Cumulative Dose Of Epinephrine Research Articles

Cumulative epinephrine dose during cardiac arrest and neurologic outcome after extracorporeal cardiopulmonary resuscitation

BackgroundEpinephrine is recommended without an apparent ceiling dosage during cardiac arrest. However, excessive alpha- and beta-adrenergic stimulation may contribute to unnecessarily high aortic afterload, promote post-arrest myocardial dysfunction, and result in cerebral microvascular insufficiency in patients receiving extracorporeal cardiopulmonary resuscitation (ECPR). MethodsThis was a retrospective cohort study of adults (≥ 18 years) who received ECPR at large academic ECMO center from 2018 to 2022. Patients were grouped based on the amount of epinephrine given during cardiac arrest into low (≤ 3 mg) and high (> 3 mg) groups. The primary endpoint was neurologic outcome at hospital discharge, defined by cerebral performance category (CPC). Multivariable logistic regression was used to assess the relationship between cumulative epinephrine dosage during arrest and neurologic outcome. ResultsAmong 51 included ECPR cases, the median age of patients was 60 years, and 55% were male. The mean cumulative epinephrine dose administered during arrest was 6.2 mg but ranged from 0 to 24 mg. There were 18 patients in the low-dose (≤ 3 mg) and 25 patients in the high-dose (> 3 mg) epinephrine groups. Favorable neurologic outcome at discharge was significantly greater in the low-dose (55%) compared to the high-dose (24%) group (p = 0.025). After adjusting for age, those who received higher doses of epinephrine during the arrest were more likely to have unfavorable neurologic outcomes at hospital discharge (odds ratio 4.6, 95% CI 1.3, 18.0, p = 0.017). ConclusionAfter adjusting for age, cumulative epinephrine doses above 3 mg during cardiac arrest may be associated with unfavorable neurologic outcomes after ECPR and require further investigation.

Cumulative dose of epinephrine and mode of death after non-shockable out-of-hospital cardiac arrest: a registry-based study

BackgroundEpinephrine increases the chances of return of spontaneous circulation (ROSC) in out-of-hospital cardiac arrest (OHCA), especially when the initial rhythm is non-shockable. However, this drug could also worsen the post-resuscitation syndrome (PRS). We assessed the association between epinephrine use during cardiopulmonary resuscitation (CPR) and subsequent intensive care unit (ICU) mortality in patients with ROSC after non-shockable OHCA.MethodsWe used data prospectively collected in the Sudden Death Expertise Center (SDEC) registry (capturing OHCA data located in the Greater Paris area, France) between May 2011 and December 2021. All adults with ROSC after medical, cardiac and non-cardiac causes, non-shockable OHCA admitted to an ICU were included. The mode of death in the ICU was categorized as cardiocirculatory, neurological, or other.ResultsOf the 2,792 patients analyzed, there were 242 (8.7%) survivors at hospital discharge, 1,004 (35.9%) deaths from cardiocirculatory causes, 1,233 (44.2%) deaths from neurological causes, and 313 (11.2%) deaths from other etiologies. The cardiocirculatory death group received more epinephrine (4.6 ± 3.8 mg versus 1.7 ± 2.8 mg, 3.2 ± 2.6 mg, and 3.5 ± 3.6 mg for survivors, neurological deaths, and other deaths, respectively; p < 0.001). The proportion of cardiocirculatory death increased linearly (R2 = 0.92, p < 0.001) with cumulative epinephrine doses during CPR (17.7% in subjects who did not receive epinephrine and 62.5% in those who received > 10 mg). In multivariable analysis, a cumulative dose of epinephrine was strongly associated with cardiocirculatory death (adjusted odds ratio of 3.45, 95% CI [2.01–5.92] for 1 mg of epinephrine; 12.28, 95% CI [7.52–20.06] for 2–5 mg; and 23.71, 95% CI [11.02–50.97] for > 5 mg; reference 0 mg; population reference: alive at hospital discharge), even after adjustment on duration of resuscitation. The other modes of death (neurological and other causes) were also associated with epinephrine use, but to a lesser extent.ConclusionsIn non-shockable OHCA with ROSC, the dose of epinephrine used during CPR is strongly associated with early cardiocirculatory death. Further clinical studies aimed at limiting the dose of epinephrine during CPR seem warranted. Moreover, strategies for the prevention and management of PRS should take this dose of epinephrine into consideration for future trials.

Epinephrine Dosing Use During Extracorporeal Cardiopulmonary Resuscitation: Single-Center Retrospective Cohort.

