Post-resuscitation myocardial microcirculatory dysfunction is ameliorated with eptifibatide

Background

The post-cardiac arrest syndrome includes a decline in myocardial microcirculation function. Inhibition of the platelet IIb/IIIa glycoprotein receptor has improved myocardial microvascular function post-percutaneous coronary intervention. Therefore, we evaluated such inhibition with eptifibatide for its effect on myocardial microcirculation function post-cardiac arrest and resuscitation.

Methods

Four groups of swine were studied in a prospective, randomized, blinded, placebo-controlled protocol including; eptifibatide administered during CPR (Group 1, n = 5), after resuscitation (Group 2, n = 4), during and after resuscitation (Group 3, n = 5), or placebo (Group 4, n = 10). CPR was initiated following 12 min of untreated VF. Those successfully resuscitated were studied during a 4-h post-resuscitation period. Coronary flow reserve, a measure of microcirculation function (in the absence of coronary obstruction), as well as parameters of left ventricular systolic and diastolic function, were measured pre-arrest and serially post-resuscitation.

Results

Coronary flow reserve was preserved during the post-resuscitation period, indicating normal microcirculatory function in the eptifibatide-treated animals, but not in the placebo-treated group. However, LV function declined equally in both groups during the first 4 h after cardiac arrest.

Conclusion

Inhibition of platelet IIb/IIIa glycoprotein receptors with eptifibatide post-resuscitation prevented myocardial microcirculation dysfunction. Left ventricular dysfunction post-resuscitation was not improved with eptifibatide, and perhaps transiently worse at 30 min post-resuscitation. Post-cardiac arrest ventricular dysfunction may require a multi-modality treatment strategy for successful prevention or amelioration.     

Intra-arrest selective brain cooling improves success of resuscitation in a porcine model of prolonged cardiac arrest

Aims of study

We have previously demonstrated that early intra-nasal cooling improved post-resuscitation neurological outcomes. The present study utilizing a porcine model of prolonged cardiac arrest investigated the effects of intra-nasal cooling initiated at the start of cardiopulmonary resuscitation (CPR) on resuscitation success. Our hypothesis was that rapid nasal cooling initiated during “low-flow” improves return of spontaneous resuscitation (ROSC).

Methods

In 16 domestic male pigs weighing 40 ± 3 kg, VF was electrically induced and untreated for 15 min. Animals were randomized to either head cooling or control. CPR was initiated and continued for 5 min before defibrillation was attempted. Coincident with starting CPR, the hypothermic group was cooled with a RhinoChill™ device which produces evaporative cooling in the nasal cavity of pigs. No cooling was administrated to control animals. If ROSC was not achieved after defibrillation, CPR was resumed for 1 min prior to the next defibrillation attempt until either successful resuscitation or for a total of 15 min.

Main results

Seven of eight animals in the hypothermic group (87.5%) and two of eight animals in control group (25%) (p = 0.04) were successfully resuscitated. At ROSC, brain temperature was increased from baseline by 0.3 °C in the control group, and decreased by 0.1 °C in the hypothermic animals. Pulmonary artery temperature was above baseline in both groups.

Conclusion

Intra-nasal cooling initiated at the start of CPR significantly improves the success of resuscitation in a porcine model of prolonged cardiac arrest. This may have occurred by preventing brain hyperthermia.     

Examining the contextual effects of neighborhood on out-of-hospital cardiac arrest and the provision of bystander cardiopulmonary resuscitation

Objective

To understand the association between neighborhood and individual characteristics in determining whether or not bystanders perform cardiopulmonary resuscitation (CPR) in cases of out-of-hospital cardiac arrest (OHCA).

Methods

Between October 1, 2005 to November 30, 2008, 1108 OHCA cases from Fulton County (Atlanta), GA, were eligible for bystander CPR. We conducted multi-level non-linear regression analysis and derived Empirical Bayes estimates for bystander CPR by census tract.

