Establishing a multicenter, preclinical consortium in resuscitation: A pilot experimental trial evaluating epinephrine in cardiac arrest.

BACKGROUND: Large animal studies are an important step in the translation pathway, but single laboratory experiments do not replicate the variability in patient populations. Our objective was to demonstrate the feasibility of performing a multicenter, preclinical, randomized, double-blinded, placebo-controlled cardiac arrest trial. We evaluated the effect of epinephrine on coronary perfusion pressure (CPP) as previous single laboratory studies have reported mixed results. METHODS: Forty-five swine from 5 different laboratories (Ann Arbor, MI; Baltimore, MD; Los Angeles, CA; Pittsburgh, PA; Toronto, ON) using a standard treatment protocol. Ventricular fibrillation was induced and left untreated for 6 min before starting continuous cardiopulmonary resuscitation (CPR). After 2 min of CPR, 9 animals from each lab were randomized to 1 of 3 interventions given over 12 minutes: (1) Continuous IV epinephrine infusion (0.00375 mg/kg/min) with placebo IV normal saline (NS) boluses every 4 min, (2) Continuous placebo IV NS infusion with IV epinephrine boluses (0.015 mg/kg) every 4 min or (3) Placebo IV NS for both infusion and boluses. The primary outcome was mean CPP during the 12 mins of drug therapy. RESULTS: There were no significant differences in mean CPP between the three groups: 14.4 ± 6.8 mmHg (epinephrine Infusion), 16.9 ± 5.9 mmHg (epinephrine bolus), and 14.4 ± 5.5 mmHg (placebo) (p = NS). Sensitivity analysis demonstrated inter-laboratory variability in the magnitude of the treatment effect (p = 0.004). CONCLUSION: This study demonstrated the feasibility of performing a multicenter, preclinical, randomized, double-blinded cardiac arrest trials. Standard dose epinephrine by bolus or continuous infusion did not increase coronary perfusion pressure during CPR when compared to placebo.

A Novel Radiofrequency Device to Monitor Changes in Pulmonary Fluid in Dialysis Patients.

BACKGROUND AND OBJECTIVES: Fluid monitoring is an important management strategy in patients with chronic kidney disease (CKD) and heart failure (HF). The µCor™ Heart Failure and Arrhythmia Management System uses a radiofrequency-based thoracic fluid index (TFI) to track pulmonary edema. During hemodialysis, the acute removal of fluid through ultrafiltration offers a model for measuring a patient's fluid status. The objective of the study was to assess the relationship between the device measured TFI and ultrafiltration volume (UFV). DESIGN SETTING PARTICIPANTS AND MEASUREMENTS: Patients undergoing chronic dialysis with and without heart failure were enrolled in the study. The relationship between TFI and UFV in each individual subject was assessed by calculating the Pearson correlation coefficient (r). The average correlation across all subjects was calculated through the use of the Fisher's z transform. Responder analysis was performed to assess the magnitude of change in TFI before and after dialysis. RESULTS: Twenty subjects were enrolled in the trial. The mean volume of fluid removal was 3.63 L (SD 0.88 L). The mean correlation based on Fisher's transform was 0.95 CI (0.92-0.99). Responder analysis showed that the mean reduction of TFI after dialysis was 5.5% ± 3.8. CONCLUSION: The µCor system provides radiofrequency-based measurements of thoracic fluid which correlate well with total body fluid removal in a real-world setting. Fluid management based on the radar-derived TFI may provide benefits to dialysis patients and serves as a potential model for pulmonary edema common to the clinical course of heart failure.

Synchronized Chest Compressions for Pseudo-PEA: Proof of Concept and a Synching Algorithm.

Objective: The two objectives of this report are: first, to describe a comparison of chest compressions unsynchronized or synchronized to native cardiac activity in a porcine model of hypotension, and second, to develop an algorithm to provide synchronized chest compressions throughout a range of native heart rates likely to be encountered when treating PEA cardiac arrest. Methods: We adapted our previously developed signal-guided CPR system to provide compressions synchronized to native electrical activity in a porcine model of hypotension as a surrogate of PEA arrest. We describe the first comparison of unsynchronized to synchronized compressions in a single animal as a proof-of-concept. We developed an algorithm to provide optimal synchronized chest compressions regardless of intrinsic PEA heart rate while simultaneously maintaining the chest compression rate within a desired range. We tested the algorithm with computer simulations measuring the proportion of intrinsic and compression beats that were synchronized, and the compression rate and its standard deviation, as a function of intrinsic heart rate and heart rate jitter. Results: We demonstrate and compare unsynchronized versus synchronized chest compressions in a single porcine model with an intrinsic rhythm and hypotension. Synchronized, but not unsynchronized, chest compressions were associated with increased blood pressure and coronary perfusion pressure. Our synchronized chest compression algorithm is able to provide synchronized chest compressions to over 90% of intrinsic beats for most heart rates while maintaining an average compression rate between 90 and 140 compressions per minute with relatively low variability. Conclusions: Synchronized chest compression therapy for pulseless electrical rhythms is feasible. A high degree of synchronization can be maintained over a broad range of intrinsic heart rates while maintaining the compression rate within a satisfactory range. Further investigation to assess benefit for treatment of PEA is warranted.

