The effects of sternal intraosseous and intravenous administration of amiodarone in a hypovolemic swine cardiac arrest model

2016 ◽  
Vol 11 (4) ◽  
pp. 271-277 ◽  
Author(s):  
Samuel Smith, BSN ◽  
Bradley Borgkvist, BSN ◽  
Teara Kist, BSN ◽  
Jason Annelin, BSN ◽  
Don Johnson, PhD ◽  
...  
Keyword(s):  
Cardiac Arrest ◽  
High Performance ◽  
Multivariate Analyses ◽  
Plasma Concentrations ◽  
Spontaneous Circulation ◽  
Blood Samples ◽  
Life Saving ◽  
Concentration Maximum ◽  
Liquid Chromatography Tandem Mass ◽  
Over Time

Objective: This study compared the effects of amiodarone via sternal intraosseous (SIO) and intravenous (IV) routes on return of spontaneous circulation (ROSC), time to ROSC, concentration maximum (Cmax), time to maximum concentration (Tmax), and mean concentrations over time in a hypovolemic cardiac arrest model.Design: Prospective, between subjects, randomized experimental design.Setting: TriService Research Facility.Subjects: Yorkshire-cross swine (n = 28).Intervention: Swine were anesthetized and placed into cardiac arrest. After 2 minutes, cardiopulmonary resuscitation was initiated. After an additional 2 minutes, amiodarone 300 mg was administered via the tibial intraosseous TIO or the IV route. Blood samples were collected over 5 minutes. The plasma concentrations were analyzed using high-performance liquid chromatography tandem mass spectrometry.Main Outcome Measurements: ROSC, time to ROSC, Cmax, Tmax, and mean concentrations over time.Results: A multivariate analyses of variance indicated that there were no significant differences in the SIO and IV groups in ROSC (p = 0.191), time to ROSC (p 0.05), Tmax mean 88.1 ± 24.8 seconds versus 49.5 ± 21.8 seconds (p = 0.317), or Cmax mean 92,700 ± 161,112 ng/mL versus 64,159.8 ± 14,174.8 ng/mL (p = 0.260). A repeated analyses of variance indicated that there were no significant differences between the groups relative to concentrations over time (p 0.05).Conclusion: The SIO provides rapid and reliable access to administer life-saving medications during cardiac arrest.

Effects of humerus intraosseous versus intravenous amiodarone administration in a hypovolemic porcine model

2016 ◽  
Vol 11 (4) ◽  
pp. 261-269 ◽  
Author(s):  
Monica M. Holloway, BSN ◽  
Shannan L. Jurina, MSN ◽  
Joshua D. Orszag, BSN ◽  
George R. Bragdon, MS ◽  
Rustin D. Green, BSN, CCRN ◽  
...  
Keyword(s):  
Cardiac Arrest ◽  
High Performance ◽  
Spontaneous Circulation ◽  
Maximum Plasma ◽  
Life Saving ◽  
Maximum Plasma Drug Concentration ◽  
Liquid Chromatography Tandem Mass ◽  
Intravenous Amiodarone ◽  
Repeated Analysis ◽  
Over Time

