Pharmacokinetic effects of endotracheal, intraosseous, and intravenous epinephrine in a swine model of traumatic cardiac arrest.

INTRODUCTION: Limited prospective data exist regarding epinephrine's controversial role in managing traumatic cardiac arrest (TCA). This study compared the maximum concentration (Cmax), time to maximum concentration (Tmax), plasma concentration over time, return of spontaneous circulation (ROSC), time to ROSC, and odds of ROSC of epinephrine administered by the endotracheal (ETT), intraosseous (IO), and intravenous (IV) routes in a swine TCA model. METHODS: Forty-nine Yorkshire-cross swine were assigned to seven groups: ETT, tibial IO (TIO), sternal IO (SIO), humeral IO (HIO), IV, CPR with defibrillation (CPRD), and CPR only. Swine were exsanguinated 31% of their blood volume and cardiac arrest induced. Chest compressions began 2 min post-arrest. At 4 min post-arrest, 1 mg epinephrine was administered, and blood specimens collected over 4 min. Resuscitation continued until ROSC or 30 min elapsed. RESULTS: The Cmax of IV epinephrine was significantly higher than the TIO group (P = 0.049). No other differences in Cmax, Tmax, ROSC, and time to ROSC existed between the epinephrine groups (P > 0.05). Epinephrine levels were detectable in two of seven ETT swine. No significant difference in ROSC existed between the epinephrine groups and CPRD group (P > 0.05). Significant differences in ROSC existed between all groups and the CPR only group (P < 0.05). No significant differences in odds of ROSC were noted. CONCLUSIONS: The pharmacokinetics of IV, HIO, and SIO epinephrine were comparable. Endotracheal epinephrine absorption was highly variable and unreliable compared to IV and IO epinephrine. Epinephrine appeared to have a lesser role than volume replacement in resuscitating TCA.

Sternal Route More Effective than Tibial Route for Intraosseous Amiodarone Administration in a Swine Model of Ventricular Fibrillation.

OBJECTIVE: The pharmacokinetics of IO administered lipid soluble amiodarone during ventricular fibrillation (VF) with ongoing CPR are unknown. This study measured mean plasma concentration over 5 minutes, maximum plasma concentration (Cmax), and time to maximum concentration (Tmax) of amiodarone administered by the sternal IO (SIO), tibial IO (TIO), and IV routes in a swine model of VF with ongoing CPR. METHODS: Twenty-one Yorkshire-cross swine were randomly assigned to three groups: SIO, TIO, and IV. Ventricular fibrillation was induced under general anesthesia. After 4 minutes in VF, 300 mg amiodarone was administered as indicated by group assignment. Serial blood specimens collected at 30, 60, 90, 120, 150, 180, 240, and 300 seconds were analyzed using high performance liquid chromatography with tandem mass spectrometry. RESULTS: The mean plasma concentration of IV amiodarone over 5 minutes was significantly higher than the TIO group at 60 seconds (P = 0.02) and 90 seconds (P = 0.017) post-injection. No significant differences in Cmax between the groups were found (P <0.05). The Tmax of amiodarone was significantly shorter in the SIO (99 secs) and IV (86 secs) groups compared to the TIO group (215 secs); P = 0.002 and P = 0.002, respectively. CONCLUSIONS: The SIO and IV routes of amiodarone administration were comparable. The TIO group took nearly three times longer to reach Tmax than the SIO and IV groups, likely indicating depot of lipid-soluble amiodarone in adipose-rich tibial yellow bone marrow. The SIO route was more effective than the TIO route for amiodarone delivery in a swine model of VF with ongoing CPR. Further investigations are necessary to determine if the kinetic differences found between the SIO and TIO routes in this study affect survival of VF in humans.

The effects of proximal and distal routes of intraosseous epinephrine administration on short-term resuscitative outcome measures in an adult swine model of ventricular fibrillation: a randomized controlled study.

