Bundled postconditioning therapies improve hemodynamics and neurologic recovery after 17 min of untreated cardiac arrest

ObjectiveIschemic postconditioning (stutter CPR) and sevoflurane have been shown to mitigate the effects of reperfusion injury in cardiac tissue after 15 min of ventricular fibrillation (VF) cardiac arrest. Poloxamer 188 (P188) has also proven beneficial to neuronal and cardiac tissue during reperfusion injury in human and animal models. We hypothesized that the use of stutter CPR, sevoflurane, and P188 combined with standard advanced life support would improve post-resuscitation cardiac and neurologic function after prolonged VF arrest.MethodsFollowing 17 min of untreated VF, 20 pigs were randomized to Control treatment with active compression/decompression (ACD) CPR and impedance threshold device (ITD) (n = 8) or Bundle therapy with stutter ACD CPR + ITD + sevoflurane + P188 (n = 12). Epinephrine and post-resuscitation hypothermia were given in both groups per standard protocol. Animals that achieved return of spontaneous circulation (ROSC) were evaluated with echocardiography, biomarkers, and a blinded neurologic assessment with a cerebral performance category score.ResultsBundle therapy improved hemodynamics during resuscitation, reduced need for epinephrine and repeated defibrillation, reduced biomarkers of cardiac injury and end-organ dysfunction, and increased left ventricular ejection fraction compared to Controls. Bundle therapy also improved rates of ROSC (100% vs. 50%), freedom from major adverse events (50% vs. 0% at 48 h), and neurologic function (42% with mild or no neurologic deficit and 17% achieving normal function at 48 h).ConclusionsBundle therapy with a combination of stutter ACD CPR, ITD, sevoflurane, and P188 improved cardiac and neurologic function after 17 min of untreated cardiac arrest in pigs.All studies were performed with approval from the Institutional Animal Care Committee of the Minneapolis Medical Research Foundation (protocol #12-11).     

Delayed and intermittent CPR for severe accidental hypothermia

IntroductionCardiac arrest (CA) in patients with severe accidental hypothermia (core temperature <28 °C) differs from CA in normothermic patients. Maintaining CPR throughout the prehospital period may be impossible, particularly during difficult evacuations. We have developed guidelines for rescuers who are evacuating and treating severely hypothermic CA patients.MethodsA literature search was performed. The authors used the findings to develop guidelines.ResultsFull neurological recovery is possible even with prolonged CA if the brain was already severely hypothermic before CA occurred. Data from surgery during deep hypothermic CA and prehospital case reports underline the feasibility of delayed and intermittent CPR in patients who have arrested due to severe hypothermia.ConclusionsContinuous CPR is recommended for CA due to primary severe hypothermia. Mechanical chest-compression devices should be used when available and CPR-interruptions avoided. Only if this is not possible should CPR be delayed or performed intermittently. Based on the available data, a patient with a core temperature <28 °C or unknown with unequivocal hypothermic CA, evidence supports alternating 5 min CPR and ≤5 min without CPR. With core temperature <20 °C, evidence supports alternating 5 min CPR and ≤10 min without CPR.     

Cerebral energy failure following experimental cardiac arrest: Hypothermia treatment reduces secondary lactate/pyruvate-ratio increase

AimThis was an experimental study performed to investigate cerebral metabolism during hypothermia treatment and rewarming after resuscitation from cardiac arrest (CA).Materials and methodsSixteen pigs underwent CA followed by cardiopulmonary resuscitation (CPR). After randomisation into one hypothermic (n = 8) and one normothermic group (n = 8) the animals received infusion of 4 or 38 °C saline, respectively. Following restoration of spontaneous circulation (ROSC) both groups were observed for 360 min. The hypothermic group was cooled for 180 min and then rewarmed. Temperature was not modulated in the normothermic group.Cerebral microdialysis was conducted and lactate/pyruvate (L/P)-ratio and glutamate were analysed. Intracranial pressure probe was inserted. Oxygen saturation in venous jugular bulb blood (SjO₂) was analysed.ResultsAll animals initially had increased L/P-ratio (>30). A total of nine animals developed secondary increase. In the hypothermic group this was observed in 2/7 animals and in the normothermic group in 7/8 (p = 0.04). Glutamate increased initially in all animals with secondary increases in two animals in each group. No differences in L/P-ratio or glutamate were detected during the rewarming phase compared to the hypothermic phase. The hypothermic group had higher SjO₂ (p = 0.04). In both groups intracranial pressure increased after ROSC.ConclusionAfter resuscitation from CA there was a risk of cerebral secondary energy failure (reflected as an increased L/P-ratio) but hypothermia treatment seemed to counteract this effect. Cerebral oxygen extraction, measured by SjO_2, was increased in the hypothermic group probably due to reduced metabolism. Rewarming did not reveal any obvious harmful events.     

