Effects of Endotracheal Epinephrine on Pharmacokinetics and Survival in a Swine Pediatric Cardiac Arrest Model.

OBJECTIVES: The aim of this study was to compare the endotracheal tube (ET) and intravenous (IV) administration of epinephrine relative to concentration maximum, time to maximum concentration, mean concentration over time (MC), area under the curve, odds, and time to return of spontaneous circulation (ROSC) in a normovolemic pediatric cardiac arrest model. METHODS: Male swine weighing 24-37 kg were assigned to 4 groups: ET (n = 8), IV (n = 7), cardiopulmonary resuscitation (CPR) + defibrillation (CPR + Defib) (n = 5), and CPR only (n = 3). Swine were placed arrest for 2 minutes, and then CPR was initiated for 2 minutes. Epinephrine (0.1 mg/kg) for the ET group or 0.01 mg/kg for the IV was administered every 4 minutes or until ROSC. Defibrillation started at 3 minutes and continued every 2 minutes for 30 minutes or until ROSC for all groups except the CPR-only group. Blood samples were collected over a period of 5 minutes. RESULTS: The MC of plasma epinephrine for the IV group was significantly higher at the 30- and 60-second time points (P = 0.001). The ET group had a significantly higher MC of epinephrine at the 180- and 240-second time points (P < 0.05). The concentration maximum of plasma epinephrine was significantly lower for the ET group (195 ± 32 ng/mL) than for the IV group (428 ± 38 ng/mL) (P = 0.01). The time to maximum concentration was significantly longer for the ET group (145 ± 26 seconds) than for the IV group (42 ± 16 seconds) (P = 0.01). No significant difference existed in area under the curve between the 2 groups (P = 0.62). The odds of ROSC were 7.7 times greater for the ET versus IV group. Time to ROSC was not significantly different among the IV, ET, and CPR + Defib groups (P = 0.31). CONCLUSIONS: Based on the results of this study, the ET route of administration should be considered a first-line intervention.

Correlative metabologenomics of 110 fungi reveals metabolite-gene cluster pairs.

Natural products research increasingly applies -omics technologies to guide molecular discovery. While the combined analysis of genomic and metabolomic datasets has proved valuable for identifying natural products and their biosynthetic gene clusters (BGCs) in bacteria, this integrated approach lacks application to fungi. Because fungi are hyper-diverse and underexplored for new chemistry and bioactivities, we created a linked genomics-metabolomics dataset for 110 Ascomycetes, and optimized both gene cluster family (GCF) networking parameters and correlation-based scoring for pairing fungal natural products with their BGCs. Using a network of 3,007 GCFs (organized from 7,020 BGCs), we examined 25 known natural products originating from 16 known BGCs and observed statistically significant associations between 21 of these compounds and their validated BGCs. Furthermore, the scalable platform identified the BGC for the pestalamides, demystifying its biogenesis, and revealed more than 200 high-scoring natural product-GCF linkages to direct future discovery.

A Survey of Didemnin Depsipeptide Production in Tistrella.

As one of the first families of marine natural products to undergo clinical trials, the didemnin depsipeptides have played a significant role in inspiring the discovery of marine drugs. Originally developed as anticancer therapeutics, the recent re-evaluation of these compounds including synthetically derived dehydrodidemnin B or Aplidine, has led to their advancement towards antiviral applications. While conventionally associated with production in colonial tunicates of the family Didemnidae, recent studies have identified their biosynthetic gene clusters from the marine-derived bacteria Tistrella mobilis. While these studies confirm the production of didemnin X/Y, the low titer and general lack of understanding of their biosynthesis in Tistrella currently prevents the development of effective microbial or synthetic biological approaches for their production. To this end, we conducted a survey of known species of Tistrella and report on their ability to produce the didemnin depsipeptides. These data were used to develop conditions to produce didemnin B at titers over 15 mg/L.

Electrodeposition and analysis of thick bismuth films.