Results

279 (25%) cardiac arrest victims received bystander CPR. Provision of bystander CPR was significantly more common in witnessed events (odds ratio [OR] 1.64; 95% confidence interval [CI] 1.21-2.22, p < 0.001) and those that occurred in public locations (OR 1.67; 95% CI 1.16-2.40, p < 0.001). Other individual-level characteristics were not significantly associated with bystander CPR. Cardiac arrests in the census tracts that rank in the highest income quintile, as compared to the lowest income quintile were much more likely (OR 4.98; 95% CI 1.65-15.04) to receive bystander CPR.

Conclusion

Cardiac arrest victims in the highest income census tracts were much more likely to receive bystander CPR than in the lowest income census tracts, even after controlling for individual and arrest characteristics. Low-income neighborhoods may be particularly appropriate targets for community-based CPR training and awareness efforts.     

Early selective trans-nasal cooling during CPR improves success of resuscitation in a porcine model of prolonged pulseless electrical activity cardiac arrest

Aim of study

In the present study, we investigated trans-nasal cooling in settings of pulseless electrical activity (PEA). We hypothesized that early trans-nasal cooling during CPR improves outcomes when cardiac arrest is associated with PEA.

Methods

Ventricular fibrillation (VF) was electrically induced in 16 domestic male pigs weighing 40 ± 3 kg. After 14 min of untreated VF, PEA was induced following delivery of one or more electrical shocks. One min after onset of PEA, CPR was started, including chest compression and ventilation. Each animal received 5 min of CPR prior to defibrillation attempt. CPR and resuscitation efforts were discontinued at 15 min unless return to spontaneous circulation was achieved. In 8 animals, selective trans-nasal cooling was begun coincident with start of CPR and 8 randomized controls were identically treated except for trans-nasal cooling. Mean aortic pressure was continuously measured together with aortic and right atrial pressure and nasal, body and right jugular vein temperatures. Coronary perfusion pressure (CPP) was computed from measured data.

Results

Six of eight animals were resuscitated after early trans-nasal cooling, while only one untreated control was resuscitated (p = 0.012). Nasal, body and jugular vein temperatures decreased after cooling. At PC (precordial compression) 5 min, the cooled group recorded a higher CPP (25 ± 5 mmHg) than the non-cooled group (15 ± 4 mmHg, p = 0.001).

Conclusion

When selective trans-nasal cooling was initiated during CPR in the animal model of prolonged cardiac arrest with PEA, CPP was higher and the likelihood of return of spontaneous circulation was improved.     

Comparison of the efficacy of nifekalant and amiodarone in a porcine model of cardiac arrest

Objective

To compare the efficacy of nifekalant and amiodarone in the treatment of cardiac arrest in a porcine model.

Methods

After 4 min of untreated ventricular fibrillation, animals were randomly treated with nifekalant (2 mg kg⁻¹), amiodarone (5 mg kg⁻¹) or saline placebo (n = 12 pigs per group). Precordial compression and ventilation were initiated after drug administration and defibrillation was attempted 2 min later. Hemodynamics were continuously measured for 6 h after successful resuscitation.

Results

Compared with saline, nifekalant and amiodarone equally decreased the number of electric shocks, defibrillation energy, epinephrine dose, and duration of cardiopulmonary resuscitation required for successful resuscitation (P < 0.01). The incidence of restoration of spontaneous circulation (ROSC) and the 24-h survival rate were higher in both antiarrhythmic drug groups (P < 0.05) vs. the saline group. Furthermore, post-resuscitation myocardial dysfunction at 4-6 h after successful resuscitation was improved in animals given antiarrhythmic drugs as compared with the saline group (P < 0.05). There were no differences between nifekalant and amiodarone for any of these parameters.

Conclusion

The effect of nifekalant was similar to that of amiodarone for improving defibrillation efficacy and for the treatment of cardiac arrest. Administration of either nifekalant or amiodarone before defibrillation increased the ROSC and 24-h survival rates and improved post-resuscitation cardiac function in this porcine model.     

Neurologic prognostication and bispectral index monitoring after resuscitation from cardiac arrest

Objective

While the use of therapeutic hypothermia (TH) has improved outcomes after resuscitation from cardiac arrest, prognostication of survival and neurologic function remains difficult during the post-arrest time period. Bispectral index (BIS) monitoring, a non-invasive measurement of simplified electroencephalographic data, is increasingly being considered for post-arrest neurologic assessment and outcomes prediction, although data supporting the technique are limited. We hypothesized that BIS values within 24 h after resuscitation would correlate with neurologic outcomes at discharge.