Cardioplegia defibrillation of circulatory and metabolic phase ventricular fibrillation in a swine model.

INTRODUCTION: We previously found potassium cardioplegia followed by rapid calcium reversal (Kplegia) can achieve defibrillation in a swine model of electrical phase of ventricular fibrillation (VF) comparable to standard care. HYPOTHESIS: Exploring 3 possible potassium dose and timing protocols, we hypothesize Kplegia may benefit resuscitation of longer duration untreated VF. METHODS: Three separate blinded randomized placebo-controlled trials were performed with electrically-induced VF untreated for durations of 6, 9, and 12min in a swine model. Experimental groups received infusion of 1 or 2 boluses of intravenous (IV) potassium followed by a single calcium reversal bolus. Potassium was replaced by saline in the control groups. Outcomes included: amplitude spectrum area (AMSA) during VF, resulting rhythms, number of defibrillations, return of spontaneous circulation (ROSC), and hemodynamics for 1h post ROSC. Binomial and interval data outcomes were compared with exact statistics. Serial interval data were assessed with mixed regression models. RESULTS: Twelve, 12, and 8 animals were included at 6, 9, and 12min VF durations for a total of 32. ROSC was achieved in: 4/6 Kplegia and 3/6 control animals in the 6min protocol, (p=1.00), 4/6 Kplegia and 2/6 control animals in the 9min protocol,(p=0.57), and 0/5 Kplegia and 1/3 control animals in the 12min protocol,(p=0.38). Two of 8 Kplegia animals achieved ROSC with chemical defibrillation alone. CONCLUSIONS: The majority of animals achieved ROSC after up to 9min of untreated VF arrest using K plegia protocols. K plegia requires further optimization for both peripheral IV and intraosseous infusion, and to assess for superiority over standard care. Institutional Animal Care and Use Committee protocol #15127224.

Intra-Arrest Administration of Cyclosporine and Methylprednisolone Does Not Reduce Postarrest Myocardial Dysfunction.

OBJECTIVE: To determine whether the administration of intra-arrest cyclosporine (CCY) and methylprednisolone (MP) preserves left ventricular ejection fraction (LVEF) and cardiac output (CO) after return of spontaneous circulation (ROSC). METHODS: Eleven, 25-30kg female swine were randomized to receive 10mg/kg CCY + 40mg MP or placebo, anesthetized and given a transthoracic shock to induce ventricular fibrillation. After 8 minutes, standard CPR was started. After two additional minutes, the experimental agent was administered. Animals with ROSC were supported for up to 12h with norepinephrine as needed. Echocardiography was performed at baseline, and 1, 2, 6 and 12h post-ROSC. Analysis was performed using generalized estimating equations (GEE) after downsampling continuously sampled data to 5 minute epochs. RESULTS: Eight animals (64%) achieved ROSC after a median of 7 [IQR 5-13] min of CPR, 2 [ IQR 1-3] doses of epinephrine and 2 [IQR 1-5] defibrillation shocks. Animals receiving CCY+MP had higher post ROSC MAP (GEE coefficient -10.2, P = <0.01), but reduced cardiac output (GEE coefficient 0.8, P = <0.01) compared to placebo. There was no difference in LVEF or vasopressor use between arms. CONCLUSIONS: Intra-arrest cyclosporine and methylprednisolone decreased post-arrest cardiac output and increased mean arterial pressure without affecting left ventricular ejection fraction.

Effects of intra-resuscitation antiarrhythmic administration on rearrest occurrence and intra-resuscitation ECG characteristics in the ROC ALPS trial.

