Abstract 272: Dose Optimization of Early High-Dose Valproic Acid for Neuroprotection After Cardiac Arrest

Circulation ◽  
2019 ◽  
Vol 140 (Suppl_2) ◽  
Author(s):  
Cindy H Hsu ◽  
Mohamad H Tiba ◽  
Brendan M McCracken ◽  
Carmen I Colmenero ◽  
Zachary Pickell ◽  
...  
Keyword(s):  
Valproic Acid ◽  
Cardiac Arrest ◽  
Spontaneous Circulation ◽  
Dose Optimization ◽  
High Dose ◽  
Large Animal ◽  
Serum Free ◽  
Neurologic Outcomes ◽  
Neuroprotective Therapy ◽  
Ca Model

Introduction: High-dose valproic acid (VPA) has been shown to improve the survival and neurologic outcomes in preclinical brain injury models including asphyxial cardiac arrest (CA) in rats. However, its pharmacokinetics, pharmacodynamics, and safety profiles in large animal CA models are unknown. Hypothesis: High-dose VPA can be safely administered after return of spontaneous circulation (ROSC) and cross the blood-brain barrier dose-dependently in a swine CA model. Methods: After 8 minutes of untreated ventricular fibrillation CA, male Yorkshire swine [43.3 (3.0) kg] were resuscitated for up to 16 minutes until ROSC. They were randomized to receive placebo, 75 mg/kg, 150 mg/kg, or 300 mg/kg VPA as 90-minute intravenous infusion (n=5 per group) beginning 20 minutes after sustained ROSC. Animals were monitored for 2 additional hours after infusion ended and then euthanized. Experimental operators were blinded to the treatments. Results: The mean total cardiac arrest duration was 15.0 (1.6) minutes, with no significant differences between groups. At end of infusion, the serum free VPA concentration increased dose dependently, from 139.2 (10.1) mcg/mL [75 mg/kg VPA] to 287.2 (24.6) mcg/mL [150 mg/kg VPA] to 565.6 (36.5) mcg/mL [300 mg/kg VPA] (p<0.05). This corresponded to a dose-dependent decrease in the fraction of serum protein-bound VPA, from 41.8% (1.8) [75 mg/kg VPA] to 23.4% (3.8) [150 mg/kg VPA] to 14.4% (3.8) [300 mg/kg VPA] (p<0.05). Brain total VPA concentrations at end of experiment were 26.1 (3.1) mcg/g [75 mg/kg VPA], 72.5 (18.9) mcg/g [150 mg/kg VPA], and 212.3 (33.4) mcg/g [300 mg/kg VPA] (p<0.05). There was a strong linear correlation between serum free VPA and brain total VPA concentrations (R 2 =0.98). All animals survived until euthanasia, although the 300 mg/kg group required more epinephrine to maintain mean arterial pressure greater than or equal to 80 mmHg and had higher lactic acidosis. Conclusion: Brain VPA concentrations correlate strongly with serum free VPA when high-dose intravenous VPA is given after ROSC in a swine CA model. These results provide the foundation for dose-optimization studies of high-dose VPA as a neuroprotective therapy following resuscitation from CA.

scholarly journals Dose optimization of early high-dose valproic acid for neuroprotection in a swine cardiac arrest model

2020 ◽  
Vol 1-2 ◽  
pp. 100007
Author(s):  
Cindy H. Hsu ◽  
Mohamad H. Tiba ◽  
Brendan M. McCracken ◽  
Carmen I. Colmenero ◽  
Zachary Pickell ◽  
...  
Keyword(s):  
Valproic Acid ◽  
Cardiac Arrest ◽  
Dose Optimization ◽  
High Dose

Effect of valproic acid on survival and neurologic outcomes in an asphyxial cardiac arrest model of rats

