TRAUMA Review Article

Trauma 14(3) 195–232 ! The Author(s) 2012 Intraosseous vascular access: Reprints and permissions: sagepub.co.uk/journalsPermissions.nav A review DOI: 10.1177/1460408611430175 tra.sagepub.com

James H Paxton

Abstract Intraosseous cannulation is an increasingly common means of achieving vascular access for the adminis- tration of fluids and medications during the emergent resuscitation of both paediatric and adult patients. Improved tools and techniques for intraosseous vascular access have recently been developed, enabling the healthcare provider to choose from a wide range of devices and insertion sites. Despite its increasing popularity within the adult population, and decades of use in the paediatric population, questions remain regarding the safety and efficacy of intraosseous infusion. Although various potential complications of intraosseous cannulation have been theorized, few serious complications have been reported. This article aims to provide a review of the current literature on intraosseous vascular access, including discussion on the various intraosseous devices currently available in the market, the advantages and disadvantages of intraosseous access compared to conventional vascular access methods, complications of intraosseous cannulation and current recommendations on the use of this approach.

Keywords Review, intraosseous, vascular access, resuscitation, infusion

Introduction Quicker alternatives to PIV access for the administration of medications and fluids include Vascular access can be difficult to obtain in both the endotracheal (ET), oral, subcutaneous (SC) children and adults, especially during emergent and intramuscular (IM) routes. But many med- resuscitations. Even under the best of circum- ications cannot be administered via one or more stances, first-attempt success rates for peripheral of these routes, and none of these routes allow intravenous (PIV) catheter placement range for blood collection for laboratory analysis. from 34% to 75%, and 1 in 10 patients will Central venous catheter (CVC) placement is still be without vascular access after two PIV attempts (Kanter et al., 1986; Frey, 1998; Lininger, 2003; Black et al., 2005; Yen et al., Department of Emergency Medicine, Detroit Medical 2008; Paxton et al., 2009). Moreover, studies Center, Detroit, MI, USA have shown that the longer healthcare pro- Corresponding author: James H Paxton, Department of Emergency Medicine, viders take in attempting PIV placement, the Detroit Medical Center, 4201 Saint Antoine Street, less likely they are to ultimately succeed Suite 3R, Detroit, MI 48201, USA. (Jacobson and Winslow, 2005). Email: [email protected] 196 Trauma 14(3) commonly used in emergency situations in (Langer, 1870; Siraud, 1895; Drinker and which PIV access is either impossible or inade- Drinker, 1916; Drinker et al., 1922). Whether quate. Yet, even in the most capable hands, or not Drinker invented the concept of ‘marrow CVC placement can take up to four times infusions’, he was among the first to go beyond longer than PIV placement, and is associated descriptive anatomic studies to show the thera- with a higher incidence of life-threatening com- peutic utility of this technique. plications (Scott, 1988; Taylor and Palagiri, In 1916, Drinker and colleagues published 2007; Zingg et al., 2008; Askegard-Giesmann their initial report of an experiment in which a et al., 2009; Leidel et al., 2009; Paxton et al., cannula was inserted through the popliteal 2009). artery of an anaesthetized dog into the mouth Problems with these conventional routes for of the tibial nutrient artery (Drinker and medication and fluid administration have led Drinker, 1916). After injecting various sub- healthcare providers to explore the utility of vas- stances into the nutrient artery (including India cular access via intraosseous (IO) infusion. ink, hirudinized blood, physiological salts and Multiple studies have shown IO access to be typhoid vaccine), Drinker studied the way in faster and easier than traditional methods of which these substances were removed by the vascular access, including umbilical vein cathe- venous drainage system. He found that sub- terization (Abe et al., 2000), peripheral IV access stances injected in this manner were more or (Banerjee et al., 1994; Paxton et al., 2009) and less evenly distributed throughout the bone, central venous (CV) access (Leidel et al., 2009; and that increased infusion pressure enabled Paxton et al., 2009). These devices are also higher rates of blood flow through the venous versatile, appropriate for a wide variety of ana- plexus. Infusing a hirudinized physiological salt tomic sites, and have been used in patients of solution at pressures up to 240 mmHg, he was every shape and size, from the super-obese to able to increase the rate of blood flow through 800 -g premature babies (Ramet et al., 1998). the dog tibia from a physiological rate of 15 mL/ Although researchers have been studying the min to as high as 60 mL/min. He was also able intraosseous circulation for centuries, we have to induce vasoconstriction of the venous plexus yet to master this potentially life-saving tech- using direct nerve stimulation and intravenous nique. The present review will provide a histor- epinephrine infusion (Drinker et al., 1922). ical perspective on the development of Charles A. Doan, a medical student at Johns medullary infusion techniques and outline Hopkins University, was also studying the recent advances in our use and understanding of venous drainage of the long bones in 1922. IO vascular access. Along the way, we will Attempting to delineate the microscopic anat- explore some of the limitations and complica- omy of the radius and ulna in several animal tions associated with IO infusion and identify models, he injected saline and India ink into areas in which further study is needed. the IO space. Constricted by the ‘rigid bony con- fines’ of the cortex, Doan found that venous History of intraosseous access drainage from the IO space was relatively con- stant, regardless of the systemic blood pressure Cecil K. Drinker (1887–1956), a Harvard phys- or volume of fluid infused. Excessive infusion iologist, is frequently cited as the inventor of pressures caused capillary rupture and extrava- therapeutic intraosseous infusion. But Drinker sation in his model, rather than increased out- himself acknowledged previous bone marrow flow. However, his examination of hypoplastic infusion studies by French anatomists Marie (‘yellow’) marrow revealed a complex network Franc¸ois Xavier Bichat (1771–1802) and M. of ‘functionally dormant’ capillaries, which he Siraud, Austrian anatomist Karl Langer (1819– theorized might be recruited to enhance outflow 1887), and the German anatomist Franz Mu¨ller in times of ‘crisis’ (Doan, 1922). Drinker also Paxton 197 believed that ‘large capillaries are frequently dye injected into the tibia of a rabbit ‘took ten practically closed to the passage of blood’, but seconds or less’ to reach the animal’s heart he remained sceptical about the existence of (Tocantins, 1940; Tocantins and O’Neill, Doan’s ‘occult’ system of capillary drainage 1940). The popularity of these articles in the (Drinker et al., 1922). United States and Great Britain initiated an Unfortunately, the progress made towards explosion of interest in IO infusion at the ster- developing a usable clinical technique for IO num and proximal tibia, and led many to believe infusion was disrupted after 1922. Drinker that Tocantins himself had originated the tech- moved on to more detailed studies of the lym- nique (Goerig and Agarwal-Koslowski, 2002). phatic and pulmonary systems, and Doan would Sternal infusions became quite popular subsequently tackle a wide variety of other hae- during World War II, both in the United matological subjects. The technique of sternal States and in Europe. Several authors com- bone marrow biopsy for diagnostic purposes mented on the ease of insertion and the massive was first described by Arinkin (1929). But the volumes that could be infused by this route first reported use of therapeutic IO infusion in (Doud and Tysell, 1942). In 1942, Doud humans came in 1933, when A. Josefson reported a case in which a young soldier with reported 10 cases in which sternal IO injection massive gastrointestinal bleeding was given of Campolon (liver extract) was used to treat 9 L of whole blood and 14 L of fluid (0.85% pernicious anaemia (Josefson, 1934). Soon normal saline and 5% dextrose solutions) other clinical researchers were experimenting through a standard 15-gauge sternal IO with medullary infusion at the sternum, includ- needle over a period of 10 days. No discomfort ing injections of radiographic contrast, bacteria, was noted under gravity infusions, but a mercury and various other medications and ‘moderate, indefinite sense of pressure’ was fluids (Benda, 1937; Benda et al., 1940). described by the patient during pressurized syr- In May of 1940, Norbert Henning, a German inge infusions. Sternal X-rays taken 25 days haematologist, reported his own study of venous after catheter removal were normal, and no drainage from the sternum in an animal model other complications were identified (Doud following injections of whole blood, glucose and and Tysell, 1942). dye. He found that substances injected into the Although Tocantins and others recom- IO space were rapidly taken up by the systemic mended IO access only ‘when quick absorption circulation, and that the time to central circula- is desired and prevailing circumstances...make tion was roughly equivalent to that for peripheral it difficult or impossible to use the common IV injection (Henning, 1940; Goerig and paths’, it is easy to understand why IO vascular Agarwal-Koslowski, 2002). access was so popular during the early 1940s Five months later, American physician (Tocantins, 1940). Peripheral IV cannulation, Leandro Tocantins (1901–1963) published the most ‘common path’ available to physicians the first in a flurry of articles describing his use of the time, involved the painful insertion of an of sternal and tibial IO access with infusions of unwieldy weighty metal trocar into delicate fluid (5% glucose and normal saline) and blood. veins. This trocar was prone to dislodgement He reported gravity infusion rates of 5–10 mL/ and extravasation, especially in small children. min for normal saline through a 15-gauge 1-in. In neonates, the superior sagittal sinus was often sternal needle in two adult male patients. used, which was considered even by contempo- Although these two patients did not experience rary practitioners to be a dangerous practice significant discomfort with the infusion, a third (Tocantins, 1940). Poor antiseptic techniques patient reported intense ‘bone pains’ with infu- also led to an unacceptable incidence of throm- sion requiring discontinuation of the infusion. bophlebitis and soft tissue infection with PIV Tocantins also demonstrated that Congo red placement (Bailey 1944). This problem was 198 Trauma 14(3) further exacerbated by the lack of effective anti- continuous infusion that Behr himself reported biotics to treat such infections (Bailey, 1944). was for 6 days, apparently without complica- Inspired by the research of Tocantins and tions (Behr, 1944a). O’Neill, several prominent practitioners pub- In 1944, British paediatrician Janet D. lished their own reports of IO infusion in the Gimson (later Roscoe) developed a smaller ver- mid-1940s. Hamilton Bailey, a British surgeon, sion of the Tocantins needle, which she felt was was a vocal supporter of sternal puncture, and better suited for paediatric tibial IO infusions. encouraged its use during war-time as it could be The Gimson needle featured a lighter handle, performed more easily than peripheral IV access with four needle lengths ranging from 1/4 to ‘under black-out conditions’ (Bailey, 1944). 5/8 –in., and a right-angle adapter to reduce Bailey was acutely aware of the risk of complete kinking and excessive pull on the attached sternal perforation with injury to the heart and tubing. The 1/4 –in. length was recommended great vessels, having seen it in his own practice. for neonates, and lengths of at least 1/2 – in. Consequently, he developed a 15-gauge ‘winged’ were advised for patients over 5 years old. needle, which he believed to be ‘fool-proof’ in Needle diameters ranged from 16 to 18 gauge preventing such injuries (Bailey, 1944; Behr, (Gimson, 1944). The Gimson needle became 1944a). Bailey was also one of the first to docu- quite popular in Great Britain, and was used ment the use of subperiosteal local anaesthetic by many paediatricians of the time (Gunz and (2 mL of 1% procaine hydrochloride) prior to Dean, 1945). needle insertion. Although he found that Emanuel M. Papper (1915–2002), chief of needle insertion was generally painless, the infu- anaesthesiology at Walter Reed US Army sion of fluids and medication ‘was inclined to Hospital, was another vocal advocate for the give pain’ under high pressures (Bailey, 1944). use of IO infusions during war-time (Papper, German surgeon Herbert Junghanns was 1942). Under his watch, a sternal trephine IO among the first to advocate IO administration needle with adjustable depth guard was devel- of anaesthestic agents, as early as 1943 oped by American physician Henry Turkel. (Junghanns, 1943; Goerig and Agarwal- The Turkel needle was adopted by the US Koslowski, 2002). National Research Council and became stan- Gerhard Behr, a British pathologist, advo- dard issue for American combat medics cated the tibial, rather than the sternal, route throughout World War II (Turkel and Bethell, in infants. This was a position that Tocantins 1944; Dubick and Holcomb, 2000). The earliest and many other IO practitioners also held, as published report of a ‘first responder’ using IO they believed that the sternum was too thin in technology to resuscitate a wounded soldier children younger than 5 years to allow for safe came in 1944, when a critically injured member and adequate IO access. By the same token, of a B-29 bomber crew was successfully resusci- early IO researchers believed that the long tated by a colleague using a sternal Turkel bones in adults did not possess enough ‘red’ vas- needle (Detroit News 13 March 1944; Bruttig cular marrow to permit adequate infusion and Kramer, 2004). volumes (Tocantins and O’Neill, 1945). Behr After World War II, the use of IO access in was also among the first to document a case of adults diminished, but its role in paediatric osteomyelitis at the tibial site, which he attrib- resuscitation was maintained. Danish paediatri- uted to needle dislodgement and subsequent cian Svend Heinild and colleagues reported by extravasation. Although this was the only case far the largest series of IO resuscitations up to of osteomyelitis that he identified in more than that time in 1947, with 982 infusions performed 60 infusions, Behr cautioned that, ‘after two or on 495 paediatric patients. Reflecting an unfor- three days the cannula will become loose and tunately common practice at the time, providers has to be removed’ (Behr, 1944b). The longest in this study did not use sterile precautions. Paxton 199

