Initial Return Of Spontaneous Circulation Research Articles

The effects of methylene blue during and after cardiac arrest in a porcine model; a randomized, blinded, placebo-controlled study

PurposeTo evaluate the effect of methylene blue administered as a bolus on return of spontaneous circulation (ROSC), lactate levels, vasopressor requirements, and markers of neurological injury in a clinically relevant pig model of cardiac arrest. Materials and methods40 anesthetized pigs were subjected to acute myocardial infarction and 7 min of untreated cardiac arrest. Animals were randomized into three groups: one group received saline only (controls), one group received 2 mg/kg methylene blue and saline (MB + saline), and one group received two doses of 2 mg/kg methylene blue (MB + MB). The first intervention was given after the 3rd rhythm analysis, while the second dose was administered one hour after achieving ROSC. Animals underwent intensive care and observation for six hours, followed by cerebral magnetic resonance imaging (MRI). The primary outcome for this study was development in lactate levels after cardiac arrest. Categorical data were compared using Fisher's exact test and pointwise data were analyzed using one-way analysis of variance (ANOVA) or equivalent non-parametric test. Continuous data collected over time were analyzed using a linear mixed effects model. A value of p < .05 was considered statistically significant. ResultsLactate levels increased in all groups after cardiac arrest and resuscitation, however lactate levels in the MB + MB group decreased significantly faster compared with the control group (p = .007) and the MB + saline group (p = .02). The proportion of animals achieving initial ROSC was similar across groups: 11/13 (85%) in the control group, 10/13 (77%) in the MB + saline group, and 12/14 (86%) in the MB + MB group (p = .81). Time to ROSC did not differ between groups (p = .67). There was no significant difference in accumulated norepinephrine dose between groups (p = .15). Cerebral glycerol levels were significantly lower in the MB + MB group after resuscitation compared with control group (p = .03). However, MRI data revealed no difference in apparent diffusion coefficient, cerebral blood flow, or dynamic contrast enhanced MR perfusion between groups. ConclusionTreatment with a bolus of methylene blue during cardiac arrest and after resuscitation did not significantly improve hemodynamic function. A bolus of methylene blue did not yield the neuroprotective effects that have previously been described in animals receiving methylene blue as an infusion.

Clinicopathological correlates of out‐of‐hospital cardiac arrests

BackgroundSudden cardiac arrest with or without sudden cardiac death (SCD) represents a heterogeneous spectrum of underlying etiology but is often a catastrophic event. Despite improvements in pre‐hospital response and post‐resuscitation care, outcomes remain grim. Thus, we aim to evaluate the predictors of survival in out‐of‐hospital cardiac arrests (OHCAs) and describe autopsy findings of those with the uncertain cause of death (COD).MethodsThis is a subgroup analysis of the Singapore cohort from the Pan Asian Resuscitation Outcome Study which studied 933 OHCAs admitted to two Singapore tertiary hospitals from April 2010 to May 2012.ResultsOf the patients analysed, 30.2% (n = 282) had an initial return of spontaneous circulation (ROSC) at the emergency department, 18.0% (n = 168) had sustained ROSC with subsequent admission and 3.4% (n = 32) had survival to discharge. On multivariate analysis, an initial shockable rhythm, a witnessed event, prehospital defibrillation, and shorter time to hospital predicted ROSC as well as survival to discharge. A total of 163 (17.5%) autopsies were performed of which a cardiac etiology of SCD was noted in 92.1% (n = 151). Ischemic heart disease accounted for 54.3% (n = 89) of the autopsy cohort, with acute myocardial infarction (26.9%, n = 44) and myocarditis (3.7%, n = 6) rounding out the top three causes of demise.ConclusionOHCA remains a clinical presentation that portends a poor prognosis. Of those with uncertain COD, cardiac etiology appears to predominate from autopsy study. Identification of prognostic factors will play an important role in improving individual‐level and systemic‐level variables to further optimize outcomes.