Objective: To compare the effects of amiodarone administration by humerus intraosseous (HIO) and intravenous (IV) routes on return of spontaneous circulation (ROSC), time to maximum concentration (Tmax), maximum plasma drug concentration (Cmax), time to ROSC, and mean concentrations over time in a hypovolemic cardiac arrest model.Design: Prospective, between subjects, randomized experimental design.Setting: TriService Research Facility.Subjects: Yorkshire-cross swine (n = 28).Intervention: Swine were anesthetized and placed into cardiac arrest. After 2 minutes, cardiopulmonary resuscitation was initiated. After an additional 2 minutes, amiodarone 300 mg was administered via the HIO or the IV route. Blood samples were collected over 5 minutes. The samples were analyzed using high-performance liquid chromatography tandem mass spectrometry.Main Outcome Measurements: ROSC, Tmax, Cmax, time to ROSC, and mean concentrations over time.Results: There was no difference in ROSC between the HIO and IV groups; each had five achieve ROSC and two that did not (p = 1). There was no difference in Tmax (p = 0.501) or in Cmax between HIO and IV groups (p = 0.232). Means ± standard deviations in seconds were 94.3 ± 78.3 compared to 115.7 ± 87.3 in the IV versus HIO groups, respectively. The mean ± standard deviation in nanograms per milliliter for the HIO was 49,041 ± 21,107 and 74,258 ± 33,176 for the IV group. There were no significant differences between the HIO and IV groups relative to time to ROSC (p = 0.220). A repeated analysis of variance indicated that there were no significant differences between the groups relative to concentrations over time (p 0.05).Conclusion: The humerus intraosseous provides rapid and reliable access to administer life-saving medications during cardiac arrest.

Effects of tibial and humerus intraosseous administration of epinephrine in a cardiac arrest swine model

2016 ◽  
Vol 11 (4) ◽  
pp. 243-251 ◽  
Author(s):  
Denise Beaumont, MSN, CRNA ◽  
Asal Baragchizadeh, MS, PhD Candidate ◽  
Charles Johnson, MA ◽  
Don Johnson, PhD
Keyword(s):  
Cardiac Arrest ◽  
Maximum Concentration ◽  
High Performance ◽  
Spontaneous Circulation ◽  
Swine Model ◽  
Epinephrine Administration ◽  
Life Saving ◽  
Significant Difference ◽  
Liquid Chromatography Tandem Mass ◽  
Over Time

Objective: Compare maximum concentration (Cmax), time to maximum concentration (Tmax), mean serum concentration of epinephrine, return of spontaneous circulation (ROSC), time to ROSC, and odds of survival relative to epinephrine administration by humerus intraosseous (HIO), tibial intraosseous (TIO), and intravenous (IV) routes in a swine cardiac arrest model.Design: Prospective, between subjects, randomized experimental design.Setting: TriService Research Facility.Subjects: Yorkshire-cross swine (n = 28).Intervention: Swine were anesthetized and placed into cardiac arrest. After 2 minutes, cardiopulmonary resuscitation was initiated. After an additional 2 minutes, a dose of 1 mg of epinephrine was administered by HIO, TIO, or the IV routes. Blood samples were collected over 4 minutes and analyzed by high-performance liquid chromatography tandem mass spectrometry.Main Outcome Measurements: ROSC, time to ROSC, Cmax, Tmax, mean concentrations over time, and odds ratio.Results: There was no significant difference in rate of the ROSC among the TIO, HIO, and IV groups (p 0.05). There were significant differences in Cmax: the HIO group was significantly higher than the TIO group (p = 0.007), but no significant difference between the IV and HIO (p = 0.33) or the IV and TIO group (p = 0.060). The Tmax was significantly shorter for both the IV and HIO versus the TIO group (p 0.05), but no difference between IV and HIO (p = 0.328). The odds of survival were higher in the HIO group compared to all other groups.Conclusion: The TIO and HIO provide rapid and reliable access to administer life-saving medications during cardiac arrest.

The effects of tibial intraosseous versus intravenous amiodarone administration in a hypovolemic cardiac arrest procine model

2016 ◽  
Vol 11 (4) ◽  
pp. 253-260 ◽  
Author(s):  
Kathryn Hampton, BSN ◽  
Eric Wang, BSN ◽  
Jerome Ivan Argame, BSN ◽  
Tom Bateman, BSN ◽  
William Craig, DNP, CRNA ◽  
...  
Keyword(s):  
Cardiac Arrest ◽  
Analysis Of Variance ◽  
Repeated Measures ◽  
High Performance ◽  
Plasma Concentrations ◽  
Spontaneous Circulation ◽  
Repeated Measures Analysis ◽  
Liquid Chromatography Tandem Mass ◽  
Intravenous Amiodarone ◽  
Over Time