INTRODUCTION: It is unknown if the anatomical distance of intraosseous (i.o.) epinephrine injection from the heart affects resuscitative outcome. The purpose of this study was to explore the relationships between the anatomical distance of i.o. epinephrine injection and measures of resuscitative outcome in an adult swine model of ventricular fibrillation (VF). METHODS: Thirty-two Yorkshire-cross swine (60-80 kg) were randomly assigned to four groups: humeral i.o. (HIO), tibial i.o. (TIO), i.v. with defibrillation and epinephrine, and i.v. control: with defibrillation but no epinephrine. Ventricular fibrillation was induced. Swine remained in VF for 4 minutes prior to mechanical chest compressions. After 6 minutes in VF, swine were defibrillated and epinephrine (0.01 mg/kg) administered by group assignment. Defibrillation was repeated every 2 minutes. Epinephrine was repeated every 4 minutes. Interventions continued until return of spontaneous circulation (ROSC) or 26 post-arrest minutes elapsed. Swine achieving ROSC were observed for 30 minutes post-ROSC. RESULTS: There were no significant differences between the HIO, TIO, and i.v. groups relative to the occurrence of ROSC (P > .05 in all cases), 30-minute post-ROSC survival (P > .05 in all cases), and time to ROSC (P = .43). There were significant differences between the HIO, TIO, and i.v. groups compared to the control group relative to the occurrence of ROSC (P = .02, .01, and .007 respectively), and 30 minute post-ROSC survival (P = .05, .03, and .007, respectively). CONCLUSION: The anatomical distance of i.o. epinephrine injection from the heart did not affect short-term measures of resuscitative outcome in an adult swine model of VF including the occurrence of ROSC, 30 minute post-ROSC survival, and time to ROSC. Rapidly administered epinephrine, irrespective of route of administration, increased the chance ROSC and survival to 30 minutes post-ROSC would occur in this study.

Effects of intraosseous transfusion of whole blood on hemolysis and transfusion time in a swine model of hemorrhagic shock: a pilot study.

This prospective, experimental, mixed study determined whether there were differences in intraosseous (IO) and intravenous (IV) whole blood transfusion relative to hemolysis and transfusion time. Swine were assigned to the IV group (n = 6) with an 18-gauge catheter in the auricular vein or the IO group (n = 7) with a 15-gauge 10 needle in the proximal humerus. Following baseline specimen collection, 900 mL of blood was collected from each animal. The collected blood was autologously transfused by the IV or IO route using a pressure infusion bag inflated to 300 mm Hg, with immediate posttransfusion specimen collection. Hemolysis was defined by the amount of plasma free hemoglobin. Multivariate analysis of variance revealed no significant differences between groups relative to posttransfusion free hemoglobin or transfusion time (P = .065). The IV group's mean free hemoglobin level was 10.23 +/- 10.52 micromol/L; the IO group, 7.2 +/- 5.82 micromol/L. The IV group's mean transfusion time was 13.48 +/- 4.1 minutes; the IO group, 28.70 +/- 19.51 minutes. Intraosseous transfusion does not significantly increase hemolysis or transfusion time compared with IV transfusion. Clinically, it can take up to twice as long to transfuse 900 mL of blood IO compared with IV.

Effects of Celox and TraumaDEX on hemorrhage control in a porcine model.

The purpose of this study was to compare the effectiveness of 2 hemostatic agents, chitosan-based Celox and the biopolymeric, microporous particles TraumaDEX, with a control group in a porcine model of hemorrhage. The animals were randomly assigned to 1 of 3 groups: Celox (n = 5), TraumaDEX (n = 5), or a standard pressure dressing alone (n = 5). To simulate a battlefield injury, the investigators generated a compound groin injury with transection of the femoral artery and vein in 15 pigs. After 1 minute of uncontrolled hemorrhage, Celox or TraumaDEX was poured into the wound, followed by standard wound packing. The control group underwent the same procedures with the exception of the hemostatic agents. In all groups, 5 minutes of direct manual pressure was applied to the wound, followed by a standard pressure dressing (3M Coban). After 30 minutes, dressings were removed, and the amount of bleeding was measured. There were statistically significant differences in bleeding between Celox and control (P = .01) and between TraumaDEX and control (P = .038), but no statistically significant difference in bleeding between Celox and TraumaDEX (P = .478). Celox and TraumaDEX may be effective hemostatic agents for use in civilian and military trauma.