Oxygen requirement during cardiopulmonary resuscitation (CPR) to effect return of spontaneous circulation

BackgroundRecent scientific evidence has demonstrated the importance of good quality chest compressions without interruption to improve cardiac arrest resuscitation rates, and suggested that a de-emphasis on minute ventilation is needed. However, independent of ventilation, the role of oxygen and the optimal oxygen concentration during CPR is not known. Previous studies have shown that ventilation with high oxygen concentration after CPR is associated with worse neurologic outcome. We tested the hypothesis that initial ventilation during CPR without oxygen improves resuscitation success.MethodsSprague–Dawley rats were anesthetized with ketamine/xylazine (IP), intubated and ventilated with room air. A KCl bolus (0.04 mg/g) was given (IV) to induce asystolic cardiac arrest and ventilation was stopped. At 6 min, CPR was started with an automated chest compressor at a rate of 200–240/min and epinephrine (0.01 mg/kg) was given 1 min later. During CPR, the ventilation rate was 50% of baseline with one of three oxygen concentrations: (1) 0% O₂ (100% N₂), (2) 21% O₂, or (3) 100% O₂. The prescribed oxygen concentration was continued for 2 min after return of spontaneous circulation (ROSC) and then all animals were switched to 100% oxygen for 1 h prior to extubation. Blood gases were measured at baseline, 2 min and 1 h after ROSC. Group comparisons were done using Fisher's exact test and ANOVA.ResultsROSC was achieved in 1/10 (0% O₂), 9/11 (21% O₂) and 10/12 (100% O₂, p < 0.001). ROSC times after starting CPR were 80 s in the 0% O₂, 115 ± 87 s in the 21% O₂ group and 95 ± 33 s in the 100% O₂ group (mean ± SD, p = 0.5). Aortic end-diastolic pressure before ROSC was not different among groups. 100% oxygen ventilation in the first 2 min resulted in higher PaO₂ at ROSC 2 min (109 ± 44 mm Hg vs. 33 ± 8 mm Hg, p < 0.001). Survival to 72 h was 0/1 (0% O₂), 7/9 (21% O₂) and 8/10 (100% O₂) with a low neurologic deficit score in both O₂ groups (NDS range 5–25).ConclusionsIn a mild cardiac arrest model with generally good neurologic recovery, initial CPR ventilation with no O₂ did not allow for ROSC. In contrast, CPR coupled with room air or higher oxygen levels result in a high rate of ROSC with good neurologic recovery. During CPR, the level of oxygenation must be considered, which if too low may preclude initial ROSC.     

Total liquid ventilation offers ultra-fast and whole-body cooling in large animals in physiological conditions and during cardiac arrest

IntroductionTotal liquid ventilation (TLV) can cool down the entire body within 10–15 min in small animals. Our goal was to determine whether it could also induce ultra-fast and whole-body cooling in large animals using a specifically dedicated liquid ventilator. Cooling efficiency was evaluated under physiological conditions (beating-heart) and during cardiac arrest with automated chest compressions (CC, intra-arrest).MethodsIn a first set of experiments, beating-heart pigs were randomly submitted to conventional mechanical ventilation or hypothermic TLV with perfluoro-N-octane (between 15 and 32 °C). In a second set of experiments, pigs were submitted to ventricular fibrillation and CC. One group underwent continuous CC with asynchronous conventional ventilation (Control group). The other group was switched to TLV while pursuing CC for the investigation of cooling capacities and potential effects on cardiac massage efficiency.ResultsUnder physiological conditions, TLV significantly decreased the entire body temperatures below 34 °C within only 10 min. As examples, cooling rates averaged 0.54 and 0.94 °C/min in rectum and esophageous, respectively. During cardiac arrest, TLV did not alter CC efficiency and cooled the entire body below 34 °C within 20 min, the low-flow period slowing cooling during CC.ConclusionUsing a specifically designed liquid ventilator, TLV induced a very rapid cooling of the entire body in large animals. This was confirmed in both physiological conditions and during cardiac arrest with CC. TLV could be relevant for ultra-rapid cooling independently of body weight.     