BACKGROUND: Intra-resuscitation antiarrhythmic drugs may improve resuscitation outcomes, in part by avoiding rearrest, a condition associated with poor out-of-hospital cardiac arrest (OHCA) outcomes. However, antiarrhythmics may also alter defibrillation threshold. The objective of this study was to investigate the relationship between rearrest and intra-resuscitation antiarrhythmic drugs in the context of the Resuscitation Outcomes Consortium (ROC) amiodarone, lidocaine, and placebo (ALPS) trial. HYPOTHESIS: Rearrest rates would be lower in cases treated with amiodarone or lidocaine, versus saline placebo, prior to first return of spontaneous circulation (ROSC). We also hypothesized antiarrhythmic effects would be quantifiable through analysis of the prehospital electrocardiogram. METHODS: We conducted a secondary analysis of the ROC ALPS trial. Cases that first achieved prehospital ROSC after randomized administration of study drug were included in the analysis. Rearrest, defined as loss of pulses following ROSC, was ascertained from emergency medical services records. Rearrest rate was calculated overall, as well as by ALPS treatment group. Multivariable logistic regression models were constructed to assess the association between treatment group and rearrest, as well as rearrest and both survival to hospital discharge and survival with neurologic function. Amplitude spectrum area, median slope, and centroid frequency of the ventricular fibrillation (VF) ECG were calculated and compared across treatment groups. RESULTS: A total of 1144 (40.4%) cases with study drug prior to first ROSC were included. Rearrest rate was 44.0% overall; 42.9% for placebo, 45.7% for lidocaine, and 43.0% for amiodarone. In multivariable logistic regression models, ALPS treatment group was not associated with rearrest, though rearrest was associated with poor survival and neurologic outcomes. AMSA and median slope measures of the first available VF were associated with rearrest case status, while median slope and centroid frequency were associated with ALPS treatment group. CONCLUSION: Rearrest rates did not differ between antiarrhythmic and placebo treatment groups. ECG waveform characteristics were correlated with treatment group and rearrest. Rearrest was inversely associated with survival and neurologic outcomes.

Effect of neuromonitor-guided titrated care on brain tissue hypoxia after opioid overdose cardiac arrest.

INTRODUCTION: Brain tissue hypoxia may contribute to preventable secondary brain injury after cardiac arrest. We developed a porcine model of opioid overdose cardiac arrest and post-arrest care including invasive, multimodal neurological monitoring of regional brain physiology. We hypothesized brain tissue hypoxia is common with usual post-arrest care and can be prevented by modifying mean arterial pressure (MAP) and arterial oxygen concentration (PaO2). METHODS: We induced opioid overdose and cardiac arrest in sixteen swine, attempted resuscitation after 9 min of apnea, and randomized resuscitated animals to three alternating 6-h blocks of standard or titrated care. We invasively monitored physiological parameters including brain tissue oxygen (PbtO2). During standard care blocks, we maintained MAP > 65 mmHg and oxygen saturation 94-98%. During titrated care, we targeted PbtO2 > 20 mmHg. RESULTS: Overall, 10 animals (63%) achieved ROSC after a median of 12.4 min (range 10.8-21.5 min). PbtO2 was higher during titrated care than standard care blocks (unadjusted ß = 0.60, 95% confidence interval (CI) 0.42-0.78, P < 0.001). In an adjusted model controlling for MAP, vasopressors, sedation, and block sequence, PbtO2 remained higher during titrated care (adjusted ß = 0.75, 95%CI 0.43-1.06, P < 0.001). At three predetermined thresholds, brain tissue hypoxia was significantly less common during titrated care blocks (44 vs 2% of the block duration spent below 20 mmHg, P < 0.001; 21 vs 0% below 15 mmHg, P < 0.001; and, 7 vs 0% below 10 mmHg, P = .01). CONCLUSIONS: In this model of opioid overdose cardiac arrest, brain tissue hypoxia is common and treatable. Further work will elucidate best strategies and impact of titrated care on functional outcomes.

Compression-to-ventilation ratio and incidence of rearrest-A secondary analysis of the ROC CCC trial.