Objective: This study compared the effects of amiodarone via tibial intraosseous (TIO) and intravenous (IV) routes on return of spontaneous circulation (ROSC), time to ROSC, maximum drug concentration (Cmax), time to maximum concentration (Tmax), and mean concentrations over time in a hypovolemic cardiac arrest model.Design: Prospective, between subjects, randomized experimental design.Setting: TriService Research Facility.Subjects: Yorkshire-cross swine (n = 28).Intervention: Swine were anesthetized and placed into cardiac arrest. After 2 minutes, cardiopulmonary resuscitation (CPR) was initiated. After an additional 2 minute, 300 mg of amiodarone were administered via the TIO or the IV route. Blood samples were collected over 5 minutes. The plasma concentrations were analyzed using high-performance liquid chromatography tandem mass spectrometry.Main Outcome Measurements: ROSC, time to ROSC, Cmax, Tmax, and mean concentrations over time.Results: A multivariate analysis of variance indicated that there were no significant differences in the TIO and IV groups in ROSC (p = 0.515), time to ROSC (p = 0.300), Cmax (p = 0.291), or Tmax (p = 0.475). The mean Cmax of the TIO group was 56,292 ± 11,504 ng/mL compared to 74,258 ± 11,504 ng/mL for the IV group. The Tmax for TIO and IV groups were 120 ± 25 and 94 ± 25, respectively. A repeated measures analysis of variance indicated that there were no significant differences between the groups relative to concentrations over time (p 0.05).Conclusion: The TIO provides rapid and reliable access to administer lifesaving medications during cardiac arrest.

scholarly journals Effects of humeral intraosseous epinephrine in a pediatric hypovolemic cardiac arrest porcine model

2020 ◽  
Vol 5 (1) ◽  
pp. e000372
Author(s):  
Michael James Neill ◽  
James M Burgert ◽  
Dawn Blouin ◽  
Benjamin Tigges ◽  
Kari Rodden ◽  
...  
Keyword(s):  
High Performance ◽  
Porcine Model ◽  
Spontaneous Circulation ◽  
Sample Collection ◽  
Return Of Spontaneous Circulation ◽  
Concentration Maximum ◽  
Group 5 ◽  
Mean Concentration ◽  
Over Time ◽  
Group 1

BackgroundAims of the study were to determine the effects of humerus intraosseous (HIO) versus intravenous (IV) administration of epinephrine in a hypovolemic, pediatric pig model. We compared concentration maximum (Cmax), time to maximum concentration (Tmax), mean concentration (MC) over time and return of spontaneous circulation (ROSC).MethodsPediatric pig were randomly assigned to each group (HIO (n=7); IV (n=7); cardiopulmonary resuscitation (CPR)+defibrillation (defib) (n=7) and CPR-only group (n=5)). The pig were anesthetized; 35% of the blood volume was exsanguinated. pigs were in arrest for 2 min, and then CPR was performed for 2 min. Epinephrine 0.01 mg/kg was administered 4 min postarrest by either route. Samples were collected over 5 min. After sample collection, epinephrine was administered every 4 min or until ROSC. The Cmax and MC were analyzed using high-performance liquid chromatography. Defibrillation began at 3 min postarrest and administered every 2 min or until ROSC or endpoint at 20 min after initiation of CPR.ResultsAnalysis indicated that the Cmax was significantly higher in the IV versus HIO group (p=0.001). Tmax was shorter in the IV group but was not significantly different (p=0.789). The MC was significantly greater in the IV versus HIO groups at 90 and 120 s (p<0.05). The IV versus HIO had a significantly higher MC (p=0.001). χ2 indicated the IV group (5 out of 7) had significantly higher rate of ROSC than the HIO group (1 out of 7) (p=0.031). One subject in the CPR+defib and no subjects in the CPR-only groups achieved ROSC.DiscussionBased on the results of our study, the IV route is more effective than the HIO route.