Rather, ‘the surgeon merely washes his hands tonsillectomy suffered anoxic brain injury due to well, not as prior to an operation, and he her physician’s inability to obtain rapid IV access. wears no gloves or mask’ (Heinild et al., 1947). He went on to suggest that obtaining IO access Heinild reported five cases of osteomyelitis in could have prevented the tragedy, although the this study, one associated with an extensive con- technique had become largely ‘ignored in medical tinuous infusion, and the other four cases schools’ (Turkel, 1983). The other two articles involving infusions of hypertonic solutions came in September 1984, beginning with Robert (50% dextrose or concentrated serum). Heinild Berg’s case report of a continuous intraosseous himself criticized other IO practitioners for their infusion of dopamine and dobutamine in a 6- insistence on sterile precautions, and many month-old child (Berg, 1984). An accompanying agreed with his position. Meanwhile, advocates editorial by James Orlowski echoed Turkel’s plea for sterile precautions pointed out that their for increased awareness of the IO route, empha- rates of infection were much lower than sizing its untapped life-saving potential in paedi- Heinild’s rates (Arbeiter and Greengard, 1944; atric resuscitation (Orlowski, 1984). Over the next Meola, 1944; Gunz and Dean, 1945). Of the decade, animal studies on the IO administration three most vocal groups, two had not yet of various resuscitative fluids and medications reported a case of osteomyelitis, and the remain- flooded into the medical literature and the ing group attributed at least one of their three manual IO needle became a part of every paedi- cases of osteomyelitis to the surgeon not wearing atrician’s armamentarium. gloves (Gunz and Dean, 1945). In July of 1985, new paediatric resuscitation By 1952, providers were also concerned about guidelines from the American Heart Association the potential for marrow embolization (Tarrow (AHA) acknowledged IO as an alternative to IV et al., 1952). Although this complication had not access, and IO cannulation would become part yet been reported in humans, it had been shown of the AHA Pediatric Advanced Life Support to occur with IO infusion in the rabbit model (PALS) training course within a few years (Wile and Schamberg, 1942). During the early (AHA, 1986). Various manual IO needles were 1950s, the IO route was also used for intraoss- resurrected, revised or invented during the eous venography (Begg, 1954). Despite their rel- 1990s. Familiar devices, such as peripheral IV ative safety and great utility, IO devices were needles, butterfly needles, spinal needles and gradually overshadowed by the introduction of bone marrow biopsy needles were also employed plastic disposable intravenous catheters and as alternatives to the traditional designs, with research into alternative (e.g. endotracheal, varying success. PALS guidelines were again intracardiac and subcutaneous) routes for fluid revised in 2000, recommending that rescuers and medication infusion (Parrish and Turkewitz, ‘establish intraosseous vascular access if reliable 1986). IO techniques remained in use in some venous access cannot be achieved rapidly’. The areas, including the USSR, Mexico, Argentina, 2000 guidelines also suggested that ‘because Africa and India, but were largely forgotten else- establishing vascular access in paediatric cardiac where (Ugarte, 1965; Kovalevich et al., 1973; arrest victims is difficult, it may be preferable to Kamerin, 1976; Kwaan et al., 1976; Valdes, attempt intraosseous access immediately’ (AHA, 1977; Shoor et al., 1979; Albonico and 2000). Ndakaiteyi, 1984; Orlowski, 1984). By the late 1990s, various manufacturers had Intraosseous infusion returned to mainstream identified the limitations of manual IO needles in medicine in the early 1980s, led by a trio of influ- penetrating the hard cortex of adult bones, and ential articles. In a July 1983 ‘letter to the edi- new ‘mechanical’ IO devices began appearing in tor’ of the American Journal of Diseases of the market. These included the FAST1Õ (Fast Children, Henry Turkel reported a case in Access for Shock and Trauma, Pyng Medical which a 3-year-old girl presenting for Corporation, Vancouver, British Columbia, 200 Trauma 14(3)