Outcome of out-of-hospital cardiac arrest over a period of 15 years in comparison to the RACA score in a physician staffed urban emergency medical service in Germany

BackgroundPatient outcome after out of hospital cardiac arrest (OHCA) depends on the cardiopulmonary resuscitation (CPR) performance and might also be influenced by organisation of the emergency medical service (EMS) and implementation of guidelines.AimTo assess the rate of return of spontaneous circulation (ROSC) after cardiac arrest to the predicted rate by the ROSC after cardiac arrest (RACA) score over a 15-year period reflecting three different implemented ALS-guidelines in a physician-staffed EMS.MethodsAll adult patients with non-traumatic OHCA in the EMS of Bonn from 1996 to 2011 were included. Utstein data from three 5-years time periods (1996–2001, 2001–2006, 2006–2011) representing different ALS-guideline implementations were collected. Group comparisons were made in terms of incidence, epidemiology and short-term outcome of CPR with emphasis on changes over time and factors of importance. In each group observed ROSC rate were compared to the predicted ROSC rates (the RACA score).ResultsCPR by the ALS unit was attempted in a total of 1989 patients (735, 666, and 588 patients in the first, second and third period, respectively). Average crude incidence of CPR per 100,000 person-years decreased over time (61.3; 55.5; 49.0/100,000/years) while patients treated were significantly older (65.5 ± 16.5; 67.9 ± 15; 68.9 ± 15.7 (p < 0.001)). Observed ROSC rates were higher than predicted by the RACA score in all time periods, however, admittance to ICU decreased significantly from 50% in the first five-year period to 38% last five-year period (p < 0.001). From first to third period the proportion of arrests with first observed rhythm of VT/VF arrests did not change (29% vs. 27%, p = 0.323) nor there were changes in bystander CPR rates (17% vs. 17%, p = 0.520).ConclusionsIn a 15-years period and in the setting of a physician-staffed EMS the ROSC rates remain higher than predicted by the RACA score but the admittance to the ICU after OHCA declined significantly. This finding was accompanied by a decrease in CPR incidence and an increase in age of patients.     

Assessment of intravascular volume by transthoracic echocardiography during therapeutic hypothermia and rewarming in cardiac arrest survivors

AimTo study haemodynamic effects and changes in intravascular volume during hypothermia treatment, induced by ice-cold fluids and maintained by ice-packs followed by rewarming in patients after resuscitation from cardiac arrest.Materials and methodsIn 24 patients following successful restoration of spontaneous circulation (ROSC), hypothermia was induced with infusion of 4 °C normal saline and maintained with ice-packs for 26 h after ROSC. This was followed by passive rewarming. Transthoracic echocardiography was performed at 12, 24 and 48 h after ROSC to evaluate ejection fraction and intravascular volume status. Central venous pressure (CVP), central venous oxygen saturation (ScvO₂) and serum lactate were measured. Fluid balance was calculated.ResultsTwelve hours after ROSC, two separate raters independently estimated that 10 and 13 out of 23 patients had a decreased intravascular volume using transthoracic echocardiography. After 24 and 48 h this number had increased further to 14 and 13 out of 19 patients and 13 and 12 out of 21 patients. Calculated fluid balance was positive (4000 ml the day 1 and 2500 ml day 2). There was no difference in ejection fraction between the recording time points. Serum lactate and ScvO₂ were in the normal range when echocardiography exams were performed. CVP did not alter over time.ConclusionsOur results support the hypothesis that inducing hypothermia following cardiac arrest, using cold intravenous fluid infusion does not cause serious haemodynamic side effects. Serial transthoracic echocardiographic estimation of intravascular volume suggests that many patients are hypovolaemic during therapeutic hypothermia and rewarming in spite of a positive fluid balance.     

Computed tomography findings of complications resulting from cardiopulmonary resuscitation

IntroductionThis retrospective study was conducted to evaluate injuries related to cardiopulmonary resuscitation (CPR) and their associated factors using postmortem computed tomography (PMCT) and whole body CT after successful resuscitation.MethodsThe inclusion criteria were adult, non-traumatic, out-of-hospital cardiac arrest patients who were transported to our emergency room between April 1, 2008 and March 31, 2013. Following CPR, PMCT was performed in patients who died without return of spontaneous circulation (ROSC). Similarly, CT scans were performed in patients who were successfully resuscitated within 72 h after ROSC. The injuries associated with CPR were analysed retrospectively on CT images.ResultsDuring the study period, 309 patients who suffered out-of hospital cardiac arrest were transported to our emergency room and received CPR; 223 were enrolled in the study.The CT images showed that 156 patients (70.0%) had rib fractures, and 18 patients (8.1%) had sternal fractures. Rib fractures were associated with older age (78.0 years vs. 66.0 years, p < 0.01), longer duration of CPR (41 min vs. 33 min, p < 0.01), and lower rate of ROSC (26.3% vs. 55.3%, p < 0.01). All sternal fractures occurred with rib fractures and were associated with a greater number of rib fractures, higher age, and a lower rate of ROSC than rib fractures only cases. Bilateral pneumothorax was observed in two patients with rib fractures.ConclusionsPMCT is useful for evaluating complications related to chest compression. Further investigations with PMCT are needed to reduce complications and improve the quality of CPR.     

