Vascular Access in Resuscitation: Is There a Role for the Intraosseous Route?

ESTABLISHING vascular access is a critical component of resuscitation during a cardiac arrest. The 2010 American Heart Association (AHA) Guidelines for Cardiopulmonary Resuscitation (CPR) and Emergency Cardiovascular Care emphasize drug administration during cardiac arrest is of secondary importance to high-quality CPR and that interruptions in CPR should be minimized while obtaining intravenous access.¹  Interruptions in CPR decrease coronary perfusion pressure which requires a “re-building” period when chest compressions are resumed.²  Vascular access, however, is still a critical component of resuscitation. A randomized, double-blinded study examining prehospital ventricular fibrillation (VF) demonstrated decreased survival rates from arrest to hospital admission when amiodarone administration was delayed.³  In addition, a swine model has shown that the time from arrest to drug administration is an independent predictor of return of spontaneous circulation.⁴  Given these data, it is clear that the benefits of early vascular access must be considered in conjunction with the importance of uninterrupted CPR. Intraosseous access can be obtained quickly with minimal or no disruption of CPR. As a result, the AHA has proposed providers establish intraosseous access if an intravenous line is not easily obtainable.¹  Similarly, the International Liaison Committee on Resuscitation, as well as the European Resuscitation Counsel, both advocate intraosseous over central venous or endotracheal drug administration if intravenous access cannot be achieved quickly in an emergency.⁵  This review aims to examine the literature regarding intraosseous vascular access in the setting of resuscitation, as well as to provide a framework for incorporating the technique into the practice of clinical anesthesia.

To answer the question posed, a systematic review was conducted using the PubMed and Ovid Medline databases through August 1, 2013. The primary aim was to determine whether there is a role for intraosseous vascular access in the resuscitation of critically ill patients. Secondary aims were to investigate the evidence regarding clinical use, drug administration, and complications of intraosseous access. The key MeSH terms included: “Infusions, Intraosseous”; “Anesthesiology”; “Critical Care”; “Tibia”; “Advanced Cardiac Life Support”; “American Heart Association”; “Cardiopulmonary Resuscitation”; “Emergency Medical Services”; “Resuscitation/Methods”; “Infusions, Intravenous”; “Catheterization, Central Venous”; “Femoral Vein”; “Sternum”; “Out-of-Hospital Cardiac Arrest”; “Blood Transfusion, Autologous”; “Colloids”; “Hetastarch/Administration and Dosage”; “Bone Marrow/Blood supply”; “Compartment Syndromes”; and “Embolism, Fat.” The search was expanded by assessing the reference lists for all retrieved literature. Individual studies were assessed for risk of bias or commercial influence. Only English-language full-text articles published in peer-reviewed journals were considered. The following inclusion criteria were applied to all studies involved in the clinical use analysis: (1) prospective studies (level of evidence III or higher); (2) focus on insertion success and/or insertion speed; and (3) reporting of complications. Studies were assigned a level of evidence based on Sackett criteria (table 1).⁶  One study was excluded over concerns for commercial bias (investigators received free needles and included a manufacturer in the acknowledgments).⁷  Another study was excluded as the authors had previously published the same data (original study was used).⁸  On the basis of these criteria, a total of 18 studies were included.

The principles of intraosseous access were first popularized in 1922 by Cecil K. Drinker, M.D. (1887–1956; Professor, Department of Physiology, Harvard Medical School, Boston, Massachusetts), an anatomist who studied hematopoiesis. He postulated that the capillaries of the marrow cavity could be used as an entry point to systemic circulation.⁹  This idea was revisited in the 1940s by Leandro M. Tocantins, M.D. (1901–1963; Professor, Department of Medicine, Jefferson Medical College, Philadelphia, Pennsylvania), who conducted a series of experiments on rabbits for examining intraosseous infusions. He first modeled a hemorrhagic state by aspirating blood from rabbits. The next day, fresh blood was transfused via an intraosseous line. Six of seven rabbits had a return to baseline hemoglobin level (one died from complications of the original phlebotomy).¹⁰  Next, he corrected insulin-induced hypoglycemic seizures in rabbits with intraosseous dextrose infusions.¹⁰  In addition, he demonstrated that Congo Red dye injected into the marrow cavity of the tibia reached the heart within 10 s.¹⁰  Tocantins also reported a case series of successful intraosseous infusions of blood and saline in nine pediatric patients with “impossible” intravenous access.¹¹ 

The field of anesthesiology first crossed paths with the concept of intraosseous infusions thanks to the work by Emanuel Papper, M.D., Ph.D. (1915–2002; Professor, Department of Anesthesiology, Columbia-Presbyterian Medical Center, New York, New York). In a study published in Anesthesiology in 1942, he demonstrated that the circulation time for fluids administered via intravenous and sternal intraosseous routes was nearly identical.¹²  In a series of seven patients, Papper injected 2% sodium cyanide via the antecubital vein as well as the sternal intraosseous route and measured the cyanide circulation time to the throat, abdomen, and perineum. Sternal intraosseous injections had an average time to endpoint of 11.4 s, whereas venous injections had an average time of 15.5 s.¹²  Papper¹²  also described the administration of sodium pentothal in a surgical patient and concluded that it is “possible to administer anesthetic drugs ordinarily given by vein into the sternal marrow with the production of anesthesia in therapeutic doses and toxic manifestations in overdose.”