Canada) in 1997, the Bone Injection Gun (BIGÕ, Two types of bones can be used for intraoss- WaisMed, Yokneam, Israel) in 1998 and the EZ- eous infusions, those possessing large quantities IOÕ (Vidacare Corporation, Shavano Park, of ‘red’ marrow and those possessing predomi- Texas, USA) in 2004. The introduction of these nantly ‘yellow’ marrow. Both types of marrow devices not only changed the future of paediatric are present in all bones, but in differing IO access, but also led to a resurgence of interest in amounts. Red (haematopoietic, or hyperplastic) IO access for adult resuscitation. marrow is responsible for the production of leu- In 2005, both the PALS and Advanced cocytes, erythrocytes and thrombocytes. This is Cardiac Life Support guidelines were again the predominant form of bone marrow present revised, recommending the IO route for both in infants and young children. Haematopoietic paediatric and adult resuscitations when IV tissue is gradually replaced by fatty tissue after access could not be established quickly. In car- the age of 5 years, converting red marrow into diac arrest patients without a pre-existing yellow (hypoplastic) marrow. By the age of 20, IV, providers were instructed to obtain ‘imme- most of the remaining red marrow is found in diate IO access’ (AHA, 2006). Also, in 2005, the cranium, vertebrae, ribs, sternum, shoulder the International Liaison Committee on blades, pelvis and the epiphyses of long bones. Resuscitation (ILCOR) promoted IO access The diaphyses of long bones contain mostly over the endotracheal route for the administra- yellow marrow (Hall, 2007). tion of medications during paediatric resuscita- Although red marrow is constantly bathed in tions (ILCOR, 2006). In 2010, the AHA PALS circulating blood, yellow marrow contains dis- guidelines upgraded their recommendation for crete capillaries and veins with a continuous IO access as ‘the initial vascular access in cases endothelium that does not permit communica- of cardiac arrest’ to Class I, Level of Evidence C, tion between the blood current and surrounding effectively equating IV and IO access for resus- marrow parenchyma (Drinker et al., 1922). citative purposes (Kleinman, 2010). This para- This venous network can expand, however, to digm shift was also reflected in the 2010 accommodate increases in blood flow through European Resuscitation Council guidelines, the bone. When blood flow within the yellow which recommended that ‘if attempts at estab- marrow is increased, medullary vessels expand lishing intravenous access are unsuccessful after and push the surrounding interstitial fluid out 1 minute, insert an intraosseous needle instead’ of the bone through draining lymphatic channels (Biarent et al., 2010). and bony foramina. In contrast, red marrow pos- sesses a discontinuous endothelium due to endo- Intraosseous anatomy thelial breakdown from pressure exerted by rapid haematopoietic cell growth. This discontinuous For purposes of IO infusion, the ‘intraosseous endothelium allows for fluids and other sub- space’ is generally defined as that space within stances to be readily exchanged with the sur- both the cancellous bone of the epiphysis and rounding stroma (Drinker et al., 1922). the medullary cavity of the diaphysis which is Substances injected into the epiphysis first cir- in continuity, allowing for the free exchange of culate within the venous sinusoids, ultimately substances (Tremlett and Bajwa, 2009). draining via medullary veins into the central The diaphysis of human long bones is composed medullary sinus, which acts as a reservoir for of a relatively thick layer of compact (cortical) substances collected within the IO space. bone, surrounding a narrow medullary cavity. Composed of only a single layer of endothelium, In contrast, the epiphyses possess a much thin- the central medullary sinus can expand to ner layer of cortical bone enveloping a much accommodate up to five times resting blood larger network of porous trabecular (cancellous) volume. It is drained by perforating nutrient bone (Laroche, 2002). veins, as well as the emissary (epiphyseal, Paxton 201 metaphyseal and centromedullary) veins Post and Shoemaker, 1962; Shim, 1968). (Laroche, 2002). The majority of blood drained Sympathetic vasomotor nerve stimulation, from the epiphysis exits the bone via the epiph- endothelin and vasopressors tend to reduce yseal and metaphyseal veins (Gu¨nal et al., 1996; IOBF through vasoconstriction (Azuma, 1964; Laroche, 2002; DeLorenzo et al., 2009). Shim, 1968; Laroche, 2002). However, in the However, local venous drainage within the case of massive blood loss, the vasoconstrictive epiphysis may become overwhelmed at high effect of endogenous vasopressors such as epi- rates of infusion because the cortical foramina nephrine seems to be negated by local (perhaps through which perforating vessels pass offer sig- metabolic) factors. Animal studies have shown nificant hydraulic resistance to flow (Watson that during continuous blood loss, bone marrow et al., 1995). Once the epiphyseal drainage perfusion and venous outflow may be preserved system becomes sufficiently congested, multiple while most other peripheral vessels constrict. This compensatory mechanisms lead to retrograde facilitates increased mobilization of red blood flow into the diaphysis and the shunting of cells from the bone marrow to meet the body’s blood through previously inactive venous chan- oxygen demands (Shim and Patterson, 1967). nels (Doan, 1922; De Lorenzo et al., 2009). Decreased intramedullary pressure is gener- While most venous blood flows centrifugally ally due to low perfusion (resulting in decreased away from the bone marrow, the periosteal IOBF), while increased intramedullary pressure venous plexus returns deoxygenated blood to is due to either excessive perfusion (resulting in the central medullary sinus via cortical perforat- elevated IOBF) or intraosseous congestion from ing veins. These perforating vessels offer an outflow obstruction (Azuma, 1964). Following additional route for the egress of fluids out of periods of ischaemia with decreased IOBF, nutri- the IO space under conditions of increased ent venous outflow increases two to three times intraosseous pressure (IOP). Blood is forced its resting rate due to venous dilatation. through these perforators into the periosteal This response is known as ‘reactive hyperemia’ venous system, and later into the veins of of bone, and it seems to be regulated almost nearby muscles which anastomose with the peri- exclusively by metabolic factors. The effect of osteal plexus (Trias and Fery, 1979). In this way, epinephrine-induced vasoconstriction on this bones can act as collateral pathways for blood increased venous outflow is questionable, as return to the central circulation when major some groups have found persistent vasodilata- limb veins are occluded (Cuthbertson et al., tion (Shim and Patterson, 1967), while others 1964). However, if venous drainage from the report nearly absent blood flow through the IO soft tissues is not adequate to relieve this con- space following resuscitation from hypovolemic gestion, hydrostatic pressures will force fluid out shock with high-dose epinephrine (Voelckel of the periosteal plexus and into the surrounding et al., 2001). While vasopressin seems to have a interstitial tissues (Drinker et al., 1922). more favourable effect on maintaining IOBFR in Intraosseous blood flow (IOBF) rates range the setting of shock (Voelckel et al., 2001), efforts from 5 to 20 mL/min per 100 g of wet bone in to augment IO infusion rates by nitroglycerin- humans and animals, and are controlled by var- induced vasodilatation have not shown any ben- ious neural, hormonal and metabolic factors. Of efit in the swine model (Miller et al., 2009a). these, metabolic factors are believed to be the most influential (Laroche, 2002). Hypoxia, hypercarbia, acidosis and various substances Insertion sites (including parathyroid hormone, nitrous oxide, Sternum certain prostacyclins and IGF-1) have been shown to increase IOBF by causing local vaso- The pioneers of intraosseous vascular access dilation (Drinker et al., 1922; Cumming, 1962; believed that red marrow was required for 202 Trauma 14(3) successful infusion. Consequently, IO infusions Clavicle in adults have traditionally focused on the manubrium and the sternum, both of which con- Although some authors have referred to the clav- tain a high degree of red marrow and are easily icle as a ‘recommended site’ for IO infusion, few accessible (Tocantins and O’Neill, 1940). published studies have validated the utility of this Early studies identified the optimal sternal punc- route (Tocantins and O’Neill, 1940; McCarthy ture site to be 3 cm inferior to the manubrioster- and Buss, 1998). In the largest study evaluating nal juncture at the midline, with the manubrium this approach, Iwama and colleagues reported 29 puncture site 5 cm superior to that location cases of clavicular IO in adults using a manual IO (Tocantins and O’Neill, 1940; Bailey, 1944; needle. They found a mean infusion rate of Tarrow et al., 1952). Because the marrow cavi- 11.9 0.68 mL/kg/h, slightly slower than direct ties of the sternum and the manubrium seldom subclavian vein infusion (15.2 1.48 mL/kg/h). communicate, both can be cannulated simulta- No complications were reported (Iwama et al., neously (Tocantins et al., 1941a). Tocantins 1994). found flow rates at both sites to average 3 mL/ min (range 0.4–25 mL/min) under gravity infu- Proximal humerus sion, and as high as 57.5 mL/min under syringe pressure (Tocantins et al., 1941a, b). IO infusion at the proximal humerus has only Advantages of the sternal site include easy recently become a subject of significant research, accessibility (superficial location and thin bony with most published studies appearing in the last cortex), close proximity to the central venous 5 years. The insertion site is located at the centre (CV) circulation and exceedingly good drainage of the greater tubercle of the proximal humerus, through the mammary veins (Tocantins and with the patient’s elbow flexed 90-degrees and O’Neill, 1940). However, sternal infusions in hand placed over the umbilicus. Potential children less than 5 years old have traditionally advantages of this site include proximity to the been associated with a high rate of complica- central circulation, high infusion rates and tions, mostly due to poor flow from the rela- decreased pain in some studies (Miller et al., tively small size of the marrow cavity and a 2010a). The humeral site may also be of value high risk of puncture through the sternum and for patients with lower extremity injuries. In one into the heart and great vessels due to the thin case, providers chose the humerus over the tibia bony cortex (Tocantins et al., 1941a). For these due to bilateral traumatic below-knee amputa- reasons, sternal infusions are no longer recom- tions (Kovar and Gillum, 2010). mended in infants or children less than 5 years of First attempt success rates for humeral age (Tocantins et al., 1941a, b; Jaimovich and IO placement range from 60 to 100% (Leidel Kecskes, 1991). et al., 2009; Ngo et al., 2009; Plancade et al., Sternal IO devices also require the rescuer to 2009; Kovar and Gillum, 2010; Wampler et al., briefly halt chest compressions during placement, 2010; Reades et al., 2011), with many authors cannot be used in patients with a history of open reporting rates >90% (Ngo et al., 2009; heart surgery and are associated with an increased Plancade et al., 2009; Wampler et al., 2010). risk of iatrogenic injury to the heart and great By far the most common reason cited for failure vessels. However, newer mechanical devices for is excessive tissue overlying the insertion site, the sternum, such as the FAST1Õ and the sternal leading to dislodgement and difficulty identify- EZ-IOÕ needle set, are generating renewed inter- ing the anatomic landmarks (Kovar and Gillum, est in this insertion site. Studies have shown that 2010; Wampler et al., 2010; Reades et al., 2011). sternal infusions reach the central circulation The use of standard 25-mm EZ-IOÕ needles faster than IO infusions at most other insertion is no longer recommended at the humeral site, sites (Hoskins et al., 2005; Kramer et al., 2005). in adults, due to extravasation rates as high as Paxton 203