During pediatric cardiac arrest, contemporary guidelines recommend dosing epinephrine at regular intervals, including in patients requiring extracorporeal membrane oxygenation (ECMO). The impact of epinephrine-induced vasoconstriction on systemic afterload and venoarterial ECMO support is not well-defined. Nested retrospective observational study within a single center. The primary exposure was time from last dose of epinephrine to initiation of ECMO flow; secondary exposures included cumulative epinephrine dose and arrest time. Systemic afterload was assessed by mean arterial pressure and use of systemic vasodilator therapy; ECMO pump flow and Vasoactive-Inotrope Score (VIS) were used as measures of ECMO support. Clearance of lactate was followed post-cannulation as a marker of systemic perfusion. PICU and cardiac ICU in a quaternary-care center. Patients 0-18 years old who required ECMO cannulation during resuscitation over the 6 years, 2014-2020. Patients were excluded if ECMO was initiated before cardiac arrest or if the resuscitation record was incomplete. None. A total of 92 events in 87 patients, with 69 events having complete data for analysis. The median (interquartile range) of total epinephrine dosing was 65 mcg/kg (37-101 mcg/kg), with the last dose given 6 minutes (2-16 min) before the initiation of ECMO flows. Shorter interval between last epinephrine dose and ECMO initiation was associated with increased use of vasodilators within 6 hours of ECMO (p = 0.05), but not with mean arterial pressure after 1 hour of support (estimate, -0.34; p = 0.06). No other associations were identified between epinephrine delivery and mean arterial blood pressure, vasodilator use, pump speed, VIS, or lactate clearance. There is limited evidence to support the idea that regular dosing of epinephrine during cardiac arrest is associated with increased in afterload after ECMO cannulation. Additional studies are needed to validate findings against ECMO flows and clinically relevant outcomes.

Temporal Changes in Epinephrine Dosing in Out-of-Hospital Cardiac Arrest: A Review of EMS Protocols across the United States.

Administration of epinephrine has been associated with worse neurological outcomes for survivors of out-of-hospital cardiac arrest. The publication of the 2018 PARAMEDIC-2 trial, a randomized and double-blind study of epinephrine in out-of-hospital cardiac arrest, provides the strongest evidence to date that epinephrine increases return of spontaneous circulation (ROSC) but not neurologically intact survival. This study aims to determine if Emergency Medical Services (EMS) cardiac arrest protocols have changed since the publication of PARAMEDIC-2. States in the US utilizing mandatory or model state-wide EMS protocols, including Washington DC, were included in this study. The nontraumatic cardiac arrest protocol as of January 1, 2018 was compared to the protocol in effect on January 1, 2021 to determine if there was a change in the administration of epinephrine. Protocols were downloaded from the relevant state EMS website. If a protocol could not be obtained, the state medical director was contacted. A 2021 state-wide protocol was found for 32/51 (62.7%) states. Data from 2018 were available for 21/51 (41.2%) states. Of the 11 states without data from 2018, all follow Advanced Cardiac Life Support (ACLS) guidelines in the 2021 protocol. Five (15.6%) of the states with a state-wide protocol made a change in the cardiac arrest protocols. Maximum cumulative epinephrine dose was limited to 4mg in Maryland and 3mg in Vermont. Rhode Island changed epinephrine in shockable rhythms to be administered after three cycles of cardiopulmonary resuscitation (CPR) and an anti-arrhythmic. Rhode Island also added an epinephrine infusion as an option. No states removed epinephrine administration from their cardiac arrest protocol. Simple statistical analysis was performed with Microsoft Excel. Several states have adjusted cardiac arrest protocols since 2018. The most frequent change was limiting the maximum cumulative dosage of epinephrine. One state changed timing of epinephrine dosing depending on the rhythm and also provided an option of an epinephrine infusion in place of bolus dosing. While the sample size is small, these changes may reflect the future direction of prehospital cardiac arrest protocols. Significant limitations apply, including the exclusion of local and regional protocols which are more capable of quickly adjusting to new research. Additionally, this study is only focused on EMS in the United States.

Effect of a Larger Flush Volume on Bioavailability and Efficacy of Umbilical Venous Epinephrine during Neonatal Resuscitation in Ovine Asphyxial Arrest.

The 7th edition of the Textbook of Neonatal Resuscitation recommends administration of epinephrine via an umbilical venous catheter (UVC) inserted 2–4 cm below the skin, followed by a 0.5-mL to 1-mL flush for severe bradycardia despite effective ventilation and chest compressions (CC). This volume of flush may not be adequate to push epinephrine to the right atrium in the absence of intrinsic cardiac activity during CC. The objective of our study was to evaluate the effect of 1-mL and 2.5-mL flush volumes after UVC epinephrine administration on the incidence and time to achieve return of spontaneous circulation (ROSC) in a near-term ovine model of perinatal asphyxia induced cardiac arrest. After 5 min of asystole, lambs were resuscitated per Neonatal Resuscitation Program (NRP) guidelines. During resuscitation, lambs received epinephrine through a UVC followed by 1-mL or 2.5-mL normal saline flush. Hemodynamics and plasma epinephrine concentrations were monitored. Three out of seven (43%) and 12/15 (80%) lambs achieved ROSC after the first dose of epinephrine with 1-mL and 2.5-mL flush respectively (p = 0.08). Median time to ROSC and cumulative epinephrine dose required were not different. Plasma epinephrine concentrations at 1 min after epinephrine administration were not different. From our pilot study, higher flush volume after first dose of epinephrine may be of benefit during neonatal resuscitation. More translational and clinical trials are needed.