Initial end-tidal carbon dioxide as a prognostic indicator for inpatient PEA arrest

AimInvestigate the relationship of initial PetCO2 values of patients during inpatient pulseless electrical activity (PEA) cardiopulmonary arrest with return of spontaneous circulation (ROSC) and survival to discharge.MethodsThis study was performed in two urban, academic inpatient hospitals. Patients were enrolled from July 2009 to July 2013. A comprehensive database of all inpatient resuscitative events is maintained at these institutions, including demographic, clinical, and outcomes data. Arrests are stratified by primary etiology of arrest using a priori criteria. Inpatients with PEA arrest for whom recorded PetCO2 was available were included in the analysis. Capnography data obtained after ROSC and/or more than 10 min after initiation of CPR were excluded. Multivariable logistic regression was used to explore the association between initial PetCO2 >20 mmHg and both ROSC and survival-to-discharge.ResultsA total of 50 patients with PEA arrest and pre-ROSC capnography were analyzed. CPR continued an average of 11.8 min after initial PetCO2 was recorded confirming absence of ROSC at time of measurement. Initial PetCO2 was higher in patients with versus without eventual ROSC (25.3 ± 14.4 mmHg versus 13.4 ± 6.9 mmHg, P = 0.003). After adjusting for age, gender, and arrest location (ICU versus non-ICU), initial PetCO2 >20 mmHg was associated with increased likelihood of ROSC (adjusted OR 4.8, 95% CI 1.2–19.2, P = 0.028). Initial PetCO2 was not significantly associated with survival-to-discharge (P = 0.251).ConclusionsInitial PetCO2 >20 mmHg during CPR was associated with ROSC but not survival-to-discharge among inpatient PEA arrest victims. This analysis is limited by relatively small sample size.     

Female sex is not associated with improved rates of ROSC or short term survival following prolonged porcine ventricular fibrillation

ObjectivesThere may be a survival benefit in female patients experiencing cardiac arrest, which could affect the interpretation of in vivo animal studies. We hypothesized that sex predicts return of spontaneous circulation (ROSC) and short-term survival (SURV) in porcine studies of prolonged ventricular fibrillation (VF).MethodsRetrospective analysis of eight comparable experiments performed in our lab using mixed-breed domestic swine of either sex. All experiments included prolonged untreated VF, CPR, defibrillation, and drugs. We defined ROSC as systolic blood pressure ≥80 mmHg for ≥1 min. Short-term survival was defined 20 or 60 min, depending on protocol. Categorical variables were compared with chi-square test and Fisher's exact test. Continuous variables were compared with two-sample t-test and one-way ANOVA. Multiple logistic regression determined predictors of ROSC and SURV, utilizing cluster analysis by experimental protocol. Candidate variables were sex, weight, anesthesia duration, VF duration, and CPR ratio.ResultsOf 263 swine analyzed (53.2% male), 58.6% of males and 68.3% of females had ROSC (p = 0.10), whereas 50.0% of males and 61.0% of females experienced SURV (p = 0.07).ResultsOf 263 swine analyzed (53.2% male), 58.6% of males and 68.3% of females had ROSC (p = 0.10), whereas 50.0% of males and 61.0% of females experienced SURV (p = 0.07). Neither sex nor any identified candidate variable predicted ROSC or SURV. Both models had acceptable fit with Hosmer–Lemeshow values of 0.35 and 0.31, respectively.ConclusionsSex predicts neither ROSC nor SURV in a swine model of prolonged VF.     