BACKGROUND: Previous work has demonstrated that when out-of-hospital cardiac arrest (OHCA) patients achieve return of spontaneous circulation (ROSC), but subsequently have another cardiac arrest prior to hospital arrival (rearrest), the probability of survival to hospital discharge is significantly decreased. Additionally, few modifiable factors for rearrest are known. We sought to examine the association between rearrest and compression-to-ventilation ratio during cardiopulmonary resuscitation (CPR) and to confirm the association between rearrest and outcomes. HYPOTHESIS: Rearrest incidence would be similar between cases treated with 30:2 or continuous chest compression (CCC) CPR, but inversely related to survival and good neurological outcome. METHODS: We conducted a secondary analysis of a large randomized-controlled trial of CCC versus 30:2 CPR for the treatment of OHCA between 2011 and 2015 among 8 sites of the Resuscitation OUTCOMES: Consortium (ROC). Patients were randomized through an emergency medical services (EMS) agency-level cluster randomization design to receive either 30:2 or CCC CPR. Case data were derived from prehospital patient care reports, digital defibrillator files, and hospital records. The primary analysis was an as-treated comparison of the proportion of patients with a rearrest for patients who received 30:2 versus those who received CCC. In addition, we assessed the association between rearrest and both survival to hospital discharge and favorable neurological outcome (Modified Rankin Score≤3) in patients with and without ROSC upon ED arrival using multivariable logistic regression adjusting for age, sex, initial rhythm and measures of CPR quality. RESULTS: There were 14,109 analyzable cases that were determined to have definitively received either CCC or 30:2 CPR. Of these, 4713 had prehospital ROSC and 2040 (43.2%) had at least one rearrest. Incidence of rearrest was not significantly different between patients receiving CCC and 30:2 (44.1% vs 41.8%; adjusted OR: 1.01; 95% CI: 0.88, 1.16). Rearrest was significantly associated with lower survival (23.3% vs 36.9%; adjusted OR: 0.46; 95%CI: 0.36-0.51) and worse neurological outcome (19.4% vs 30.2%; adjusted OR: 0.46; 95%CI: 0.38, 0.55). CONCLUSION: Rearrest occurrence was not significantly different between patients receiving CCC and 30:2, and was inversely associated with survival to hospital discharge and MRS.

Energy conserving chemical defibrillation of ventricular fibrillation: A randomized two phase controlled blinded trial.

OBJECTIVES: Potassium cardioplegia-induced transient asystole may conserve myocardial energy, foster chemical defribrillation, and improve VF arrest outcome. A trial of potassium infusion with or without calcium reversal was conducted to test for improvement in intra-arrest VF waveform and post-ROSC hemodynamics. METHODS: Eighteen swine were randomized to three treatment arms in two phases. VF was electrically induced and untreated for 4min. The animals then received 6min of mechanical CPR. Blinded investigators infused two study medicines peripherally during this interval. One group received 1.5mEq/kg KCl with CPR initiation followed 3min later by CaCl 10% infusion 0.12cm(3)/kg, the second group received 1.5mEq/kg KCl without CaCl, and the third group received placebo infusions. Ten minutes post VF initiation, defibrillation was performed, as appropriate, followed by ACLS for continued arrest or observation for 30min if ROSC. AMSA change from before to 5min post study drug infusion was compared with nonparametric statistics. MAP post ROSC was compared using mixed linear regression analysis. RESULTS: Average normalized AMSA change was -0.15, -0.63, and +0.27 in the KCl, KCl+CaCl, and placebo groups, respectively (p=0.01). Three KCl+CaCl animals developed on organized rhythm chemically without electrical defibrillation. One, 3, and 4 animals in the KCl, KCl+CaCl, and placebo groups, respectively, survived post ROSC. Post ROSC, MAP decreased 1.8mmHg (95% CI -1.4 to 5.1) min(-1) less in the KCl+CaCl group compared to placebo. CONCLUSIONS: Chemical defibrillation and ROSC are possible post potassium-induced asystole. Potassium followed by calcium reversal, but not potassium alone, led to ROSC and post-ROSC hemodynamics comparable to recommended therapy.

Feasibility of Biosignal-guided Chest Compression During Cardiopulmonary Resuscitation: A Proof of Concept.