Due to its unique physical and chemical properties, bismuth is an attractive candidate for a wide range of applications such as battery anodes, radiation shielding, and semiconductors, to name a few. This work presents the electrodeposition of mechanically stable and homogenous bismuth films at micron-scale thicknesses. A simple one-step electrodeposition process using either a pulse/reverse or direct current source yielded thick, homogenous, and mechanically stable bismuth films. Morphology, electrochemical behavior, adhesion, and mechanical stability of bismuth coatings plated with varying parameters were characterized via optical profilometry, cyclic voltammetry, electron microscopy, and tribology. Scratch testing on thick electroplated coatings (> 100 µm) revealed similar wear resistance properties between the pulse/reverse plated and direct current electroplated films. This study presents a versatile bismuth electroplating process with the possibility to replace lead in radiation shields with an inexpensive, non-toxic metal, or to make industrially relevant electrocatalytic devices.

Durability and disinfection of single-use endotracheal tubes following exposure to commonly available medical disinfecting compounds.

BACKGROUND: Reusing single-use medical supplies offers a capability enhancement during massive casualty incidents when resupply of medical supplies is unavailable in times of national health care crises. This pilot study determined the feasibility of disinfection of endotracheal tubes with commonly used chemical disinfecting agents. METHODS: Endotracheal tubes (ETTs) were subjected to either CaviCide, Neutral Disinfectant Cleaner, Cidex, or saline according to the manufacturer's recommended disinfection contact times. Alterations to the polyvinyl chloride (PVC) integrity by disinfecting agents were determined by volume/pressure measurements within the ETT cuff. To test the disinfection rate, ETTs were inoculated with Staphylococcus Aureus and subjected to experimental disinfection protocol. FINDINGS: There were no significant alterations to ETT tracheal cuff function and mixed results in disinfection among ETTs. ETTs bacterial culture data presented possible contamination among the groups. DISCUSSION: These data support the feasibility of single-use ETT reuse as a last resort while making every attempt and effort to follow established protocols to minimize harm to the patient.

Humerus Intraosseous and Intravenous Administration of Epinephrine in Normovolemic and Hypovolemic Cardiac Arrest Porcine Models.

OBJECTIVE: The aim of this study was to compare area under the curve (AUC), frequency, and odds of return of spontaneous circulation (ROSC) when epinephrine was administered in hypovolemic and normovolemic cardiac arrest models. METHODS: Twenty-eight adult swine were randomly assigned to 4 groups: HIO Normovolemia Group (HIONG); HIO Hypovolemia Group (HIOHG); IV Normovolemia (IVNG); and IV Hypovolemia Group (IVHG). Swine were anesthetized. The HIOH and IVH subjects were exsanguinated 35% of their blood volume. Each was placed into arrest. After 2 minutes, cardiopulmonary resuscitation was initiated. After another 2 minutes, 1 mg of epinephrine was given by IV or HIO routes; blood samples were collected over 5 minutes and analyzed by high-performance liquid chromatography. Subjects were defibrillated every 2 minutes. RESULTS: The AUC in the HIOHG was significantly less than both the HIONG (p = 0.047) and IVHG (p = 0.021). There were no other significant differences in the groups relative to AUC (p > 0.05). HIONG had a significantly higher occurrence of ROSC compared to HIOHG (p = 0.018) and IVH (p =0.018) but no other significant differences (p > 0.05). The odds of ROSC were 19.2 times greater for HIONG compared to the HIOHG. CONCLUSION: The study strongly supports the effectiveness of HIO administration of epinephrine and should be considered as a first-line intervention for patients in cardiac arrest related to normovolemic causes. However, our findings do not support using HIO access for epinephrine administration for patients in cardiac arrest related to hypovolemic reasons.

Tibial Intraosseous Administration of Epinephrine Is Effective in Restoring Return of Spontaneous Circulation in a Pediatric Normovolemic But Not Hypovolemic Cardiac Arrest Model.