Liquid ventilation with perfluorocarbons facilitates resumption of spontaneous circulation in a swine cardiac arrest model

BACKGROUND: Induced external hypothermia during ventricular fibrillation (VF) improves resuscitation outcomes. Our objectives were twofold (1) to determine if very rapid hypothermia could be achieved by intrapulmonary administration of cold perfluorocarbons (PFC), thereby using the lungs as a vehicle for targeted cardiopulmonary hypothermia, and (2) to determine if this improved resuscitation success. METHODS: Part 1: Nine female swine underwent static intrapulmonary instillation of cold perfluorocarbons (PFC) during electrically induced VF. Part 2: Thirty-three female swine in VF were immediately ventilated via total liquid ventilation (TLV) with pre-oxygenated cold PFC (-15 degrees C) or warm PFC (33 degrees C), while control swine received no ventilation during VF. All swine in both Parts 1 and 2 underwent VF arrest for 11 min, then defibrillation, ventilation and closed chest massage until resumption of spontaneous circulation (ROSC). The endpoint was continued spontaneous circulation for 1h without pharmacologic support. RESULTS: Static intrapulmonary instillation of cold PFC achieved rapid cardiopulmonary hypothermia; pulmonary artery (PA) temperature of 33.5+/-0.2 degrees C was achieved by 10 min. Nine of 9 achieved ROSC. Hypothermia was achieved faster using TLV: at 6 min VF, cold TLV temperature was 32.9+/-0.4 degrees C vs. cold static instillation temperature 34.3+/-0.2 degrees C. Nine of 11 cold TLV swine achieved ROSC for 1h vs. 3 of 11 control swine (p=0.03). Warm PFC also appeared to be beneficial, with a trend toward greater achievement of ROSC than control (ROSC; warm PFC 8 of 11 vs. control 3 of 11, p=0.09). CONCLUSION: Targeted cardiopulmonary intra-arrest moderate hypothermia was achieved rapidly by static intrapulmonary administration of cold PFC and more rapidly by total liquid ventilation with cold PFC; resumption of spontaneous circulation was facilitated. Warm PFC showed a trend toward facilitating ROSC.     

Perfluorocarbon induced intra-arrest hypothermia does not improve survival in a swine model of asphyxial cardiac arrest

Background

Pulseless electrical activity is an important cause of cardiac arrest. Our purpose was to determine if induction of hypothermia with a cold perfluorocarbon-based total liquid ventilation (TLV) system would improve resuscitation success in a swine model of asphyxial cardiac arrest/PEA.

Methods

Twenty swine were randomly assigned to control (C, no ventilation, n = 11) or TLV with pre-cooled PFC (n = 9) groups. Asphyxia was induced by insertion of a stopper into the endotracheal tube, and continued in both groups until loss of aortic pulsations (LOAP) was reached, defined as a pulse pressure less than 2 mmHg. The TLV animals underwent asphyxial arrest for an additional 2 min after LOAP, followed by 3 min of hypothermia, prior to starting CPR. The C animals underwent 5 min of asphyxia beyond LOAP. Both groups then underwent CPR for at least 10 min. The endpoint was the resumption of spontaneous circulation maintained for 10 min.

Results

Seven of 9 animals achieved resumption of spontaneous circulation (ROSC) in the TLV group vs. 5 of 11 in the C group (p = 0.2). The mean pulmonary arterial temperature was lower in total liquid ventilation animals starting 4 min after induction of hypothermia (TLV 36.3 ± 0.2 °C vs. C 38.1 ± 0.2 °C, p < 0.0001). Arterial pO₂ was higher in total liquid ventilation animals at 2.5 min of CPR (TLV 76 ± 12 mmHg vs. C 44 ± 2 mmHg; p = 0.03).

Conclusion

Induction of moderate hypothermia using perfluorocarbon-based total liquid ventilation did not improve ROSC success in this model of asphyxial cardiac arrest.     

Shen-fu injection attenuates postresuscitation lung injury in a porcine model of cardiac arrest

ObjectiveTo investigate the effects of Shen-Fu injection (SFI) on postresuscitation lung injury in a porcine model of cardiac arrest.MethodsTwenty-four anaesthetised male Landrace pigs were subjected to 4 min of untreated ventricular fibrillation (VF), followed by standard cardiopulmonary resuscitation. Sixteen successfully resuscitated pigs were randomised into two groups (eight pigs per group); one group received an SFI infusion and the other group received a normal saline infusion, at an infusion rate of 0.24 mg/min from 15 min after the return of spontaneous circulation (ROSC) until 6 h after ROSC.ResultsOxygenation index, respiratory index, oxygen delivery, oxygen consumption, oxygen extraction, dynamic lung compliance, airway resistance, external vascular lung water index, and pulmonary vascular permeability index at 15 min, 30 min, 1 h, 2 h, 4 h, and 6 h after ROSC were all worse than baseline in the saline group, and were all better in the SFI group than in the saline group. The pulmonary protective effects of SFI were further confirmed by histopathological and ultrastructural observations of lung tissue. SFI infusion resulted in lower apoptosis index, caspase-3 protein expression, and malondialdehyde content of lung tissue after ROSC, and increased Bcl-2 protein expression and superoxide dismutase, Na⁺-K⁺-ATPase, and Ca²⁺-ATPase activity compared with the saline group.ConclusionShen-Fu injection can attenuate postresuscitation lung injury through suppression of lung cell apoptosis and improvement of energy metabolism and antioxidant capacity.     