World War II provided an opportunity for wide-spread application of the intraosseous technique. Hamilton Bailey, F.R.C.S., F.A.C.S. (1894–1961; Emeritus Surgeon, Royal Northern Hospital, London, United Kingdom), noted that the sternal intraosseous route could be effectively used even in black-out conditions.¹³  He developed a special trocar to prevent the needle from penetrating the back wall of the sternum and injuring the heart. As a result, sternal intraosseous needles were included in emergency medical supply kits during World War II.¹⁴  As military medical personal returned home after the war, the practice of intraosseous infusion was largely forgotten. This can be explained by both the development of better plastic intravenous catheters and the absence of formal paramedics groups. The concept of intraosseous access was “re-discovered” in the early 1980s by James P. Orlowski, M.D. (Department of Pediatrics, Cleveland Clinic Foundation, Cleveland, Ohio). Orlowski, a pediatrician, visited India during a cholera epidemic and observed intraosseous infusions saving the lives of severely dehydrated children. He subsequently published an editorial entitled “My kingdom for an intravenous line” which helped lead to the incorporation of intraosseous access into Pediatric Advanced Life Support.¹⁵ 

Peripheral veins can collapse in a state of hemorrhage or dehydration. The intraosseous space, however, is a noncollapsible entry point into the systemic circulation. A vast central sinus, composed of distensible endothelium, runs in the middle of the diaphysis. This sinus can distend to accommodate a five-fold increase in volume.¹⁶  Blood vessels of the intraosseous space are connected to the systemic circulation by a series of longitudinal Haversian canals containing a small artery and vein. The Haversian canals are linked to a system of Volkmann canals which penetrate the cortex and terminate in connections with the osseous venous drainage. The proximal tibia, a common site of intraosseous insertion, ultimately drains to the popliteal vein. The distal tibia drains to the saphenous vein, whereas the proximal humerus connects with the axillary vein.

The mean blood pressure in the medullary space is approximately 20 to 30 mmHg, or approximately one third of systemic mean pressure.¹⁷  Therefore, fluid administration often requires a pressure bag to achieve optimal flow rates. Depending on the infusion characteristics and clinical scenario, it will likely be necessary to augment the infusion rates of intraosseous lines with a pressure bag or rapid infusion device. Flow rates can also be influenced by hypoxia, hypercarbia, and acidosis (often present during resuscitation) leading to local vasodilation and increased intraosseous blood flow.

The 2010 AHA guidelines state that “it is reasonable for providers to establish intraosseous access if intravenous access is not readily available.”¹  This recommendation is in part due to several studies^18–22  demonstrating that intraosseous access can be achieved quickly and effectively in a variety of clinical settings. One trial examining 60 dehydrated children (aged from 3 months to 2 yr) found a 5-min success rate of 100% for intraosseous insertion versus just 67% success for peripheral intravenous catheter placement.¹⁸  A prospective study of adult patients (medical and trauma patients in the emergency department setting) compared intraosseous cannulation with central venous access in patients with “impossible” intravenous access. Intraosseous access was achieved on the first attempt 90% of the time versus just a 60% first-attempt success rate for central line placement.¹⁹  In addition, intraosseous cannulation took significantly less time than central line placement (intraosseous: 2.3 ± 0.8 min vs. central line: 9.9 ± 3.7 min; P < 0.001).¹⁹  A prospective simulation study examining intraosseous insertion in the prehospital setting found that access could be established in less than 1 min 84.8% of the time, even in an ambulance traveling 35 mph speed with sudden starting and stopping.²⁰ 

Establishing peripheral venous access in a prehospital setting can be challenging. Prehospital success rates vary from 43 to 91%.^18,21,23,24  A retrospective chart review of 641 adult patients with attempted intravenous catheter placement in a moving ambulance found a success rate of just 80%.²³  Intraosseous cannulation has been shown to be rapid and effective specifically in the setting of prehospital cardiac arrest. In a randomized trial of 182 patients receiving vascular access for nontraumatic cardiac arrest, tibial intraosseous access was achieved on the first attempt 91% of the time as compared with just a 43% first-attempt success rate for peripheral venous access.²¹  In another trial, emergency medicine residents treating cardiac arrest in a high-fidelity simulator placed intraosseous lines significantly faster than central lines (intraosseous: 49.0 s vs. central: 194.6 s).²²  When considered collectively, these studies indicate that intraosseous access can be achieved faster and with fewer attempts in critical situations.

