低温关胸心肺转流行心肺复苏的实验研究

目的　观察狗心脏停搏15min后深低温(26℃～27℃)和浅低温(33℃～34℃)关胸心肺转流(CPB)对心肺复苏(CPR)的影响。方法　10只麻醉狗,分2组,每组各5只。第1组为浅低温组,第2组为深低温组,用10%氯化钾静注后,使心脏停搏15min,然后用动静脉插管方法立即行关胸心肺转流。第1组食道温度降至33℃～34℃,第2组降至26℃～27℃,15min后逐渐升温至正常范围(36℃～37℃)。复苏期间监测心电图、平均动脉压、中心静脉压和瞳孔直径,3h后观察颅内压和最终效果。结果　第1组全部恢复自主循环(100%),第2组仅3只(60%)恢复自主循环;第1组的自主循环恢复时间为(444±192.2)sec,明显短于第2组(1980±681.5)sec(P＜0.05),其复苏后3h颅内压为(2.4±0.44)cmH     

Emergency preservation and delayed resuscitation allows normal recovery after exsanguination cardiac arrest in rats: a feasibility trial

OBJECTIVE: Emergency preservation and resuscitation (EPR) comprise a novel approach for resuscitation of exsanguination cardiac arrest victims. EPR uses a cold aortic flush to induce deep hypothermic preservation, followed by resuscitation with cardiopulmonary bypass. Development of a rat EPR model would enable study of the molecular mechanisms of neuronal injury and the screening of novel agents for emergency preservation. DESIGN: A prospective, randomized study. SETTING: University research facility. SUBJECTS: Adult male Sprague-Dawley rats. INTERVENTIONS: Isoflurane-anesthetized rats were subjected to lethal hemorrhage (12.5 mL for 5 mins), followed by KCl-induced cardiac arrest and 1 min of no flow. Three groups (n=6) were studied: hypothermic EPR (H-EPR; 0 degrees C flush; target temperature, 15 degrees C); normothermic EPR (N-EPR; 38 degrees C flush); and controls. After 20 mins of H-EPR or N-EPR, resuscitation was initiated with cardiopulmonary bypass for 60 mins and mechanical ventilation. Controls were subjected to complete experimental preparation and anesthesia without cardiac arrest, followed by 60 mins of cardiopulmonary bypass and mechanical ventilation. Surviving rats were extubated 2 hrs later. Survival, Overall Performance Category (1, normal; 5, death), Neurologic Deficit Score, Histologic Damage Score, and biochemistry were assessed in survivors on day 7. MEASUREMENTS AND MAIN RESULTS: All rats in H-EPR and control groups survived, whereas none of the rats in the N-EPR group had restoration of spontaneous circulation. All rats in the H-EPR and control groups achieved Overall Performance Category 1, normal Neurologic Damage Score, and normal or near normal Histologic Damage Score and biochemical markers of organ injury. CONCLUSIONS: We have established an EPR model in rats showing no neurologic injury, despite an exsanguination cardiac arrest, followed by 20 mins of EPR using miniaturized cardiopulmonary bypass. Establishment of this model should facilitate application of molecular tools to study the effects of hypothermic preservation and reperfusion and to screen novel pharmacologic adjuncts.     

New conventional long-term survival normovolemic cardiac arrest pig model

Aim of the study

A reproducible long-term intensive care and outcome cardiac arrest model for exploring new cerebral preservation strategies is needed. We tried to determine effects and limitations of current therapies after different ‘no-flow’ times.

Methods

Thirty-five female Large White Breed pigs (26-37 kg) were included in the study. Three pigs served as sham animals without cardiac arrest (CA). Ventricular fibrillation (VF) CA was induced in 32 animals for 0, 7, 10 and 13 min (each group consisting of 8 animals), followed by 8 min of chest compressions, mechanical ventilation and vasopressors. Thereafter, up to 3 defibrillations were delivered. After restoration of spontaneous circulation (ROSC), the animals underwent intensive care for 20 h. Neurologic examination was performed at designated time points using a neurologic deficit (ND) and an overall performance category (OPC) score.