OBJECTIVES: Cardiac arrest is one of the leading causes of death in the United States and is treated by cardiopulmonary resuscitation (CPR). CPR involves both chest compressions and positive pressure ventilations when given by medical providers. Mechanical chest compression devices automate chest compressions and are beginning to be adopted by emergency medical services with the intent of providing high-quality, consistent chest compressions that are not limited by human providers who can become fatigued. Biosignals acquired from cardiac arrest patients have been characterized in their ability to track the effect of CPR on the patient. The authors investigated the feasibility and appropriate response of a biosignal-guided mechanical chest compression device in a swine model of cardiac arrest. METHODS: After a custom signal-guided chest compression device was engineered, its ability to respond to biosignal changes in a swine model of cardiac arrest was tested. In a preliminary series of six swine, two biosignals were used: mean arterial pressure (MAP) and a mathematical derivative of the electrocardiogram waveform, median slope (MS). How these biosignals changed was observed when chest compression rate and depth were adjusted by the signal-guided chest compression device, independent of the user. Chest compression rate and depth were adjusted by the signal-guided chest compression device according to a preset threshold algorithm until either of the biosignals improved to satisfy a set "threshold" or until the chest compression rate and depth achieved maximum values. Defibrillation was attempted at the end of each resuscitation in an effort to achieve return of spontaneous circulation (ROSC). RESULTS: The signal-guided chest compression device responded appropriately to biosignals by changing its rate and depth. All animals exhibited positive improvements in their biosignals. During the course of the resuscitation, three of the six animals improved their MS biosignal to reach the MS threshold, while two of the six animals improved their MAP biosignal to reach the MAP threshold. In the six experiments conducted, defibrillation was attempted on five animals, and two animals achieved ROSC. CONCLUSIONS: In this proof-of-concept study, a signal-guided chest compression device was demonstrated to be capable of responding to biosignal input and delivering chest compressions with a broad range of rates and depths.

Inaccuracy of patient care reports for identification of critical resuscitation events during out-of-hospital cardiac arrest.

OBJECTIVE: Out-of-hospital cardiac arrest (OHCA) is a leading cause of mortality in the United States. We sought to evaluate the accuracy of the patient care report (PCR) for detection of 2 clinically important events: return of spontaneous circulation (ROSC) and rearrest (RA). METHODS: We used defibrillator recordings and PCRs for Emergency Medical Services-treated OHCA collected by the Resuscitation Outcomes Consortium's Pittsburgh site from 2006 to 2008 and 2011 to 2012. Defibrillator data included electrocardiogram rhythm tracing, chest compression measurement, and audio voice recording. Sensitivity analysis was performed by comparing the accuracy of the PCR to detect the presence and number of ROSC and RA events to integrated defibrillator data. RESULTS: In the 158 OHCA cases, there were 163 ROSC events and 53 RA events. The sensitivity of PCRs to identify all ROSC events was 85% (confidence interval [CI], .795-.905); to identify primary ROSC events, it was 85% (CI, .793-.907); and to identify secondary ROSC events, it was 78% (CI, .565-.995). The sensitivity of PCRs to identify the presence of all RA events was .60 (CI, .469-.731); to identify primary RA events, it was 71% (CI, .578-.842); and to identify secondary RA events, it was 0. Of the 32 RA incidents captured by the PCR, only 15 (47%) correctly identified the correct lethal arrhythmia. CONCLUSIONS: We found that PCRs are not a reliable source of information for assessing the presence of ROSC and post-RA electrocardiogram rhythm. For quality control and research purposes, medical providers should consider augmenting data collection with continuous defibrillator recordings before making any conclusions about the occurrence of critical resuscitation events.

Incidence and outcomes of rearrest following out-of-hospital cardiac arrest.

INTRODUCTION: Rearrest occurs when a patient experiences cardiac arrest after successful resuscitation. The incidence and outcomes of rearrest following out-of-hospital cardiac arrest have been estimated in limited local studies. We sought provide a large-scale estimate of rearrest incidence and its effect on survival. METHODS: We obtained case data from emergency medical services-treated, out-of-hospital cardiac arrest from the Resuscitation Outcomes Consortium, a multi-site clinical research network with clinical centers in 11 regions in the US and Canada. The cohort comprised all cases captured between 2006 and 2008 at 10 of 11 regions with prehospital return of spontaneous circulation. We used three methods to ascertain rearrest via direct signal analysis, indirect signal analysis, and emergency department arrival vital status. Rearrest incidence was estimated as the proportion of cases with return of spontaneous circulation that experience rearrest. Regional rearrest incidence estimates were compared with the χ(2)-squared test. Multivariable logistic regression was used to assess the relationship between rearrest and survival to hospital discharge. RESULTS: Out of 18,937 emergency medical services-assessed cases captured between 2006 and 2008, 11,456 (60.5%) cases were treated by emergency medical services and 4396 (38.4%) had prehospital return of spontaneous circulation. Of these, rearrest ascertainment data was available in 3253 cases, with 568 (17.5%) experiencing rearrest. Rearrest differed by region (10.2% to 21.2%, p < 0.001). Rearrest was inversely associated with survival (OR: 0.19, 95% CI: 0.14-0.26). CONCLUSIONS: Rearrest was found to occur frequently after resuscitation and was inversely related to survival.