Epinephrine treatment but not time to ROSC is associated with intestinal injury in patients with cardiac arrest

AimCurrent guidelines suggest the use of epinephrine in patients with cardiac arrest (CA). However, evidence for increased survival in good neurological condition is lacking. In experimental settings, epinephrine-induced impairment of microvascular flow was shown. The aim of our study was to analyze the association between epinephrine treatment and intestinal injury in patients after CA. MethodsWe have included 52 patients with return of spontaneous circulation (ROSC) after CA admitted to our medical intensive care unit (ICU). Blood was taken on admission and levels of circulating intestinal fatty acid binding protein (iFABP) were analyzed. ResultsPatients were 64 (49.8–73.8) years old and predominantly male (76.9%). After six months, 50% of patients died and 38.5% of patients had a cerebral performance category (CPC)-score of 1–2. iFABP levels were lower in survivors (234 IQR 90–399 pg/mL) as compared to non-survivors (283, IQR 86–11500 pg/mL; p < 0.05). Plasma levels of iFABP were not associated with time to ROSC but correlated with epinephrine-dose (R = 0.32; p < 0.05). 40% of patients receiving ≥3 mg of epinephrine as compared to 10.5% of patients treated with <3 mg (p < 0.05) developed iFABP plasma levels >1500 pg/mL, which was associated with dramatically increased mortality (HR4.87, 95%CI 1.95–12.1; p < 0.001). iFABP levels predicted mortality independent from time to ROSC and the disease severity score SAPS II. In contrast to mortality, iFABP plasma levels were not associated with neurological outcome. ConclusionsIn this small, single centre study, cumulative dose of epinephrine used in cardiac arrest patients was associated with an increase in biomarker indicative of intestinal injury and 6-month mortality.

Pupillary Light Reflex Is Not Abolished by Epinephrine and Atropine Given During Advanced Cardiac Life Support in Patients Who Achieve Return of Spontaneous Circulation.

Absence of pupillary light reflex (PLR) is a well-studied indicator of poor neurologic recovery after cardiac arrest. Interpretation of absent PLR is difficult in patients with hypothermia or hypotension, or who have electrolyte or acid-base disturbances. Additionally, many studies exclude patients who receive epinephrine or atropine from their analysis on the basis that these drugs are thought to abolish the PLR. This observational cohort study assessed for presence or absence of PLR in in-hospital cardiac arrest patients who received epinephrine with or without atropine during advanced cardiac life support and achieved return of spontaneous circulation (ROSC). Pupil size and reactivity were assessed in adult patients who had an in-hospital cardiac arrest, received epinephrine with or without atropine, and achieved ROSC. Measurements were taken using a NeurOptics NPi-200 infrared pupillometer. Forty patients had pupillometry performed within 1 hour (median: 6 minutes) after ROSC. Of these only 1 (2.5%) patient had nonreactive pupils at first measurement after ROSC. The remaining 39 (97.5%) had reactive pupils. Of the 19 patients who had pupils checked within 3 minutes of ROSC, 100% had reactive pupils. Degree of pupil responsiveness was not correlated with cumulative dose of epinephrine. Ten patients received atropine in addition to epinephrine, including the sole patient with nonreactive pupils. The remaining 9 (90%) had reactive pupils. Epinephrine and atropine do not abolish the PLR in patients who achieve ROSC after in-hospital cardiac arrest. Lack of pupillary response in the post-arrest patient should not be attributed to these drugs.

Abstract 220: More Patience to the Patient? -The Timing of Initiating Targeted Temperature Management