Effects of arterial blood pressure on rebleeding using Celox and TraumaDEX in a porcine model of lethal femoral injury.

This study was designed to identify the systolic blood pressure (SBP) and mean arterial pressure (MAP) at which rebleeding occurs when a clot is formed by a hemostatic agent, Celox or TraumaDEX, compared with a standard dressing. Fifteen pigs (5 each) were assigned randomly to 1 of 3 groups: Celox, TraumaDEX, or standard pressure dressing as a control. In all animals, the femoral artery and vein were transected to simulate traumatic injury. Subjects were allowed to hemorrhage 1 minute before treatment. Direct pressure was held 5 minutes followed by application of elastic dressings for 30 minutes. Dressings were removed after 30 minutes, and the wound was observed for rebleeding. Animals demonstrating hemostasis received phenylephrine infusion to increase SBP in 10-mm Hg increments until SBP reached 210 mm Hg or hemorrhage recurred. There were statistically significant differences between Celox (mean SBP, 166.4 mm Hg; mean MAP, 1376 mm Hg) and the control (mean SBP, 88.25 mm Hg; mean MAP, 59.7 mm Hg), and between TraumaDEX (mean SBP, 152.2 mm Hg; mean MAP, 113.2 mm Hg) and the control (P < .05). However, no statistically significant difference existed between Celox and TraumaDEX. Celox and TraumaDEX effectively prevent rebleeding compared with standard dressing.

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.

Intraosseous infusion of blood products and epinephrine in an adult patient in hemorrhagic shock.

A 79-year-old woman presented in the postanesthesia care unit with hematemesis following replacement of a jejunostomy tube. Her medical history included recurrent stage IIIC ovarian cancer. The patient rapidly decompensated despite blood products administered through the patient's implanted medication port. The anesthesia service was consulted for resuscitative support. Examination revealed an alert, hypotensive elderly female in hemorrhagic shock. While peripheral intravenous (IV) access was sought, her condition further deteriorated. Attempts at peripheral access were determined futile and central venous access would be required. An intraosseous (IO) catheter was placed in the proximal medial aspect of the left tibia using the EZ-IO device (Vidacare Corp, San Antonio, Texas). Crystalloid and colloid fluids, blood products, and drugs were administered via the IO route, stabilizing the patient's condition during the central access procedure. The IO route was used throughout the resuscitative effort. Hemostasis was achieved, and the patient was admitted to the intensive care unit. Intraosseous infusion is a valuable and underutilized technique in managing patients in hemorrhagic shock with poor IV access. Anesthesia providers should seek education and training from those experienced in IO placement techniques and consider use of the IO route early in the resuscitative process.

The Resuscitative and Pharmacokinetic Effects of Humeral Intraosseous Vasopressin in a Swine Model of Ventricular Fibrillation.