Results

Restoration of spontaneous circulation was achieved in 8 of 8 animals in the 0 min-group, 6 of 8 in the 7 min-group, 7 of 8 in the 10 min-group and 0 of 8 in the 13 min-group. All animals of the sham-group and 0 min-group were neurologically intact survivors; the 7 and 10 min-groups showed a median ND of 55%(26;94) and 73%(58;78), respectively. There were no significant differences between the 7 and 10 min-groups regarding OPC and NDS. Coronary perfusion pressure during CPR decreased concordantly with ‘no-flow’ times with a tendency towards significance.

Conclusion

This study established a reproducible cardiac arrest and resuscitation model in pigs which will be used to test novel resuscitation strategies to improve neurologic outcome after cardiac arrest.     

Ibuprofen improves survival and neurologic outcome after resuscitation from cardiac arrest

Post-ischemic inflammatory changes in the central nervous system (CNS) following cardiac arrest and resuscitation are potentially responsible for ultimate survival and much of the neurologic damage, producing greater morbidity and mortality in successfully resuscitated patients. This study was undertaken to assess the non-steroidal anti-inflammatory agent, ibuprofen, in a controlled and monitored experimental model of canine cardiac arrest and resuscitation. With the investigator blinded as to the intervention, eight of 21 dogs were randomly assigned to receive ibuprofen as an i.v. bolus (10 mg/kg) and a 6-h i.v. infusion (5 mg/kg per h). The other 13 dogs received an equivalent volume of 0.9% NaCl to serve as controls. No statistically significant differences between the two groups were detected in any pre-arrest variables. All 21 dogs were successfully resuscitated. At 24 h, dogs receiving ibuprofen exhibited 100% survival, while control dogs exhibited only 54% survival (P = 0.03). The majority of deaths for the control group occurred within the first 6 h. Neurologic deficit scores were assigned at 1, 2, 6 and 24 h after resuscitation. A general trend occurred such that dogs treated with ibuprofen improved over time, while the control dogs remained severely impaired. A significant difference in neurologic deficit score was detected at 6 h (P = 0.01). At 24 h the ibuprofen group exhibited minimal neurologic deficit (5.9 +/- 3.2), and the control group exhibited significantly more severe neurologic impairment (52.2 +/- 13.0, P = 0.01). These results suggest that ibuprofen may be helpful in the pharmacologic management of cardiac arrest as a means of increasing survival and decreasing neurologic impairment.     

Successful resuscitation of a child with severe hypothermia after cardiac arrest of 88 minutes

A 4-year-old boy broke through the ice of a frozen lake and drowned. The boy was extricated from the icy water by a rescue helicopter that was dispatched shortly after the incident. Although the boy was severely hypothermic, no cardiac response could be induced with field resuscitation measures, including intubation, ventilation, suction, and cardiopulmonary resuscitation. On admission, the primary findings included fixed, nonreacting pupils and asystole. The first core temperature measured was 19.8 degrees C (67.6 degrees F). During active, external warming, the first ventricular beats were observed 20 minutes after admission, and changed 10 minutes later to a sinus rhythm. Continuous monitoring included repeated arterial blood gas and electrolyte tests; prophylaxis for cerebral edema was performed with hyperventilation and administration of sodium Brevimytal and dexamethasone. Seventy minutes after admission, hemodynamics stabilized and the boy was transferred to the pediatric intensive care unit (PICU), where active external warming was continued to raise the core temperature at a rate of 1 degree C/hour. Adult respiratory distress syndrome developed, and the boy had to be ventilated in the PICU for 10 days. He was discharged home after another two weeks. He recovered fully. The rapid heat loss with the induction of severe hypothermia (< 20 degrees C; 68 degrees F) was the main reason for survival in this rare event of a patient with cardiac arrest lasting 88 minutes after accidental hypothermia.     

Erythropoietin improved initial resuscitation and increased survival after cardiac arrest in rats

Introduction

Recent data have demonstrated potent cardioprotective and neuroprotective effects of the application of growth hormones like erythropoietin (EPO) after focal cardiac or cerebral ischemia. In order to assess possible benefits regarding survival and resuscitation conditions, EPO was tested against placebo in a model of cardiac arrest in the rat.