Successful prolonged cardiopulmonary resuscitation in a Siamese cat: A case of post‐cardiac arrest concerns

AbstractA 4.5‐year‐old male neutered Siamese cat was admitted to referral hospital for medical work‐up of chronic anorexia and emesis. No severe abnormalities were detected on routine blood work; however thickened gastric wall and small intestines were noted on abdominal ultrasonography. The cat was premedicated with buprenorphine followed by a diazepam‐propofol co‐induction. Endotracheal intubation was performed, and anaesthesia was maintained using isoflurane in oxygen for endoscopic investigation of the thickened gastric wall and biopsies retrieval. During the anaesthetic recovery, the animal went into cardiopulmonary arrest. Successful ROSC (return of spontaneous circulation) was achieved at approximate 40 minutes (prolonged) post‐arrest, and the animal had a survived event (ROSC &gt; 20 minutes). However, failure to identify the inciting cause of the CPA and laxity in the post‐cardiac arrest care resulted in rearrest of the cat, 77 hours after the initial ROSC with no success of a second ROSC.

Supplement of levosimendan to epinephrine improves initial resuscitation outcomes from asphyxial cardiac arrest

BackgroundLevosimendan exerted favorable effects on the initial outcome in the treatment of ventricular fibrillation cardiac arrest. This study investigated the efficacy of levosimendan in the treatment of asphyxia-induced cardiac arrest in rats.MethodsAnimals underwent asphyxial cardiac arrest/cardiopulmonary resuscitation, randomized to three treatment groups: epinephrine (10 μg/kg) supplemented with levosimendan (bolus 12 μg/kg and infusion for 1 h, EL group); epinephrine only (10 μg/kg, E group), or levosimendan only (bolus 12 μg/kg and infusion for 1 h, L group). The resuscitation success rate, wet-to-dry ratio of lung, and rate of alveolar and blood gas analysis were recorded.Results10 rats in the EL group, 8 in the E group, and 2 in the L group showed an initial return of spontaneous circulation (P < 0.001); among them, 10, 4, and 2 rats survived at the end of a 60-min observation period from each group, respectively (P = 0.001). The coronary perfusion pressure in the EL group was higher than that of either the E or L group (P < 0.05). The lung wet-to-dry weight ratio and rate of damaged alveoli were lower in the EL group than the E group (P < 0.05).ConclusionsIn the early stage of resuscitation for asphyxia-induced cardiac arrest in rats, levosimendan supplemented with epinephrine can significantly increase coronary perfusion pressure, reduce lung injury, and ultimately enhance the survival rate.

Dantrolene versus amiodarone for cardiopulmonary resuscitation: a randomized, double-blinded experimental study

Dantrolene was introduced for treatment of malignant hyperthermia. It also has antiarrhythmic properties and may thus be an alternative to amiodarone for the treatment of ventricular fibrillation (VF). Aim of this study was to compare the return of spontaneous circulation (ROSC) with dantrolene and amiodarone in a pig model of cardiac arrest. VF was induced in anesthetized pigs. After 8 min of untreated VF, chest compressions and ventilation were started and one of the drugs (amiodarone 5 mg kg−1, dantrolene 2.5 mg kg−1 or saline) was applied. After 4 min of initial CPR, defibrillation was attempted. ROSC rates, hemodynamics and cerebral perfusion measurements were measured. Initial ROSC rates were 7 of 14 animals in the dantrolene group vs. 5 of 14 for amiodarone, and 3 of 10 for saline). ROSC persisted for the 120 min follow-up in 6 animals in the dantrolene group, 4 after amiodarone and 2 in the saline group (n.s.). Hemodynamics were comparable in both dantrolene group amiodarone group after obtaining ROSC. Dantrolene and amiodarone had similar outcomes in our model of prolonged cardiac arrest, However, hemodynamic stability was not significantly improved using dantrolene. Dantrolene might be an alternative drug for resuscitation and should be further investigated.

Older Adults Had Similar Survival Rates Compared to Their Younger Counterparts Following Cardiopulmonary Resuscitation

Background: Several factors affect the outcome of cardiopulmonary resuscitation (CPR) following in hospital cardiac arrests, including presence of comorbidities, arrest characteristics, and resuscitation efforts. We sought to determine the outcome of CPR provided to elders suffering from in-hospital cardiopulmonary arrest and to compare it to the survival of their younger counterparts in a tertiary care center in Lebanon. Methods: Retrospective chart review of all patients suffering from cardiac arrests who received CPR during a one year period in a tertiary care center located in a rural area. Results: A total of 98 cardiac arrests were identified who received CPR according to advance cardiac life support protocols (ACLS). Initial return of spontaneous circulation was higher among younger subjects but the difference was not statistically significant (52.6% vs 34.2%, p = 0.136). Survival to discharge was low but slightly higher in the younger subgroup, yet the difference was not statistically significant (5% vs 3%, p = 0.535). Conclusions: Physicians need to be aware of the outcome of CPR in the hospitals they practice in. They can educate their patients about CPR outcome. Such education may help patients and their next of kin make informed decisions jointly with their physician regarding resuscitation.