Introduction: The timing of Targeted Temperature Management (TTM) after Return of spontaneous circulation (ROSC) is controversial. Spontaneous neurological recovery can avoid the resource-wasting and adverse events of TTM. The purpose of this study is to determine the percentage of spontaneous recovery in a three-hour interval post ROSC, and to predict factors of recovery to Glasgow-Coma-Scale (GCS) Motor response 6 (M6). Hypothesis: Some patients may recover to GCS M6 in the early post ROSC period. These patients may also have favorable neurological outcome at discharge. Methods: This was a single center observational study which enrolled 541 patients with ROSC after OHCA. We recorded the motor response post ROSC, the motor response at 3hr, the patients’ characteristics, and resuscitation variables. Predictors of GCS M6 were assessed by multiple logistic regression analysis. Results: Graph 1 showed the number of patients with motor response change in a three-hour interval. All 96 patients with GCS M6 at 3hr had favorable neurological outcome, except 6 died from cardiogenic shock and 7 died from terminal cancer status. GCS M6 at 3hr, instead of GCS M6 post ROSC, was a predictor for favorable neurological outcome (OR, 2.09; 95%CI, 1.80-2.42; P= 0.0001) when adjusted with demographic and resuscitation variables. There were three factors predicting the GCS M6 at 3hr, including the cumulative epinephrine dose (OR, 0.81; 95% CI, 0.70 - 0.93; P=0.003), the CPR duration (OR, 0.957; 95% CI, 0.93 -0.98; P=0.001), and the initial shockable rhythm (OR, 4.41; 95% CI, 2.44 - 7.85; P=0.0001). Conclusions: A significant portion of patients had spontaneous recovery to GCS M6 within 3 hours, and had favorable neurological outcome. Certain factors could be used to predict the recovery in early post ROSC period. The optimal timing of TTM could be re-evaluated. Close monitoring GCS together with appropriate usage of sedation are critical for patients with higher chance of neurological recovery.

Epinephrine administration in non-shockable out-of-hospital cardiac arrest

BackgroundEpinephrine is recommended for the treatment of non-shockable out of hospital cardiac arrest (OHCA) to obtain return of spontaneous circulation (ROSC). Epinephrine efficiency and safety remain under debate. ObjectiveWe propose to describe the association between the cumulative dose of epinephrine and the failure of ROSC during the first 30 min of advanced life support (ALS). MethodologyA retrospective observational cohort study using the Paris SAMU 75 registry including all non-traumatic OHCA. All OHCA receiving epinephrine during the first 30 min of ALS were enrolled. Cumulative epinephrine dose given during ALS to ROSC was retrieved from medical reports. ResultsAmong 1532 patients with OHCA, 776 (51%) had initial non-shockable rhythm. Fifty-four patients were excluded for missing data.The mean value of cumulative dose of epinephrine was 10 ± 4 mg in patients who failed to achieve ROSC (ROSC−) and 4 ± 3 mg (p = 0.04) for those who achieved ROSC.ROC curve analysis indicated a cut-off point of 7 mg total cumulative epinephrine associated with ROSC− (AUC = 0.89 [0.86–0.92]).Using propensity score analysis including age, sex and no-flow duration, association with ROSC− only remained significant for epinephrine > 7 mg (p ≤10–3, OR [CI95] = 1.53 [1.42–1.65]). ConclusionAn association between total cumulative epinephrine dose administered during OHCA resuscitation and ROSC− was reported with a threshold of 7 mg, best identifying patients with refractory OHCA. We suggest using this threshold in this context to guide the termination of ALS and early decide on the implementation of extracorporeal life support or organ harvesting in the first 30 min of ALS.

Vasopressor Cumulative Dose Requirement and Risk of Early Death During Septic Shock: An Analysis From The EPISS Cohort.

Septic shock is the primary cause of death in intensive care units, with about 20% of patients dying in the first 3 days. To design future trials focused on early mortality, we require knowledge of early indicators that can detect patients at high risk of early death from refractory septic shock. The aim of this study was to assess whether the cumulative dose of vasopressors (CDV), calculated as the cumulative dose of epinephrine + norepinephrine, is a predictor of early death (within 72 h) attributable to refractory septic shock (EDASS). This substudy of the EPISS trial was based on 370 patients admitted to a French ICU for septic shock between 2009 and 2011. The area under the receiving operating characteristic curve was calculated for the CDV at 6, 12, 24, 36, and 48 h after vasopressor initiation, and a strategy to predict the risk of EDASS was built based on selected times and thresholds. Among the 370 patients included, 51 (14%) died within the first 72 h with 40 (11%) EDASS. A strategy in two steps (CDV ≥ 800 μg/kg at 6 h and/or CDV ≥ 2,600 μg/kg at 24 h) was able to predict EDASS with sensitivity of 45%, specificity 97%, positive predictive value 78% and negative predictive value 94%. Overall, our results confirm that early death directly attributable to septic shock could be effectively predicted by the CDV in the first hours of treatment. These results will help to select patients eligible for innovative therapies aimed at improving early mortality in septic shock.