Resuscitation ◽  
2013 ◽  
Vol 84 (10) ◽  
pp. 1443-1449 ◽  
Author(s):  
Jae Hyuk Lee ◽  
Kyuseok Kim ◽  
You Hwan Jo ◽  
Soo Hoon Lee ◽  
Changwoo Kang ◽  
...  
Keyword(s):  
Valproic Acid ◽  
Cardiac Arrest ◽  
Neurologic Outcomes ◽  
Asphyxial Cardiac Arrest

scholarly journals Association between Achievement of Estimated Average Glucose Level and 6-Month Neurologic Outcome in Comatose Cardiac Arrest Survivors: A Propensity Score-Matched Analysis

2019 ◽  
Vol 8 (9) ◽  
pp. 1480
Author(s):  
Yong Hun Jung ◽  
Byung Kook Lee ◽  
Kyung Woon Jeung ◽  
Dong Hun Lee ◽  
Hyoung Youn Lee ◽  
...  
Keyword(s):  
Cardiac Arrest ◽  
Propensity Score ◽  
Glucose Level ◽  
Neuron Specific Enolase ◽  
Spontaneous Circulation ◽  
Neurologic Outcome ◽  
Glucose Levels ◽  
Neurologic Outcomes ◽  
The Mean ◽  
Average Glucose

We investigated whether achieving estimated average glucose (EAG) levels versus achieving standard glucose levels (180 mg/dL) was associated with neurologic outcome in cardiac arrest survivors. This single-center retrospective observational study included adult comatose cardiac arrest survivors undergoing therapeutic hypothermia (TH) from September 2011 to December 2017. EAG level was calculated using HbA1c obtained after the return of spontaneous circulation (ROSC), and the mean glucose level during TH was calculated. We designated patients to the EAG or standard glucose group according to whether the mean blood glucose level was closer to the EAG level or 180 mg/dL. Patients in the EAG and standard groups were propensity score- matched. The primary outcome was the 6-month neurologic outcome. The secondary outcomes were hypoglycemia (≤70 mg/dL) and serum neuron-specific enolase (NSE) at 48 h after ROSC. Of 384 included patients, 137 (35.7%) had a favorable neurologic outcome. The EAG group had a higher favorable neurologic outcome (104/248 versus 33/136), higher incidence of hypoglycemia (46/248 versus 11/136), and lower NSE level. After propensity score matching, both groups had similar favorable neurologic outcomes (24/93 versus 27/93) and NSE levels; the EAG group had a higher incidence of hypoglycemia (21/93 versus 6/93). Achieving EAG levels was associated with hypoglycemia but not neurologic outcome or serum NSE level.

scholarly journals The effect of high-dose intramuscular epinephrine on the recovery of spontaneous circulation in an asphyxia‐induced cardiac arrest rat model

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Daesung Lim ◽  
Soo Hoon Lee ◽  
Dong Hoon Kim ◽  
Changwoo Kang ◽  
Jin Hee Jeong ◽  
...  
Keyword(s):  
Cardiac Arrest ◽  
Rat Model ◽  
Saline Group ◽  
Spontaneous Circulation ◽  
Rank Test ◽  
High Dose ◽  
Sprague Dawley ◽  
Epinephrine Administration ◽  
Arterial Blood ◽  
Induced Cardiac Arrest

Abstract Background Obtaining vascular access can be challenging during resuscitation following cardiac arrest, and it is particularly difficult and time-consuming in paediatric patients. We aimed to compare the efficacy of high-dose intramuscular (IM) versus intravascular (IV) epinephrine administration with regard to the return of spontaneous circulation (ROSC) in an asphyxia-induced cardiac arrest rat model. Methods Forty-five male Sprague-Dawley rats were used for these experiments. Cardiac arrest was induced by asphyxia, and defined as a decline in mean arterial pressure (MAP) to 20 mmHg. After asphyxia-induced cardiac arrest, the rats were randomly allocated into one of 3 groups (control saline group, IV epinephrine group, and IM epinephrine group). After 540 s of cardiac arrest, cardiopulmonary resuscitation was performed, and IV saline (0.01 cc/kg), IV (0.01 mg/kg, 1:100,000) epinephrine or IM (0.05 mg/kg, 1:100,000) epinephrine was administered. ROSC was defined as the achievement of an MAP above 40 mmHg for more than 1 minute. Rates of ROSC, haemodynamics, and arterial blood gas analysis were serially observed. Results The ROSC rate (61.5%) of the IM epinephrine group was less than that in the IV epinephrine group (100%) but was higher than that of the control saline group (15.4%) (log-rank test). There were no differences in MAP between the two groups, but HR in the IM epinephrine group (beta coefficient = 1.02) decreased to a lesser extent than that in the IV epinephrine group with time. Conclusions IM epinephrine induced better ROSC rates compared to the control saline group in asphyxia-induced cardiac arrest, but not compared to IV epinephrine. The IM route of epinephrine administration may be a promising option in an asphyxia-induced cardiac arrest.