30–44% in several studies (Paxton et al., 2009; IO studies, the iliac crest has rarely been used Reades et al., 2011). Vidacare has recently intro- for IO resuscitation (Glaeser and Losek, 1986). duced a new 45-mm IO needle specifically Tarrow reported in 1952 that ‘there is little designed to address this issue, and now recom- danger of injury’ with the iliac crest site, although mends the 45 mm needle with all humeral IO he provided no objective evidence to support this insertions in patients weighing >40 kg. claim. He identified the site of insertion as ‘one- Humeral flow rates have been found to be at quarter the distance from the anterior superior least equivalent, if not superior to sternal flow iliac spine to the posterior spine’. The needle is rates (Hoskins et al., 2007). In fact, one recent advanced in the direction of the leg, angled 45 manufacturer-sponsored study of the EZ-IOÕ from the long axis of the body (Tarrow et al., found that pressure bag infusion (300 mmHg) 1952). Disadvantages of this route include the yielded flow rates of 5093 2632 mL/h (range potential for extravasation in the setting of 828–9000 mL/h) at the proximal humerus, com- pelvic fracture and difficulty immobilizing the pared to 828–1048 mL/h (range 336–3300 mL/h) site with combative or seizing patients. at the tibia (Miller et al., 2010b). Iwama and colleagues reported 21 manual IO insertions at the iliac crest in adults, with a mean Radius and ulna infusion rate of 32.2 4.48 mL/kg/h. This rate was much higher than direct subclavian vein Providers seem to be hesitant to utilize these sites, infusion (15.2 1.48 mL/kg/h) in this study. based upon the paucity of literature. In 1995, No complications of IO cannulation or infusion Waisman and colleagues reported the results of were observed (Iwama et al., 1994). a contrast study in dogs that identified the ‘best sites for intraosseous infusion’ of the upper limb Distal femur as the distal radial metaphysis and the distal ulnar metaphysis. No mention was made of the Although the distal femur has been used exten- humerus, and no flow data was reported to sup- sively in paediatric IO infusions since the 1940s, port this contention (Waisman et al., 1995). Two this site has not yet been reported in adults years later, the same group reported nine clinical (Tocantins, 1940; Tocantins and O’Neill, 1940; cases of BIGÕ insertion at the distal radius, with Tocantins et al., 1941a). The distal femur pos- 100% success at insertion and no identifiable sesses an extremely large epiphysis and has been complications. They recommended a depth of used with success in both neonates and infants, insertion of 1.0–1.5 cm. Rates of infusion and but overlying muscle makes it less accessible in medications administered through this route adults. The proper insertion site is 2–3 cm prox- were not reported (Waisman and Waisman, imal to the external condyles at the longitudinal 1997). In 2003, McCarthy and colleagues midline of the femur (Fiser, 1990). As with the attempted four adult radial styloid insertions proximal tibia, the needle should be inserted at using methyl green dye injected into a cadaver an angle 10–30 away from the joint space to arm through a 14-gauge Dieckmann intraosseous avoid injury to the epiphyseal growth plate needle. Two of the four attempts were successful, (Fiser, 1990). Tarrow reported using a 37 mm but two failed due to reflux of the dye back needle to reach the femur, compared to the stan- through the insertion site around the IO needle dard 17 mm needle that he used for the proximal (McCarthy et al., 2003). tibia (Tarrow et al., 1952).

Iliac crest Proximal tibia Although commonly used for bone marrow First described in 1940, the proximal tibia biopsies, and anecdotally referenced in early remains the most popular site for IO needle 204 Trauma 14(3) insertion, both in children and in adults insertion is 2 cm at the medial malleolus and (Tocantins, 1940; Tocantins and O’Neill, 1940; 1.0–1.5 cm at the lateral malleolus (Waisman Molin et al., 2010). In fact, one recent study and Waisman, 1997). reported that 84% of providers preferred the Advocates for the distal tibia site point out proximal tibial site over the humerus (10%) or that the cortex appears to be thinner at this site the distal tibia (10%) (Molin et al., 2010). The than at the proximal tibia, facilitating easier conventional bias against proximal tibial infu- insertion (Berg, 1984; Iserson and Criss, 1986; sion in adults seems to have originated with Iserson, 1989; Wheeler, 1989). In 1977, Valdes Tocantins in 1945, for anatomic reasons. Not reported 12 cases of manual IO insertion at the only is the adult tibial cortex much harder to medial malleolus and 3 cases at the lateral mal- penetrate using manual IO needles, but the leolus. Thirteen of the 15 cases had adequate decreased concentration of red marrow com- flow, and he was able to infuse an average of pared to the sternum was believed to limit IO 4 L (range 2–42 L) over an average of 5.4 days infusion rates (Tocantins and O’Neill, 1945). (range 3.5 h to 30 days). He reported only ‘mod- In adults and children, the proper insertion erate fluid infiltration in a few patients’, without site is described as 2 cm distal and 1–2 cm any cases of compartment syndrome or infec- medial to the inferior edge of the anterior tious complications (Valdes, 1977). In 1997, tibial tuberosity (ATT) (Gimson, 1944; Gunz Waisman and colleagues reported two cases of and Dean, 1945; Tarrow et al., 1952; Vidal IO placement at the medial malleolus, and one et al., 1993; Buck et al., 2007). Using manual placement at the lateral malleolus using the needles, providers have traditionally been BIGÕ. No complications were reported instructed to angle the needle 10–30 away (Waisman and Waisman, 1997). from the knee joint to avoid injury to the epiph- yseal growth plate (Gimson, 1944). The patient’s leg should be semi-externally rotated to bring Calcaneus this flat plane parallel to the surface of the bed (Gimson, 1944). In newborns, a site 1 cm distal Like the clavicle, the adult calcaneus does not to the ATT has been advocated, since this is have a significant amount of red marrow. sufficiently far from the newborn growth plate However, it is composed of cancellous bone, and avoids the harder bone more distally (Boon, with an open trabecular structure that permits 2003). flow of fluids inside the bone to be absorbed by a network of capillaries. The insertion site is Distal tibia located at the anterior aspect of the medial pro- cess of the calcaneal tuberosity, 2 cm from the Both the medial and lateral malleoli have been calcaneal tuberosity, situated on a line between used for IO infusion in children and adults, the calcaneal tuberosity and the medial promi- although the medial malleolus appears to be nence of the first metatarsal (Clem and Tierney, favoured (Valdes, 1977; Berg, 1984; Iserson 2004). Providers should use caution to avoid the and Criss, 1986; Iserson, 1989; Wheeler, 1989; epiphyseal plate posteriorly and the posterior Waisman and Waisman, 1997). The usual inser- tibial vessels anterosuperiorly (McCarthy and tion site is 3 cm proximal to the most prominent Buss, 1998). point of the medial malleolus, at the longitudinal McCarthy and colleagues reported the first midline of the tibia, directed 20–30 cephalad case of calcaneal IO placement in 1998. They (Valdes, 1977; Iserson and Criss, 1986; selected this site after an unsuccessful attempt Wheeler, 1989). Providers must use caution to at tibial insertion, but were able to infuse avoid the more anteriorly-situated saphenous 1800 mL of crystalloid over 6 h during the resus- vein (Iserson and Criss, 1986). Depth of citation of a 3-year-old boy (McCarthy and Paxton 205

Buss, 1998). No complications were identified. needles is the high frequency of bending and Although some respondents to a recent IO obstruction encountered during placement survey indicated that they had inserted a calca- (Iserson and Criss, 1986). neal IO, no other therapeutic uses of this route The bone marrow aspiration needles most have been reported in the English-speaking lit- commonly used for IO infusion are the erature (Lavis, 2000). Two adult cadaver studies Jamshidi needle (Baxter Health Corp, Valencia, have subsequently shown 70–75% success with California, USA) and the Illinois needle infusion at this site, using a 14 - or 16-gauge (Monoject, a division of Sherwood Medical, St. manual Dieckmann intraosseous needle with Louis, Missouri, USA). Bone marrow needles are 45 trocar (McCarthy et al., 2003; Clem and generally available in 15 -, 16 - or 18-gauge sizes. Tierney, 2004). The Illinois model has a lancet tip and an adjust- able depth guard, permitting insertion depths ranging from 1 to 4.8 cm. The Jamshidi needle Intraosseous devices weighs approximately 16 g in packaging, and pro- Needle design trudes approximately 2 in. from the tibia after placement (Calkins et al., 2000). In its most abstract form, the IO needle is a Manual needles developed specifically for IO hollow steel tube that is inserted through the infusion include the standard Cook intraosseous overlying soft tissue, periosteum, and bony needle, the Sussmane–Raszynski modification, cortex to access the porous interior of a bone. the Dieckmann modification and the Sur-FastÕ Internal needle diameters range from 12 - to 20- needle (Cook Critical Care, Bloomington, gauge, although the standard diameter for Indiana, USA). These needles range in diameter modern IO needles is 15 - to 16-gauge from 12 - to 20-gauge, and are constructed of (Vidacare, 2011). Needle lengths range from 7.5 type 316 stainless steel (chromium–nickel stain- to 68 mm, with the optimal length being deter- less steel containing molybdenum) (AK Steel, mined by the combined thickness of the overlying 2011). The standard Cook needle comes in soft tissue and cortex of the target bone. Needles pencil point, 35- and 45-tip angles, and bears should be long enough to reach a few millimetres a positioning mark to indicate the usual depth beyond the cortex without indenting the overly- limit for placement (Fernandes, 1991). ing soft tissues, but short enough to maintain a The Sussmane–Raszynski and Sur-FastÕ nee- low profile and avoid ‘levering’ torque with inten- dles both have screw tips, intended to facilitate tional or accidental manipulation (Vidacare, placement and prevent extravasation. The 2011). The distal end of an IO needle is usually Dieckmann and Sur-FastÕ needles both have sharply angled to reduce the likelihood of flow an additional pair of small holes on opposing obstruction due to abutment against trabecular sides of the tip, intended to enhance flow. The bone spicules. Some models have additional side Sur-FastÕ weighs approximately 88 g in packag- ports to further reduce this effect. ing (Calkins et al., 2000). Prices for these single- use manual IO devices range from $US 45–75 (BoundTree, 2011; Life-Assist, 2011; Chinook, Manual devices 2011; Combat Medical Systems, 2011; Surgical Solutions USA, 2011). Over the last 90 years, various implements have Various studies comparing the first-attempt been developed or modified to access the IO and ultimate placement success rates between space, including winged phlebotomy needles, different bone marrow and manual IO needles PIV needles, spinal puncture needles and various appeared throughout the literature during the bone marrow aspiration needles. The main dis- 1980s and 1990s. In general, all bone marrow advantage of using PIV, phlebotomy or spinal and manual IO needles can be placed within 206 Trauma 14(3)