Levosimendan combined with epinephrine improves rescue outcomes in a rat model of lipid-based resuscitation from bupivacaine-induced cardiac arrest

BackgroundThe effectiveness of a combination of a lipid emulsion with epinephrine in reversing local anesthetic-induced cardiac arrest has been confirmed. The combination of a lipid emulsion with levosimendan, was shown to be superior to administration of a lipid emulsion alone with regard to successful resuscitation. In this study, we compared the reversal effects of levosimendan, epinephrine, and a combination of the two agents in lipid-based resuscitation in a rat model of bupivacaine-induced cardiac arrest.MethodsFifty-four adult male Sprague-Dawley rats were subjected to bupivacaine (15 mg·kg−1) –induced asystole and were then randomly divided into 3 groups. A lipid emulsion was used as the basic treatment, and administration of drug combinations varied in each group as follows: (1) levosimendan combined with epinephrine (LiEL); (2) epinephrine (LiE); and (3) levosimendan (LiL). The resuscitation outcomes were recorded and included the rate of return of spontaneous circulation (ROSC) and survival at 40 min, time to first heartbeat, time to ROSC, and cumulative dose of epinephrine. We calculated the wet-to-dry ratio of the lung, blood gas values at 40 min and bupivacaine concentration of cardiac tissue and plasma.ResultsThe rates of ROSC in LiEL and LiE groups were higher than LiL group (P < 0.001; LiEL vs LiL, P = 0.001; LiE vs LiL, P = 0.007). The survival rate in LiEL group was higher than LiE group (P = 0.003; LiEL vs LiE, P = 0.008; LiEL vs LiL, P = 0.001). The time to first heart beat in LiEL group was shorter than LiE, LiL groups. (P < 0.001; LiE vs LiEL, P = 0.001; LiL vs LiEL, P < 0.001). The time to ROSC in LiEL group was shorter than LiE, LiL groups (P < 0.001; LiEL vs LiE, P < 0.001; LiEL vs LiL, P < 0.001). The result was similar for the bupivacaine concentration of cardiac tissue and plasma (cardiac tissue: P = 0.002; plasma: P = 0.011). Furthermore, there were significant differences in the blood-gas values at 40 min, wet-to-dry lung weight ratio, and ratio of damaged alveoli among groups. The LiEL group had the best result for all parameters (P < 0.01, P = 0.008, P < 0.001, respectively). Additionally, significantly less epinephrine was used in the LiEL group (P < 0.001).ConclusionsLevosimendan combined with epinephrine may be superior to either drug alone for lipid-based resuscitation in a rat model of bupivacaine-induced cardiac arrest. The drug combination was associated with a higher survival rate as well as decreased epinephrine consumption and lung damage.

Abstract 12857: Echocardiographic Patterns of Post-cardiac Arrest Myocardial Dysfunction

Purpose: Post-cardiac arrest myocardial dysfunction can be developed after successful resuscitation from cardiac arrest. However, echocardiographic patterns of post-cardiac arrest myocardial dysfunction are not yet known. The purpose of this study was to investigate the manifestations of post-cardiac arrest myocardial dysfunction with serial echocardiography during post-cardiac arrest period. Materials and Methods: We enrolled non-traumatic out-of-hospital cardiac arrest patients older than 18 years old who were successfully resuscitated after CPR. The patients with myocardial infarction and pre-existing cardiac disease including heart failure or myocardial disease were excluded. Transthoracic echocardiography was performed within 24 hours, between 24 to 48 hours, after 48 hour since restoration of spontaneous circulation (ROSC) was achieved. Results: Out of 263 patients, 186 patients (122 males) were enrolled in the analysis. No left ventricular (LV) dysfunction was observed in 120 patients (64.5%). Abnormal LV dysfunction was observed in 66 patients (35.5%). Abnormal LV dysfunctions included global hypokinesis in 32 patients (17.2%), regional wall motion abnormalities (RWMA) in 25 patients (13.4%), and abnormalities like stress-induced cardiomyopathy in 9 patients (4.8%). There were no differences in etiology (p=0.275), duration of cardiac arrest (p=0.078), cumulative dose of epinephrine (p=0.336), and hospital mortality (p=0.140) according to the pattern of post-cardiac arrest myocardial dysfunction. In subgroup analysis of the patients with shockable rhythm, cumulative defibrillation energy (joules) was lower in patients without LV dysfunction (101±41) than in patients with RWMA (200±74) or global hypokinesis (408±131) (p=0.011). Cut-off value of 220 J had 21% of sensitivity and 91% of specificity for development of LV dysfunction (AUC=0.572). Conclusion: Post-cardiac arrest myocardial dysfunction occurs in one thirds of patients resuscitated from cardiac arrest. Echocardiographic patterns of post-cardiac arrest LV dysfunction include global hypokinesis, regional wall motion abnormalities, and abnormalities like stress-induced cardiomyopathy.

Feasibility and influence of hTEE monitoring on postoperative management in cardiac surgery patients.