Methods

We prospectively collected BIS data in consecutive patients initially resuscitated from cardiac arrest and treated with TH in one academic medical center. We assessed BIS values in context of cerebral performance category (CPC) assessment on the day of discharge.

Results

Data were collected in 62 post-arrest patients, of whom 26/62 (42%) survived to hospital discharge. Mean BIS values at 24 h post-resuscitation were significantly different in the survivors with CPC 1-2 (“good” outcome) vs those with CPC 3-5 (“poor” outcome) or death during hospitalization (49 ± 13 vs 30 ± 20; p < 0.001). Receiver operator characteristic analysis suggested that 24 h BIS was most predictive of CPC 1-2 outcome compared to the other timepoints; a BIS cutpoint of 45 exhibited a sensitivity of 63% and a specificity of 86%, with a positive likelihood ratio of 4.67. Sixteen patients exhibited a BIS of zero during at least one timepoint; all of these patients died during hospitalization.

Conclusions

BIS monitoring values at 24 h post-resuscitation are correlated with neurologic outcomes in patients undergoing TH treatment. In 16/62 patients, a BIS of zero at any timepoint was observed, which was uniformly correlated with poor outcome after resuscitation from cardiac arrest; however, a non-zero BIS is insufficient as a sole predictor of good neurologic survival.     

Cariporide given during resuscitation promotes return of electrically stable and mechanically competent cardiac activity

Episodes of ventricular fibrillation (VF) and myocardial dysfunction commonly occur after cardiac resuscitation compromising the return of stable circulation. We investigated in a pig model of VF whether limiting Na⁺-induced cytosolic Ca²⁺ overload using the sarcolemmal sodium-hydrogen exchanger isoform-1 (NHE-1) inhibitor cariporide promotes resuscitation with stable circulation.

Methods

VF was electrically induced in 20 male pigs and left untreated for 6 min after which CPR was initiated and continued for 8 min before attempting defibrillation. Pigs were randomized to receive 3-mg/kg cariporide (n = 10) or 0.9%-NaCl (n = 10) before chest compression.

Results

Seven of 10 pigs in each group were successfully resuscitated and survived 2 h. Cariporide ameliorated post-resuscitation ventricular ectopic activity such that fewer singlets (5 ± 5 vs. 26 ± 21; p < 0.05) and fewer bigemini (1 ± 3 vs. 33 ± 25; p < 0.05) were observed during the initial 5 min post-resuscitation. Additionally, cariporide-treated pigs did not require additional post-resuscitation shocks for ventricular tachycardia or recurrent VF (0.0 ± 0.0 vs. 5.3 ± 7.8 shocks; p = 0.073). During the initial 60 min cariporide-treated pigs had higher, cardiac index (6.1 ± 0.7 vs. 4.4 ± 1.1 L/min/m²; p < 0.01), left ventricular stroke work index (45 ± 9 vs. 36 ± 10 gm m/beat/m²; p < 0.05), and numerically higher mean aortic pressure (104 ± 11 vs. 91 ± 12 mmHg; p = 0.054).

Conclusion

Cariporide administered at the start of chest compression may help restore electrically and mechanically stable circulation after resuscitation from cardiac arrest.     

Hypocalcemia following resuscitation from cardiac arrest revisited

Objective

Hypocalcemia associated with cardiac arrest has been reported. However, mechanistic hypotheses for the decrease in ionized calcium (iCa) vary and its importance unknown. The objective of this study was to assess the relationships of iCa, pH, base excess (BE), and lactate in two porcine cardiac arrest models, and to determine the effect of exogenous calcium administration on post-resuscitation hemodynamics.

Methods

Swine were instrumented and VF was induced either electrically (EVF, n = 65) or spontaneously, ischemically induced (IVF) with balloon occlusion of the LAD (n = 37). Animals were resuscitated after 7 min of VF. BE, iCa, and pH, were determined prearrest and at 15, 30, 60, 90, 120 min after ROSC. Lactate was also measured in 26 animals in the EVF group. Twelve EVF animals were randomized to receive 1 g of CaCl₂ infused over 20 min after ROSC or normal saline.