Methods

Thirty-four male Wistar rats were randomized into two groups (EPO versus control; n = 17 per group). Under anesthesia, cardiac arrest was induced by asphyxia after neuromuscular blockade. After 6 min of global ischemia, animals were resuscitated by external chest compression combined with epinephrine administration. An intravenous bolus of recombinant human EPO (rhEPO, 3000 UI kg⁻¹ body weight, i.v.) or saline (in control group) was performed 15 min before cardiac arrest, by a blinded investigator. Restoration of spontaneous circulation (ROSC), survival at 1, 24, 48 and 72 h and hemodynamic changes after cardiac arrest were studied.

Results

Survival to 72 h was significantly improved in the EPO group (n = 15/17) compared to the control group (n = 7/17). All the EPO-treated rats were successfully resuscitated whereas only 13 of 17 control animals resuscitated. EPO-treated animals required a significantly smaller dose of epinephrine before resuscitation, compared to control rats. Time course of systolic arterial blood pressure after resuscitation revealed no significant differences between both groups.

Conclusion

EPO, when administrated before cardiac arrest, improved initial resuscitation and increased the duration of post-resuscitation survival.     

Factors influencing variable outcomes after ventricular fibrillation cardiac arrest of 15 minutes in dogs

Animal experiments with cardiac arrest and cardiopulmonary resuscitation (CPR) despite controlled insult and postinsult life support, have yielded variable individual outcomes. This report concerns 10 dog experiments with a standardized model of VF cardiac arrest with no flow for 10 min followed by CPR basic life support (BLS) from VF 10 to 15 min and then CPR advanced life support (ALS) with epinephrine at 15 min. Defibrillating countershocks began at 17 min, for restoration of spontaneous circulation. After controlled ventilation to 20 h and intensive care to 96 h, outcome was evaluated using the overall performance category (OPC) 1 (normal) (n5) vs. OPC 2-4 (impaired) (n5) (P less than 0.001). We searched for correlations between normal vs. impaired outcome in various prearrest, arrest and postarrest factors that are suspected to influence postarrest neurologic deficit. Prearrest variables were similar in the normal and impaired groups. Resuscitation variables were similar in both. Coronary perfusion pressure during CPR-ALS was higher in the normal outcome group (P = 0.03). Among postarrest variables, postarrest reperfusion pressure pattern (initial hypertensive bout), blood glucose, cardiac output, Hct, pHa, PaO2 and PaCO2 were the same. Our data support the importance of maximizing coronary perfusion pressure not only for restoration of heart beat but also as a possible predictor of improved cerebral outcome.     

Sodium bicarbonate improves the chance of resuscitation after 10 minutes of cardiac arrest in dogs.

The likelihood of successful defibrillation and resuscitation decreases as the duration of cardiac arrest increases. Prolonged cardiac arrest is also associated with the development of acidosis. These experiments were designed to determine whether administration of sodium bicarbonate and/or adrenaline in combination with a brief period of cardiopulmonary resuscitation (CPR) prior to defibrillation would improve the outcome of prolonged cardiac arrest in dogs. Ventricular fibrillation (VF) was induced by a.c. shock in anaesthetised dogs. After 10 min of VF, animals received either immediate defibrillation (followed by treatment with bicarbonate or control) or immediate treatment with bicarbonate or saline (followed by defibrillation). Treatment with bicarbonate was associated with increased rates of restoration of spontaneous circulation. This was achieved with fewer shocks and in a shorter time. Coronary perfusion pressure was significantly higher in NaHCO3-treated animals than in control animals. There were smaller decreases in venous pH in NaHCO3-treated animals than in controls. The best outcome in this study was achieved when defibrillation was delayed for approximately 2 min, during which time NaHCO3 and adrenaline were administered with CPR. The results of the present study indicate that in prolonged arrests bicarbonate therapy and a period of perfusion prior to defibrillation may increase survival.     

Emergency department factors associated with survival after sudden cardiac arrest

Background

Sudden cardiac arrest (SCA) is a leading cause of death in the US. Recent innovations in post-arrest care have been demonstrated to increase survival. However, little is known about the impact of emergency department (ED) and hospital characteristics on survival to hospital admission and ultimate outcome.

Objective

We sought to describe the incidence of SCA presenting to the ED and to identify ED and hospital characteristics associated with survival to hospital admission.

