variables. CONCLUSIONS Partial asphyxiation using a 16% oxygen/84% nitrogen mix is a reliable laboratory method to create a prolonged state of pseudo-PEA in a swine model. The mechanism generating pseudo-PEA is hypoxemia-induced systemic acidosis. This model will allow sufficient time in this low-flow cardiac state for future research to be conducted.

Right atrial-jugular venous pressure gradients during CPR in children

OBJECTIVE This study measured the internal jugular vein and right atrium pressures during pediatric CPR to detect and quantify venous pressure gradients across the thoracic inlet. DESIGN Ten children from 2 months to 15 years old who underwent CPR had simultaneous pressure measurements recorded from the right atrium and jugular vein. RESULTS The right atrium-jugular vein peak compression-phase gradient was 18.3 +/- 4.7 mm Hg (mean +/- SD), and the end-relaxation gradient was 0.7 +/- 0.6. Jugular vein pressure exceeded the right atrium only in the early-relaxation phase (right atrium-jugular vein = -2.1 +/- 1.2). Thoracic inlet venous valving persisted throughout the duration of CPR. CONCLUSION There is a large venous gradient across the thoracic inlet during chest compressions in children, facilitating cerebral blood flow. This gradient reversed only in the early-relaxation phase. The data suggest that jugular venous return occurs only in the early-relaxation phase, whereas cerebral venous drainage persists throughout the CPR cycle.