Factors associated with re-arrest following initial resuscitation from cardiac arrest

BackgroundTo examine patient- and arrest-level factors associated with the incidence of re-arrest in the hospital setting, and to measure the association between re-arrest and survival to discharge. MethodsThis work represents a retrospective cohort study of adult patients who were successfully resuscitated from an initial out-of-hospital cardiac arrest (OHCA) or in-hospital cardiac arrest (ICHA) of non-traumatic origin at two urban academic medical centers. In this study, re-arrest was defined as loss of a pulse following 20min of sustained return of spontaneous circulation (ROSC). ResultsBetween 01/2005 and 04/2016, 1961 patients achieved ROSC following non-traumatic cardiac arrest. Of those, 471 (24%) experienced at least one re-arrest. In re-arrest patients, the median time from initial ROSC to first re-arrest was 5.4h (IQR: 1.1, 61.8). The distribution of initial rhythms between single- and re-arrest patients did not vary, nor did the median duration of initial arrest. Among 108 re-arrest patients with an initial shockable rhythm, 60 (56%) experienced a shockable re-arrest rhythm. Among 273 with an initial nonshockable rhythm, 31 (11%) experienced a shockable re-arrest rhythm. After adjusting for significant covariates, the incidence of re-arrest was associated with a lower likelihood of survival to discharge (OR: 0.32; 95% CI: 0.24–0.43; p<0.001). ConclusionsRe-arrest is a common complication experienced by cardiac arrest patients that achieve ROSC, and occurs early in the course of their post-arrest care. Moreover, re-arrest is associated with a decreased likelihood of survival to discharge, even after adjustments for relevant covariates.

Rates of organ donation in a UK tertiary cardiac arrest centre following out-of-hospital cardiac arrest

AimTo ascertain the rate of successful organ donation (OD) within patients who sustained an out of hospital cardiac arrest (OHCA) with initial return of spontaneous circulation (ROSC) and survival to hospital admission, but whom subsequently do not survive to hospital discharge. MethodsA retrospective audit of ambulance service and hospital databases from January 2010 to January 2015 was undertaken in a United Kingdom tertiary-referral regional cardiac arrest centre. Crude denominator data for cardiac arrests was obtained from the regional ambulance service; the ICU database was interrogated for OHCA patient admissions and outcomes. Patients who died were cross-referenced against the local Organ Donation service database. ResultsFive hundred and fourteen {514} patients were admitted to ICU following OHCA over this five year period. Two hundred and forty-one {241} patients (47%) survived to hospital discharge and 273 (53%) died of whom 106 (39%) were referred to a Specialist Nurse for Organ Donation (SNOD). The conversion rate after the family was approached was 64%. Twenty-eight {28} patients proceeded to donation and 25 patients (24%) successfully donated at least one organ. On average, a patient proceeding to donation provided 1.9 organs. ConclusionsA proactive, systematic approach to OD in OHCA patients can provide a good conversion rate and substantial number of donors. Most donations occur after death from circulatory criteria. There is a positive socio-economic benefit with nearly £4m in savings to the health service within the next 5 years potentially being realised during this period by liberating patients from dialysis.

The Filipino Cardiopulmonary Resuscitation Outcomes Study (Filipino CPR 2015) Among Adult Cardiac Arrest Patients in Tertiary Hospitals in the Philippines: A Prospective Study