Methods

We identified patients with diagnoses of atraumatic cardiac arrest or ventricular fibrillation (ICD-9 427.5 or 427.41) in the 2007 Nationwide Emergency Department Sample (NEDS), a nationally representative estimate of all ED admissions in the United States. We defined SCA as cardiac arrest in the out-of-hospital or ED settings. We used the NEDS sample design to generate nationally representative estimates of the incidence of SCA that presents to EDs. We performed unadjusted and adjusted analyses to examine the relation between patient, ED, and hospital characteristics and outcome using logistic regression. Our primary outcome was survival to hospital admission. Survival to hospital discharge was a secondary outcome. Data are presented as odds ratios (OR) with 95% confidence intervals (CI).

Results

Of the 966 hospitals in the NEDS, 933 (96.6%) reported at least one SCA and were included in the analysis. We identified 38,593 cases of cardiac arrest representing an estimated 174,982 cases nationally. Overall ED SCA survival to hospital admission was 26.2% and survival to discharge was 15.7%. Greater survival to admission was seen in teaching hospitals (OR 1.3 95% CI 1.1–1.5, p = 0.001), hospitals with ≥20,000 annual ED visits (OR 1.3 95% CI 1.1–1.6, p = 0.003), and hospitals with percutaneous coronary intervention capability (OR 1.6 95% CI 1.4–1.8, p < 0.001). Higher SCA volume (>40 annually) was associated with lower survival overall (OR 0.7 95% 0.6–0.9, p = 0.010), but not when transferred patients were excluded from the analysis (OR 0.8 95% CI 0.6–1.1, p = 0.116).

Conclusions

An estimated 175,000 cases of SCA present to or occur in US EDs each year. Percutaneous coronary intervention capability, ED volume, and teaching status were associated with higher survival to hospital admission. Emergency departments with higher annual SCA volume had lower survival rates, possibly because they transfer fewer patients. An improved understanding of the contribution of ED care to survival following SCA may be useful in advancing our understanding of how best to organize a system of care to ensure optimal outcomes for patients with SCA.     

Soluble epoxide hydrolase gene deletion reduces survival after cardiac arrest and cardiopulmonary resuscitation

The P450 eicosanoids epoxyeicosatrienoic acids (EETs) are produced by cytochrome P450 arachidonic acid epoxygenases and metabolized through multiple pathways, including soluble epoxide hydrolase (sEH). Pharmacological inhibition and gene deletion of sEH protect against ischemia/reperfusion injury in brain and heart, and against hypertension-related end-organ damage in kidney. We tested the hypothesis that sEH gene deletion improves survival, recovery of renal function and pathologic ischemic renal damage following transient whole-body ischemia induced by cardiac arrest (CA) and resuscitation. Mice with targeted deletion of sEH (sEH knockout, sEHKO) and C57Bl/6 wild-type control mice were subjected to 10-min CA, followed by cardiopulmonary resuscitation (CPR). Survival in wild-type mice was 93% and 80% at 10 min and 24 h after CA/CPR (n=15). Unexpectedly, survival in sEHKO mice was significantly lower than WT. Only 56% of sEHKO mice survived for 10 min (n=15, p=0.014 compared to WT) and no mice survived for 24 h after CA/CPR (p<0.0001 versus WT). We conclude that sEH plays an important role in cardiovascular regulation, and that reduced sEH levels or function reduces survival from cardiac arrest.     

Emergency cardiopulmonary bypass for resuscitation from prolonged cardiac arrest

After cardiac arrest (no flow) of more than approximately 5 minutes' duration, standard external cardiopulmonary resuscitation (CPR) basic, advanced, and prolonged life support (BLS, ALS, PLS) do not reliably produce cerebral and coronary perfusion pressures to maintain viability and achieve stable spontaneous normotension; nor do they provide prolonged control over pressure, flow, composition, and temperature of blood. Since these capabilities are often needed to achieve conscious survival, emergency closed-chest cardiopulmonary bypass (CPB) by veno-arterial pumping via oxygenator is presented in this review as a potential addition to ALS-PLS for selected cases. In six dog studies by the Pittsburgh group (n = 221; 1982 through 1988), all 179 dogs that received CPB after prolonged cardiac arrest (no flow) or after CPR (low flow) states had restoration of stable spontaneous circulation. The use of CPB enhanced survival and neurological recovery over those achieved with CPR-ALS attempts only. With CPB and standard intensive care, it was possible to reverse normothermic ventricular fibrillation (VF) cardiac arrest (no flow) of up to 15 minutes and to achieve survival without neurologic deficit; VF of 20 minutes to achieve survival but with neurologic deficit; and VF of 30 minutes to achieve transient restoration of spontaneous circulation followed by secondary cardiac death. CPB could restore stable spontaneous circulation after ice water submersion of up to 90 minutes. Other groups' laboratory and clinical results agree with these findings in general. Clinical feasibility trials are needed to work out logistic problems and to meet clinical challenges. Future possibilities for emergency CPB require further research and development.     