Extracorporeal life support during cardiac arrest resuscitation in a porcine model of ventricular fibrillation.

Implementation barriers for extracorporeal life support in out-of-hospital cardiac arrest (OHCA) include initiation delay and candidate selection. We explored ischemia duration, cardiopulmonary resuscitation (CPR) duration, and physiologic variables that discriminated animals with return of spontaneous circulation (ROSC). We instrumented eight female swine (31.9 +/- 9.8 kg) with femoral artery and external jugular vein cannula. After 8 (n = 4) or 15 (n = 4) minutes ventricular fibrillation (VF), animals received 30, 40, 50, or 60 minutes of CPR and then drugs (.6 U/kg vasopressin, .1 mg/kg epinephrine, .1 mg/kg propranolol, sodium bicarbonate as indicated) after 5 minutes of CPR. Extracorporeal membrane oxygenation (ECMO) flow rate was 3 L/min < or =2 hours and then 1.5 L/min < or =2 hours before weaning. Animals were defibrillated (150 J biphasic) > or =15 minutes ECMO. Primary outcome for successful resuscitation was ROSC (organized rhythm with systolic blood pressure >80 mmHg). We measured arterial blood gas, electrolytes, mean arterial pressure (MAP), coronary perfusion pressure (CPP), and five quantitative VF waveform measures at key intervals. Continuous variables were compared with two-sample t test. All 8-minute VF animals were successfully resuscitated and had ROSC. MAP was higher at the beginning (27.0 +/- 7.1 vs. 15.0 +/- 4.4; p = .03) and end (31.3 +/- 12.8 vs. 11.5 +/- 7.3; p = .03) of CPR in animals successfully resuscitated. CPP was higher at the beginning of CPR (11.9 +/- 4.6 vs. 3.3 +/- 2.2;p = .01) and the end of CPR (18.5 + 12.1 vs..9 +/- 1.4; p = .03) among animals with ROSC. Amplitude spectrum area (AMSA) was superior at the end of CPR (-2.0 +/- 1.8 vs. -5.0 +/- 1.4; p = .04) in animals successfully resuscitated. In a porcine OHCA model, MAP and CPP at the beginning and end of CPR were higher in animals successfully resuscitated. AMSA was superior at the end of CPR in animals successfully resuscitated.

Tissue oximetry by near-infrared spectroscopy in a porcine model of out-of-hospital cardiac arrest and resuscitation.

INTRODUCTION: Monitoring during resuscitation remains relatively crude. Near-infrared spectroscopy (NIRS) measures aggregate oxygen saturation in a volume of tissue. We assessed the utility of continuous StO2 measurement in a porcine model of cardiac arrest, and explored the effects of differential vasoconstriction on StO2. We hypothesized that (1) StO2 trends correspond with the onset of loss of pulses, resuscitation, and return of spontaneous circulation (ROSC); (2) epinephrine has a dose-dependent effect on StO2. METHODS: We anesthetized and instrumented 7 female swine, placing a NIRS probe on the left forelimb to recorded StO2. After 8 min of untreated VF and 2 min of CPR, we randomized animals to 0.015 mgkg(-1) (SDE) or 0.1mgkg(-1) (HDE) epinephrine. After 3 min of CPR, animals were defibrillated. Animals with ROSC were given SDE, then HDE for subsequent hemodynamic deteriorations. Data were analyzed with descriptive statistics and generalized linear model (alpha=0.05) to determine overall slope of pooled StO2 across animals for resuscitation segments. RESULTS: Four animals received HDE and three SDE. All achieved ROSC. Significant coefficients (ΔStO2 min(-1)) were noted for resuscitation segments. StO2 decreased after loss of pulses (-29.1; 95%CI -33.4, -24.7; p<0.01) but plateaued during CPR (-0.2; 95%CI -1.2, 0.8; p=0.71). There was a graded decline in StO2 between SDE (-1.3; 95%CI -1.5, -1.2; p<0.01) and HDE (-3.1; 95%CI -5.8, -0.4; p=0.03). The slowest change occurred with ROSC (0.4; 95%CI 0.3, 0.5; p<0.01). CONCLUSIONS: In a porcine model of OHCA, peripheral StO2 rapidly decreased after loss of pulses, but did not improve with CPR or epinephrine. It increased extremely slowly after ROSC.