Cardiopulmonary resuscitation (CPR) saves lives, but proper techniques must be taught and practiced. Outcomes have to be assessed to improve patient survival. Methods: This is an observational, analytical, prospective study of CPR in adult cardiac arrest cases from selected tertiary hospitals in the Philippines. It describes the characteristics and clinical factors associated with CPR survival in the Philippines based on the American Heart Association 2010 guidelines. Validated Philippine Heart Association hospital cardiac arrest collection forms were used to gather data on the demographics, pre-arrest and CPR/code characteristics of the cases. The investigators analyzed survival outcomes from first arrest to initial return of spontaneous circulation (ROSC) to hospital discharge. Epi Info 6 and STATA 11 statistical software were used for descriptive and inferential statistics, while the chi-square test was used for the association of variables (significant P-value set at &lt;0.05). Stratified analysis and logistic regression analysis were done for confounders. Odds ratios (OR), 95% CI, and p-values were reported. Results: Out of 156 patients, 101 (65%) survived up to ROSC and hospital discharge. The investigators found significant differences in patient survival under the following factors: CPR medications (OR=16.729; 95% CI 1.979, 141.375; P=0.0097); and post-arrest therapeutic hypothermia (OR=8.745; CI 1.826, 41.882; P=0.0067). There were some decision errors on the use of defibrillation for shockable rhythms (26%) and non-shockable rhythms (14.5%). Eighteen rhythms were not properly identified. Conclusion: Decreased interval time from arrest to intubation and from arrest to call for code, CPR medications, and post-arrest therapeutic hypothermia were the most significant contributors to CPR survival in this study. Future training should address the errors in cardiac rhythm interpretation and defibrillator use. Keywords: CPR, ROSC, defibrillation, hypothermia, survival

Re-examining outcomes after unsuccessful out-of-hospital resuscitation in the era of field termination of resuscitation guidelines and regionalized post-resuscitation care

BackgroundDismal prognosis after failed out-of-hospital resuscitation has previously been demonstrated. Changes in resuscitation and post-resuscitation care may affect patient outcomes. We describe characteristics and outcomes of patients with out-of-hospital cardiac arrest (OOHCA) transported to specialty cardiac centers after failure of out-of-hospital interventions. MethodsIn Los Angeles (LA) County, patients with non-traumatic OOHCA with return of spontaneous circulation (ROSC) are transported to specialized cardiac care centers. Outcomes are reported to a registry maintained by the LA County Emergency Medical Services (EMS) Agency. We report patient characteristics and outcomes for the subset of patients treated at these specialty centers in whom initial ROSC was achieved in the ED. The primary outcome was neurologically intact survival, defined by a cerebral performance category (CPC) score of 1 or 2. Results105 patients transported to the SRC after failure to achieve ROSC with out-of-hospital resuscitation were successfully resuscitated in the ED. The median age was 68 years (IQR 57–78); 74 (70%) were male. The presenting rhythm was ventricular fibrillation or ventricular tachycardia in 40 patients (38%) and 86 (82%) were witnessed. Twenty-two patients (21%) survived to hospital discharge. Of the 103 patients with known CPC scores, 13 (13% [95% CI 7–21%]) survived to hospital discharge with a CPC score of 1 or 2. No patient who survived with good neurologic outcome met criteria for termination of resuscitation in the field. ConclusionFailure of out-of-hospital resuscitation is not universally predictive of poor neurologic outcome.

Prophylactic lidocaine for post resuscitation care of patients with out-of-hospital ventricular fibrillation cardiac arrest

BackgroundAntiarrhythmic drugs like lidocaine are usually given to promote return of spontaneous circulation (ROSC) during ongoing out-of-hospital cardiac arrest (OHCA) from ventricular fibrillation/tachycardia (VF/VT). Whether administering such drugs prophylactically for post-resuscitation care after ROSC prevents re-arrest and improves outcome is unstudied. MethodsWe evaluated a cohort of 1721 patients with witnessed VF/VT OHCA who did (1296) or did not receive prophylactic lidocaine (425) at first ROSC. Study endpoints included re-arrest, hospital admission and survival. ResultsProphylacic lidocaine recipients and non-recipients were comparable, except for shorter time to first ROSC and higher systolic blood pressure at ROSC in those receiving lidocaine. After initial ROSC, arrest from VF/VT recurred in 16.7% and from non-shockable arrhythmias in 3.2% of prophylactic lidocaine recipients, 93.5% of whom were admitted to hospital and 62.4% discharged alive, as compared with 37.4%, 7.8%, 84.9% and 44.5%, of corresponding non-recipients (all p<0.0001). Adjusted for pertinent covariates, prophylactic lidocaine was independently associated with reduced odds of re-arrest from VF/VT, odds ratio, (95% confidence interval) 0.34 (0.26–0.44) and from nonshockable arrhythmias (0.47 (0.29–0.78)); a higher hospital admission rate (1.88, (1.28–2.76)) and improved survival to discharge (1.49 (1.15–1.95)). However in a propensity score-matched sensitivity analysis, lidocaine's only beneficial association with outcome was in a lower incidence of recurrent VF/VT arrest. ConclusionsAdministration of prophylactic lidocaine upon ROSC after OHCA was consistently associated with less recurrent VF/VT arrest, and therapeutic equipoise for other measures. The prospect of a promising association between lidocaine prophylaxis and outcome, without evidence of harm, warrants further investigation.