Obtaining access quickly in cardiac arrest can have a substantial impact on outcome. In a prospective study, 30 swine in VF were randomized to receive epinephrine (intravenous or intraosseous) or placebo.²⁵  To simulate realistic scenarios of successful vascular access, intraosseous epinephrine was administered 1 min after onset of CPR, whereas intravenous epinephrine was administered after an 8-min delay. At equivalent doses, early intraosseous epinephrine administration resulted in a shorter time to return of spontaneous circulation, decreased total defibrillation energy, and better 24-h survival than delayed intravenous epinephrine.²⁵  These results are consistent with another swine model of VF which concluded that early intraosseous epinephrine resulted in decreased time to return of spontaneous circulation, faster termination of VF, and better 20-min survival.²⁶ 

Historically, resuscitation drugs have been administered via an endotracheal tube in instances where intravenous access cannot be obtained. However, resuscitation drugs administered via the trachea have lower peak plasma concentrations compared with the peak plasma concentrations of the same drugs given intravenously.²⁷  Therefore, the 2010 AHA guidelines stipulate that endotracheal administration of resuscitation drugs should only be considered if attempts at both intravenous and intraosseous access have failed.¹ 

It is difficult to directly compare the infectious risk of central venous catheters and intraosseous lines placed during a resuscitation event as there are no head-to-head studies in this setting. In most instances, central lines are left in place for extended periods of time, whereas intraosseous lines generally serve as a short-term means of vascular access. The infection risks of these routes independently have been described. A recent meta-analysis of central venous catheters found no significant difference in the risk of catheter-related bloodstream infections between the femoral and internal jugular sites (risk ratio, 1.35; 95% CI, 0.84–2.19; P = 0.2; I = 0%).²⁸  Despite these findings, the 2013 Joint Commission National Patient Safety Goals state that providers should “NOT insert catheters into the femoral veins unless other sites are unavailable.”^* Central venous access during code situations is often obtained with suboptimal sterile technique and without the use of proper barrier precautions. In a retrospective review of adult trauma patients (emergency department, operating room, and intensive care settings), 25 of 35 (71%) diagnosed central line–associated blood stream infections occurred in patients with known breaches in sterile technique.²⁹ 

The use of intraosseous access in an emergency setting allows clinicians to avoid placing femoral lines and obviates the potential for improper barrier precautions and less than ideal sterile technique. A meta-analysis examining 30 studies and 4,270 patients concluded that there was a 0.6% incidence rate of osteomyelitis attributed to intraosseous cannulation.³⁰  Most infections occurred during prolonged infusions or in situations of concurrent bacteremia at the time of insertion.³⁰  This dated meta-analysis was conducted before the advent of insertion-assist devices and looked only at manual needle insertion. A more recent prospective, randomized trial involving the EZ-IO^® (Vidacare Corporation, San Antonio, TX) and Bone Injection Gun (BIG^®; Waismed, Houston, TX) intraosseous insertion devices in adult patients was conducted in an emergency department resuscitation setting. In this study, zero infections were reported in 40 patients receiving intraosseous lines with one of the two devices.³¹  Similarly, two prospective studies of 60 (adult) and 30 (25 adult and 5 pediatric cardiac arrest patients) intraosseous insertions using the EZ-IO^® device, both reported no cases of infection.^32,33  Larger studies, including direct comparisons of central and intraosseous lines placed during resuscitation, represent an area of future research.

Intraosseous access is equivalent to intravenous access in terms of functionality and drug delivery. This was demonstrated by Papper¹²  in 1942 and has subsequently been verified in other studies. Orlowski used a canine model to examine peak effect and serum concentrations of commonly used emergency drugs. He demonstrated equivalency of the intraosseous route to peripheral and central venous drug administration for epinephrine, sodium bicarbonate, calcium chloride, hydroxyethyl starch, and normal saline.³⁴  A prospective, randomized, crossover pharmacokinetic study was conducted to compare the bioequivalence of morphine administered by intraosseous and intravenous routes in adult patients with cancer (nonresuscitation setting). Each patient had both an intravenous and intraosseous line and was randomized to receive 5 mg of morphine via one route, followed by 5 mg of morphine by the other route 24 h later. No statistically significant differences were observed between the intravenous and intraosseous routes in calculated pharmacokinetic data including peak concentration and time to peak concentration.³⁵  Another study used a swine model of VF to demonstrate intraosseous epinephrine administered during CPR is rapidly transported to the central circulation and results in a dose-dependent increase in mean arterial blood pressure.³⁶  More recently, the pharmacokinetics of intraosseous drug delivery has been compared with central venous drug delivery. A “double dye tracer technique” was used in a swine cardiac arrest model to compare simultaneous epinephrine injections in the sternum and tibia. Peak plasma concentrations were achieved faster with the sternal route than the tibia route (sternal: 53 ± 11 s vs. tibia: 107 ± 27 s; P = 0.03).³⁷  The time to peak blood concentration was similar for both routes (sternal: 97 ± 17 s vs. central: 70 ± 12 s; P = 0.17).³⁷  The authors concluded that intraosseous administration of medications through both the sternum and tibia are effective during CPR in anesthetized swine, but the sternal route results in faster uptake.³⁷  As per the 2010 AHA guidelines, all Advanced Cardiac Life Support medications are administered at the same doses regardless of route.¹  A summary of available clinical data showing intraosseous medication dosing in adult and pediatric patients is presented in table 2.^{1,11,30,34,35,38–59} 