Introduction The American Heart Association (AHA; Dallas, Texas USA) and European Resuscitation Council (Niel, Belgium) cardiac arrest (CA) guidelines recommend the intraosseous (IO) route when intravenous (IV) access cannot be obtained. Vasopressin has been used as an alternative to epinephrine to treat ventricular fibrillation (VF). Hypothesis/Problem Limited data exist on the pharmacokinetics and resuscitative effects of vasopressin administered by the humeral IO (HIO) route for treatment of VF. The purpose of this study was to evaluate the effects of HIO and IV vasopressin, on the occurrence, odds, and time of return of spontaneous circulation (ROSC) and pharmacokinetic measures in a swine model of VF. METHODS: Twenty-seven Yorkshire-cross swine (60 to 80 kg) were assigned randomly to three groups: HIO (n=9), IV (n=9), and a control group (n=9). Ventricular fibrillation was induced and untreated for two minutes. Chest compressions began at two minutes post-arrest and vasopressin (40 U) administered at four minutes post-arrest. Serial blood specimens were collected for four minutes, then the swine were resuscitated until ROSC or 29 post-arrest minutes elapsed. RESULTS: Fisher's Exact test determined ROSC was significantly higher in the HIO 5/7 (71.5%) and IV 8/11 (72.7%) groups compared to the control 0/9 (0.0%; P=.001). Odds ratios of ROSC indicated no significant difference between the treatment groups (P=.68) but significant differences between the HIO and control, and the IV and control groups (P=.03 and .01, respectively). Analysis of Variance (ANOVA) indicated the mean time to ROSC for HIO and IV was 621.20 seconds (SD=204.21 seconds) and 554.50 seconds (SD=213.96 seconds), respectively, with no significant difference between the groups (U=11; P=.22). Multivariate Analysis of Variance (MANOVA) revealed the maximum plasma concentration (Cmax) and time to maximum concentration (Tmax) of vasopressin in the HIO and IV groups was 71753.9 pg/mL (SD=26744.58 pg/mL) and 61853.7 pg/mL (SD=22745.04 pg/mL); 111.42 seconds (SD=51.3 seconds) and 114.55 seconds (SD=55.02 seconds), respectively. Repeated measures ANOVA indicated no significant difference in plasma vasopressin concentrations between the treatment groups over four minutes (P=.48). CONCLUSIONS: The HIO route delivered vasopressin effectively in a swine model of VF. Occurrence, time, and odds of ROSC, as well as pharmacokinetic measurements of HIO vasopressin, were comparable to IV. Burgert JM , Johnson AD , Garcia-Blanco J , Fulton LV , Loughren MJ . The resuscitative and pharmacokinetic effects of humeral intraosseous vasopressin in a swine model of ventricular fibrillation. Prehosp Disaster Med. 2017;32(3):305-310.

A primer on intraosseous access: History, clinical considerations, and current devices.

OBJECTIVE: Intraosseous (IO) access is a method recommended by the American Heart Association and the European Resuscitation Council to administer resuscitative drugs and fluids when intravenous (IV) access cannot be rapidly or easily obtained. Many clinicians have limited knowledge or experience with the IO route. The purpose of this review was to provide the reader with a succinct review of the history, clinical considerations, and devices associated with IO access. DESIGN: Narrative review. SETTING: University-based academic research cell. MAIN OUTCOME MEASURES: Not applicable. RESULTS: Not applicable. CONCLUSIONS: IO access is a lifesaving bridge to definitive vascular access that may be considered when an IV cannot be rapidly attained and the patient's outcome may be negatively affected without prompt circulatory access. The IO route has few contraindications for use and a low rate of serious complications. Multiple manual and powered devices that may be placed in several anatomic sites are commercially available. All clinicians who provide acute care or respond to cardiovascular emergencies should obtain training and maintain proficiency in placing and using IO devices as the IO route is recommended by the major resuscitation organizations as the preferred route of infusion when rapid, reliable IV access is unavailable.

Intraosseous vascular access in disasters and mass casualty events: A review of the literature.

OBJECTIVE: The intraosseous (IO) route of vascular access has been increasingly used to administer resuscitative fluids and drugs to patients in whom reliable intravenous (IV) access could not be rapidly or easily obtained. It is unknown that to what extent the IO route has been used to gain vascular access during disasters and mass casualty events. The purpose of this review was to examine the existing literature to answer the research question, "What is the utility of the IO route compared to other routes for establishing vascular access in patients resulting from disasters and mass casualty events?" DESIGN: Keyword-based online database search of PubMed, CINAHL, and the Cochrane Database of Systematic Reviews. SETTING: University-based academic research cell. EVIDENCE SOURCES: Included evidence were randomized and nonrandomized trials, systematic reviews with and without meta-analysis, case series, and case reports. Excluded evidence included narrative reviews and expert opinion. MAIN OUTCOME MEASURES: Not applicable. RESULTS: Of 297 evidence sources located, 22 met inclusion criteria. Located evidence was organized into four categories including chemical agent poisoning, IO placement, while wearing chemical protective clothing (PPE), military trauma, and infectious disease outbreak. CONCLUSIONS: Evidence indicates that the IO route of infusion is pharmacokinetically equal to the IV route and superior to the intramuscular (IM) and endotracheal routes for the administration of antidotal drugs in animal models of chemical agent poisoning while wearing full chemical PPE. The IO route is superior to the IM route for antidote administration during hypovolemic shock. Civilian casualties of explosive attacks and mass shootings would likely benefit from expanded use of the IO route and military resuscitation strategies. The IO route is useful for fluid resuscitation in the management of diarrheal and hemorrhagic infectious disease outbreaks.