Age Alone May Not Predict Immediate Survival Outcome in Sudden and Unexpected In-hospital Cardiac Arrest

It is unknown whether outcome after unexpected in-hospital cardiopulmonary resuscitation (CPR) differs in the elderly (≥ 65 years) compared to the non-elderly (< 65 years). This study aimed to compare the rate of sustained return of spontaneous circulation (ROSC) in the elderly and those < 65 years old experiencing unexpected in-hospital cardiac arrest (CA). We conducted a retrospective chart review of all resuscitation attempts in cases that involved 65 years of age or older patients following in-hospital CA, in a medical center during a 3-year study period (January 2007 to December 2009). Patients were stratified a priori by type of CA (sudden and expected) and age groups (< 65 years and ≥ 65 years). The variables that lead to sustained ROSC and those that did not lead to sustained ROSC were analyzed. Logistic regression analyses were calculated separately to identify independent risk factors for ROSC. Altogether, 283 unexpected CA were analyzed and among these 191 patients were ≥ 65 years old. There were no significant differences in terms of the rate of sustained ROSC between unexpected and expected CA regardless of age. Less than half of the patients died immediately; an initial ROSC rate as high as 72% for unexpected CA was established in those < 65 years old and the elderly ( p = 0.998). However, underlying diseases could affect the rate of sustained ROSC in geriatric patients with unexpected in-hospital CA. Selected geriatric hospitalized patients may benefit from a short resuscitation attempt. Initial successful resuscitation rate was not inferior to those < 65 years, indicating that initiation of resuscitation should not be affected by age. Patients who are unlikely to benefit from CPR should be identified at or during hospital admission and the possibility of DNR (Do Not Resuscitate) orders should be discussed to avoid inappropriate treatment and potential patient suffering.

Abstract 286: Resuscitation After Traumatic Cardiac Arrest

Introduction In severe trauma patients with cardiac arrest (CA), pre-hospital CPR is performed infrequently and resuscitation outcome is much worse compared to cardiac causes. The purpose of the present study is to analyze CPR outcome in trauma patients with CA using two large German Registries - the German Resuscitation Registry (GRR) and the Trauma Registry of the German Society for Trauma Surgery (TR-DGU). Methods We combined two independent l registries to analyze outcome of trauma patients with CA. The GRR includes patients with pre-hospital CA followed by any resuscitation attempt, whereas the TR-DGU includes patients with severe trauma who reached a hospital alive. Combining both registries may have the potential to enable follow up of patients outcome from scene up to hospital discharge. Individual patients in both registries, however, were not identical. Results and Conclusions Within the GRR database data from 368 (2.8%) trauma CA patients were identified out of 13,329 CA patients. Compared to CA patients with cardiac cause (n=8637), trauma patients had a mean age of 51.2 +/-22.4 years (vs. 68.4 +/-15.2 years in cardiac patients, p&lt;0.001), initial return of spontaneous circulation could be restored in 107(29,1%) patients (vs. 3980 (46,1%) in cardiac patients), and 95 (25,8%) trauma patients had ROSC on admission at hospital (vs. 3673 (42,5%) in cardiac patients). Within the TR-DGU resuscitation attempts were reported in 814 trauma patients (3%) out of 27,592 documented trauma patients. The overall in-hospital mortality rate of these trauma CA patients was 72.9% (n=593 of 814). A two-step approach including both registries revealed that 13% survived 24 hours and 2% had good neurological outcome at hospital discharge out of 100% with a pre-clinical traumatic CA. Trauma patients with CA, however, were significant younger than CA patients with cardiac origin. Therefore, starting CPR in each CA patient, irrespective of the primary cause of CA, should be recommended.