Results

iCa, BE, and pH declined significantly over the 60 min following ROSC, regardless of VF type, with the lowest levels observed at the nadir of left ventricular stroke work post-resuscitation. Lactate was strongly correlated with BE (r = −0.89, p < 0.0001) and iCa (r = −0.40, p < 0.0001). In a multivariate generalized linear mixed model, iCa was 0.005 mg/dL higher for every one unit increase in BE (95% CI 0.003-0.007, p < 0.0001), while controlling for type of induced VF. While there was a univariate correlation between iCa and BE, when BE was included in the regression analysis with lactate, only lactate showed a statistically significant relationship with iCa (p = 0.02). Post-resuscitation CaCl₂ infusion improved post-ROSC hemodynamics when compared to saline infusion (LV stroke work control 8 ± 5 g m vs 23 ± 4, p = 0.014, at 30 min) with no significant difference in tau between groups.

Conclusions

Ionized hypocalcemia occurs following ROSC. CaCl₂ improves post-ROSC hemodynamics suggesting that hypocalcemia may play a role in early post-resuscitation myocardial dysfunction.     

Improving outcome after out-of-hospital cardiac arrest by strengthening weak links of the local Chain of Survival; quality of advanced life support and post-resuscitation care

Background

Survival after out-of-hospital cardiac arrest (OHCA) depends on a well functioning Chain of Survival. We wanted to assess if targeted attempts to strengthen the weak links of our local chain; quality of advanced life support (ALS) and post-resuscitation care, would improve outcome.

Materials and methods

Utstein data from all OHCAs in Oslo during three distinct 2-year time periods 1996-1998, 2001-2003 and 2004-2005 were collected. Before the second period the local ALS guidelines changed with increased focus on good quality chest compressions with minimal pauses, while standardized post-resuscitation care including goal directed therapy with therapeutic hypothermia and percutaneous coronary intervention was added in the third period. Additional a priori sub-group analyses of arrests with cardiac aetiology as well as bystander witnessed ventricular fibrillation/tachycardia (VF/VT) arrests with cardiac aetiology were performed.

Results

ALS was attempted in 454, 449, and 417 patients with OHCA in the first, second and last time period, respectively. From the first to the third period VF/VT arrests declined (40% vs. 33%, p = 0.039) and fewer arrests were witnessed (80% vs. 72%, p = 0.022) and response intervals increased (7 ± 4 to 9 ± 4 min, p < 0.001). Overall survival increased from 7% (first period) to 13% (last period), p = 0.002, and survival in the sub-group of bystander witnessed VF/VT arrests with cardiac aetiology increased from 15% (first period) to 35% (last period), p = 0.001.

Conclusions

Survival after OHCA was increased after improving weak links of our local Chain of Survival, quality of ALS and post-resuscitation care.     

Survival Increases with CPR by Emergency Medical Services before defibrillation of out-of-hospital ventricular fibrillation or ventricular tachycardia: Observations from the Resuscitation Outcomes Consortium

Background

Immediate defibrillation is the traditional approach to resuscitation of cardiac arrest due to ventricular fibrillation or tachycardia (VF/VT). Delaying defibrillation to provide chest compressions may improve survival. We examined the effect of the duration of Emergency Medical Services (EMS) cardiopulmonary resuscitation (CPR) prior to first defibrillation on survival in patients with out-of-hospital VF/VT.

Materials and methods

From a prospective multi-center observational registry of EMS-treated out-of-hospital cardiac arrest, we identified 1638 EMS-treated cardiac arrests with first recorded rhythm VF/VT or “shockable” and complete data for analysis. Survival to hospital discharge was determined as a function of EMS CPR duration prior to first shock.