OBJECTIVE: We compared the efficacy of tibial intraosseous (TIO) administration of epinephrine in a pediatric normovolemic versus hypovolemic cardiac arrest model to determine the incidence of return of spontaneous circulation (ROSC) and plasma epinephrine concentrations over time. METHODS: This experimental study evaluated the pharmacokinetics of epinephrine and/or incidence of ROSC after TIO administration in either a normovolemic or hypovolemic pediatric swine model. RESULTS: All subjects in the TIO normovolemia cardiac arrest group experienced ROSC after TIO administration of epinephrine. In contrast, subjects experiencing hypovolemia and cardiac arrest were significantly less likely to experience ROSC when epinephrine was administered TIO versus intravenous (TIO hypovolemia: 14% [1/7] vs IV hypovolemia: 71% [5/7]; P = 0.031). The TIO hypovolemia group exhibited significantly lower plasma epinephrine concentrations versus IV hypovolemia at 60, 90, 120, and 150 seconds (P < 0.05). Although the maximum concentration of plasma epinephrine was similar, the TIO hypovolemia group exhibited significantly slower time to maximum concentration times versus TIO normovolemia subjects (P = 0.004). CONCLUSIONS: Tibial intraosseous administration of epinephrine reliably facilitated ROSC among normovolemic cardiac arrest pediatric patients, which is consistent with published reports. However, TIO administration of epinephrine was ineffective in restoring ROSC among subjects experiencing hypovolemia and cardiac arrest. Tibial intraosseous-administered epinephrine during hypovolemia and cardiac arrest may have resulted in a potential sequestration of epinephrine in the tibia. Central or peripheral intravascular access attempts should not be abandoned after successful TIO placement in the resuscitation of patients experiencing concurrent hypovolemia and cardiac arrest.

Endotracheal Administered Epinephrine Is Effective in Return of Spontaneous Circulation Within a Pediatric Swine Hypovolemic Cardiac Arrest Model.

OBJECTIVE: Early administration of epinephrine increases the incidence of return of spontaneous circulation (ROSC) and improves outcomes among pediatric cardiac arrest victims. Rapid endotracheal (ET) intubation can facilitate early administration of epinephrine to pediatric victims. To date, no studies have evaluated the use of ET epinephrine in a pediatric hypovolemic cardiac arrest model to determine the incidence of ROSC. METHODS: This prospective, experimental study evaluated the pharmacokinetics and/or incidence of ROSC following ET administered epinephrine and compared it to these experimental groups: intravenous (IV) administered epinephrine, cardiopulmonary resuscitation only (CPR), and CPR + defibrillation (CPR + Defib). RESULTS: Endotracheal administered epinephrine, at the Pediatric Advanced Life Support (PALS) recommended dose, was not significantly different than IV administered epinephrine in maximum plasma concentrations, time to maximum plasma concentration, area under the curve, or ROSC, or mean plasma concentrations at various time points (P > 0.05). The odds of ROSC in the ET group were 2.4 times greater than the IV group. The onset to ROSC in the ET group was significantly shorter than the IV group (P < 0.0001). CONCLUSIONS: These data support that ET epinephrine administration remains an alternative to IV administered epinephrine and faster at restoring ROSC among pediatric hypovolemic cardiac arrest victims in the acute setting when an endotracheal tube is present. Although further research is required to determine long-term outcomes of high-dose ET epinephrine administration, these data reinforce the therapeutic potential of ET administration of epinephrine to restore ROSC before IV access.

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

BACKGROUND: Aims 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). METHODS: Pediatric 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. RESULTS: Analysis 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. DISCUSSION: Based on the results of our study, the IV route is more effective than the HIO route.

The effects of QuikClot Combat Gauze and Celox Rapid on hemorrhage control.