Cardiovascular collapse after return of spontaneous circulation in human out-of-hospital cardiopulmonary arrest

ObjectiveAnimal studies describe cardiovascular collapse (CVC; hypotension or reoccurrence of cardiac arrest) after return of spontaneous circulation (ROSC) from cardiopulmonary arrest. Few studies describe CVC in humans. This study aimed...

Postresuscitation care with mild therapeutic hypothermia and coronary intervention after out-of-hospital cardiopulmonary resuscitation: a prospective registry analysis

IntroductionMild therapeutic hypothermia (MTH) has been shown to result in better neurological outcome after cardiopulmonary resuscitation. Percutaneous coronary intervention (PCI) may also be beneficial in patients after out-of-hospital cardiac arrest (OHCA).MethodsA selected cohort study of 2,973 prospectively documented adult OHCA patients within the German Resuscitation Registry between 2004 and 2010. Data were analyzed by backwards stepwise binary logistic regression to identify the impact of MTH and PCI on both 24-hour survival and neurological outcome that was based on cerebral performance category (CPC) at hospital discharge. Odds ratios (95% confidence intervals) were calculated adjusted for the following confounding factors: age, location of cardiac arrest, presumed etiology, bystander cardiopulmonary resuscitation, witnessing, first electrocardiogram rhythm, and thrombolysis.ResultsThe Preclinical care dataset included 2,973 OHCA patients with 44% initial return of spontaneous circulation (n = 1,302) and 35% hospital admissions (n = 1,040). Seven hundred and eleven out of these 1,040 OHCA patients (68%) were also registered within the Postresuscitation care dataset. Checking for completeness of datasets required the exclusion of 127 Postresuscitation care cases, leaving 584 patients with complete data for final analysis. In patients without PCI (n = 430), MTH was associated with increased 24-hour survival (8.24 (4.24 to 16.0), P < 0.001) and the proportion of patients with CPC 1 or CPC 2 at hospital discharge (2.13 (1.17 to 3.90), P < 0.05) as an independent factor. In normothermic patients (n = 405), PCI was independently associated with increased 24-hour survival (4.46 (2.26 to 8.81), P < 0.001) and CPC 1 or CPC 2 (10.81 (5.86 to 19.93), P < 0.001). Additional analysis of all patients (n = 584) revealed that 24-hour survival was increased by MTH (7.50 (4.12 to 13.65), P < 0.001) and PCI (3.88 (2.11 to 7.13), P < 0.001), while the proportion of patients with CPC 1 or CPC 2 was significantly increased by PCI (5.66 (3.54 to 9.03), P < 0.001) but not by MTH (1.27 (0.79 to 2.03), P = 0.33), although an unadjusted Fisher exact test suggested a significant effect of MTH (unadjusted odds ratio 1.83 (1.23 to 2.74), P < 0.05).ConclusionsPCI may be an independent predictor for good neurological outcome (CPC 1 or CPC 2) at hospital discharge. MTH was associated with better neurological outcome, although subsequent logistic regression analysis did not show statistical significance for MTH as an independent predictor for good neurological outcome. Thus, postresuscitation care on the basis of standardized protocols including coronary intervention and hypothermia may be beneficial after successful resuscitation. One of the main limitations may be a selection bias for patients subjected to PCI and MTH.

Genetic deletion of NOS3 increases lethal cardiac dysfunction following mouse cardiac arrest