Results

Compared to the reference group of first EMS CPR duration ≤45 s, the odds of survival was greater among patients who received between 46 and 195 s of EMS CPR before first shock (46-75 s odds ratio [OR] 1.15, 95% confidence interval [CI] 0.71-1.87; 76-105 s, OR 1.37, 95% CI 0.80-2.35; 106-135 s, OR 1.53, 95% CI 0.96-2.45; 136-165 s, OR 1.24, 95% CI 0.71-2.15; 166-195 s, OR 1.47, 95% CI 0.85-2.52). The benefit of EMS CPR before defibrillation was reduced when the duration of CPR exceeded 195 s (196-225 s, OR 0.95, 95% CI 0.47-1.81; 226-255 s, OR 0.91, 95% CI 0.46-1.79; 256-285 s, OR 0.46, 95% CI 0.17-1.29; 286-315 s, OR 1.29, 95% CI 0.59-2.85). An optimal EMS CPR duration was not identified and no duration achieved statistical significance.

Conclusion

In this observational analysis of VF/VT arrest, between 46 and 195 s of EMS CPR prior to defibrillation was weakly associated with improved survival compared to ≤45 s. Randomized trials are needed to confirm the optimal duration of EMS CPR prior to defibrillation and to assess the impact of first CPR duration on all initial rhythms.     

Feasibility of initiating extracorporeal life support during mechanical chest compression CPR: a porcine pilot study

Background

Recently, portable extracorporeal membrane oxygenation (ECMO) machines have become commercially available. This creates the potential to utilize extracorporeal life support (ECLS) for the treatment of sudden cardiac arrest in the emergency department, and potentially in the out-of-hospital setting.

Objective

We sought to determine the feasibility of installing the ECMO circuit during delivery of mechanical chest compression CPR.

Methods

We used 5 mixed-breed domestic swine with a mean mass of 26.0 kg. After induction of anesthesia, animals were instrumented with micromanometer-tipped transducers placed in the aorta and right atrium via the left femoral artery and vein. Ventricular fibrillation (VF) was induced electrically with a transthoracic shock and left untreated for 8 min. Then, mechanical chest compressions were begun (LUCAS, Jolife, Lund, Sweden) and manual ventilations were performed to maintain ETCO₂ between 35 and 45 Torr. Compressions continued until ECMO flow was started. Ten minutes after induction of VF, drugs were given (epinephrine, vasopressin, and propranolol). ECMO installation was started via cutdown on the right external jugular vein and right femoral artery for placement of venous and arterial catheters while chest compressions continued. ECMO installation start time varied from 17 to 30 min after start of compressions and continued until ECG indicated a shockable rhythm. First rescue shocks were given at 22, 32, 35, 44, and 65 min.

Results

ECMO was successfully installed in all five animals without incident. It was necessary to briefly discontinue chest compressions during the most delicate part of inserting the catheters into the vessels. ECMO also allowed for very rapid cooling of the animals and facilitated post-resuscitation hemodynamic support. Only the 65-min animal did not attain return of spontaneous circulation (ROSC).

Conclusion

Mechanical chest compression may be a suitable therapeutic bridge to the installation of ECMO and does not interfere with ECMO catheter placement.     

Effect of cardiopulmonary resuscitation on restoration of myocardial ATP in prolonged ventricular fibrillation

Background

There has been controversy over whether a short period of cardiopulmonary resuscitation (CPR) prior to defibrillation improves survival in patients who experienced a sudden cardiac arrest. However, there have been no reports about whether CPR restores the myocardial energy source during prolonged ventricular fibrillation (VF). The aim of this study is to investigate the effect of CPR in restoring myocardial high energy phosphates during prolonged VF.

Methods and results

Seventy-two adult male Sprague-Dawley rats were used in this study. Baseline adenosine triphosphate (ATP) and adenosine diphosphate (ADP) prior to induction of VF were measured in nine rats, the No-VF group. Sixty-three rats were subjected to 4 min of untreated VF. Animals were then randomized into two groups: No-CPR (n = 37) and CPR (n = 26). In the No-CPR group, ATPs and ADPs were measured at 4 min (No-CPR4), 6 min (No-CPR6), 8 min (No-CPR8) or 10 min (No-CPR10) after the induction of VF. The CPR group received 2 min (CPR2), 4 min (CPR4) or 6 min (CPR6) of mechanical chest compressions before ATP was measured.Myocardial ATP (nmol/mg protein) was decreased as VF duration was prolonged (No-VF: 5.49 ± 1.71, No-CPR4: 4.27 ± 1.58, No-CPR6: 4.13 ± 1.31, No-CPR8: 3.77 ± 1.42, No-CPR10: 3.52 ± 0.90, p < 0.05 between each of No-CPRs vs. No-VF). Two minutes of CPR restored myocardial ATP to the level of No-VF group (5.27 ± 1.67 nmol/mg protein in CPR2, p > 0.05 vs. No-VF group). However, myocardial ATP (nmol/mg protein) decreased if the duration of CPR was longer than 2 min (CPR4: 3.77 ± 1.05, CPR6: 3.49 ± 1.08, p < 0.05 between CPR4 and CPR6 vs. No-VF).