Induction of mild hypothermia with infusion of cold (4 degrees C) fluid during ongoing experimental CPR

INTRODUCTION: Therapeutic hypothermia after resuscitation has been shown to improve the outcome regarding neurological state and to reduce mortality. The earlier hypothermia therapy is induced probably the better. We studied the induction of hypothermia with a large volume of intravenous ice-cold fluid after cardiac arrest during ongoing cardiopulmonary resuscitation (CPR). METHODS: Twenty anaesthetised piglets were subjected to 8 min of ventricular fibrillation, followed by CPR. They were randomized into two groups. The hypothermic group was given an infusion of 4 degrees C acetated Ringer's solution 30 ml/kg at an infusion rate of 1.33 ml/kg/min, starting after 1 min of CPR. The control group received the same infusion at room temperature. All pigs received a bolus dose of vasopressin after 3 min of CPR. After 9 min, defibrillatory shocks were applied to achieve restoration of spontaneous circulation (ROSC). Core temperature and haemodynamic variables were measured at baseline and repeatedly until 180 min after ROSC. Cortical cerebral blood flow was measured, using Laser-Doppler flowmetry. RESULTS: All pigs had ROSC, except one animal in the hypothermic group. Only one animal in the hypothermic group died during the observation period. The calculated mean temperature reduction was 1.6+/-0.35 degrees C (S.D.) in the hypothermic group and 1.1+/-0.37 degrees C in the control group (p=0.009). There was no difference in cortical cerebral blood flow and haemodynamic variables. CONCLUSION: Inducing hypothermia with a cold infusion seems to be an effective method that can be started even during ongoing CPR. This method might warrant consideration for induction of early therapeutic hypothermia in cardiac arrest victims.     

An investigation of thrust,depth and the impedance cardiogram as measures of cardiopulmonary resuscitation efficacy in a porcine model of cardiac arrest

ObjectiveOptimising the depth and rate of applied chest compressions following out of hospital cardiac arrest is crucial in maintaining end organ perfusion and improving survival. The impedance cardiogram (ICG) measured via defibrillator pads produces a characteristic waveform during chest compressions with the potential to provide feedback on cardiopulmonary resuscitation (CPR) and enhance performance. The objective of this pre-clinical study was to investigate the relationship between mechanical and physiological markers of CPR efficacy in a porcine model and examine the strength of correlation between the ICG amplitude, compression depth and end-tidal CO₂ (ETCO₂).MethodsTwo experiments were performed using 24 swine (12 per experiment). For experiment 1, ventricular fibrillation (VF) was induced and mechanical CPR commenced at varying thrusts (0–60 kg) for 2 min intervals. Chest compression depth was recorded using a Philips QCPR device with additional recording of invasive physiological parameters: systolic blood pressure, ETCO2, cardiac output and carotid flow. For experiment 2, VF was induced and mechanical CPR commenced at varying depths (0–5 cm) for 2 min intervals. The ICG was recorded via defibrillator pads attached to the animal's sternum and connected to a Heartsine 500P defibrillator. ICG amplitude, chest compression depth, systolic blood pressure and ETCO₂ were recorded during each cycle. In both experiments the within-animal correlation between the measured parameters was assessed using a mixed effect model.ResultsIn experiment 1 moderate within-animal correlations were observed between physiological parameters and compression depth (r = 0.69–0.77) and thrust (r = 0.66–0.82). A moderate correlation was observed between compression depth and thrust (r = 0.75). In experiment 2 a strong within-animal correlation and moderate overall correlations were observed between ICG amplitude and compression depth (r = 0.89, r = 0.79) and ETCO₂ (r = 0.85, r = 0.64).ConclusionIn this porcine model of induced cardiac arrest moderate within animal correlations were observed between mechanical and physiological markers of chest compression efficacy demonstrating the challenge in utilising a single mechanical metric to quantify chest compression efficacy. ICG amplitude demonstrated strong within animal correlations with compression depth and ETCO₂ suggesting its potential utility to provide CPR feedback in the out of hospital setting to improve performance.     