Study aimsCardiac arrest mortality is significantly affected by failure to obtain return of spontaneous circulation (ROSC) despite cardiopulmonary resuscitation (CPR). Severe myocardial dysfunction and cardiovascular collapse further affects mortality within hours of initial ROSC. Recent work suggests that enhancement of nitric oxide (NO) signaling within minutes of CPR can improve myocardial function and survival. We studied the role of NO signaling on cardiovascular outcomes following cardiac arrest and resuscitation using endothelial NO synthase knockout (NOS3−/−) mice. MethodsAdult female wild-type (WT) and NOS3−/− mice were anesthetized, intubated, and instrumented with left-ventricular pressure-volume catheters. Cardiac arrest was induced with intravenous potassium chloride. CPR was performed after 8min of untreated arrest. ROSC rate, cardiac function, whole-blood nitrosylhemoglobin (HbNO) concentrations, heart NOS3 content and phosphorylation (p-NOS3), cyclic guanosine monophosphate (cGMP), and phospho-troponin I (p-TnI) were measured. ResultsDespite equal quality CPR, NOS3−/− mice displayed lower rates of ROSC compared to WT (47.6% [10/21] vs. 82.4% [14/17], p<0.005). Among ROSC animals, NOS3−/− vs. WT mice exhibited increased left-ventricular dysfunction and 120min mortality. Prior to ROSC, myocardial effectors of NO signaling including cGMP and p-TnI were decreased in NOS3−/− vs. WT mice (p<0.05). Following ROSC in WT mice, significant NOS3-dependent increases in circulating HbNO were seen by 120min. Significant increases in cardiac p-NOS3 occurred between end-arrest and 15min post-ROSC, while total NOS3 content was increased by 120min post-ROSC (p<0.05). ConclusionsGenetic deletion of NOS3 decreases ROSC rate and worsens post-ROSC left-ventricular function. Poor cardiovascular outcomes are associated with differences in NOS3-dependent myocardial cGMP signaling and circulating NO metabolites.

THIS MONTH IN Anesthesiology

Use of ephedrine versus phenylephrine for treatment of hypotension during spinal anesthesia for cesarean delivery remains controversial despite the observation that ephedrine use is associated with depression of fetal acid–base status. The authors hypothesized that the mechanism underlying this fetal acidosis is transfer of ephedrine across the placenta and stimulation of metabolism in the fetus. In this randomized double-blind study, 104 women undergoing elective cesarean delivery with spinal anesthesia received infusion of phenylephrine or ephedrine titrated to systolic blood pressure. Placental transfer was greater for ephedrine (median umbilical venous [UV]/maternal arterial [MA] plasma concentration ratio 1.13 vs. 0.17). Ephedrine crosses the placenta to a greater extent and the associated increased fetal concentrations of lactate, glucose, and catecholamines support the hypothesis that depression of fetal pH and base excess with ephedrine is related to metabolic effects secondary to stimulation of fetal beta adrenergic receptors. See the accompanying Editorial View on page 470 This study compared the effect of escalating doses of epinephrine in combination with lipid infusion on recovery from bupivacaine overdose using a rat model. Epinephrine improved the initial return of spontaneous circulation (rate-pressure product &gt; 30% baseline) but only 3 of 5 rats at 10 mcg/kg and 1 of 5 rats at 25 mcg/kg sustained return of spontaneous circulation by 15 min. Lipid alone resulted in slower but more sustained recovery. Epinephrine doses greater than 10 mcg/kg increased lactate, worsened acidosis, and resulted in poor recovery at 15 min compared with the lipid only group. Epinephrine doses greater than 10 mcg/kg impair lipid resuscitation from bupivacaine overdose in rats, possibly by inducing hyperlactatemia. See the accompanying Editorial View on page 467 In previous studies, postoperative pain was an independent predictor of postoperative delirium. This study examined whether postoperative delirium affects patient-controlled analgesia (PCA) use in older patients undergoing noncardiac surgery and receiving PCA for postoperative analgesia. Of 335 elderly patients, 68% developed delirium by postoperative day 2. Despite more opioid use, patients with delirium reported higher visual analog scale scores than those without delirium. Future studies on delirium should consider the role of pain and pain management as potential etiologic factors.Traditional approaches to the lumbar plexus (LP) using surface landmarks can be inaccurate. The aim of this study was to determine the accuracy of traditional approaches to the LP and determine if modifications could increase their accuracy. The LP region of 48 formalin-fixed cadavers was dissected and relevant landmarks were marked. Analyses showed that Pandin’s approach was too medial (13 ± 5 mm) and all others were too lateral: Winnie (17 ± 8 mm), Chayen (8 ± 5 mm), Capdevila (6 ± 4 mm), and Dekrey (17 ± 6 mm). Using the posterior superior iliac spine (PSIS) and third lumbar vertebra as landmarks, a proximity to the LP &lt; 5.0 ± 0.3 mm was reached. Relying on the position of the PSIS eliminates the gender and sided differences as well as individual body size that can be problematic for LP blockade.Preexisting pain, anxiety, age, and type of surgery are significant predictors for postoperative pain.Databases were searched for peripheral nerve injuries over a 10-year period at a single institution. See the accompanying Editorial View on page 464 Coadministration of opioids challenges the reliability of the spectral properties of the electroencephalogram in the depth-of-anesthesia estimation.Venous oxygen saturation as a therapeutic target may be associated with improvements in outcome.