Both the intraosseous and intravenous routes also offer equivalent delivery of resuscitative fluid. The safety and efficacy of intraosseous packed erythrocyte transfusion are well documented. A prospective study (swine model) demonstrated that radiolabeled erythrocytes administered via the intraosseous route were rapidly delivered to systemic circulation (30 s to 1 min).⁶⁰  The safety of intraosseous blood transfusion was shown in a randomized, controlled, blinded swine study. Phlebotomized animals received a transfusion by either an intravenous catheter or an intraosseous line. In both groups, blood pressure returned to baseline values within 15 min, and laboratory studies assessing for disseminated intravascular coagulation were negative.⁶¹  In addition, there was no evidence of fat embolism or inflammation on pathologic examination of the lungs or kidneys in the intraosseous group.⁶¹  Crystalloids and colloids have also been effectively administered through the intraosseous route. An analysis of hydroxyethyl starch pharmacokinetics demonstrated no significant difference between intravenous and intraosseous administration in hypovolemic swine.⁶²  Crystalloid infusion via the intraosseous route has been demonstrated to be as effective as the central or peripheral route in treating hemorrhagic shock in a swine model.⁶³ 

The intraosseous medullary space can also serve as a source of blood for laboratory analysis. The initial aspirate after intraosseous line placement can be used for routine laboratory tests after wasting 2 ml of the marrow/blood mixture.⁶⁴  In a study involving human volunteers, blood samples were drawn simultaneously from both a peripheral vein and the intraosseous space. Analysis revealed a significant correlation between venous and intraosseous samples for hemoglobin, hematocrit, glucose, blood urea nitrogen, and creatinine. Carbon dioxide and platelet measurements may be lower in intraosseous samples, whereas the leukocyte count may be higher.⁶⁴  Blood gas measurements from intraosseous blood are “intermediate” between arterial and venous blood gases, suggesting intraosseous samples correspond with arterialized capillary blood samples.⁶⁵  Intraosseous blood samples can also be used to obtain a reliable type and cross. A prospective study comparing simultaneous intraosseous and venous blood draws in humans found no difference in the accuracy of ABO and Rh typing.⁶⁶  Laboratory values from an intraosseous line may not be accurate after a sustained infusion.⁵²  Given these data, it is evident that blood samples drawn immediately after intraosseous cannulation can provide accurate laboratory and blood bank data to aid in resuscitation.

A multicenter, observational study compared the costs of central venous catheter insertion with the cost of intraosseous insertion in unstable patients presenting to the emergency department. A total of 105 patients received intraosseous access (85% were “medical” patients and 53% presented with cardiac or respiratory arrest), and costs were compared with published central line data. Cost savings of intraosseous placement over of central venous access were found to be $195 per procedure.⁶⁷  However, this study has limitations that must be considered. It focused only on initial insertion costs in the emergency department and did not address issues such as daily central line maintenance costs or the percentage of patients in the intraosseous group who eventually received central lines during their hospital admission. The percentage of patients who later require central access has not been studied and must be determined before true conclusions of “overall” cost effectiveness can be made.

Early pioneers of intraosseous access tended to focus on the sternum as the preferred insertion site. The sternum offers easy accessibility and close proximity to the central venous circulation via the mammary veins. Time to peak blood concentration of epinephrine injected through a sternal intraosseous needle is similar to epinephrine injected through a central line (intraosseous: 97 ± 17 s vs. central: 70 ± 12 s) in a swine model of cardiac arrest.³⁷  In the same study, the sternal intraosseous site achieved peak arterial epinephrine concentrations significantly faster than the tibial intraosseous site (sternum: 53 ± 11 s vs. tibial: 107 ± 27 s; P = 0.3).³⁷  There are, however, several disadvantages of the sternal site. Chest compressions must be briefly interrupted during insertion. It also carries the risk of inadvertently puncturing the heart or great vessels. Pediatric patients are more susceptible to injury from sternal intraosseous insertion due to the proximity to the great vessels and the small size of the marrow cavity (with subsequent poor flow). As a result, the FAST1^® (Pyng Medical Corporation, Richmond, British Columbia, Canada) sternal insertion device is not approved for patients less than 12 yr of age.