Monoplane hemodynamic TEE (hTEE) monitoring (ImaCor(®) ClariTEE(®)) might be a useful alternative to continuously evaluate cardiovascular function and we aimed to investigate the feasibility and influence of hTEE monitoring on postoperative management in cardiac surgery patients. After IRB approval we reviewed the electronic data of cardiac surgery patients admitted to our intensive care between 01/01/2012 and 30/06/2013 in a case-controlled matched-pairs design. Patients were eligible for the study when they presented a sustained hemodynamic instability postoperatively with the clinical need of an extended hemodynamic monitoring: (a) hTEE (hTEE group, n = 18), or (b) transpulmonary thermodilution (control group, n = 18). hTEE was performed by ICU residents after receiving an approximately 6-h hTEE training session. For hTEE guided hemodynamic optimization an institutional algorithm was used. The hTEE probe was blindly inserted at the first attempt in all patients and image quality was at least judged to be adequate. The frequency of hemodynamic examinations was higher (ten complete hTEE examinations every 2.6 h) in contrast to the control group (one examination every 8 h). hTEE findings, including five unexpected right heart failure and one pericardial tamponade, led to a change of current therapy in 89% of patients. The cumulative dose of epinephrine was significantly reduced (p = 0.034) and levosimendan administration was significantly increased (p = 0.047) in the hTEE group. hTEE was non-inferior to the control group in guiding norepinephrine treatment (p = 0.038). hTEE monitoring performed by ICU residents was feasible and beneficially influenced the postoperative management of cardiac surgery patients.

Abstract 270: Developing a Ventricular Fibrillation Cardiac Arrest Rat Model - Pitfalls and Challenges

Introduction: The ideal rodent model of ventricular fibrillation (VF) cardiac arrest (CA) produces consistent histologic and neurologic damage as target for novel therapies and shows a high survival rate to minimize animal use and allow for long term outcome. VF induction, chest compressions and ventilation are crucial techniques and published in many variants in literature. We report our experiences during model development. Materials and Methods: A non-randomized cohort study evaluating different methods of VF induction, chest compressions techniques, mechanical ventilation and defibrillation was performed with regards to it’s feasibility, complications, ROSC rate and survival. Results: Male Sprague-Dawley rats (350g, anesthetised, instrumented) underwent VF induction with 2 min endocardial fibrillation via a transjugular neonatal pacing catheter with minimal current use, low incidence of autodefibrillation and good resuscitability. Mechanical chest compressions with approx. 30% of thorax diameter depth were applied with a pneumatic thumper 200/min placed mid-sternally, tilted upwards. Strong fixation with tapes avoided throrax-instability. Epinephrine (20μg/kg) and NaHCO3 (1mmol/ kg) were administered before CPR start and epinephrine repeatedly given after defibrillations every 2min. For defibrillations (5J, biphasic) modified paediatric defi pads were used. ROSC was achieved in 7/10 animals in a 6 min CA group and 6/11 in a 8 min CA group. CPR time was 2.6±1.0 min (mean±SD), number of defibrillations needed 2±1 and a cumulative epinephrine dose of 46±10 μg/kg with no differences between groups. Conclusions: Researchers developing a VF CA model are facing a multitude of difficulties, a lack of data on model development and many variations published in literature, often without detailed description. We developed a CPR rat model for VF CA with graded cognitive deficits and long-term survival. We propose detailed description of model development, including ineffective methods, to facilitate experience exchange between research groups, to avoid that future experimental groups repeat possible mistakes.

Vasopressin reduces the cumulative epinephrine dose in hypothermic swine with traumatic brain injury

Prevention of secondary neurologic injuries is paramount for improved neurologic outcomes after traumatic brain injury (TBI). Evidence suggests that although therapeutic hypothermia (TH) lowers intracranial pressure and attenuates secondary cerebral insults after TBI [1], it also induces hypotension. Brief episodes of mild hypotension in brain-injured patients can trigger secondary injuries, which have been associated with increased mortality in patients with TBI [2]. Vasopressin mitigates hypotension in septic shock and improves coronary perfusion in hypothermic cardiac arrest models [3]. We hypothesized that a low-dose vasopressin infusion may reduce the cumulative epinephrine dose in hypothermic, brain-injured swine.

Total epinephrine dose during asystole and pulseless electrical activity cardiac arrests is associated with unfavourable functional outcome and increased in-hospital mortality

AimEpinephrine is the drug of choice during advanced cardiac life support. The cumulative dose of epinephrine applied during resuscitation was shown to be independently associated with unfavourable outcome after ventricular fibrillation cardiac arrest in humans. Our objective was to investigate the association between the cumulative dose of epinephrine applied during resuscitation and unfavourable functional outcome and in-hospital mortality, in patients with asystole and pulseless electric activity. MethodsData on 946 patients admitted to the emergency department after resuscitation of witnessed in-hospital and out-of hospital cardiac arrest with asystole or pulseless electric activity were retrieved from the cardiac arrest registry of the emergency department at the Vienna General Hospital/Medical University of Vienna. Data were documented according to Utstein Style. The risk factor was cumulative epinephrine categorized into quartiles. The endpoints were unfavourable functional outcome and in-hospital mortality. ResultsThe median cumulative amount of epinephrine administered was 2mg (IQR 0–5), ranging from 1 to 50mg. Of all patients 643/946 (68%) had an unfavourable functional outcome, 649/946 (69%) died during hospital stay. The multivariable analysis showed a statistically significant increasing risk for unfavourable functional outcome and in-hospital mortality outcome with increasing cumulative doses of epinephrine (unfavourable functional outcome: OR 1–1.45–2.25–2.95 over quartiles of epinephrine; in hospital mortality: OR 1–1.35–2.15–2.82 over quartiles of epinephrine). ConclusionOur results show that an increasing cumulative dose of epinephrine during resuscitation of patients with asystole and pulseless electric activity is an independent risk factor for unfavourable functional outcome and in-hospital mortality.