Epinephrine Impairs Lipid Resuscitation from Bupivacaine Overdose

Lipid emulsion infusion reverses local anesthetic-induced cardiac toxicity, but the effect of adding epinephrine has not been studied. We compared escalating doses of epinephrine on recovery with lipid infusion in a rat model of bupivacaine overdose. Rats anesthetized with isoflurane received an IV bolus of 20 mg/kg bupivacaine, producing asystole (zero time) in all animals. Ventilation (100% oxygen) and chest compressions were started immediately, and at 3 min the rats received one of six IV treatments (n = 5 for all groups): 5 ml/kg saline followed by infusion for 2 min at 1.0 ml x kg x min, and a second 5 ml/kg bolus at 5 min; or the same bolus and infusion treatment using 30% lipid emulsion plus a single injection of epinephrine at one of five doses: 0 (lipid control), 1, 2.5, 10, or 25 mcg/kg. An electrocardiogram and arterial pressure were monitored continuously, and arterial blood gas was measured at 7.5 and 15 min. Epinephrine improved initial return of spontaneous circulation (rate-pressure product > 30% baseline) but only 3 of 5 rats at 10 mcg/kg and 1 of 5 rats at 25 mcg/kg sustained return of spontaneous circulation by 15 min. Lipid alone resulted in slower but more sustained recovery. Epinephrine doses above a threshold near 10 mcg/kg increased lactate, worsened acidosis, and resulted in poor recovery at 15 min, as compared with lipid controls. There was tight correlation of epinephrine dose to serum lactate at 15 min. Epinephrine over a threshold dose near 10 mcg/kg impairs lipid resuscitation from bupivacaine overdose, possibly by inducing hyperlactatemia.

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

Background Recent 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. Methods Sprague–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% O 2 (100% N 2), (2) 21% O 2, or (3) 100% O 2. 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. Results ROSC was achieved in 1/10 (0% O 2), 9/11 (21% O 2) and 10/12 (100% O 2, p < 0.001). ROSC times after starting CPR were 80 s in the 0% O 2, 115 ± 87 s in the 21% O 2 group and 95 ± 33 s in the 100% O 2 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 PaO 2 at ROSC 2 min (109 ± 44 mm Hg vs. 33 ± 8 mm Hg, p < 0.001). Survival to 72 h was 0/1 (0% O 2), 7/9 (21% O 2) and 8/10 (100% O 2) with a low neurologic deficit score in both O 2 groups (NDS range 5–25). Conclusions In a mild cardiac arrest model with generally good neurologic recovery, initial CPR ventilation with no O 2 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.

Inter-hospital variability in post-cardiac arrest mortality

A growing body of evidence suggests that variability in post-cardiac arrest care contributes to differential outcomes of patients with initial return of spontaneous circulation after cardiac arrest. We examined hospital-level variation in mortality of patients admitted to United States intensive care units (ICUs) with a diagnosis of cardiac arrest. Patients with a primary ICU admission diagnosis of cardiac arrest were identified in the 2002--2005 Acute Physiology and Chronic Health Evaluation (APACHE) IV dataset, a multicenter clinical registry of ICU patients. We identified 4674 patients from 39 hospitals. The median number of annual patients was 33 per hospital (range: 12-116). Mean APACHE score was 94 (+/-38), and overall mortality was 56.8%. Age, severity of illness (acute physiology score), and admission Glasgow Coma Scale were all associated with increased mortality (p<0.001). There was no survival difference for patients admitted from the emergency department vs. the inpatient floor. Among institutions, unadjusted in-hospital mortality ranged from 41% to 81%. After adjusting for age and severity of illness, institutional mortality ranged from 46% to 68%. Patients treated at higher volume centers were significantly less likely to die in the hospital. We demonstrate hospital-level variation in severity adjusted mortality among patients admitted to the ICU after cardiac arrest. We identify a volume-outcome relationship showing lower mortality among patients admitted to ICUs that treat a high volume of post-cardiac arrest patients. Prospective studies should identify hospital-level and patient care factors that contribute to post-cardiac arrest survival.