1 min (Wagner and McCabe, 1988; Banerjee tubing to extract it after use, but the latest version et al., 1994; Halm and Yamamoto, 1998; Jun can be extracted by hand. The company has also et al., 2000), with 75–93% first-attempt success released a similar device without the spring- rate (Wagner and McCabe, 1988; Miner et al., loaded mechanism, called the FASTxTM. 1989; Jun et al., 2000; Fiorito et al., 2005) and According to the manufacturer, infusion rates 70–100% overall success rate (Smith et al., 1988; through the FAST1Õ are 15–80 mL/min by grav- Wagner and McCabe, 1988; Miner et al., 1989; ity, approximately 125 mL/min by pressure bag Glaeser et al., 1993; Guy et al., 1993). at 300 mmHg, and 150–250 mL/min by syringe (Macnab et al., 2000; Pyng Medical Mechanical devices Corporation, 2011). The device in packaging weighs approximately 162 g (Calkins et al., 2000). There are currently three mechanical IO devices The FAST1Õ has a first-attempt success rate approved by the United States Food and of 72–74% (Macnab et al., 2000; Frascone et al., Drug Administration (FDA): the FAST1Õ 2007), with an overall success rate of 72–100% (Pyng Medical Corporation, Vancouver, British (Tiffany et al., 1999; Calkins et al., 2000; Columbia, Canada), the BIGÕ (WaisMed, Macnab et al., 2000; Frascone et al., 2007; Yokneam, Israel), and the EZ-IOÕ (Vidacare Pointer et al., 2008; Hartholt et al., 2010). Corporation Shavano Park, Texas, USA). Mean time to insertion is about 1 min (Tiffany The BIGÕ and FAST1Õ are both spring-loaded, et al., 1999; Macnab et al., 2000; Hartholt et al., disposable, single-use devices. The EZ-IOÕ includes 2010). Overall, it measures up well against the a reusable power driver with single-use needle sets. other two mechanical devices with regard to suc- cessful deployment. However, device failures FAST1Õ have been more commonly reported with the FAST1Õ than with either of the other two The FAST1Õ (Fast Access for Shock and mechanical devices. Failure to secure placement Trauma) was approved by the FDA in 1997, has been reported with the ‘very obese’ (Macnab and was the first mechanical IO device to et al., 2000; Frascone et al., 2007), and the device appear in the market. The insertion site is in has also been criticized for being difficult to the manubrium in the midline, 1.6 cm below remove (Tiffany et al., 1999). In fact, three the sternal notch (Day, 2003). Placement of a cases have been reported in which the metal tip target patch outlines the proper insertion site, was retained in the sternum after removal of the approximately 15 mm in diameter. Manual pres- infusion tubing (Frascone et al., 2007; Fenton sure, enhanced by a spring-loaded mechanism, is et al., 2009; Helm et al., 2011), including two used to insert the device. A stainless-steel intro- that required surgical removal (Fenton et al., ducer pierces the cortex to embed the infusion 2009; Helm et al., 2011). In response to these tubing approximately 6 mm into the marrow cases, the manufacturer has redesigned the infu- space (Frascone et al., 2001). Meanwhile, a bed sion tubing so that it can be extracted manually of 10 needles surrounding the introducer helps without a removal tool (Fenton et al., 2009). to stabilize the position and prevent excessive depth of insertion. A hard protective dome can BIGÕ be placed over the device to allow chest com- pressions during resuscitation. Use of this The BIGÕis FDA-approved for use in the prox- device is restricted to the sternum and to imal tibia (1998 in adults and 2002 in children) patients 12 years or older (Pyng Medical and proximal humerus (2006 in adults), Corporation, 2011). although it has also been used successfully in An early version of the FAST1Õ included a the distal tibia, radius and ulna. The BIGÕ is a remover tool that threaded inside the infusion triggered, spring-loaded, single-use, disposable Paxton 207

IO injector. The device is held perpendicular to EZ-IOÕ the insertion site, the safety pin is removed and the trigger is pulled to release the spring. The EZ-IOÕ is FDA-approved for use at the After the needle has been inserted into the proximal tibia (2004 in adults and 2005 in chil- bone, the internal trocar is removed and the dren), proximal humerus (2005 in adults), ster- needle is flushed and connected to standard num (2007 in adults) and distal tibia (2007 in IV tubing with an adapter. The safety latch adults). In May 2011, the European Union is then repurposed to help stabilize the cannula. expanded the CE mark for this device to include This device comes in adult (blue, 15-gauge) placement at the distal femur in paediatric and paediatric (red, 18-gauge) sizes. The paedi- patients, and also extended the maximum dwell atric size is recommended for patients from time to 72 h (Vidacare, 2011). The EZ-IOÕis the term newborn to 12 years of age. This device is first battery-powered mechanical IO device to not battery-powered, and the spring mechanism appear on the market, but an optional balled has an estimated shelf life of 5 years. The handle adapter for manual insertion has recently BIGÕ weighs approximately 99 g (3.5 ounces), been introduced. The original power driver is a has a cannula length of 43.3 mm and the paedi- 456 -g weight, handheld drill base with a sealed atric model has an adjustable penetration lithium battery capable of powering up to 1000 depth (5–15 mm). The adult device is preset to needle insertions. Vidacare has also developed a an insertion depth of 25 mm. The range of rec- lighter model, the G3 Power Driver (315 g), ommended insertion depths depends upon which is capable of 500þ insertions, with a patient age (5 to 10 mm for <3 years old, 10 to colour-coded battery life indicator and trigger 15 mm for 3–6 years old, 15 mm for 6–12 years guard. Both driver models have an estimated old and 25 mm for >12 years old). This device shelf life of 10 years, and are not rechargeable has been in use by the Israeli military for more (Vidacare, 2011). than 15 years (Lindsey, 2003; WaisMed Ltd., Four needle lengths are available: ster- 2011). nal (green, 7.5 mm, 15-gauge), paediatric Studies comparing the BIGÕ to manual IO (PD, pink, 15 mm, 15-gauge), adult (AD, blue, needles have been favourable, with faster inser- 25 mm, 15-gauge) and large (LD, yellow, 45 mm, tion than Jamshidi in two trials (Spriggs et al., 15-gauge). These needles are constructed of type 2000; Olsen et al., 2002). First-attempt success 304 stainless steel, and have a circumferential rates range from 70 to 91% (Vardi et al., 2004; black line 5 mm from the hub to assist with Schwartz et al., 2008; Gerritse et al., 2009; Leidel depth estimation (Vidacare, 2011). All needle et al., 2010), with overall success rates generally sets fit all drivers. The PD needle set is recom- in the 73–100% range (Waisman and Waisman, mended for children from 3 to 39 kg, and the LD 1997; Calkins et al., 2000; Olsen et al., 2002; needle set is recommended for sites with exces- Miller and Morissette, 2004; Vardi et al., 2004; sive overlying soft tissue, most commonly the David et al., 2009; Gerritse et al., 2009; Hartholt proximal humerus (Vidacare, 2011). et al., 2010; Leidel et al., 2010). However, at Published reports on the EZ-IOÕ are promis- least two studies have found success rates for ing, with a first attempt insertion rate ranging BIGÕ in the 45–55% range (David et al., 2009; from 84% to 98% (Harrington et al., 2007; Sunde et al., 2010). Time to insertion is roughly Brenner et al., 2008; Leidel et al., 2010; Gazin equivalent to the EZ-IOÕ (Olsen et al., 2002; et al., 2011) and ultimate success rate of Miller and Morissette, 2004). Device failures 92–100% (Miller and Morissette, 2004; including the inability to remove the trocar Gillum and Kovar, 2005; Harrington et al., after placement and an overly sensitive trigger 2007; Stouffer et al., 2007; Brenner et al., 2008; have been reported (Calkins et al., 2000; Cooper et al., 2008; Pointer et al., 2008; Levitan Schwartz et al., 2008; Gerritse et al., 2009). et al., 2009; Gazin et al., 2011). Time to insertion 208 Trauma 14(3) with this device is reported to average 3–32 s, 3. Fracture of more proximal bone within the with infusion possible within 1 min in most same extremity as the selected insertion site cases (Davidoff et al., 2005; Gillum and Kovar, (risk of poor flow or compartment syndrome). 2005; Stouffer et al., 2007; Brenner et al., 2008; 4. Inability to immobilize the selected bone after Levitan et al., 2009). Early problems with ‘bind- IO placement. ing’ (reduced torque) were encountered with the drill’s previous 12 -V battery pack, but have been eliminated with the new lithium ion Intraosseous medications battery pack (Frascone et al., 2007; Horton and Beamer, 2008). Fracture or deformity of the IO Most drugs given IO have been shown to have needle’s plastic hub have also been reported equal availability and physiologic effect as the (Frascone et al., 2007; Horton and Beamer, same dose given through peripheral IV (AHA, 2008). 2010). Drugs that require central venous access for administration should not be infused Contraindications through an IO catheter. Medications that have been safely administered via the IO route in There are very few absolute contraindications to humans are listed in Table 1. IO use, most of which are related to anatomic With certain drugs, there does appear to be a considerations. In most cases, if one bone is dis- ‘depot effect’, with drug lingering in the IO space, qualified from IO insertion, other insertion resulting in a lower peak concentration and a sites should be available. In the case of rela- longer time to reach peak concentration (Buck tive contraindications, the benefits of immediate et al., 2007). This effect can be reduced by flush- IO access must be weighed against the potential for ing the IO needle with 10 mL of normal saline complications. Current contraindications for after medication infusion. Higher doses may be intraosseous access include the following. needed for IO administration of these drugs, although further research is needed to determine Absolute contraindications optimal dosing. Drugs that may require higher dosing with IO 1. Unhealed fracture or surgical division of the administration include Amikacin (Butt, 2001), selected bone (allowing extravasation of fluid). Ceftriaxone (Pollack, 1991), Chloramphenicol 2. History of prior sternotomy (for sternal (Jaimovich and Kecskes, 1991), Epinephrine infusions). (Spivey, 1992), Phenytoin (Jaimovich, 1989), 3. Active infection at the selected insertion site Tobramycin (Jaimovich and Kecskes, 1991) (e.g. cellulitis and abscess). and Vancomycin (Jaimovich, 1991; Chastagner 4. Recent IO access attempt at same bone and Kecskes, 2001). (within last 48 h). Macht, in his original investigation of 5. Inability to identify appropriate external land- the IO route for epinephrine administration marks (increased risk of improper placement). in animal models, noted that aqueous solutions 6. Prosthetic bone or joint at selected insertion site. of epinephrine were absorbed just as quickly via IO as PIV routes. Effects on heart rate and blood pressure were also similar in Relative contraindications duration. However, suspensions of epinephrine in oil showed a significantly longer duration 1. Bacteremia or sepsis (increased risk of of pressor effect. He speculated that these oil emul- osteomyelitis). sions remained in the marrow for a long time, and 2. Abnormalities of bone strength (e.g. osteogene- ‘act as reservoirs for a drug that is slowly liberated sis imperfecta, osteopetrosis and osteoporosis). and dispensed by the oil’ (Macht, 1943). Paxton 209