Conclusions

CPR for 2 min helps to maintain myocardial ATP after prolonged VF.     

Comparing the survival between extracorporeal rescue and conventional resuscitation in adult in-hospital cardiac arrests: Propensity analysis of three-year data

Aim

Extracorporeal cardiopulmonary resuscitation (ECPR) has been shown to have survival benefit over conventional CPR (CCPR) in patients with in-hospital cardiac arrest of cardiac origin. We compared the survival of patients who had return of spontaneous beating (ROSB) after ECPR with the survival of those who had return of spontaneous circulation (ROSC) after conventional CPR.

Methods

Propensity score-matched cohort of adults with in-hospital prolonged CPR (>10 min) of cardiac origin in a university-affiliated tertiary extracorporeal resuscitation center were included in this study. Fifty-nine patients with ROSB after ECPR and 63 patients with sustained ROSC by CCPR were analyzed. Main outcome measures were survival at hospital discharge, 30 days, 6 months, and one year, and neurological outcome.

Results

There was no statistical difference in survival to discharge (29.1% of ECPR responders vs. 22.2% of CCPR responders, p = 0.394) and neurological outcome at discharge and one year later. In the propensity score-matched groups, 9 out of 27 ECPR patients survived to one month (33.3%) and 7 out of 27 CCPR patients survived (25.9%). Survival analysis showed no survival difference (HR: 0.856, p = 0.634, 95% CI: 0.453-1.620) between the groups, either at 30 days or at the end of one year (HR: 0.602, p = 0.093, 95% CI: 0.333-1.088).

Conclusions

This study failed to demonstrate a survival difference between patients who had ROSB after institution of ECMO and those who had ROSC after conventional CPR. Further studies evaluating the role of ECMO in conventional CPR rescued patients are warranted.     

Clinical predictors of survival in patients treated with therapeutic hypothermia following cardiac arrest

Introduction

Therapeutic hypothermia has been shown to provide neuroprotection and improved survival in patients suffering a cardiac arrest. We report outcomes of consecutive patients receiving therapeutic hypothermia for cardiac arrest and describe predictors of short and long-term survival.

Methods

Eighty patients receiving therapeutic hypothermia between January 2005 and December 2008 were identified and categorized as those who survived and died. Outcomes and predictors of survival were determined.

Results

Forty-five patients (56%) survived to hospital discharge and were alive at 30 days and among survivors 41 (91%) were alive 1 year after discharge. Survivors were younger, were more likely to present with VF, required less epinephrine during resuscitation, were more likely to have preserved renal function, and were less likely to be taking beta-blockers and ACE inhibitors. Predictors of survival included VF on presentation (OR 14.9, CI 2.7-83.2, p = 0.002), pre-cardiac arrest aspirin use (OR 9.7, CI 1.6-61.1, p = 0.02), return of spontaneous circulation <20 min (OR 9.4, CI 2.2-41.1, p = 0.003), absence of coronary artery disease (OR 5.3, CI 1.1-24.7, p = 0.002) and preserved renal function.

Conclusion

Therapeutic hypothermia is useful in the treatment of patients suffering a cardiac arrest. Several clinical factors may aid in predicting patients who are likely to survive after a cardiac arrest.     

Does prearrest adrenergic integrity affect pressor response? A comparison of epinephrine and vasopressin in a spontaneous ventricular fibrillation swine model

Objectives

Coronary perfusion pressure (CPP) during resuscitation from cardiac arrest has been shown to correlate with return of spontaneous circulation. Adrenergic blockade of beta-1 and alpha-1 receptors is common in the long-term management of ischemic heart disease and congestive heart failure. We sought to compare the CPP response to vasopressin vs. epinephrine in a swine model of cardiac arrest following pre-arrest adrenergic blockade.