Total epinephrine dose during resuscitation is associated with unfavorable functional outcome after cardiac arrest with asystole and pulseless electric activity in humans

Purpose of the study: Epinephrine is the drug of choice during advanced cardiac life support. The cumulative dose of epinephrine applied during resuscitation was shown to be independently associated with unfavorable outcome after ventricular fibrillation cardiac arrest in humans. Our objective was to investigate the association between the cumulative dose of epinephrine applied during resuscitation and in-hospital mortality and functional outcome, in patients with asystole and pulseless electric activity.Materials and methods: This retrospective cohort study is based on a cardiac arrest registry of the emergency department at the Vienna General Hospital/Medical University of Vienna. It comprises 946 patients admitted to the emergency department after resuscitation of witnessed cardiac arrest with asystole or pulseless electric activity. Data were documented according to Utstein Style. The risk factor was cumulative epinephrine categorized into quartiles. The endpoints were in-hospital mortality and unfavorable functional outcome.Results: The median cumulative amount of epinephrine administered was 2 mg (IQR 0–5), ranging from 1 to 50 mg. Of all patients 649 (69%) died during hospital stay, 643 (69%) had an unfavorable functional outcome. The multivariate analysis showed a statistically significant increasing risk for in-hospital mortality and unfavorable functional outcome with increasing cumulative doses of epinephrine (in hospital mortality: OR 1–1.54–2.73–4.42 over quartiles of epinephrine; unfavorable functional outcome: OR 1–1.8–3.66–6.45 over quartiles of epinephrine).Conclusion: Our results show that an increasing cumulative dose of epinephrine during resuscitation of patients with asystole and pulseless electric activity is an independent risk factor for in-hospital death and unfavorable functional outcome. Purpose of the study: Epinephrine is the drug of choice during advanced cardiac life support. The cumulative dose of epinephrine applied during resuscitation was shown to be independently associated with unfavorable outcome after ventricular fibrillation cardiac arrest in humans. Our objective was to investigate the association between the cumulative dose of epinephrine applied during resuscitation and in-hospital mortality and functional outcome, in patients with asystole and pulseless electric activity. Materials and methods: This retrospective cohort study is based on a cardiac arrest registry of the emergency department at the Vienna General Hospital/Medical University of Vienna. It comprises 946 patients admitted to the emergency department after resuscitation of witnessed cardiac arrest with asystole or pulseless electric activity. Data were documented according to Utstein Style. The risk factor was cumulative epinephrine categorized into quartiles. The endpoints were in-hospital mortality and unfavorable functional outcome. Results: The median cumulative amount of epinephrine administered was 2 mg (IQR 0–5), ranging from 1 to 50 mg. Of all patients 649 (69%) died during hospital stay, 643 (69%) had an unfavorable functional outcome. The multivariate analysis showed a statistically significant increasing risk for in-hospital mortality and unfavorable functional outcome with increasing cumulative doses of epinephrine (in hospital mortality: OR 1–1.54–2.73–4.42 over quartiles of epinephrine; unfavorable functional outcome: OR 1–1.8–3.66–6.45 over quartiles of epinephrine). Conclusion: Our results show that an increasing cumulative dose of epinephrine during resuscitation of patients with asystole and pulseless electric activity is an independent risk factor for in-hospital death and unfavorable functional outcome.

Pharmacokinetics of epinephrine in patients with septic shock: modelization and interaction with endogenous neurohormonal status