Humerus intraosseous administration of epinephrine in normovolemic and hypovolemic porcine model

2018 ◽  
Vol 13 (2) ◽  
pp. 97-106
Author(s):  
LTC Robert P. Long, II, PhD, CRNA ◽  
LTC Stephanie M. Gardner, DNP, CRNA ◽  
James Burgert, DNAP, CRNA ◽  
LTC Craig A. Koeller, DVM, DACLAM, AFRL ◽  
LTC Joseph O’Sullivan, PhD, CRNA ◽  
...  
Keyword(s):  
Cardiac Arrest ◽  
Blood Volume ◽  
Maximum Concentration ◽  
Porcine Model ◽  
Spontaneous Circulation ◽  
Rate Of Return ◽  
Blood Samples ◽  
Return Of Spontaneous Circulation ◽  
Mean Concentration ◽  
Over Time

Objective: Compare the maximum concentration (Cmax), time to maximum concentration (Tmax), mean concentration, rate of return of spontaneous circulation (ROSC), time to ROSC, and odds of ROSC when epinephrine is administered by humerus intraosseous (HIO) compared to intravenous (IV) routes in both a hypovolemic and normovolemic cardiac arrest model.Design: Prospective, between subjects, randomized experimental study.Setting: TriService Facility.Subjects: Twenty-eight adult Yorkshire Swine were randomly assigned to four groups: HIO normovolemia; HIO hypovolemia; IV normovolemia; and IV hypovolemia.Intervention: Swine were anesthetized. The hypovolemic group was exsanguinated 31 percent of their blood volume. Subjects were placed into arrest. After 2 minutes, cardiopulmonary resuscitation (CPR) was initiated. After another 2 minutes, 1 mg epinephrine was given by IV or HIO routes; blood samples were collected over 4 minutes. Hypovolemic groups received 500 mL of 5 percent albumin following blood sampling. CPR continued until ROSC or for 30 minutes.Main outcome measures: ROSC, time to ROSC, Cmax, Tmax, mean concentrations over time, odds of ROSC.Results: Cmax was significantly higher, the Tmax, and the time to ROSC were significantly faster in the HIO normovolemic compared to the HIO hypovolemic group (p 0.05). All seven in the HIO normovolemic group achieved ROSC compared to three of the HIO hypovolemic group. Odds of ROSC were 19.2 times greater in the HIO normovolemic compared the HIO hypovolemic group.Conclusion: The HIO is an effective route in a normovolemic model. However, the findings indicate that sufficient blood volume is essential for ROSC in a hypovolemic scenario.

Abstract 246: Therapeutic Hypothermia Mimicking Peptide Administration During Cardiopulmonary Resuscitation Improved Cardiac Arrest Survival in Swine

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_4) ◽  
Author(s):  
Matt Oberdier ◽  
Jing Li ◽  
Dan Ambinder ◽  
Xiangdong Zhu ◽  
Sarah Fink ◽  
...  
Keyword(s):  
Cardiac Arrest ◽  
Therapeutic Hypothermia ◽  
Venous Blood ◽  
Plasma Concentrations ◽  
Sudden Cardiac Arrest ◽  
The United States ◽  
Rapid Onset ◽  
Spontaneous Circulation ◽  
Control Group ◽  
Swine Model