Methods

Eight anesthetized and instrumented swine were administered 0.1 mg epinephrine and arterial pressure and heart rate response were measured. An infusion of labetalol was then initiated and animals periodically challenged with epinephrine until adrenergic blockade was confirmed. The left anterior descending coronary artery was occluded to produce ventricular fibrillation (VF). After 7 min of untreated VF, mechanical chest compressions were initiated. After 1 min of compressions, 1 mg epinephrine was given while CPP was recorded. When CPP values had returned to pre-epinephrine levels, 40 U of bolus vasopressin was given. Differences in CPP (post-vasopressor-pre-vasopressor) were compared within animals for the epinephrine and vasopressin response and with eight, non-adrenergically blocked, historical controls using Bayesian statistics with a non-informative prior.

Results

The CPP response following epinephrine was 15.1 mmHg lower in adrenergically blocked animals compared to non-adrenergically blocked animals (95% Highest Posterior Density [HPD] 2.9-27.2 mmHg lower). CPP went up 18.4 mmHg more following vasopressin when compared to epinephrine (95% HPD 8.2-29.1 mmHg). The posterior probability of a higher CPP response from vasopressin (vs. epinephrine) in these animals was 0.999.

Conclusions

Pre-arrest adrenergic blockade blunts the CPP response to epinephrine. Superior augmentation of CPP is attained with vasopressin under these conditions.     

Potassium induced cardiac standstill during conventional cardiopulmonary resuscitation in a pig model of prolonged ventricular fibrillation cardiac arrest: A feasibility study

Aim of the study

Potassium-based cardioplegia has been the gold standard for cardioprotection during cardiac surgery. We sought to evaluate the feasibility and the effects of potassium-induced cardiac standstill during conventional cardiopulmonary resuscitation (CPR) in a pig model of prolonged ventricular fibrillation (VF).

Methods

VF was induced in 20 pigs, and circulatory arrest was maintained for 14 min. Animals were then resuscitated by standard CPR. Coincident with the start of CPR, 20 ml of saline (control group) or 0.9 mequiv. kg⁻¹ of potassium chloride diluted to 20 ml (potassium group) was administered into right atrium.

Results

Administration of potassium resulted in asystole lasting for 1.0 min (0.2) in the potassium group animals. VF reappeared in all but one animal, in which wide QRS complex bradycardia followed. Restoration of spontaneous circulation (ROSC) was attained in two animals (20%) in the control group and in seven animals (70%) in the potassium group (p = 0.070). Resuscitated animals in the potassium group required fewer countershocks (3, 4 vs. 2 (1–2)), smaller doses of adrenaline (1.84, 1.84 vs. 0.94 (0.90–1.00) mg), and shorter duration of CPR (8, 10 vs. 4.0 (4.0–4.0) min) than did the control group. Potassium concentrations normalised rapidly after ROSC in both groups, and the potassium concentrations at 5 min (5.5, 6.6 vs. 6.8 (6.5–7.8) mequiv. l⁻¹) and 4 h (4.9, 5.4 vs. 5.9 (5.1–6.4) mequiv. l⁻¹) after ROSC were similar in the both groups.

Conclusion

In a pig model of untreated VF cardiac arrest for 14 min, resuscitation with potassium-induced cardiac standstill during conventional CPR was found to be feasible.     

Post-resuscitation intestinal microcirculation: Its relationship with sublingual microcirculation and the severity of post-resuscitation syndrome

Objective

Post-resuscitation syndrome has been recognized as one of the major causes of the poor outcomes of cardiopulmonary resuscitation. The aims of this study were to investigate the intestinal microcirculatory changes following cardiopulmonary resuscitation and relate those changes to sublingual microcirculation and the severity of post-resuscitation syndrome as measured by myocardial function and serum inflammatory cytokine levels.