The duration of cardiopulmonary resuscitation in emergency departments after out-of-hospital cardiac arrest is associated with the outcome: A nationwide observational study

Aim of the studyThe appropriate duration of cardiopulmonary resuscitation (CPR) for patients who experience out-of-hospital cardiac arrest (OHCA) remains unknown. This study aimed to evaluate the duration of CPR in emergency departments (EDs) and to determine whether the institutions’ median duration of CPR was associated with survival-to-discharge rate.MethodsA cohort of adult patients from a nationwide OHCA registry was retrospectively evaluated. The main variable was the median duration of CPR for each ED (institutional duration), and the main outcome was survival to discharge. Multivariable logistic regression analysis was performed to adjust for individual and aggregated confounders.ResultsAmong the 107,736 patients who experienced OHCA between 2006 and 2010, 30,716 (28.5%) were selected for analysis. The median age was 65 years, and 67.1% were men. The median duration of CPR for all EDs was 28 min, ranging from 11 to 45 min. EDs were categorized into 3 groups according to their institutional duration of CPR: groups A (<20 min), B (20–29 min), C (≥30 min). The observed survival rates of the 3 groups were 2.11%, 5.20%, and 5.62%, respectively. Compared with group B, the adjusted difference (95% confidence interval) for survival to discharge was 3.01% (1.90–4.11, P < 0.001) for group A, and 0.33% (−0.64 to 1.30, P = 0.51) for group C.ConclusionThe duration of CPR varied widely among hospitals. The institutional duration of CPR less than 20 min was significantly associated with lower survival-to-discharge rate.     

Cannabinoid 1 (CB1) receptor mediates WIN55, 212-2 induced hypothermia and improved survival in a rat post-cardiac arrest model

AimThe nonselective Cannabinoid (CB) receptor agonist, WIN55, 212-2, was demonstrated to induce hypothermia and improve post-resuscitation outcomes in a rat post-cardiac arrest model. The present study was to explore the potential mechanisms of WIN55, 212-2 on thermoregulation following resuscitation and to investigate which class of CB receptors was involved in WIN55, 212-2-induced hypothermia.MethodsVentricular fibrillation (VF) was induced and untreated for 6 min in 20 male Sprague-Dawley rats. Defibrillation was attempted after 8 min of Cardiopulmonary resuscitation (CPR). Five min post-resuscitation, resuscitated animals were randomized to receive an intramuscular injection of selective CB1 receptors antagonist, SR141716A (5 mg kg^?1); selective CB2 receptors antagonist SR144528 (5 mg kg^?1); or placebo. Thirty min after injection, animals received continuous intravenous infusion of WIN55, 212-2 (1.0 mg kg^?1 h^?1) for 4 h while control animals received placebo. The identical temperature environment was maintained in all animals.ResultsIn animals treated with WIN55, 212-2, blood temperatures decreased progressively from 37 °C to 34 °C within 4 h. This hypothermic effect was completely blocked by CB1 but not CB2 antagonist. Accordingly, significantly better cardiac output, ejection fraction and myocardial performance index, reduced neurological deficit scores, improved microcirculation and longer duration of survival were observed in WIN55, 212-2-treated animals, which were also completely abolished by pretreatment with CB1 antagonist.ConclusionsPharmacologically induced hypothermia with WIN55, 212-2 improved post-resuscitation myocardial and cerebral function, associated with a significantly increased duration of survival in a rat post-cardiac arrest model. The hypothermic and resulted beneficial effects of WIN55, 212-2 were mediated through CB1 receptors.     

Early goal-directed hemodynamic optimization combined with therapeutic hypothermia in comatose survivors of out-of-hospital cardiac arrest

