Don Johnson

Effects of humeral intraosseous versus intravenous epinephrine on pharmacokinetics and return of spontaneous circulation in a porcine cardiac arrest model: A randomized control trial

Cardiopulmonary Resuscitation (CPR), defibrillation, and epinephrine administration are pillars of advanced cardiac life support (ACLS). Intraosseous (IO) access is an alternative route for epinephrine administration when intravenous (IV) access is unobtainable. Previous studies indicate the pharmacokinetics of epinephrine administration via IO and IV routes differ, but it is not known if the difference influences return of spontaneous circulation (ROSC). The purpose of this prospective, experimental study was to determine the effects of humeral IO (HIO) and IV epinephrine administration during cardiac arrest on pharmacokinetics, ROSC, and odds of survival. Swine (N = 21) were randomized into 3 groups: humeral IO (HIO), peripheral IV (IV) and CPR/defibrillation control. Cardiac arrest was induced under general anesthesia. The swine remained in arrest for 2 min without intervention. Chest compressions were initiated and continued for 2 min. Epinephrine was administered and serial blood samples collected for pharmacokinetic analysis over 4 min. Defibrillation and epinephrine administration proceeded according to ACLS guidelines continuing for 20 min or until ROSC. Seven HIO swine, 4 IV swine, and no control swine had ROSC. There were no significant differences in ROSC, maximum concentration; except at 30 s, and time-to-concentration-maximum between the HIO and IV groups. Significant differences existed between the experimental groups and the control. The HIO delivers a higher concentration of epinephrine than the IV route at 30 s which may be a survival advantage. Clinicians may consider using the IO route to administer epinephrine during CA when there is no preexisting IV access or when IV access is unobtainable.

The Effects of QuikClot Combat Gauze, Fluid Resuscitation, and Movement on Hemorrhage Control in a Porcine Model

The purpose of this study was to compare the effectiveness of QuikClot Combat Gauze (QCG) compared to a control group on hemorrhage control; the amount of crystalloid volume infusion on rebleeding; the effect of movement on hemorrhage. This was a prospective, experimental design. Swine were randomly assigned to either the QCG () or the control group (). Investigators transected the femoral artery and vein in each swine. After one minute of uncontrolled hemorrhage, the hemostatic agent, QCG, was placed into the wound followed by standard wound packing. The control group underwent the same procedures but without a hemostatic agent. After five minutes of direct pressure, a standard pressure dressing was applied. After 30 minutes, dressings were removed, and the wound was observed for rebleeding for 5 minutes. If hemostasis occurred, 5 liters of crystalloid was given over 5 minutes, and the wound was observed for rebleeding for 5 additional minutes. If no bleeding occurred, the extremity on the side of the injury was moved. There were significant differences in the amount of hemorrhage (), the amount of fluid administration (), and the number of movements () between the QCG and control.

Onset and Duration of Intravenous and Intraosseous Rocuronium in Swine

Introduction The intraosseous (IO) route has become a popular method to gain access to the peripheral circulation in emergency situations. Despite little supporting data, it is generally believed that IO absorption is immediate and equivalent to the intravenous (IV) route. It is important to determine if rocuronium can effectively be administered by the IO route. The aim of the study was to determine and compare the onset and duration of rocuronium when administered via the IO and IV routes in a normovolemic pig model. Methods We recorded electromyographic (EMG) data following tibial IO and peripheral IV administration of rocuronium (1.2 mg/kg) in 10 swine weighing between 56 and 71 Kg. We transformed data were transformed to percent of baseline, determined onset and recovery characteristics. Results The onset EMG-time profiles for IO and IV administration were very similar: tibial IO compared to IV administration did not statistically alter the onset of paralysis. The IO group took statistically longer than the IV group to return to 50 (p=0.042), 75 (p=0.034) and 95 (p=0.036) percent of baseline activity. Conclusion The duration of effect is statistically longer after IO administration but is more of an academic interest than a clinical concern. The results of this study suggest that rocuronium can effectively be administered via the IO route without the need for dose adjustments.

Effects of Intraosseous Tibial vs. Intravenous Vasopressin in a Hypovolemic Cardiac Arrest Model

Introduction This study compared the effects of vasopressin via tibial intraosseous (IO) and intravenous (IV) routes on maximum plasma concentration (Cmax), the time to maximum concentration (Tmax), return of spontaneous circulation (ROSC), and time to ROSC in a hypovolemic cardiac arrest model. Methods This study was a randomized prospective, between-subjects experimental design. A computer program randomly assigned 28 Yorkshire swine to one of four groups: IV (n=7), IO tibia (n=7), cardiopulmonary resuscitation (CPR) + defibrillation (n=7), and a control group that received just CPR (n=7). Ventricular fibrillation was induced, and subjects remained in arrest for two minutes. CPR was initiated and 40 units of vasopressin were administered via IO or IV routes. Blood samples were collected at 0.5, 1, 1.5, 2, 2.5, 3, and 4 minutes. CPR and defibrillation were initiated for 20 minutes or until ROSC was achieved. We measured vasopressin concentrations using high-performance liquid chromatography. Results There was no significant difference between the IO and IV groups relative to achieving ROSC (p=1.0) but a significant difference between the IV compared to the CPR+ defibrillation group (p=0.031) and IV compared to the CPR-only group (p=0.001). There was a significant difference between the IO group compared to the CPR+ defibrillation group (p=0.031) and IO compared to the CPR-only group (p=0.001). There was no significant difference between the CPR + defibrillation group and the CPR group (p=0.127). There was no significant difference in Cmax between the IO and IV groups (p=0.079). The mean ± standard deviation of Cmax of the IO group was 58,709±25, 463pg/mL compared to the IV group, which was 106,198±62, 135pg/mL. There was no significant difference in mean Tmax between the groups (p=0.084). There were no significant differences in odds of ROSC between the tibial IO and IV groups. Conclusion Prompt access to the vascular system using the IO route can circumvent the interruption in treatment observed with attempting conventional IV access. The IO route is an effective modality for the treatment of hypovolemic cardiac arrest and may be considered first line for rapid vascular access.