Although the sternal site is of important historical significance, most providers favor the proximal tibial site. In a survey of emergency-room physicians, 84% selected the proximal tibia as their preferred insertion site. Just 10% of physicians surveyed preferred the humerus and another 10% chose the medial malleolus.⁶⁸  Although the sample size of this survey was small, it is consistent with newer intraosseous studies supporting the proximal tibia as a safe, easily accessible site. A prospective study of 182 patients compared proximal tibia and humeral intraosseous insertion sites head-to-head. The proximal tibia group had a higher first-attempt success rate (tibia: 91% vs. humerus: 51%) and faster insertion time (tibia: 4.6 min vs. humerus: 7.0 min) than the humeral group.²¹  In newborns, the needle should be inserted 10-mm distal to the anterior tibial tuberosity and aimed in a slight posterior and inferior direction to avoid damaging the growth plate.⁶⁹  In children and adults, the needle insertion site is 2 cm below the tibial tuberosity and 1 cm medially on the tibial plateau (fig. 1) (see video, Supplemental Digital Content 1, https://links.lww.com/ALN/B32, which is a guide to intraosseous insertion).⁴⁸ 

For adults or skeletally mature adolescents, the proximal humerus is another potential intraosseous site. The patient is positioned with their arm adducted and internally rotated (placing the patient’s hand on their abdomen facilitates proper positioning). The acromion process is then palpated and the greater tubercle of the humerus is located 2 cm distal to this point (fig. 2) (see video, Supplemental Digital Content 1, https://links.lww.com/ALN/B32, which is a guide to intraosseous insertion). The humeral site has a lower first-attempt success rate compared with the tibia and it has a higher rate of needle dislodgement.²¹  This can delay medication administration during cardiac arrest and may lead to more complications from fluid extravasation.²¹ 

Although there are practical disadvantages such as needle dislodgement with the humeral intraosseous site, it may offer the benefit of higher flow rates. Flow rates of fluid through EZ-IO^® needles placed in the humerus, tibia, and femur of swine were compared in a prospective interventional study. The humerus had a statistically significant (P < 0.001) higher flow rate (213 ml/min) compared with that of the tibia (103 ml/min) or femur (138 ml/min) when saline was infused via a pressure bag.⁷⁰  Human studies comparing flow rates of the humerus and tibia offer mixed results. A study of 10 human volunteers demonstrated a significantly higher mean flow rate at the humeral site (humerus: 5,093 ± 2,632 ml/h vs. tibia 1,048 ± 831 ml/h) with a pressurized infusion.⁷¹  However, a prospective observational study of 24 critically ill patients (emergency department setting) comparing humeral and tibial EZ-IO^® flow rates demonstrated no statistically significant difference between sites (humerus: 153 ml/min vs. tibia: 165 ml/min). Both sites in this study had significantly faster flow rates with a pressurized infusion bag than with gravity drip.⁷²  On the basis of these small swine and human studies, the humeral site may offer higher flow rates than the tibia, but trials with larger sample sizes are needed to make a conclusive determination. For comparison, a prospective study of human volunteers showed a mean infusion rate of 35.6 ml/min via an 18-gauge intravenous catheter (gravity drip).⁷³  Higher intravenous flow rates (18 gauge: 205 ml/min; 16 gauge: 412 ml/min) have been demonstrated using a Rapid Infusion System (Haemonetics Corp., Braintree, MA).⁷⁴ 

Manually inserted intraosseous needles have evolved significantly since the early experiments in the 1920s. Several manufacturers now produce inexpensive needles with specialized handles specifically designed for intraosseous use (fig. 3). Insertion techniques are similar for all of the manual needle types. The needle is oriented perpendicular to the entry site and pressure is applied in conjunction with a twisting motion until a “loss of resistance” is felt as the needle enters the marrow cavity (see video, Supplemental Digital Content 1, https://links.lww.com/ALN/B32, which is a guide to intraosseous insertion).

The Near Needle Holder (Near Manufacturing, Camrose, Alberta, Canada) is a reusable handle device which allows a standard hollow needle to be inserted in the intraosseous space (fig. 4). A group of physicians and medical students in Guyana attempted simulated insertion of both needle types after watching a short training video. Insertion times for both types were nearly identical (Near Needle Holder: 32 ± 13.2 s vs. Cook: 32 ± 12.3 s), and most users rated the Near Needle Holder as safe and easy to use.⁷⁵  The Near Needle Holder may potentially be a safe, inexpensive option in developing countries (it is not approved for use in the United States) or areas with limited resources.

Reported first-attempt success rates with manual needles range widely. One study demonstrated an overall success rate of 67.7% with four needle types (standard hypodermic, bone marrow needle, spinal needle, and manual intraosseous needle) inserted by resident physicians in anesthetized piglets.⁷⁶  In another simulation study, medical students had a 95% success rate inserting a SurFast^® (Cook Critical Care, Bloomington, IN) needle in animal bones.⁷⁷  Success rates as high as 85% have been reported in pediatric patients (less than 5 yr old) presenting in prehospital cardiac arrest.^77,78  More recently, prehospital first-attempt success rates were found to be 78% using a variety of intraosseous needles.⁴⁵ 

The FAST1^® is a single-use device designed for placement in the manubrium (fig. 5). Insertion is aided by user-applied force. A stick-on target placed at the sternal notch guides proper placement. The device has 10 stabilizing needles (which do not enter the bone), which are used to prevent overpenetration through the sternum. Reported infusion rates are 30 to 80 ml/min by gravity drip, 120 ml/min by pressurized source, and 250 ml/min by syringe injection.^† The FAST1^® device may be of particular value in cases of traumatic amputation of the extremities.