IntroductionIn septic patients, an unpredictable response to epinephrine may be due to pharmacodynamic factors or to non-linear pharmacokinetics. The purpose of this study was to investigate the pharmacokinetics of epinephrine and its determinants in patients with septic shock.MethodsThirty-eight consecutive adult patients with septic shock were prospectively recruited immediately before epinephrine infusion. A baseline blood sample (C0) was taken to assess endogenous epinephrine, norepinephrine, renin, aldosterone, and plasma cortisol levels before epinephrine infusion. At a fixed cumulative epinephrine dose adjusted to body weight and under steady-state infusion, a second blood sample (C1) was taken to assess epinephrine and norepinephrine concentrations. Data were analyzed using the nonlinear mixed effect modeling software program NONMEM.ResultsPlasma epinephrine concentrations ranged from 4.4 to 540 nmol/L at steady-state infusion (range 0.1 to 7 mg/hr; 0.026 to 1.67 μg/kg/min). A one-compartment model adequately described the data. Only body weight (BW) and New Simplified Acute Physiologic Score (SAPSII) at intensive care unit admission significantly influenced epinephrine clearance: CL (L/hr) = 127 × (BW/70)0.60 × (SAPS II/50)-0.67. The corresponding half-life was 3.5 minutes. Endogenous norepinephrine plasma concentration significantly decreased during epinephrine infusion (median (range) 8.8 (1 – 56.7) at C0 vs. 4.5 (0.3 – 38.9) nmol/L at C1, P < 0.001).ConclusionsEpinephrine pharmacokinetics is linear in septic shock patients, without any saturation at high doses. Basal neurohormonal status does not influence epinephrine pharmacokinetics. Exogenous epinephrine may alter the endogenous norepinephrine metabolism in septic patients.

Abstract P153: The Cumulative Dose of Epinephrine During Cardiopulmonary Resuscitation Increases Mortality and Functional Outcome after Non-Ventricular Fibrillation Cardiac Arrest

Background - Epinephrine is the drug of choice during advanced cardiac life support. The cumulative dose of epinephrine applied during resuscitation was shown to be independently associated with unfavorable outcome after ventricular fibrillation cardiac arrest in humans. We investigated the association between the cumulative dose of epinephrine applied during resuscitation and outcome after non-ventricular fibrillation cardiac arrest. Methods - Adults admitted to the University Hospital Emergency Department with witnessed, non-traumatic, normothermic, non-ventricular fibrillation cardiac arrest of cardiac or pulmonary origin were included. The primary endpoint was in-hospital mortality, the secondary endpoint was unfavorable functional outcome (best cerebral performance category within 6 months; CPC 1, normal, CPC 2, moderate disability; CPC 3, severe disability and not able to live independently; CPC 4, coma; CPC 5, dead or brain dead; CPC 3–5 considered as unfavorable). Results - Of 2716 enrolled patients 578 patients fulfilled the inclusion criteria. The median cumulative amount of epinephrine administered during resuscitation was 3 mg (IQR 2– 6), ranging from 1 to 50 mg. Of all patients, 390 (67%) died during their hospital stay, 310 (62%) showed an unfavorable functional outcome. Patients, who died during hospital stay, received a statistically higher cumulative dose of epinephrine than patients, who survived, median (IQR) 4 mg (2– 6) vs. 2 mg (2– 4), p&lt;0.01. After controlling for possible confounders (patient characteristics, resuscitation factors, comorbidities), logistic regression analysis showed that higher doses of epinephrine were independently associated with an increased mortality (OR 1.3 per quartile administered epinephrine, 95% CI 1.07–1.65, p=0.01), and unfavorable functional outcome (OR 1.4 per quartile administered epinephrine, 95% CI 1.12–1.81, p=0.004). Conclusions -Our results indicate that an increasing cumulative dose of epinephrine during resuscitation independently increases the risk for in-hospital death and unfavorable functional outcome after non-ventricular fibrillation cardiac arrest. Further studies are needed to re-evaluate the use of epinephrine during resuscitation in humans.

Cumulative epinephrine dose during cardiopulmonary resuscitation and neurologic outcome.

Epinephrine is the drug of choice in advanced cardiac life support, but it can have deleterious side effects after restoration of spontaneous circulation. To investigate the association between the cumulative epinephrine dose used in advanced cardiac life support and neurologic outcome after cardiac arrest. Retrospective cohort study. University hospital. Adults admitted to the emergency department with witnessed, nontraumatic, normothermic ventricular fibrillation cardiac arrest and unsuccessful initial defibrillation. Functional neurologic outcome was regularly assessed by cerebral performance category (CPC) within 6 months after cardiac arrest. A CPC of 1 or 2 was defined as favorable recovery. Among 178 enrolled patients, the median cumulative epinephrine dose administered was 4 mg (range, 0 to 50 mg). In 151 patients (84%), spontaneous circulation was restored; 63 of these 151 patients (42%) had favorable neurologic recovery. Patients with an unfavorable CPC received a significantly higher cumulative dose of epinephrine than did patients with a favorable CPC (4 mg compared with 1 mg; P < 0.001). This finding persisted after stratification by duration of resuscitation. After possible cofounders were controlled for, the cumulative epinephrine dose remained an independent predictor of unfavorable neurologic outcome. The results indicate that an increasing cumulative dose of epinephrine administered during resuscitation is independently associated with unfavorable neurologic outcome after ventricular fibrillation cardiac arrest.