OBJECTIVE: Compare QuikClot Combat Gauze (QCG) and Celox Rapid (CR) for initial hemostasis and over a 1-hour period. DESIGN: Experimental study. SETTING: Approved animal laboratory. SUBJECTS: Twenty-one Yorkshire swine. INTERVENTIONS: Subjects were randomly assigned to either the QCG (n = 11) or CR (n = 10) group. An arteriotomy was made in the right femoral artery with a 6-mm vascular punch. Bleeding was allowed for 45 seconds. QCG or CR was applied followed by firm pressure for 3 minutes according to Committee on Tactical Combat Casualty Care guidelines. A 10-pound weight simulating a pressure dressing was applied, and the wound was observed for 1 hour. Dressing failure was bleeding > 2 percent of blood volume. MAIN OUTCOME MEASURES: Achievement and maintenance of hemostasis and amount of hemorrhage during observation. Odds of successful hemostasis. RESULTS: QCG was significantly better than CR in initial hemostasis (p = 0.049) and maintaining hemostasis over 1 hour (p = 0.020). One hundred percent of QCG subjects and 70 percent of CR subjects achieved initial hemostasis. During the 1-hour observation, one additional CR subject failed to maintain hemostasis. CR had significantly more hemorrhage than QCG during the 1-hour observation (p = 0.027). QCG had no bleeding compared to CR that had a mean of 162 ± 48 mL (standard error of mean) over 2 minutes. QCG had 15.9 times greater odds of success compared to CR over a period of 1 hour. Over the 1-hour observation time, 100 percent of QCG achieved hemostasis compared to 60 percent of CR.

Sublethal Effects of Imidacloprid on Honey Bee Colony Growth and Activity at Three Sites in the U.S.

Imidacloprid is a neonicotinoid pesticide heavily used by the agricultural industry and shown to have negative impacts on honey bees above certain concentrations. We evaluated the effects of different imidacloprid concentrations in sugar syrup using cage and field studies, and across different environments. Honey bee colonies fed sublethal concentrations of imidicloprid (0, 5, 20 and 100 ppb) over 6 weeks in field trials at a desert site (Arizona), a site near intensive agriculture (Arkansas) and a site with little nearby agriculture but abundant natural forage (Mississippi) were monitored with respect to colony metrics, such as adult bee and brood population sizes, as well as pesticide residues. Hive weight and internal hive temperature were monitored continuously over two trials in Arizona. Colonies fed 100 ppb imidacloprid in Arizona had significantly lower adult bee populations, brood surface areas and average frame weights, and reduced temperature control, compared to colonies in one or more of the other treatment groups, and consumption rates of those colonies were lower compared to other colonies in Arizona and Arkansas, although no differences in capped brood or average frame weight were observed among treatments in Arkansas. At the Mississippi site, also rich in alternative forage, colonies fed 5 ppb imidacloprid had less capped brood than control colonies, but contamination of control colonies was detected. In contrast, significantly higher daily hive weight variability among colonies fed 5 ppb imidacloprid in Arizona suggested greater foraging activity during a nectar flow post treatment, than any other treatment group. Imidacloprid concentrations in stored honey corresponded well with the respective syrup concentrations fed to the colonies and remained stable within the hive for at least 7 months after the end of treatment.

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 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, 463 pg/mL compared to the IV group, which was 106,198±62, 135 pg/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.

Effects of tibial intraosseous and IV administration of vasopressin on kinetics and survivability in cardiac arrest.

PURPOSE: Purposes of this study were to compare tibial intraosseous (TIO) and intravenous (IV) administration of vasopressin relative to return of spontaneous circulation (ROSC) and time to ROSC in an adult swine cardiac arrest model. In addition, the purposes were to compare the concentration maximum (Cmax), time to maximum concentration (Tmax), and odds of ROSC. METHODS: This was a between-subjects, prospective experimental study. Yorkshire swine (N = 21) were randomly assigned to 1 of 3 groups: TIO, IV, or control groups. The swine were anesthetized and instrumented, and then cardiac arrest was induced and sustained for 2 minutes. Cardiopulmonary resuscitation was initiated and continued for 2 minutes. Vasopressin was then administered via the TIO or IV route. Blood samples were collected for 4 minutes to determine the Cmax and Tmax of vasopressin. Concentration maximum and Tmax were calculated by use of liquid chromatography with mass spectrometry. RESULTS: There was no difference in ROSC between the TIO and IV groups (P = .63). The Cmax of vasopressin was significantly higher in the IV group compared to the TIO group (P = .017). However, there was no significant difference in ROSC, time to ROSC, or Tmax between groups (P > .05). All subjects had ROSC in both the IV and TIO groups, and none had ROSC in the control group. There was 225 times greater chance of survival for both the IV and TIO groups compared to the control group. CONCLUSION: The data support that the TIO is an effective route for vasopressin in a cardiac arrest model.