Comparative Resuscitative Methods for Venlafaxine Toxicity in a Swine Model

OBJECTIVES Venlafaxine overdose can lead to cardiovascular collapse that is difficult to resuscitate with traditional Advanced Cardiovascular Life Support protocols. Evidence has suggested that lipid emulsion infusion therapy has been successful in the treatment of antidepressant overdose. No studies have determined the optimal combination of lipid/advanced cardiovascular life support therapy for treatment. METHODS This study was a prospective, experimental, between subjects design with a swine model investigating the effectiveness of drug combinations administered with cardiopulmonary resuscitation (CPR) postvenlafexine overdose. Subjects were randomly assigned to 1 of eight groups containing seven subjects. The groups tested were CPR only and CPR with epinephrine alone; vasopressin alone; lipid alone; epinephrine and vasopressin; epinephrine and lipid; vasopressin and lipid; and epinephrine, vasopressin, and lipid. The outcomes of interest were survival odds and time to return of spontaneous circulation. RESULTS Results on these swine models indicate that the use of vasopressin coupled with lipids for venlafaxine overdose resulted in a higher survival rate when compared to the control group (p = 0.023). Groups receiving vasopressin experienced statistically faster times to return of spontaneous circulation than other groups (p = 0.019). CONCLUSIONS The results suggest that in swine models, the optimal treatment for venlafaxine overdose would include vasopressin with lipids.

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

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.

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

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.

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

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.

Onset and duration of intravenous and intraosseous rocuronium in hypovolemic swine.

OBJECTIVE Compare the onset and duration of rocuronium administered via the intravenous (IV), and intraosseous (IO) routes in a hypovolemic swine model. DESIGN Prospective, between subjects, experimental study. SETTING Vivarium. SUBJECTS Yorkshire-cross swine (N = 8). INTERVENTION Electromyography (EMG) amplitudes were recorded at baseline and for every 15 seconds after administering 1.2 mg/kg of rocuronium via IV or IO routes to hypovolemic swine. EMG amplitudes were measured until termination of EMG activity and then measured every 5 minutes until there was a return to baseline values. Individual data were transformed to percent baseline. MAIN OUTCOME MEASUREMENTS The time from the end of injection to 90 percent reduction of baseline EMG activity (Onset90), the time to maximum reduction (Onsetpeak), and the maximum reduction of the neuromuscular response (peak effect), as well as, time from the end of injection to the return of 25, 50, 75, and 95 percent of baseline EMG activity was used to characterize onset and recovery of neuromuscular function. RESULTS Maximum reduction, Onset 90 and Onset peak times were not statistically different between groups. The IV groups mean time to recovery of all benchmarks was faster than the IO group. The IO group took statistically longer than the IV group to return to 25, 50, 75, and 95 percent of baseline activity. CONCLUSION The IO route is an effective method of administering rocuronium and is comparable to the IV route even under conditions of significant hemorrhage.

Effects of tibial and humerus intraosseous and intravenous vasopressin in porcine cardiac arrest model

OBJECTIVE Compare maximum concentration (Cmax), time to maximum concentration (Tmax), mean serum concentration of vasopressin, return of spontaneous circulation (ROSC), time to ROSC, and odds of survival relative to vasopressin administration by tibial intraosseous (TIO), humerus intraosseous (HIO), and intravenous (IV) routes in a hypovolemic cardiac arrest model. DESIGN Prospective, between subjects, randomized experimental design. SETTING TriService Research Facility. SUBJECTS Yorkshire-cross swine (n = 40). INTERVENTION Swine were anesthetized, exsanguinated to a Class III hemorrhage, and placed into cardiac arrest. After 2 minutes, cardiopulmonary resuscitation was initiated. After an additional 2 minutes, a dose of 40 units of vasopressin was administered by TIO, HIO, 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 ROSC or time to ROSC between the TIO, HIO, and IV groups (p > 0.05). The Cmax was significantly higher in the IV group compared to the TIO group (p = 0.015), but no significant difference between the TIO versus HIO or HIO versus IV groups (p > 0.05). The Tmax was significantly shorter for the HIO compared to the TIO group (p = 0.034), but no significant differences between the IV group compared to the TIO or HIO groups (p > 0.05). 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.