Table 1. Medications safely infused via IO route in humans.

Adenosine (Spivey, 1987; Friedman, 1996) P Albumin (4.5%) (Kelsall, 1993) P Aminophylline (Davidoff et al., 2005) A/P Amiodarone (Davidoff et al., 2005; Ruiz-Hornillos, 2011) A/P Ampicillin (McNamara et al., 1987; Moscati and Moore, 1990; Vidal et al., 1993; Joseph and Tobias, 2008) P Anti-Serum (Arbeiter and Greengard, 1944) A Anti-meningococcal antitoxin (Meola, 1944) P Antitetanus serum (Heinild et al., 1947) P Anti-pneumococcus serum (Meola, 1944; Heinild et al., 1947) P Atracurium besylate (Katan et al., 1988) P Atropine (Valdes, 1977; McNamara et al., 1987; Spivey, 1987; Tobias and Nichols, 1990; Glaeser and Losek, 1993; Guy et al., 1993; Davidoff et al., 2005; Fiorito et al., 2005; Joseph, 2008; Valde´s et al., 2010) A/P Blood Products (Doud and Tysell, 1942; Arbeiter and Greengard, 1944; Gunz and Dean, 1945; Heinild et al., 1947; Tarrow et al., 1952; Valdes, 1977; Davidoff et al., 2005; Burgert, 2009) A/P Bretylium (Glaeser et al., 1993) A/P Calcium chloride (Brunette and Fischer, 1988; Moscati and Moore, 1990; Glaeser et al., 1993; Guy et al., 1993; Fiorito et al., 2005) A/P Calcium gluconate (Heinild et al., 1947; Rosetti et al., 1985) P Cefotaxime (Moscati and Moore, 1990; Vidal et al., 1993) P Contrast agents (Heinild et al., 1947; Tarrow et al., 1952; Iwama et al., 1994; Knuth et al., 2011) A/P Dexamethasone (Valdes, 1977; Guy et al., 1993; Fiorito et al., 2005) A/P Dextran-40 (Valdes, 1977) A Dextrose 5% (Spivey, 1987; Brunette and Fischer, 1988; Davidoff et al., 2005) P Dextrose 10% (Glaeser et al., 1993; Kelsall, 1993) A/P Dextrose 25% (Glaeser et al., 1993) A/P Diazepam (McNamara et al., 1987; Spivey, 1987; Goldstein et al., 1990; Glaeser et al., 1993) A/P Diazoxide (Valdes, 1977) A Digitalis (Tarrow et al., 1952) A/P Dilantin (Guy et al., 1993) P Dobutamine (Berg, 1984; Goldstein et al., 1990) P Dopamine (Berg, 1984; Spivey, 1987; Goldstein et al., 1990; Davidoff et al., 2005) A/P Epinephrine (Berg, 1984; McNamara et al., 1987; Spivey, 1987; Brunette and Fischer, 1988; Glaeser et al., 1993; Guy et al., 1993; Davidoff et al., 2005; Fiorito et al., 2005; Valde´s et al., 2010; Gazin et al., 2011) A/P Etomidate (Davidoff et al., 2005) A Fentanyl (Davidoff et al., 2005; Valde´s et al., 2010) A Furosemide (Davidoff et al., 2005) A Glucose (5–10% in water) (Papper, 1942; Meola, 1944) A/P Glucose (20% in water) (Meola, 1944) P Glucose (25% in water) (Glaeser and Losek, 1986) P Glucose (50% in water) (Heinild et al., 1947) P Hartmann’s Solution (Gunz and Dean, 1945) P Heparin (Tarrow et al., 1952; Valdes et al., 1977; Ruiz-Hornillos et al., 2011) A Hypertonic saline/dextran (Cha´vez-Negrete et al., 1991; Dubick and Kramer, 1997) A Iced Saline (Myers, 2007; Truhlar et al., 2009) A/P Influenza B serum (Meola, 1944) P Insulin (Tarrow et al., 1952; Fiorito et al., 2005) A/P Lactated Ringers (Glaeser et al., 1993; Davidoff et al., 2005) A (continued) 210 Trauma 14(3)

Table 1. Continued.

Lactated Ringers (Glaeser and Losek, 1986) P Lidocaine (Rosetti et al., 1985; Tobias and Nichols, 1990; Glaeser et al., 1993; Davidoff et al., 2005) A/P Mannitol (Guy et al., 1993; Fiorito et al., 2005) P Mercupurin (Papper, 1942) A Methylene blue (Herman et al., 1999) P Midazolam (Goldstein et al., 1990; Davidoff et al., 2005; Valde´s, 2010) A/P Morphine (Goldstein et al., 1990; Guy et al., 1993; Von Hoff, 2008) A/P Naloxone (Spivey, 1987; Glaeser et al., 1993; Davidoff et al., 2005) A/P Norepinephrine (Davidoff et al., 2005) A Pancuronium (Goldstein et al., 1990; Stewart and Kain, 1992) P Penicillin (Tarrow et al., 1952; Goldstein et al., 1990) P Perabrodil (iodinated contrast agent) (Heinild et al., 1947) P Phenytoin (Walsh-Kelly et al., 1986; Spivey, 1987; Fiorito et al., 2005) P Promethazine (Davidoff et al., 2005) A Rocuronium (Davidoff et al., 2005) A Saline (Meola, 1944; Davidoff et al., 2005; Valde´s et al., 2010) A/P Sodium bicarbonate (Rosetti et al., 1985; McNamara et al., 1987; Spivey, 1987; Brunette and Fischer, 1988; Davidoff et al., 2005; Fiorito et al., 2005) A/P Sodium sulphate (30%) (Heinild et al., 1947) P Sodium sulphadiazine (Meola, 1944) P Sodium sulphapyridine (Papper, 1942) P Succinylcholine (Spivey, 1987; McNamara et al., 1987; Katan et al., 1988; Tobias and Nichols, 1990; Guy et al., 1993; Davidoff et al., 2005; Fiorito et al., 2005) P Tenecteplase 7000 IU (Ruiz-Hornillos et al., 2011; Valde´s et al., 2010) A Thiamine (Davidoff et al., 2005) A Thiopental sodium (Katan et al., 1988; Guy et al., 1993) P Vancomycin (Joseph and Tobias, 2008) P Vasopressin (Davidoff et al., 2005) A Vecuronium (Guy et al., 1993; Fiorito et al., 2005; Valde´s et al., 2010) A/P A, adults and P, paediatrics.