Rapid induction of cerebral hypothermia by aortic flush during normovolemic cardiac arrest in pigs

OBJECTIVE: Induction of deep cerebral hypothermia before reperfusion might improve neurologic outcome after cardiac arrest. We hypothesized that an aortic flush with cold saline during cardiac arrest is able to induce deep cerebral hypothermia and that the cooling efficiency can be enhanced by a) increasing the arteriovenous pressure gradient during the flush with vasopressin; b) improving the cerebral microcirculation during the flush with the thrombolytic agent alteplase; and c) increasing the arteriovenous pressure gradient further with venting the right heart by draining blood during the flush. DESIGN: Prospective randomized experimental study. SETTING: University research laboratory. SUBJECTS: Twenty-four pigs Large White breed (31-42 kg). INTERVENTIONS: After 10 mins of ventricular fibrillation, pigs received an aortic flush (100 mL/kg, 4 degrees C, flow rate 35 mL/kg/min) into the descending aorta via a balloon catheter. The animals were subjected randomly to either an aortic flush with saline, saline plus vasopressin 1.2 IU/kg, saline plus alteplase 1 mg/kg, saline plus a combination of vasopressin 1.2 IU/kg and alteplase 1 mg/kg, or saline plus vasopressin 1.2 IU/kg and venting the right heart. Arterial and venous pressures and brain temperatures were recorded for an observation time of 10 mins after flush. MEASUREMENTS AND MAIN RESULTS: A sufficient arteriovenous pressure gradient and deep cerebral hypothermia were only achieved with a flush containing vasopressin (brain temperature 16.1+/-1.3 degrees C in the vasopressin group vs. 35.4+/-1.5 degrees C in the saline group, p<.001); combining vasopressin with alteplase, or venting the right heart, did not further enhance the cooling efficiency of the flush. CONCLUSIONS: A cold saline aortic flush with vasopressin rapidly decreases brain temperature during prolonged normovolemic cardiac arrest in pigs. Whether deep cerebral hypothermia induced before reperfusion can improve neurologic outcome after cardiac arrest needs further investigation in large animal outcome studies.     

Failure of nimodipine to improve neurologic outcome after eighteen minutes of cardiac arrest in the cat.

The calcium entry blocker nimodipine was administered to cats following resuscitation from 18 min of cardiac arrest to evaluate its effect on neurologic and neuropathologic outcome in a clinically relevant model of complete cerebral ischemia. Cardiac arrest (ventricular fibrillation) was maintained for 18 min and resuscitation was performed by a standardized protocol in 40 cats. Beginning at 5 min post-resuscitation, nimodipine, 10 micrograms/kg over 2 min followed by 1 microgram/kg per min for 10 h, or the same volume of placebo was administered in a randomized, blinded fashion. Neurologic deficits were scored at 2, 4, and 7 days post-resuscitation by observers blinded to the treatment group. Thirty cats were evaluated neurologically at 7 days post-resuscitation and were entered into data analysis (n = 15 per group). Neither neurologic deficit scores nor neuropathologic scores were significantly different between groups. The authors conclude that nimodipine administration in the manner and doses stated does not improve neurologic outcome in cats following resuscitation from cardiac arrest.     