The FAST1^® device seems to have a quick learning curve. A pilot study of success rates found that first-time users of FAST1^® had a 74% rate of success.⁷⁹  After just one experience using the device, the success rate increased to 95% on subsequent attempts with the median insertion time for all subjects being 60 s (prehospital and emergency department setting).⁷⁹  A simulation study found that after a 2-h lecture, 96.6% of emergency medical technician students properly identified anatomic landmarks and 100% placed the target sticker correctly. Overall, students had a 93.1% rate of successful needle deployment in a mannequin.⁸⁰  Given the usage of the FAST1^® device in patients with extremity amputations, a study was conducted to examine the training required for military medical personnel to become proficient in its use. After a 60-min lecture, a training video and simulation session, study subjects correctly placed the FAST1^® in a cadaver 29 of 30 times (94%) with a mean time of 114 ± 36 s.⁸¹  Some failed attempts at FAST1^® in these studies have been attributed to technical difficulties arising from patient obesity.⁷⁹  For a summary of recent prospective studies examining FAST1^®, see table 3.^79,81–83 

The BIG^® is a single-use, spring-loaded insertion device which is available in adult (15 gauge) and pediatric (18 gauge) sizes (fig. 6). The device is held perpendicular to the insertion site and the spring released. After deployment, an internal trocar is removed and the safety latch is used to help secure the device in place. Reported first-attempt insertion success rates for the BIG^® range from 71 to 91%.^31,84,85  A prehospital study evaluating BIG^® use by a helicopter-transport emergency medical team found a 71% overall success rate (adult and pediatric) and reported no complications.⁸⁵  In a canine study, success rates for manual needle and BIG^® insertion were similar. Insertion of the BIG^® device, however, was significantly faster (BIG^®: 22.4 ± 8.2 s vs. manual: 42.0 ± 28.1 s).⁸⁶  The BIG^® device is easy to learn and requires minimal training. Military medical personal with no previous experience were successful in 29 of 31 BIG^® insertion attempts (in cadavers) after a lecture and training video.⁸¹  For a summary of recent prospective studies examining BIG^® use, see table 4.^31,81,84,85 

The EZ-IO^® is a lithium-battery–powered driver with three different needle sizes to choose from (fig. 7). The needles are all 15 gauge and differ only in length (15, 25, and 45 mm). A number of studies have been conducted to look at the speed and accuracy of EZ-IO^® insertion. A randomized trial compared EZ-IO^® insertion with a manual needle technique in adult cadavers. Although insertion times were similar (EZ-IO^®: 32 ± 11 s vs. manual: 33 ± 28 s), the EZ-IO^® had a higher “user friendliness” rating and a better first-attempt success rate (EZ-IO^®: 97.8% vs. manual: 79.5%).⁸⁷  When compared head-to-head with BIG^® insertion, the EZ-IO^® device has a higher first-attempt success rate (EZ-IO^®: 90% vs. BIG^®: 80%) and faster insertion times (EZ-IO^®: 1.8 min vs. BIG^®: 2.2 min) in the emergency department resuscitation setting (trauma and medical patients).³¹  A 7-yr retrospective analysis of prehospital insertion determined that EZ-IO^® placement has a significantly higher first-attempt success rate compared with the first-attempt success rate of both manual and BIG^® insertion (EZ-IO^®: 96% vs. manual: 50% vs. BIG^®: 55%).⁸⁸ 

The EZ-IO^® device is easy to use and requires minimal training. A group of 99 medical providers with no EZ-IO^® experience were given a 5-min presentation with one insertion demonstration. They each then performed three tibia insertions on cadavers. Success rates for the three attempts were 96.9, 94.9, and 100%, respectively, with a median time of just 6 s.⁸⁹  In another study, paramedic students received a video-based training on EZ-IO^® and BIG^® devices. Participants had a significantly higher first-attempt success rate (in turkey bones) with the EZ-IO^® (EZ-IO^®: 28 of 29 vs. BIG^®: 19 of 29).⁹⁰  These studies suggest that the EZ-IO^® is an easy to use, easy to learn tool that can be used successfully in resuscitation scenarios with minimal training. For a summary of recent prospective studies examining EZ-IO^® use, see table 5.^{8,21,31–33,46,67,72,82,91–95} 

Intraosseous vascular access may be indicated in emergency situations where venous access cannot be obtained quickly. These include trauma, cardiac arrest, status epilepticus, burn, and shock patients.⁹⁶  Several prospective human studies have examined intraosseous insertion speed and success rate (with multiple insertion devices) in the prehospital and emergency department setting. In the studies cited in this review, the overall insertion success rate was 90% (1,228 of 1,367) across all devices. Individually, the FAST1^®, BIG^®, and EZ-IO^® devices had insertion success rates of 79, 87, and 90%, respectively (tables 3–5). The mean insertion time was relatively fast for all the three insertion devices (FAST1^®: 86 s; BIG^®: 101 s; and EZ-IO^®: 60 s) (tables 3–5). For a summary guide to clinical use, see figure 8.