Effects of intravenous, sternal, and humerus intraosseous administration of Hextend on time of administration and hemodynamics in a hypovolemic swine model.

OBJECTIVE: To determine if there were significant differences among humerus intraosseous (HIO), sternal intraosseous (SIO), and intravenous (IV) administration of 500 mL Hextend in hemodynamics or administration time in a hypovolemic swine model. SETTING: Vivarium. SUBJECTS: Yorkshire swine; sample size was based on a large effect size of 0.5, an α of 0.05, and a power of 80 percent Swine were randomly assigned to one of four groups: HIO (n = 9), SIO (n = 9), IV (n = 9), and control (n = 9). INTERVENTION: Swine were exsanguinated 30 percent of their blood volume. Hextend (500 mL) was administered by either the HIO, SIO, or IV route; the control group received none. MAIN OUTCOME: Time of administration of Hextend; systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), heart rate (HR), cardiac output (CO), and stroke volume (SV) data were collected every 2 minutes and compared by group over 8 minutes. RESULTS: A repeated analysis of variance found that there were no significant differences in SBP, DBP, MAP, HR, CO, and SV among HIO, SIO, and IV groups over 8 minutes (p > 0.05). An analyses of variance determined that there was no significant difference between groups relative to time of administration (p = 0.521). CONCLUSION: When IV access is difficult, both HIO and SIO are effective techniques for rapid vascular access and the administration of Hextend for patients in hypovolemic shock.

Effects of tibial intraosseous and intravenous administration of Hextend on time of administration and hemodynamics in a hypovolemic swine model.

OBJECTIVE: To determine if there were significant differences between the tibial intraosseous (TIO) and intravenous (IV) administration of Hextend relative to time and in hemodynamics in a hypovolemic model. SETTING: Vivarium. SUBJECTS: Yorkshire swine; sample size was based on a power of 80 percent, α of 0.05, and a large effect size of 0.6. Swine were randomly assigned to one of three groups: TIO (n = 7), IV (n = 7), and control (n = 7). INTERVENTION: Swine were exsanguinated 30 percent of their blood volume. Hextend (500 mL) was administered either by the TIO or IV route; the control group received none. MAIN OUTCOME: Time of administration of Hextend; systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), heart rate (HR), cardiac output (CO), and stroke volume (SV) data were collected every 2 minutes and compared by group over 8 minutes. RESULTS: An independent t test determined that there was no significant difference between groups relative to time of administration (p = 0.001). A repeated analysis of variance found that there were no significant differences in SBP, DBP, MAP, HR, CO, and SV between the TIO and IV groups over 8 minutes (p > 0.05) but significant differences between both TIO and IV compared to the control group (p < 0.05). CONCLUSION: TIO is an effective and easily used method to administer Hextend for patients in hypovolemic shock. Based upon the findings of this study, the TIO route might be considered the first choice for rapid vascular access and the administration of Hextend.

The effects of sternal and intravenous vasopressin administration on pharmacokinetics.

OBJECTIVE: Purposes of this study were to compare intravenous (IV) and sternal intraosseous (SIO) administration of vasopressin relative to concentration maximum (Cmax), time to maximum concentration (Tmax), and mean concentration in a cardiac arrest model. DESIGN: Prospective, between subjects, randomized experimental design. SETTING: Vivarium. SUBJECTS: Yorkshire-cross swine (N = 16) INTERVENTION: Swine were anesthetized, placed into cardiac arrest, and after 2 minutes, cardiopulmonary resuscitation was initiated. After additional 2 minutes, 40 units of vasopressin was administered either by SIO or IV route. Blood samples were collected over 4 minutes. Cmax and means were analyzed using high-performance liquid chromatography tandem mass spectrometry. MAIN OUTCOME MEASUREMENTS: Cmax, Tmax, and mean plasma concentrations. RESULTS: There were no significant differences in the SIO and IV groups in Cmax (p = 0.96) or Tmax (p = 0.27). The IV and SIO group had a mean Cmax of 68,151 ± SD 21,534 and 69,034 ± SD 40,169 pg/mL, respectively. The IV and SIO vasopressin groups had a mean Tmax of 105 ± SD 39 and 80 ± SD 41 seconds, respectively. CONCLUSION: A multivariate analyses of variance indicated that there were no statistically significant differences in pretest data, Cmax, and Tmax; a repeated analyses of variance indicated that there were no significant differences between the groups relative to mean concentrations of serum vasopressin over time (p > 0.05). CONCLUSION: When a patient is in cardiac arrest, it is essential to establish rapid and reliable access to blood vessels so that life-saving drugs can be administered and the SIO provides such a route.