Background: Out-of-hospital sudden cardiac arrest is a leading cause of death in the United States, affecting over 350,000 people per year with an overall survival rate around 10%. CPR, defibrillation, and therapeutic hypothermia are common resuscitation strategies, but hypothermia is difficult to implement timely to achieve survival benefit. A cell-permeable peptide TAT-PHLPP9c has been shown to alter metabolic pathways similar to hypothermia, and decreases the release of two biomarkers, taurine and glutamate, during the high osmotic stress of heart stunning and brain injury in a mouse arrest model. Hypothesis: TAT-PHLPP9c, given during CPR, enhances 24-hour survival in a swine ventricular fibrillation (VF) model. Methods: In 14 (8 controls and 6 treated) sedated, intubated, and mechanically ventilated swine, after 5 min of VF, ACLS with vest CPR and periodic defibrillations was performed. Venous blood samples were collected at baseline, after 2 min of CPR, and at 2 and 30 min after return of spontaneous circulation (ROSC). The animals were survived up to 24 hrs and plasma samples were analyzed for glutamate and taurine in 2 controls and 1 animal given peptide. Results: Three of the control animals had ROSC, but none survived for 24 hrs, while 4 of 6 treated animals achieved neurologically intact survival at 24 hrs (p < 0.02). Compared to baseline, both taurine and glutamate plasma concentrations increased in the control group, but the increase was reduced substantially by the peptide treatment at 30 min after ROSC (Figure). Conclusion: The use of the cooling mimicking peptide TAT-PHLPP9c administered during CPR significantly improved 24-hour survival in this swine model of cardiac arrest. It reduced the increase of cerebral and myocardial metabolic biomarkers, which encourages utilizing a strategy of cell-permeable peptides for intravenous administration for more rapid onset of hypothermia-like salutary effects than are possible with current CPR cooling devices.

Non-Linear Pharmacokinetics of Atomoxetine in Adult Japanese Patients With ADHD

2016 ◽  
Vol 24 (3) ◽  
pp. 490-493
Author(s):  
Atsunori Sugimoto ◽  
Yutaro Suzuki ◽  
Naoki Orime ◽  
Taketsugu Hayashi ◽  
Jun Egawa ◽  
...  
Keyword(s):  
High Performance ◽  
Plasma Concentrations ◽  
Japanese Patients ◽  
High Dose ◽  
Linear Pharmacokinetics ◽  
Blood Samples ◽  
Non Linear ◽  
The Difference ◽  
The Relationship ◽  
Atomoxetine Treatment

Objective: The objective was to reveal the relationship between dose and concentration of atomoxetine. Method: Fifty-five blood samples of 33 patients with ADHD were examined using high-performance liquid chromatography. Results: The plasma concentrations were 53.2 ± 67.0, 298.0 ± 390.5, and 639.3 ± 831.9 ng/mL at doses of 40 mg, 80 mg, and 120 mg, and the concentration/dose were 1.33 ± 1.67, 3.73 ± 4.88, and 5.33 ± 6.93 ng/mL/mg, respectively. Statistical analyses revealed a significant correlation between the concentration and the dose of atomoxetine ( p = .004), and a trending toward significance in the difference in the concentration/dose in the three dosage groups ( p = .064). The concentration/dose at 40 and 80 + 120 mg/day were 1.33 ± 1.67 and 4.22 ± 5.53 ng/mL/mg, the latter was significantly higher than the former ( p = .006), which suggested non-linear pharmacokinetics. Conclusion: Clinicians should carefully titrate in high dose atomoxetine treatment.

Pharmacokinetics of Prilocaine after Intravenous Administration in Volunteers 

1999 ◽  
Vol 90 (4) ◽  
pp. 988-992 ◽  
Author(s):  
Auke Dirk van der Meer ◽  
Anton G. L. Burm ◽  
Rudolf Stienstra ◽  
Jack W. van Kleef ◽  
Arie A. Vletter ◽  
...  
Keyword(s):  
Intravenous Administration ◽  
High Performance ◽  
Equilibrium Dialysis ◽  
Plasma Concentrations ◽  
Volume Of Distribution ◽  
Metabolic Clearance ◽  
Unbound Fraction ◽  
Blood Samples ◽  
The Mean ◽  
The Difference