Brain function after resuscitation from cardiac arrest

PURPOSE OF REVIEW: In industrial countries the incidence of cardiac arrest is still increasing. Almost 80% of cardiac arrest survivors remains in coma for varying lengths of time and full cerebral recovery is still a rare event. After successful cardiopulmonary resuscitation, cerebral recirculation disturbances and complex metabolic postreflow derangements lead to death of vulnerable neurons with further deterioration of cerebral outcome. This article discusses recent research efforts on the pathophysiology of brain injury caused by cardiac arrest and reviews the beneficial effect of therapeutic hypothermia on neurologic outcome along with the recent approach to prognosticate long-term outcome by electrophysiologic techniques and molecular markers of brain injury. RECENT FINDINGS: Recent experimental studies have brought new insights to the pathophysiology of secondary postischemic anoxic encephalopathy demonstrating a time-dependent cerebral oxidative injury, increased neuronal expression, and activation of apoptosis-inducing death receptors and altered gene expression with long-term changes in the molecular phenotype of neurons. Recently, nuclear MR imaging and MR spectroscopic studies assessing cerebral circulatory recovery demonstrated the precise time course of cerebral reperfusion after cardiac arrest. Therapeutic hypothermia has been shown to improve brain function after resuscitation from cardiac arrest and has been introduced recently as beneficial therapy in ventricular fibrillation cardiac arrest. SUMMARY: Electrophysiologic techniques and molecular markers of brain injury allow the accurate assessment and prognostication of long-term outcome in cardiac arrest survivors. In particular, somatosensory evoked potentials have been identified as the method with the highest prognostic reliability. A recent systematic review of 18 studies analyzed the predictive ability of somatosensory evoked potentials performed early after onset of coma and found that absence of cortical somatosensory evoked potentials identify patients not returning from anoxic coma with a specificity of 100%.     

Estimating cost-effectiveness of mass cardiopulmonary resuscitation training strategies to improve survival from cardiac arrest in private locations

Introduction

Most cardiopulmonary resuscitation (CPR) trainees are young, and most cardiac arrests occur in private residences witnessed by older individuals.

Objective

To estimate the cost-effectiveness of a CPR training program targeted at citizens over the age of 50 years compared with that of current nontargeted public CPR training.

Methods

A model was developed using cardiac arrest and known demographic data from a single suburban zip code (population 36,325) including: local data (1997-1999) regarding cardiac arrest locations (public vs. private); incremental survival with CPR (historical survival rate 7.8%, adjusted odds ratio for CPR 2.0); arrest bystander demographics obtained from bystander telephone interviews; zip code demographics regarding population age and distribution; and $12.50 per student for the cost of CPR training. Published rates of CPR training programs by age were used to estimate the numbers typically trained. Several assumptions were made: 1) there would be one bystander per arrest; 2) the bystander would always perform CPR if trained; 3) cardiac arrest would be evenly distributed in the population; and 4) CPR training for a proportion of the population would proportionally increase CPR provision. Rates of arrest, bystanders by age, number of CPR trainees needed to result in increased arrest survival, and training cost per life saved for a one-year study period were calculated.

Results

There were 24.3 cardiac arrests per year, with 21.9 (90%) occurring in homes. In 66.5% of the home arrests, the bystander was more than 50 years old. To yield one additional survivor using the current CPR training strategy, 12,306 people needed to be trained (3,510 bystanders aged ≤50 years and 8,796 bystanders aged >50 years), which resulted in CPR provision to 7.14 additional patients. The training cost per life saved for a bystander aged ≤50 years was $313,214, and that for a bystander aged >50 years was $785,040. Using a strategy of training only those ≤50 years, 583 elders per cardiac arrest would need to be trained, with a cost of $53,383 per life saved.

Conclusion

Using these assumptions, current CPR training strategy is not a cost-effective intervention for home cardiac arrests. The high rate of elders witnessing CPR mandates focused CPR interventions for this population.     

Long-term survival after out-of-hospital cardiac arrest

OBJECTIVE: The purpose of this study was to assess the long-term survival after OHCA. METHODS: All OHCA-calls where the Copenhagen Mobile Emergency Care Unit (MECU) was involved from 1994 to1998 are included in this study. Data were collected prospectively. Data on long-term survival was obtained from the Danish Causes of Death Registry and the Danish Civil Registration System. We conducted a search to find out whether patients were still alive on 31 January 2005. RESULTS: Resuscitation was indicated and attempted in 1095 cases and 95 patients (8.7%) survived to discharge. Of these 75% had an initial rhythm of VF, 13% had asystole, 10% had PEA and 2% were unknown. Survival was 87% after one year and survival after 10 years was 46% with a significantly lower survival for patients over 60 years. CONCLUSION: Long-term survival after out-of-hospital cardiac arrest in a physician-staffed emergency system was comparable to survival after myocardial infarction with 46% being alive after ten years.