Methods

Twenty-five rats were randomized into three groups: (1) short duration of cardiac arrest (n = 10): ventricular fibrillation (VF) was untreated for 4 min prior to 6 min of cardiopulmonary resuscitation (CPR); (2) long duration of cardiac arrest (n = 10): VF was untreated for 8 min followed by 8 min of CPR; (3) sham control group (n = 5): a sham operation was performed without VF induction and CPR. Intestinal and sublingual microcirculatory blood flow was visualized by a sidestream dark-field (SDF) imaging device at baseline and 1, 2, 4, 6, 8 h post-resuscitation. Myocardial function was measured by echocardiography and serum cytokine levels (TNF-α and IL-6) were measured by enzyme-linked immunosorbent assay (ELISA).

Results

Both intestinal and sublingual microcirculatory blood flow decreased significantly with increasing duration of cardiac arrest and resuscitation. The decreases in intestinal microcirculatory blood flow were closely correlated with the reductions of sublingual microcirculatory blood flow (perfused small vessels density: r = 0.772, p < 0.01; microcirculatory flow index: r = 0.821, p < 0.01). The decreased microcirculatory blood flow was closely correlated with weakened myocardial function and elevated inflammatory cytokine levels.

Conclusions

The severity of post-resuscitation intestinal microcirculatory dysfunction is closely correlated with that of myocardial function and inflammatory cytokine levels. The measurement of sublingual microcirculation reflects changes of intestinal microcirculation and may therefore provide a new option for post-resuscitation monitoring.     

Association between deprivation status at community level and outcomes from out-of-hospital cardiac arrest: a nationwide observational study

Study objectives

We sought to examine the association between area deprivation and outcomes of out-of-hospital cardiac arrest in Korea.

Methods

Data were obtained from the emergency medical service (EMS) system. A nationwide OHCA cohort database from January2006 to December 2007 was constructed via hospital chart review and ambulance run sheet data. We enrolled all EMS-assessed OHCA victims and excluded cases without available hospital outcome data or residential address. The Carstairs index was used to categorize districts according to level of deprivation into five quintiles, from (Q1, the least deprived) to (Q5, the most deprived). Main outcomes were survival to hospital discharge, survival to admission, and return of spontaneous circulation (ROSC).

Results

34,227 patients were included. Initial rhythm, witnessed status, attempted bystander cardiopulmonary resuscitation (CPR), CPR by EMS, CPR in the emergency department (ED), and elapsed time interval significantly varied according to area deprivation level (p < 0.001). OHCA outcomes were consistently worse in the most deprived areas. The adjusted OR (95% CI) for survival to hospital discharge was 0.58 (0.45-0.77) in the most deprived areas compared to the least deprived areas.

Conclusion

Community deprivation was strongly associated with survival among out-of-hospital cardiac arrest patients in Korea.     

Early kynurenine pathway activation following cardiac arrest in rats,pigs, and humans

Aim of the study

Kynurenine pathway (KP) is a major route of the tryptophan (TRP) catabolism. In the present study, TRP and KP metabolites concentrations were measured in plasma from rats, pigs and humans after cardiac arrest (CA) in order to assess KP activation and its potential role in post-resuscitation outcome.

Methods

Plasma was obtained from: (A) 24 rats, subjected to 6 min CA and 6 min of cardiopulmonary resuscitation (CPR); (B) 10 pigs, subjected to 10 min CA and 5 min CPR; and (C) 3 healthy human volunteers and 5 patients resuscitated from CA. KP metabolites were quantified by liquid chromatography multiple reaction monitoring mass spectrometry. Assessments were available at baseline, and 1–4 h, and 3–5 days post-CA.

Results

KP was activated after CA in rats, pigs, and humans. Decreases in TRP occurred during the post-resuscitation period and were accompanied by significant increases in its major metabolites, 3-hydroxyanthranilic acid (3-HAA) and kynurenic acid in each species, that persisted up to 3–5 days post-CA (p < 0.01). In rats, changes in KP metabolites reflected changes in post-resuscitation myocardial function. In pigs, changes in TRP and increases in 3-HAA were significanlty related to the severity of cerebral histopathogical injuries. In humans, KP activation was observed, together with systemic inflammation. Post-CA increases in 3-HAA were greater in patients that did not survive.

Conclusion

In this fully translational investigation, the KP was activated early following resuscitation from CA in rats, pigs, and humans, and might have contributed to post-resuscitation outcome.