scholarly journals Survival analysis in out-of-hospital cardiac arrest patients with shockable rhythm directly transport to Heart Centers

2021 ◽  
Keyword(s):  
Cardiac Arrest ◽  
Survival Analysis ◽  
Cerebral Performance Category ◽  
Spontaneous Circulation ◽  
Transport Time ◽  
Neurological Outcomes ◽  
Neurologic Outcomes ◽  
Shockable Rhythm ◽  
Short Time ◽  
Hospital Cardiac Arrest

Background: This study aimed to evaluate whether out-of-hospital cardiac arrest (OHCA) patients with initial shockable rhythm without prehospital return of spontaneous circulation (ROSC) who are directly transported to Heart Centers in appropriate time will have better post-cardiac arrest four months survival and neurological outcomes at discharge. Methods: This retrospective study assessed the data of 1,588 OHCA patients with shockable rhythm and without prehospital ROSC collected from the registry database of Taoyuan City between January 2014 and June 2018. The relationships of transport time to Heart Centers with survival at discharge and with neurological outcomes were investigated for survival analysis. Results: Among the 1,588 OHCA patients with initial shockable rhythm and without prehospital ROSC, 1,222 (77.0%) and 366 (23.0%) were transported to Heart Centers and non-Heart Centers, respectively. However, the transport to Heart Centers was associated with an increased survival at discharge (adjusted odds ratio [aOR] 2.00, 95% confidence interval [CI], 1.42–2.81) and good neurological outcomes (cerebral performance category [CPC] 1 and 2) (aOR 3.14, 95% CI, 1.88–5.23), regardless of the transport time. The overall mortality reduction for Heart Centers was 39% (hazard ratio [HR] = 0.61; 95% CI 0.47–0.78), compared to that for non-Heart Centers. At 120 days of follow-up, the results showed a higher survival rate for patients who were transported to Heart Centers within a short time. The percentages of good CPC showed a better distribution for non-Heart Centers versus those for Heart Centers. Conclusions: Adult OHCA patients with initial shockable rhythm and without prehospital ROSC who were transported to Heart Centers directly had better post-cardiac arrest survival and good neurologic outcomes, regardless of the transport time.

Abstract 17412: Current Experience and Limitations of Extracorporeal Cardiopulmonary Resuscitation for Cardiac Arrest: A Single-Center Retrospective Study

Circulation ◽  
2018 ◽  
Vol 138 (Suppl_1) ◽  
Author(s):  
Aditi Singhvi ◽  
Nirav Patel ◽  
Jason A Gluck
Keyword(s):  
Cardiac Arrest ◽  
Cardiopulmonary Resuscitation ◽  
Selection Criteria ◽  
Spontaneous Circulation ◽  
Extracorporeal Cardiopulmonary Resuscitation ◽  
Neurologic Outcomes ◽  
Time To Initiation ◽  
Central Access ◽  
Refractory Cardiac Arrest