There are few absolute contraindications to intraosseous use as the route is primarily used in life-threatening situations. Most absolute contraindications are related to anatomic abnormalities.

1. Fracture in target bone (risk of fluid extravasation)

2. Compartment syndrome in target extremity

3. Vascular injury in target extremity

4. Acute infection at insertion site

5. Previous orthopedic surgery with hardware at insertions site

6. Recent failed intraosseous attempt in same extremity (within 24–48 h)

7. Inability to identify landmarks

8. History of sternotomy (for FAST1^®)

9. Sternal thickness less than 6.5 mm (for FAST1^®)

1. Cellulitis or burns of target extremity

2. Osseous abnormalities such as osteogenesis imperfect or severe osteoporosis

3. Right-to-left intracardiac shunts (fat or bone marrow cerebral embolic risk)

4. Sepsis or bacteremia

5. Inferior vena cava injury

A total of 1,367 intraosseous insertions were reported in the studies cited in this review (908 EZ-IO^®; 249 BIG^®; 210 FAST1^®). These insertions were associated with 23 reported complications for an overall complication rate of 1.6%. Of these 23 complications, 12 can be considered “minor” (10 needle dislodgements and 2 reports of minor bleeding at site). Excluding these minor complications, the overall complication rate for studies cited in this review was 0.80% (tables 3–5). A recent retrospective cohort study involving 291 pediatric patients with intraosseous lines placed in a variety of settings found zero associated complications.¹⁰⁰  The most commonly reported complication is extravasation of fluids. Reported extravasation rates vary widely, ranging from 1 to 22%.¹⁰¹  Risk factors include: incorrect needle placement, multiple punctures in the same bone, and incorrect needle length.¹⁰¹  Osseous punctures can take 12 to 48 h to clot; therefore, subsequent intraosseous placement in the same bone should be avoided during that period. Inadequate needle length can lead to higher rates of dislodgement and extravasation. Alternatively, excessive length increases the risk of puncturing the posterior cortex leading to infusion of fluids into the deep compartments of the extremity.¹⁰²  As a result, some authors advocate using tissue thickness to determine proper needle size rather than relying on weight-based parameters.⁷ 

There have been at least eight published case reports of compartment syndrome secondary to intraosseous line extravasation.^103–110  Risk factors for developing compartment syndrome include: total fluid volume and infusion rate, bone fracture, needle dislodgement, fluid osmolarity (hypertonic saline), and recent cortical puncture in the same bone.¹¹¹  A compartment syndrome can potentially occur in the absence of technical errors. A canine study was conducted with 20-gauge intraosseous needles inserted surgically under direct visualization and cemented in place to eliminate the possibility of dislodgement or extravasation. Saline, with a radio-opaque dye, was infused at a rate of 480 ml/h. Serial radiographic examinations and compartment pressure measurements were performed. After 350 ml of fluid infusion, dye was detected in the surrounding soft tissue and compartment pressures increased to 35 mmHg. Compartment pressures continued to increase in direct proportion to the amount of dye injected leading the authors to conclude that a dose- and time-dependent scale for safe intraosseous infusion should be established in humans.¹¹² 

There are several case reports from the 1940s detailing osteomyelitis attributable to intraosseous infusions. However, the incidence of infections from both intraosseous and intravenous infusions was similar during this time period suggesting poor sterile technique played a role in both groups. In 1985, a large review examining 30 studies and 4,270 patients concluded that there was a 0.6% incidence of osteomyelitis attributed to intraosseous use.³⁰  However, this meta-analysis predates the advent of new battery-powered intraosseous insertion devices (as well as modern day aseptic technique). In this review, zero infectious complications were reported in 1,367 total intraosseous insertions with modern devices (tables 3–5).

Fat or bone marrow embolism is another potential complication of intraosseous therapy. Even small increases in intraosseous pressure can lead to fat embolism.¹¹³  Levels of radioactivity in the lungs were measured after injection of Triolein-¹³¹I–labeled fat into the tibia of rabbits. After 2 to 5 h, 44.8% of the injected radioactive substance was present in the lungs on histologic examination.¹¹³  More recently, Orlowski et al.⁹⁸  demonstrated that bone marrow and fat emboli in the lungs (mean, 0.91 emboli per square millimeter lung) were present in 89 to 100% of dogs after 4 h of intraosseous infusion. In addition, they demonstrated an average of 0.23 and 0.71 emboli per square millimeter lung, respectively, in pulmonary autopsy specimens of two children who received intraosseous infusions during resuscitation attempts. The incidence of fat embolism does not seem to be related to the rate of intraosseous infusion.¹¹⁴ 

The incidence of fat embolism after CPR with concurrent intraosseous infusion has been studied in a piglet model of hypoxic cardiac arrest. There was no statistically significant difference in the quantity of pulmonary emboli between the intraosseous and intravenous resuscitated groups.¹¹⁵  These results correlate with recent human findings. Autopsies conducted on 50 decedents showed a pulmonary fat emboli rate of 76% in patients who received CPR without an intraosseous line.¹¹⁶  These collective data suggest that patients undergoing CPR are at risk for pulmonary fat emboli with or without the presence of an intraosseous infusion.