Spivey (1992) and colleagues observed that (Bailey, 1946; Tarrow et al., 1952; Goldstein IO epinephrine at standard IV doses (0.01 mg/ et al., 1990; Sarkar and Philbeck, 2009). In kg) had no significant effect on diastolic or mean animal studies, IO vascular access has been blood pressure in an anaesthetized swine model. shown to be just as effective as PIV or CVC Higher doses (0.1 mg/kg) produced a more pro- access in facilitating successful fluid resuscita- nounced effect on blood pressure. One recent tion (Morris et al., 1987; Neufeld et al., 1993; study showed that early IO epinephrine leads Fisher and Prosser, 2000; Mader et al., 2010). to better neurological outcomes than delayed Medications administered via the IO route IV epinephrine in a swine model of prolonged reach the central circulation at approximately ventricular fibrillation (Zuercher, 2011). the same time as those administered by PIV (Cameron et al., 1989; Warren et al., 1994). Flow rates Yet intraosseous infusion flow rates vary widely between studies, even when the same The medical literature is replete with case size and design of needle are used at the same reports of patients in extremis being successfully insertion site. Many different factors affect flow fluid resuscitated using IO vascular access through the IO needle, including infusion Paxton 211 pressure, fluid viscosity width and length of the This law states that linear flow (Q) is predicted needle, hydraulic resistance within the bone by an equation describing the relationship marrow and venous system, insertion site, size between the pressure gradient (P), the radius of the IO space, the presence of clots and other of the tube (r), fluid viscosity () and the length obstructive debris, and the local vascular tone of the needle (l) within the medullary cavity and surrounding tissues. Q ¼ Pr4=8 l Blood pressure in the IO space is normally maintained at one-third to one-quarter of the According to this law, flow rates should systemic arterial blood pressure (Arbeiter and increase in a manner directly proportional to Greengard, 1944; Stein et al., 1957; Shaw, the fourth power of a needle’s internal radius 1964; Michelsen, 1967). Consequently, attempts and inversely proportional to its length, all to infuse fluids into the IO space must first over- other factors being held constant. While this come the intrinsic resistance of this pressure gra- law does hold true for in vitro experiments, dient between the IO space and the infusion in vivo experiments have shown that shortening system. This can be achieved with gravity infu- the PIV cannulae by 25% only increases flow by sion (producing 100 mmHg infusion pressure 5–18%, or one-third of the improvement pre- suspended at a standard height of 100 cm dicted by H–PL (Jayanthi and Dabke, 2006). above the needle), or the use of a standard pres- This is because flow in vivo is affected by turbu- sure bag, infusion pump or by syringe infusion. lence within the IV tubing and cannula as well as Generally, syringe infusion is the most rapid hydraulic resistance from the veins (and technique as it produces the highest infusion marrow) through which the blood must flow. pressures (760–1520 mmHg with a 50 mL syr- With regard to viscosity, multiple studies have inge) (Tarrow et al., 1952; Feenstra et al., confirmed that whole blood runs through an 1994). Faster rates of infusion are generally pos- IO device at rates near 50% that of crystal- sible at increased infusion pressures for all inser- loid through the same needle (Arbeiter tion sites. Under syringe pressure, flow rates of and Greengard, 1944; Tarrow et al., 1952; 250 mL/min have been reported (Bailey, 1946; Schoffstall et al., 1989; Waisman and Elston et al., 1947; Johnson et al., 1998; Waisman, 1997). Tiffany et al., 1999). But this increase in flow Several authors have proposed that IO needle rate comes at a price. Rubal et al. (2010) size does not significantly affect the flow rate showed that high IO infusion pressures signifi- (Hodge et al., 1987; Watson et al., 1995), leading cantly increase intramedullary pressure in a some to claim that as much as 90% of the resis- linear fashion. Medullary compression and tance to flow in IO infusion is due to hydraulic shear strain increase dramatically between 30 resistance within the bone marrow (Watson and 60 mL/min. At 120 mL/min, peak medullary et al., 1995). This seems to be supported by anec- pressure was 1213 422 mmHg, with an axial dotal evidence that IO infusion rates ‘slow down shear strain of 15 4 in that bone model. The automatically as body fluids become replen- physiologic effects of increased IOP with high- ished’ (Gunz and Dean, 1945). Gunz noted pressure infusion have not been completely that flow rates seem to be related to the weight described. Increased IOP is associated with a of the child and the degree of dehydration (Gunz subjective experience of pain, and has been and Dean, 1945). Further support for this theory linked to an increased risk of fluid extravasation is provided by Schoffstall et al. (1989), who from within the IO space (Laroche, 2002). found three-fold improvement in flow rates An appreciation of Hagen–Poiseuille’s law with 13-gauge IO versus 18-gauge IO in large (H–PL) is essential to understanding the dynam- swine, but no difference between these different ics that affect flow rates though IO catheters. needles in smaller swine. This was true both with 212 Trauma 14(3) gravity infusion (at 100 cm height) and needle seem to accurately reflect CV values for 300 mmHg pressure infusion. pH (Grisham and Hastings, 1991; Kissoon et al., Several studies have shown that the humeral 1994; Ummenhofer et al., 1994), base excess site is capable of infusing significantly larger vol- (Grisham and Hastings, 1991), bicarbonate umes of fluid than the tibial site in a swine model (Grisham and Hastings, 1991; Kissoon et al., under high infusion pressures (Warren et al., 1994; Ummenhofer et al., 1994), sodium, chlo- 1993; Lairet et al., 2010, 2011). However, results ride, creatinine, blood urea nitrogen (Unger from human studies comparing the humeral and et al., 1986; Orlowski et al., 1989b; Grisham tibial sites have been mixed. Ong and colleagues and Hastings, 1991; Ummenhofer et al., 1994; compared flow rates through tibial and humeral Miller et al., 2009b), magnesium (Johnson EZ-IOÕ needles in the same patients, with 24 et al., 1999), phosphorus (Orlowski et al., patients receiving a tibial IO and 11 also receiv- 1989b), total calcium (Unger et al., 1986; ing a humeral IO. The mean tibial flow rate in Orlowski et al., 1989b), haemoglobin and hae- this study was 165 mL/min using a 300-mmHg matocrit (Unger et al., 1986; Orlowski et al., pressure bag and 73 mL/min under gravity infu- 1989b; Grisham and Hastings, 1991; sion, compared to 153 and 84 mL/min, respec- Ummenhofer et al., 1994), albumin (Orlowski tively, at the humerus (Ong et al., 2009). et al., 1989b; Miller et al., 2009b), bilirubin In contrast, one manufacturer-sponsored study (Orlowski et al., 1989b; Ummenhofer et al., of the same device found that the mean humeral 1994), total protein (Orlowski et al., 1989b; flow rate using a 300-mmHg pressure bag was Miller et al., 2009b), and uric acid (Orlowski 5093 2632 mL/h (range 828–9000 mL/h). This et al., 1989b). Bone marrow aspirates can also was nearly five times the proximal tibial rate be accurately used for the typing and screening found with the same infusion pressure (Miller of blood (Brickman et al., 1992). et al., 2010b). Mixed results have been found for potassium, Needle obstruction from clots and bone or glucose, PCO2, lactate dehydrogenase and marrow debris has led some authors to recom- aspartate aminotransferase (SGOT) (Unger mend against the aspiration of bone marrow et al., 1986; Orlowski et al., 1989b; Grisham to confirm proper placement prior to IO infu- and Hastings, 1991; Kissoon et al., 1994; sion (Frascone et al., 2007). Others have Ummenhofer et al., 1994; Johnson et al., 1999; found that heparinized saline flushes or infu- Miller et al., 2009b). There seems to be agree- sions through the IO needle are effective at ment within the current literature that IO speci- improving flow, presumably by preventing mens should not be used to predict CV PO2, local activation of the clotting cascade ionized calcium, alkaline phosphatase, alanine (Rubal et al., 2009). aminotransferase, platelets or white blood cell levels (Orlowski et al., 1989b; Grisham and Laboratory studies Hastings, 1991; Ummenhofer et al., 1994; Miller et al., 2009b). One recent study has The reliability of laboratory values obtained by shown that bone marrow PCO2 levels are reli- marrow aspiration through an IO needle able for the first 7 min of cardiopulmonary remains a controversial topic, despite the size- resuscitation with chest compressions, but are able number of studies addressing this topic consistently lower than CV levels thereafter over the last 20 years. Since central venous (Kissoon et al., 1997). Another study found blood is generally regarded as the ‘gold stan- good reliability for intraosseous pH and PCO2 dard’ for most laboratory studies, many authors for resuscitation times <15 min with or without have chosen to compare IO to CV blood values. infusion of epinephrine and normal saline, but In normovolemic patients, bone marrow sam- found poor reliability with resuscitations lasting ples drawn prior to infusion through the IO >15 min or associated with bicarbonate infusion Paxton 213