Background Prilocaine exists in two stereoisomeric configurations, the enantiomers S(+)- and R(-)-prilocaine. The drug is clinically used as the racemate. This study examined the pharmacokinetics of the enantiomers after intravenous administration of the racemate. Methods Ten healthy male volunteers received 200 mg racemic prilocaine as a 10-min intravenous infusion. Blood samples were collected for 8 h after the start of the infusion. Plasma concentrations were measured by stereoselective high-performance liquid chromatography (HPLC). Unbound fractions of the enantiomers in blank blood samples, spiked with racemic prilocaine, were determined using equilibrium dialysis. Results The unbound fraction of R(-)-prilocaine (mean +/- SD, 70%+/-8%) was smaller (P &lt; 0.05) than that of S(+)-prilocaine (73%+/-5%). The total plasma clearance of R(-)-prilocaine (2.57+/-0.46 l/min) was larger (P &lt; 0.0001) than that of S(+)-prilocaine (1.91+/-0.30 l/min). The steady-state volume of distribution of R(-)-prilocaine (279+/-94 l) did not differ from that of S(+)-prilocaine (291+/-93 l). The terminal half-life of R(-)-prilocaine (87+/-27 min) was shorter (P &lt; 0.05) than that of S(+)-prilocaine (124+/-64 min), as was the mean residence time of R(-)-prilocaine (108+/-30 min) compared with S(+)-prilocaine (155+/-59 min; P &lt; 0.005). Conclusions The pharmacokinetics of prilocaine are enantioselective. The difference in clearance is most likely a result of a difference in intrinsic metabolic clearance. The difference in the pharmacokinetics of the enantiomers of prilocaine does not seem to be clinically relevant.

scholarly journals Elevated Plasma Soluble PD-L1 Levels in Out-of-Hospital Cardiac Arrest Patients

2021 ◽  
Vol 10 (18) ◽  
pp. 4188
Author(s):  
Miho Sumiyoshi ◽  
Eiji Kawamoto ◽  
Yuki Nakamori ◽  
Ryo Esumi ◽  
Kaoru Ikejiri ◽  
...  
Keyword(s):  
Cardiac Arrest ◽  
Ischemia Reperfusion ◽  
Plasma Concentrations ◽  
Spontaneous Circulation ◽  
University Hospital ◽  
Soluble Form ◽  
Enzyme Linked Immunosorbent Assay ◽  
Immune Functions ◽  
Protein Levels ◽  
Hospital Cardiac Arrest

Background: A deregulated immune system has been implicated in the pathogenesis of post-cardiac arrest syndrome (PCAS). A soluble form of programmed cell death-1 (PD-1) ligand (sPD-L1) has been found at increased levels in cancer and sustained inflammation, thereby deregulating immune functions. Here, we aim to study the possible involvement of sPD-L1 in PCAS. Methods: Thirty out-of-hospital cardiac arrest (OHCA) patients consecutively admitted to the ER of Mie University Hospital were prospectively enrolled. Plasma concentrations of sPD-L1 were measured by an enzyme-linked immunosorbent assay in blood samples of all 30 OHCA patients obtained during cardiopulmonary resuscitation (CPR). In 13 patients who achieved return-of-spontaneous-circulation (ROSC), sPD-L1 levels were also measured daily in the ICU. Results: The plasma concentrations of sPD-L1 in OHCA were significantly increased; in fact, to levels as high as those observed in sepsis. sPD-L1 levels during CPR correlated with reduced peripheral lymphocyte counts and increased C-reactive protein levels. Of 13 ROSC patients, 7 cases survived in the ICU for more than 4 days. A longitudinal analysis of sPD-L1 levels in the 7 ROSC cases revealed that sPD-L1 levels occurred in parallel with organ failure. Conclusions: This study suggests that ischemia- reperfusion during CPR may aberrantly activate immune and endothelial cells to release sPD-L1 into circulation, which may play a role in the pathogenesis of immune exhaustion and organ failures associated with PCAS.

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