Comparison of the effects of sternal and tibial intraosseous administered resuscitative drugs on return of spontaneous circulation in a swine model of cardiac arrest.

OBJECTIVE: Compare vasopressin, amiodarone, and epinephrine administration by sternal intraosseous (SIO), tibial intraosseous (TIO), and intravenous (IV) routes in a swine model of cardiac arrest. DESIGN: Prospective, randomized, between subjects, experimental design. SETTING: Laboratory. SUBJECTS: Male Yorkshire-cross swine (N = 35), seven per group. INTERVENTION: Swine were randomized to SIO, TIO, IV, cardiopulmonary resuscitation (CPR) with defibrillation, or CPR-only groups. Ventricular fibrillation (VF) was induced under general anesthesia. Mechanical CPR began 2 minutes postarrest. Vasopressin (40 U) was administered to the SIO, TIO, and IV groups 4 minutes postarrest. Defibrillation was performed and amiodarone (300 mg) was administered 6 minutes postarrest. Defibrillation was repeated, and epinephrine (1 mg) was administered 10 minutes postarrest. Defibrillation was repeated every 2 minutes and epinephrine repeated every 4 minutes until return of spontaneous circulation (ROSC) or 26 postarrest minutes elapsed. MAIN OUTCOME MEASURES: Rate of ROSC, time to ROSC, and odds of ROSC. RESULTS: There were no significant differences in rate of ROSC between the SIO and TIO (p = 0.22) or IV groups (p = 1.0). Time to ROSC was five times less in the SIO group than the TIO group (p = 0.003) but not compared to IV (p = 0.125). Time to ROSC in the IV group was significantly less than the TIO group (p = 0.04). Odds of ROSC for the SIO group were five times higher compared to the TIO group but same as IV. Odds of ROSC in the IV group were higher than the TIO group. CONCLUSION: There was a statistically significant delay in the time to ROSC and a clinically significant difference in odds of ROSC when resuscitative drugs, including lipophilic amiodarone, were administered by the TIO route compared to the SIO and IV routes in a swine model of sudden cardiac arrest. Further investigations are warranted to isolate the mechanism behind these findings.

A Comparison of the Effects of Intraosseous and Intravenous 5% Albumin on Infusion Time and Hemodynamic Measures in a Swine Model of Hemorrhagic Shock.

UNLABELLED: Introduction Obtaining intravenous (IV) access in patients in hemorrhagic shock is often difficult and prolonged. Failed IV attempts delay life-saving treatment. Intraosseous (IO) access may often be obtained faster than IV access. Albumin (5%) is an option for prehospital volume expansion because of the absence of interference with coagulation and platelet function. Hypothesis/Problem There are limited data comparing the performance of IO and IV administered 5% albumin. The aims of this study were to compare the effects of tibial IO (TIO) and IV administration of 500 mL of 5% albumin on infusion time and hemodynamic measurements of heart rate (HR), mean arterial pressure (MAP), cardiac output (CO), and stroke volume (SV) in a swine model of hemorrhagic shock. METHODS: Sixteen male swine were divided into two groups: TIO and IV. All subjects were anesthetized and a Class III hemorrhage was achieved by exsanguination of 31% of estimated blood volume (EBV) from a femoral artery catheter. Following exsanguination, 500 mL of 5% albumin was administered under pressurized infusion (300 mmHg) by the TIO or IV route and infusion time was recorded. Hemodynamic measurements of HR, MAP, CO, and SV were collected before and after exsanguination and every 20 seconds for 180 seconds during 5% albumin infusion. RESULTS: An independent t-test determined that IV 5% albumin infusion was significantly faster compared to IO (P=.01). Mean infusion time for TIO was seven minutes 35 seconds (SD=two minutes 44 seconds) compared to four minutes 32 seconds (SD=one minute 08 seconds) in the IV group. Multivariate Analysis of Variance was performed on hemodynamic data collected during the 5% albumin infusion. Analyses indicated there were no significant differences between the TIO and IV groups relative to MAP, CO, HR, or SV (P>.05). CONCLUSION: While significantly longer to infuse 5% albumin by the TIO route, the longer TIO infusion time may be negated as IO devices can be placed more quickly compared to repeated IV attempts. The lack of significant difference between the TIO and IV routes relative to hemodynamic measures indicate the TIO route is a viable route for the infusion of 5% albumin in a swine model of Class III hemorrhage. Muir SL , Sheppard LB , Maika-Wilson A , Burgert JM , Garcia-Blanco J , Johnson AD , Coyner JL . A comparison of the effects of intraosseous and intravenous 5% albumin on infusion time and hemodynamic measures in a swine model of hemorrhagic shock. Prehosp Disaster Med. 2016;31(4):436-442.