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.

Pharmacokinetics of sternal intraossesous atropine administration in normovolemic and hypovolemic swine.

OBJECTIVE: Characterize and compare the pharmacokinetics of atropine administered via the sternal intraosseous (IO) route in a normovolemic and hypovolemic swine model. DESIGN: Prospective, experimental study. SETTING: Vivarium. SUBJECTS: Yorkshire-cross swine (N = 12). INTERVENTION: Atropine was administered via the sternal IO route to normovolemic and hypovolemic swine. Blood samples were drawn at regular intervals after atropine administration and analyzed for plasma atropine concentration. Pharmacokinetic parameters were obtained from modeling the plasma concentrations. MAIN OUTCOME MEASUREMENTS: Pharmacokinetic parameters, maximum concentration (Cmax), and time to maximum concentration (Tmax). RESULTS: The normovolemic and hypovolemic models reached peak plasma concentration immediately and had a very rapid distribution phase with no apparent absorption phase for the IO groups. The hypovolemic group had slower clearance and longer half-life compared to the normovolemic group. CONCLUSION: The sternal IO route is an effective method of administering atropine and is comparable to the previously reported tibial IO and intravenous data even under conditions of significant hemorrhage.

The comparison of humeral intraosseous and intravenous administration of vasopressin on return of spontaneous circulation and pharmacokinetics in a hypovolemic cardiac arrest swine model.

INTRODUCTION: The American Heart Association (AHA) recommends intravenous (IV) or intraosseous (IO) vasopressin in Advanced Cardiac Life Support (ACLS). Obtaining IV access in hypovolemic cardiac arrest patients can be difficult, and IO access is often obtained in these life threatening situations. No studies have been conducted to determine the effects of humeral IO (HIO) access with vasopressin in the return of spontaneous circulation (ROSC). Our study compared the kinetics of vasopressin and ROSC with HIO with IV access in the hypovolemic swine model. METHODS: Twenty-two Yorkshire swine were divided into three groups: HIO (n = 7), IV (n = 8), and a control group (n = 7). The IV and HIO group received vasopressin and cardiopulmonary resuscitation (CPR), while the control group received only CPR. All subjects were exsanguinated 31 percent of their blood volume, placed in cardiac arrest, and resuscitated per ACLS. Subjects that achieved ROSC were then monitored for 20 minutes. Blood samples (10 mL) collected at 0.5, 1, 1.5, 2, 2.5, 3, and 4 minutes after vasopressin injection and analyzed for maximum concentration (Cmax) and time to maximum concentration (Tmax). Data were analyzed using a multivariate analysis of variance (MANOVA) and a Fisher's Exact Test. RESULTS: ROSC was achieved in every subject that received vasopressin via the HIO route. Data analysis using a MANOVA pairwise comparison revealed no difference between mean Cmax (p = 0.601) and Tmax (p = 0.771) of vasopressin administered IV versus HIO routes. Analysis of the mean serum concentrations at time intervals using a repeated measures analysis of variance found no difference (p > 0.05). A Fisher's Exact Test revealed no difference in rate of ROSC between HIO and IV groups (p > 0.05). Odds ratio determined that there was a 33 times higher chance of survival among HIO subjects versus control (CPR and Defibrillation; p = 0.03) and no difference in the survivability of the HIO or IV groups (p = 0.52). CONCLUSION: The data from this study strongly suggest that there is no significant difference in ROSC, time to ROSC, hemodynamics, or pharmacokinetics between HIO vasopressin and IV vasopressin. This research reinforces current AHA guidelines recommending the use of HIO route early over delaying care awaiting IV access.