Introduction: Extracorporeal cardiopulmonary resuscitation (ECPR) may be considered for select cardiac arrest patients for whom the suspected etiology of the arrest is potentially reversible. In adults, the survival to discharge with ECPR is reportedly 22% to 33%, with better outcomes for in-hospital arrests. Outcomes with ECPR depend on multiple factors including, location of arrest, etiology, duration and quality of CPR, time to initiation of ECMO, and post-arrest management. There is no consensus regarding patient selection or management of these patients. We report our preliminary experiences with ECPR for refractory cardiac arrest. Methods: Patients who underwent ECPR between January 2013 and May 2018 were identified. The characteristics of the arrest, CPR duration, cannulation procedure, post-arrest management, complications, survival and neurologic outcomes were retrospectively reviewed. Results: A total of 24 ECPR events were identified. The median age was 60 years. The median CPR duration and time from collapse to initiation of ECMO were 35 (IQR 25.5-68) and 68 (IQR 45.5-144.5) min, respectively. Peripheral and central access sites were employed in 19 and 5 cases, respectively. Return of spontaneous circulation was achieved in 21 patients (87.5%). PCI was performed on 4 and pulmonary embolectomy on 3 patients. Median duration of ECMO support was 84 (IQR 24-168) hours. Major complications occurred in 17 patients (70.8%). Nine patients (37.5%) were successfully weaned from ECMO and 7 (29.2%) survived to hospital discharge. All of the survivors had a favorable neurologic outcome. Conclusions: ECPR as part of a comprehensive multi-faceted approach for select patients with refractory cardiac arrest may improve outcomes. We noted an improvement in outcomes over time. This could be attributed to improved selection criteria as well as clinical management. The development of selection criteria may help identify patients most likely to benefit from the use of ECPR. This would have significant resource implications for hospitals with ECMO programs.

scholarly journals Inter-Hospital Transfer after Return of Spontaneous Circulation Shows no Correlation with Neurological Outcomes in Cardiac Arrest Patients Undergoing Targeted Temperature Management in Cardiac Arrest Centers

2020 ◽  
Vol 9 (6) ◽  
pp. 1979
Author(s):  
Yoon Hee Choi ◽  
Dong Hoon Lee ◽  
Je Hyeok Oh ◽  
Jin Hong Min ◽  
Tae Chang Jang ◽  
...  
Keyword(s):  
Cardiac Arrest ◽  
Spontaneous Circulation ◽  
Targeted Temperature Management ◽  
Temperature Management ◽  
Return Of Spontaneous Circulation ◽  
Neurological Outcomes ◽  
Neurologic Outcomes ◽  
Hospital Transfer ◽  
St Elevation ◽  
Transferred Patients

This study evaluated whether inter-hospital transfer (IHT) after the return of spontaneous circulation (ROSC) was associated with poor neurological outcomes after 6 months in post-cardiac-arrest patients treated with targeted temperature management (TTM). We used data from the Korean Hypothermia Network prospective registry from November 2015 to December 2018. These out-of-hospital cardiac arrest (OHCA) patients had either received post-cardiac arrest syndrome (PCAS) care at the same hospital or had been transferred from another hospital after ROSC. The primary endpoint was the neurological outcome 6 months after cardiac arrest. Subgroup analyses were performed to determine differences in the time from ROSC to TTM induction according to the electrocardiography results after ROSC. We enrolled 1326 patients. There were no significant differences in neurological outcomes between the direct visit and IHT groups. In patients without ST elevation, the mean time to TTM was significantly shorter in the direct visit group than in the IHT group. IHT after achieving ROSC was not associated with neurologic outcomes after 6 months in post-OHCA patients treated with TTM, even though TTM induction was delayed in transferred patients.

scholarly journals Fever After Rewarming

2013 ◽  
Vol 29 (6) ◽  
pp. 365-369 ◽  
Author(s):  
Michael N. Cocchi ◽  
Myles D. Boone ◽  
Brandon Giberson ◽  
Tyler Giberson ◽  
Emily Farrell ◽  
...  
Keyword(s):  
Cardiac Arrest ◽  
Core Body Temperature ◽  
Cerebral Performance Category ◽  
Standard Of Care ◽  
Spontaneous Circulation ◽  
Neurologic Outcome ◽  
Temperature Management ◽  
Fisher Exact Test ◽  
Exact Test ◽  
Neurologic Outcomes