An Effective and Reproducible Model of Ventricular Fibrillation in Crossbred Yorkshire Swine (Sus scrofa) for Use in Physiologic Research.

Transcutaneous electrical induction (TCEI) has been used to induce ventricular fibrillation (VF) in laboratory swine for physiologic and resuscitation research. Many studies do not describe the method of TCEI in detail, thus making replication by future investigators difficult. Here we describe a detailed method of electrically inducing VF that was used successfully in a prospective, experimental resuscitation study. Specifically, an electrical current was passed through the heart to induce VF in crossbred Yorkshire swine (n = 30); the current was generated by using two 22-gauge spinal needles, with one placed above and one below the heart, and three 9V batteries connected in series. VF developed in 28 of the 30 pigs (93%) within 10 s of beginning the procedure. In the remaining 2 swine, VF was induced successfully after medial redirection of the superior parasternal needle. The TCEI method is simple, reproducible, and cost-effective. TCEI may be especially valuable to researchers with limited access to funding, sophisticated equipment, or colleagues experienced in interventional cardiology techniques. The TCEI method might be most appropriate for pharmacologic studies requiring VF, VF resulting from the R-on-T phenomenon (as in prolonged QT syndrome), and VF arising from other ectopic or reentrant causes. However, the TCEI method does not accurately model the most common cause of VF, acute coronary occlusive disease. Researchers must consider the limitations of TCEI that may affect internal and external validity of collected data, when designing experiments using this model of VF.

Argyria resulting from chronic use of colloidal silver in a patient presenting for colonoscopy.

An elderly male with a history of argyria caused by chronic ingestion of colloidal silver presented for elective colonoscopy. The patient's skin was a profound blue-gray color that caused concern among staff until his condition was identified through his medical and medication history. Colonoscopy and anesthesia proceeded without incident. The anesthetic management concerns include differentiating argyria from hypoxemia and other pathologies with similar appearance and clearly communicating the patient's history of argyria to follow-on caregivers to prevent unneeded diagnostic or interventional procedures. It is also important for caregivers to understand that the altered skin pigmentation of argyria does not interfere with pulse oximetry.

An evidence-based review of epinephrine administered via the intraosseous route in animal models of cardiac arrest.

OBJECTIVES: Intraosseous (IO) access, enabling the rapid administration of epinephrine during cardiac arrest (CA), is crucial in promoting optimal postresuscitation outcomes in patients with poor vascular access. There is a question whether IO-administered epinephrine is equivalent to intravenously administered epinephrine during CA. METHODS: The question guiding this evidence-based review was as follows: in adults suffering CA given epinephrine via the IO route, what is the resulting serum concentration of the drug compared to when administered intravenously? A search was conducted and the evidence appraised and leveled. RESULTS: Four animal studies met the inclusion criteria. The sources showed no definitive evidence supporting equivalence between intravenous and IO epinephrine administered during CA. Intravenously administered epinephrine provides increased and faster appearing serum concentrations than IO-administered epinephrine. Evidence indicated epinephrine given via the sternal IO route more closely approaches equivalence with intravenously administered epinephrine than when administered by the tibial IO route. CONCLUSIONS: The clinician should consider using proximal IO infusion sites such as the sternum or humerus when administering advanced cardiac life support drugs to rapidly achieve maximal therapeutic concentrations. Further studies are needed to determine the differences seen when epinephrine is administered by these routes during CA.