BackgroundComatose survivors of out-of-hospital cardiac arrest (OHCA) have high in-hospital mortality due to a complex pathophysiology that includes cardiovascular dysfunction, inflammation, coagulopathy, brain injury and persistence of the precipitating pathology. Therapeutic hypothermia (TH) is the only intervention that has been shown to improve outcomes in this patient population. Due to the similarities between the post-cardiac arrest state and severe sepsis, it has been postulated that early goal-directed hemodyamic optimization (EGDHO) combined with TH would improve outcome of comatose cardiac arrest survivors.ObjectiveWe examined the feasibility of establishing an integrated post-cardiac arrest resuscitation (PCAR) algorithm combining TH and EGDHO within 6 h of emergency department (ED) presentation.MethodsIn May, 2005 we began prospectively identifying comatose (Glasgow Motor Score < 6) survivors of OHCA treated with our PCAR protocol. The PCAR patients were compared to matched historic controls from a cardiac arrest database maintained at our institution.ResultsBetween May, 2005 and January, 2008, 18/20 (90%) eligible patients were enrolled in the PCAR protocol. They were compared to historic controls from 2001 to 2005, during which time 18 patients met inclusion criteria for the PCAR protocol. Mean time from initiation of TH to target temperature (33 °C) was 2.8 h (range 0.8–23.2; SD = h); 78% (14/18) had interventions based upon EGDHO parameters; 72% (13/18) of patients achieved their EGDHO goals within 6 h of return of spontaneous circulation (ROSC). Mortality for historic controls who qualified for the PCAR protocol was 78% (14/18); mortality for those treated with the PCAR protocol was 50% (9/18) (p = 0.15).ConclusionsIn patients with ROSC after OHCA, EGDHO and TH can be implemented simultaneously.     

The need to resume chest compressions immediately after defibrillation attempts: An analysis of post-shock rhythms and duration of pulselessness following out-of-hospital cardiac arrest

AimCurrent consensus guidelines for cardiopulmonary resuscitation (CPR) recommend that chest compressions resume immediately after defibrillation attempts and that rhythm and pulse checks be deferred until completion of 5 compression:ventilation cycles or minimally for 2 min. However, data specifically confirming the post-shock duration of asystole or pulseless electrical activity before return of spontaneous circulation (ROSC) are lacking. Our aim was to describe the frequency of the various post-shock cardiac rhythms and the duration of post-shock pulselessness in out-of-hospital non-traumatic cardiac arrest.MethodUsing prospectively-collected data from the Resuscitation Outcomes Consortium (ROC) Epistry database, the investigators reviewed monitor-defibrillator recordings of 176 patients who received defibrillation attempts in the out-of-hospital setting for ventricular fibrillation (VF) or ventricular tachycardia (VT) with absent pulses,.ResultsAmong 376 different defibrillation attempts delivered in the 176 patients, there were 182 resulting episodes of post-shock asystole. The mean interval of asystole after defibrillation was 69 ± 136 s (median 20 s; IQR 36) and the mean interval for return of an organized rhythm was 64 ± 157 s (median 7 s; IQR 26). The mean time to ROSC was 280 ± 320 s (median 136 s; IQR 445).ConclusionAfter defibrillation attempts, the majority of patients remain pulseless for over 2 min and the duration of asystole before return of pulses is longer than 120 s beyond the shock gap in as many as 25%. These data support the recommendation to immediately resume chest compressions for 2 min following attempted defibrillation.     

Correlation between initial serum levels of lactate after return of spontaneous circulation and survival and neurological outcomes in patients who undergo therapeutic hypothermia after cardiac arrest

ObjectivesWe analysed the relationship between serum levels of lactate within 1 h of return of spontaneous circulation (ROSC) and survival and neurological outcomes in patients who underwent therapeutic hypothermia (TH).MethodsThis was a multi-centre retrospective and observational study that examined data from the first Korean Hypothermia Network (KORHN) registry from 2007 to 2012. The inclusion criteria were out-of-hospital cardiac arrest (OHCA) and examination of serum levels of lactate within 1 h after ROSC, taken from KORHN registry data. The primary endpoint was survival outcome at hospital discharge, and the secondary endpoint was poor neurological outcome (Cerebral Performance Category, CPC, 3–5) at hospital discharge. Initial lactate levels and other variables collected within 1 h of ROSC were analysed via multivariable logistic regression.ResultsData from 930 cardiac arrest patients who underwent TH were collected from the KORHN registry. In a total of 443 patients, serum levels of lactate were examined within 1 h of ROSC. In-hospital mortality was 289/443 (65.24%), and 347/443 (78.33%) of the patients had CPCs of 3–5 upon hospital discharge. The odds ratios of lactate levels for CPC and in-hospital mortality were 1.072 (95% confidence interval (CI) 1.026–1.121) and 1.087 (95% CI = 1.031–1.147), respectively, based on multivariate ordinal logistic regression analyses.ConclusionHigh levels of lactate in serum measured within 1 h of ROSC are associated with hospital mortality and high CPC scores in cardiac arrest patients treated with TH.