Background: Induction of mild therapeutic hypothermia (TH; temperature 32-34°C) has become standard of care in many hospitals for comatose survivors of cardiac arrest. Pyrexia, or fever, is known to be detrimental in patients with neurologic injuries such as stroke or trauma. The incidence of pyrexia in the postrewarming phase of TH is unknown. We attempted to determine the incidence of fever after TH and hypothesized that those patients who were febrile after rewarming would have worse clinical outcomes than those who maintained normothermia in the postrewarming period. Methods: Retrospective data analysis of survivors of out-of-hospital cardiac arrest (OHCA) over a period of 29 months (December 2007 to April 2010). Inclusion criteria: OHCA, age >18, return of spontaneous circulation, and treatment with TH. Exclusion criteria: traumatic arrest and pregnancy. Data collected included age, sex, neurologic outcome, mortality, and whether the patient developed fever (temperature > 100.4°F, 38°C) within 24 hours after being fully rewarmed to a normal core body temperature after TH. We used simple descriptive statistics and Fisher exact test to report our findings. Results: A total of 149 patients were identified; of these, 82 (55%) underwent TH. The mean age of the TH cohort was 66 years, and 28 (31%) were female. In all, 54 patients survived for >24 hours after rewarming and were included in the analysis. Among the analyzed cohort, 28 (52%) of 54 developed fever within 24 hours after being rewarmed. Outcome measures included in-hospital mortality as well as neurologic outcome as defined by a dichotomized Cerebral Performance Category (CPC) score. When comparing neurologic outcomes between the groups, 16 (57%) of 28 in the postrewarming fever group had a poor outcome (CPC score 3-5), while 15 (58%) of 26 in the no-fever group had a favorable outcome ( P = .62). In the fever group, 15 (52%) of 28 died, while in the no-fever group, 14 (54%) of 26 died ( P = .62). Conclusion: Among a cohort of patients who underwent mild TH after OHCA, more than half of these patients developed pyrexia in the first 24 hours after rewarming. Although there were no significant differences in outcomes between febrile and nonfebrile patients identified in this study, these findings should be further evaluated in a larger cohort. Future investigations may be needed to determine whether postrewarming temperature management will improve the outcomes in this population.

scholarly journals Predictive Utility of Changes in Optic Nerve Sheath Diameter After Cardiac Arrest for Neurologic Outcomes

2021 ◽  
Author(s):  
Heekyung Lee ◽  
Joonkee Lee ◽  
Hyungoo Shin
Keyword(s):  
Cardiac Arrest ◽  
Optic Nerve ◽  
Optic Nerve Sheath Diameter ◽  
Spontaneous Circulation ◽  
Optic Nerve Sheath ◽  
Neurologic Outcome ◽  
Return Of Spontaneous Circulation ◽  
Brain Ct ◽  
Neurologic Outcomes ◽  
Nerve Sheath

Abstract Background: Optic nerve sheath diameter (ONSD) is effective in predicting the neurologic outcome of patients with post-cardiac arrest (CA) return of spontaneous circulation. This study aimed to investigate the effect of ONSD changes before and after CA on neurologic outcomes in patients with return of spontaneous circulation after CA using brain computed tomography (CT).Methods: We included patients who were hospitalized after CA and underwent pre- and post-CA brain CT from January 2001 to September 2020. They were divided into the good and poor neurologic outcome (GNO and PNO, respectively) groups based on the neurologic outcome at hospital discharge. We performed between-group comparisons of the amount and rate of post-CA changes on brain CT. Moreover, we calculated the area under the curve to determine the predictive value of ONSD changes for neurologic outcomes.Results: We included 96 enrolled patients; among them, 25 had GNO. The amount of change was significantly higher in the PNO group than in the GNO group (0.63 vs. 0.30 mm; p = 0.030). Moreover, there was a higher rate of change in the PNO group than in the GNO group (12.29 vs. 5.26 %; p = 0.041). The AUC for predicting PNO was 0.64 (95% CI = 0.53–0.73; p = 0.04) and patients with a rate of ONSD change > 27.2% had PNO with specificity and positive predictive values of 100%.Conclusion: The amount and rate of ONSD changes on brain CT were significantly associated with the neurologic outcomes in post-CA patients. ONSD changes may predict neurologic outcomes in post-CA patients.

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