Interestingly, despite the high percentage of fat and marrow emboli occurring with intraosseous infusions, there does not seem to be a detrimental clinical correlation. Despite an 89 to 100% incidence of emboli in his experiments, Orlowski et al.⁹⁸  found no significant alterations in Pao₂ and no evidence of intrapulmonary shunting. There is at least a theoretical risk of cerebral emboli if right-to-left intracardiac shunts are present.⁹⁸  There is one case report of death from fat embolism after intraosseous phlebography to examine inferior vena cava obstruction in a patient with reticulum-cell sarcoma.¹¹⁷  To date, however, there are no case reports of death or significant morbidity from marrow or fat emboli after resuscitation with an intraosseous infusion. Despite the near-universal occurrence of emboli, intraosseous infusions seem safe to use during resuscitation.

There is a theoretical potential for both acute and long-term osseous injury related to intraosseous infusions. Bilateral tibia fractures were reported in a 3-month-old septic patient after unsuccessful intraosseous attempts.¹¹⁸  Iatrogenic fracture has also been documented after aggressive intraosseous placement with “considerable force” during an unsuccessful resuscitation of a 2-yr-old trauma patient.¹¹⁹  Overall, reports of fracture or acute boney injury attributable to intraosseous insertion are rare. Pig models have been used to demonstrate no long-term effects on bone marrow after intraosseous drug administration. Animals received sodium bicarbonate, epinephrine, and dopamine in one extremity while another extremity served as the control. Bone marrow examination revealed normal cellular differentiation in all groups.¹²⁰  In a similar study, experimental and control legs were harvested 6 months after intraosseous infusion. No differences in bone growth, degree of epiphyseal closure, or radiographic properties were observed between groups.¹²¹  The rate or osmolality of intraosseous infusion does not appear to have an influence on long-term histologic changes of the marrow space in humans.¹²² 

Data from more recent human studies support the findings of these pig models. A prospective radiographic analysis of pediatric patients with tibial intraosseous infusions placed in emergency situations was conducted. After a mean follow-up period of 29.2 months, there was no statistically significant difference (in a variety of radiographic measurements) between the punctured and control legs.¹²³  Similarly, a small study (prospective, observer-blinded) found no difference in tibial length 1 yr after intraosseous infusion.¹²⁴  Given the rarity of iatrogenic fractures attributed to intraosseous cannulation and the lack of evidence showing adverse long-term bone growth effects, the intraosseous route seems to be low risk in terms of osseous complications.

The available intraosseous literature has some limitations that must be considered. Most data come from prehospital or emergency department insertion. In this setting, intraosseous access is often used only after intravenous attempts have failed. As such, it is difficult to conduct large, randomized, clinical trials because the patients studied are already “self-selected” as difficult access patients. Therefore, we are left with primarily prospective observational studies. However, the findings of level III evidence were generally consistent in this review, allowing for a higher grade of recommendation.

Anesthesiologists frequently respond to in-hospital cardiac arrest situations, and literature specifically in this setting is scant. Head-to-head in-hospital studies comparing central and intraosseous access in terms of insertion speed and accuracy are lacking. There are no studies directly comparing the infection risks of the two routes when these lines are inserted during cardiac arrest. Furthermore, there are no studies comparing mortality data in cardiac arrest patients resuscitated with either central or intraosseous access.

Finally, long-term follow-up studies on the safety of intraosseous infusions are absent, particularly with newer insertion devices. Most of the recent literature tends to focus on speed and success of insertion. Therefore, we are left to rely on a few case reports and animal studies when considering the risk of delayed complications.

Intraosseous cannulation is a time-tested procedure that will play a role in the resuscitation of patients in the future. Intravenous access is often difficult to achieve in shock patients and central line placement can be time consuming. This literature review has demonstrated that intraosseous vascular access can be achieved quickly and accurately in emergency situations. Given the efficiency of insertion combined with a favorable complication profile, there is clearly a role for intraosseous vascular access in the resuscitation of critically ill patients. Therefore, anesthesiologists should become familiar with intraosseous insertion techniques and understand how to properly use this potentially life-saving procedure. In the 1940s, Dr. Papper played an important early role in advancing the field of intraosseous infusions. Today, anesthesiologists have the opportunity to follow Dr. Papper’s footsteps and be at the forefront of the intraosseous resurgence as we adopt this technique in our clinical practice.

Support was provided solely from institutional and/or departmental sources.

The author declares no competing interests.