(Abdelmoneim et al., 1999). Johnson and col- Hsu et al., 2005; Nicks and McGinnis, 2005; leagues have shown that IO infusions of epi- Hallaj et al., 2006; Stone et al., 2007). nephrine, normal saline and sodium bicarbonate all significantly decrease marrow Extravasation and compartment syndrome levels of potassium, glucose, haemoglobin and magnesium and increase local marrow sodium Extravasation of fluids due to IO needle dis- levels. This change was not seen when heparin- lodgement is the most common complication ized saline flushes were given without other infu- reported in the literature, with rates rang- sions (Johnson et al., 1999). ing from 1% to 22% (Anderson et al., 1994; Claudet et al., 2003; Fiorito et al., 2005; Fowler et al., 2008; Frascone et al., 2009). Complications Multiple punctures within the same bone have Confirmation of proper placement long been discouraged, primarily due to the risk of extravasation of fluid through prior puncture Avoiding complications with IO access is usually holes with infusion (Tocantins and O’Neill 1945; best achieved by ensuring proper IO placement. Gunz and Dean, 1945). Tocantins recom- Traditionally, providers have been told that mended an interval of at least 12 h between proper IO placement may be assured if proper attempts on the same bone, which was the technique is followed and the needle is well amount of time that he anecdotally found was lodged in bone with successful bone marrow required for a puncture site to clot (Tocantins aspiration after placement (Papper, 1942). and O’Neill, 1945). Other providers have recom- However, bone marrow aspiration may not mended an interval of up to 48 h (Gunz and always be possible even with perfect placement Dean, 1945). (Frascone et al., 2009). Consequently, various Inadequate needle length hasalso been cited as a alternative methods have been advocated to cause of extravasation, prompting at least one confirm proper needle placement in the group to endorse using tissue thickness as the deter- marrow, including standard radiographs (La minant of which EZ-IOÕ needle to use, rather than Fleche et al., 1989; Wright et al., 1994) and fluo- weight-based parameters (Frascone et al., 2009). roscopic miniature C-arm imaging (Garcia and However, exceedingly long needles may also pre- Cohen, 1996). Strausbaugh and colleagues have dispose to dislodgment, due to the ‘fulcrum effect’ shown that circumferential pressure applied to experienced during needle manipulation while the IO insertion site can be used to identify attaching IV tubing or during transport (Glaeser incorrect placement of an IO needle. They and Losek, 1988–2). Long needles may also found that a blood pressure cuff inflated to increase the risk of penetrating both the cis and 120 mmHg at the site of a subcutaneous IO infu- trans cortex of the bone, leading to inadvertent sion reduced the mean gravity flow rate by 95%, infusion of fluids or medication into the deep com- with complete cessation of flow in two-thirds of partments of the limb (LaSpada et al., 1995). cases. This was compared to a 48% mean reduc- Compartment syndrome is the most extreme tion in flow with correctly placed IO needles complication of fluid extravasation. The risk of using the same technique (Strausbaugh et al., compartment syndrome appears to be influenced 1995). Studies using ultrasound imaging with by multiple factors including fluid osmolarity, colour-flow Doppler to evaluate IO placement the total volume and rate of fluid infused, and have reported sensitivities and specificities of the presence of cortical disruption from 94–100%, but appear to be more helpful in iden- additional puncture sites, fracture or needle dis- tifying misplaced needles or leakage around lodgement (Alam et al., 2002). poorly fitted needles than identifying flow With proximal tibial IO insertions, compart- within the bone itself (Korszun et al., 2004; ment syndrome usually occurs in the anterolateral 214 Trauma 14(3) compartment of the leg if it is due to leakage from the subcutaneous extravasation of norepinephrine around the insertion site, and in the posterior com- administered through a dislodged IO needle was partment following penetration of both cortices described by Pillar (1954) as early as 1954. Since (Alam et al., 2002; Ribeiro et al., 1993). To date, that time, many other cases of soft tissue or bony compartment syndrome requiring fasciotomy fol- necrosis have been identified due to IO extravasa- lowing IO infusion has been reported in 16 cases tion of high volumes of catecholamines or hyper- (Rimar et al., 1988; Moscati and Moore, 1990; tonic solutions of saline, glucose and bicarbonate Galpin et al., 1991; Burke and Kehl, 1993; (Wallden and Lennart, 1947; Spivey, 1987; Ribeiro et al., 1993; Vidal et al., 1993; Wright Christensen et al., 1991; Ellemunter, 1999; Alam et al., 1994; Gayle and Kissoon, 1994; Simmons et al., 2002; Khan et al., 2011). In at least two cases, et al., 1994; Launay et al., 2003; Moen and such soft tissue injury has been associated with Sarwark, 2008; Taylor and Clarke, 2011; Khan arterial thrombosis (Meola, 1944; Launay et al., et al., 2011). Of these 16 cases, 4 were shown to 2003). It is not clear whether these arterial throm- be due to needle dislodgement (Ribeiro et al., 1993; boses result from elevated compartment pressures, Wright et al., 1994; Launay et al., 2003; Taylor and direct vascular injury from extravasated sub- Clarke, 2011) and 5 were associated with cortical stances, or some other process. fracture or multiple puncture attempts (Moscati Alam and colleagues found that IO infusion of and Moore, 1990; Burke and Kehl, 1993; 7.5% hypertonic saline in a hypovolemic swine Simmons et al., 1994; Taylor and Clarke, 2011). model was associated with soft tissue or bone Five of these 16 cases ultimately required limb marrow necrosis in 50% of cases. Histological amputation (Moscati and Moore, 1990; Vidal evaluation revealed thromboses of numerous et al., 1993; Launay et al., 2003; Taylor and superficial veins, deep vein thrombosis and hae- Clarke, 2011). morrhage/necrosis within the marrow. Marked The development of compartment syndrome leucocyte infiltration was seen in the subcutane- does not require cortical disruption or leakage ous tissue, causing microvascular inflammation from around the IO needle. Gunal and col- and thrombosis. These complications were not leagues have shown that anterolateral compart- observed until >48 h after infusion was com- ment pressures begin to rise after total contrast pleted, leading the authors to speculate that dye infusion volume reaches 18–28 mL/kg in a soft tissue necrosis in other short-term survival canine proximal tibial model. At this point, dye studies using hypertonic saline for resuscitation becomes visible in the soft tissues and compart- may not have been identified due to delayed pre- ment pressures quickly rise with additional fluid sentation. The authors further speculated that infusion (Gunal, 1996). In this study, a 20-gauge compartment syndrome may have developed in spinal needle was placed under direct visualiza- this model due to sclerosis of the popliteal vein. tion after dissection and secured to the tibia with The high osmolarity caused fluid shifts and bone cement to prevent extravasation from the muscle swelling (Alam et al., 2002). insertion site (Gunal, 1996). Bone injury Soft tissue necrosis Bony injuries have been identified following IO Skin or bone ‘pressure necrosis’ was a well-known needle placement on both a gross and micro- complication of manual IO devices in the 1940s, scopic scale. Early studies found a 3–25% due to too short a needle being used with resultant incidence of periosteal elevation and subperios- excessive pressure on the overlying tissue/perios- teal bone formation due to subperiosteal infiltra- teum surrounding the needle. These were generally tion, but these findings invariably resolved self-limiting and did not require intervention within a few weeks of needle removal (Arbeiter (Massey, 1950). Extensive tissue damage due to and Greengard, 1944; Heinild et al., 1947). Paxton 215

Iatrogenic fractures with IO needle placement O’Neill, 1945; Massey, 1950), illustrating the are rare, and are usually associated with exces- likely role of poor sterile technique in the high sive force, improper site selection or multiple incidence of IO-associated osteomyelitis during attempts at needle insertion (LaFleche et al., this time period. 1989; Katz and Wojtowycz, 1994; Bowley, Tocantins recommended that IO needles be 2003). The introduction of cortical microfrac- left in place for no longer than 12 h to avoid tures during IO needle insertion has been osteomyelitis (Tocantins and O’Neill, 1945). noted, but the clinical significance of these However, some authors have reported up to 30 microfractures is not clear (Olsen et al., 2002). days of infusion through an IO needle without Although injury to the epiphyseal growth any infectious complications (Valdes, 1977). plate is a common concern with paediatric In 1950, Massey was the first to report the rate tibial IO placement, several studies have failed of osteomyelitis to be around 0.6%, which was to find any long-term effects on tibial growth reiterated in Rosetti’s review of the literature in (Spivey, 1987; Brickman et al., 1988; Dedrick 1985 (Massey, 1950; Rosetti et al., 1985). Since et al., 1992; Brickman et al., 1996; Fiser et al., 1985, five cases of osteomyelitis attributed to IO 1997; Claudet et al., 2003). Similarly, studies on infusion have been reported (Platt et al., 1993; the bone marrow have found only transient local Stoll et al., 2002; Claudet et al., 2003; Dog˘ an decreases in marrow cellularity immediately fol- et al., 2004; Henson et al., 2011). One of these lowing infusion of fluids and medications was identified in an adult patient several months (Pender et al., 1991; Neufeld et al., 1993; after catheter removal (Henson et al., 2011). Brickman et al., 1996). High infusion rates do Candida albicans was cultured from the wound not appear to increase the severity of these in two of these cases, and both resolved rapidly changes (Brickman et al., 1996). with the administration of antifungal agents (Platt et al., 1993; Dog˘ an et al., 2004). Osteomyelitis Injury to thoracic structures In 1947, Heinild reported five cases of osteomy- elitis in 982 IO infusions, which he associated Death following diagnostic or therapeutic ster- with the use of continuous infusions, or hyper- nal puncture is uncommon, but has occurred. tonic solutions such as concentrated serum and To date, at least 20 cases of death from iatro- 50% glucose (Heinild et al., 1947). Other early genic sternal puncture have been reported in the studies reported high rates of osteomyelitis in medical literature (Bakir, 1963; Ro¨thig, 1965; patients who received whole blood infusions Pu¨schel et al., 1985; Pascali et al., 1987; through the needle, suggesting that the blood Bhootra, 2004). Bakir reviewed the first 10 of may have been contaminated with bacteria these cases in 1963. He found that the mecha- (Tocantins, 1943; Gunz and Dean, 1945; nism of death for all cases in which autopsy was Ravitch, 1943; Tocantins and O’Neill, 1945). performed was right ventricular laceration with In 1945, Ellison detailed five cases of osteomye- resultant haemopericardium and cardiac tampo- litis in 130 IO insertions, with another four cases nade. In most cases, the patient died within of osteomyelitis occurring in 100 patients who 5 min of injury. In one case, the internal mam- had only a PIV placed. This led the author to mary artery was injured and the patient died conclude that ‘the fact of its occurrence at all is within 1 min of injury (Marill, 1954). In another due to bacteria already in the blood stream look- case, pericardial laceration was attributed to an ing for a suitable nidus’ (Ellison, 1945). abnormally thin sternum (2–3 mm) (Bhootra, Comparable rates of osteomyelitis associated 2004). Only one of these 20 fatal sternal punc- with both IO and PIV infusions were reported tures occurred during an attempt to establish IO by other authors of the time (Tocantins and access for resuscitative purposes (Papper, 1942). 216 Trauma 14(3)

Embolic complications flush the line. In this case, air was identified in the hepatic veins, the right atrium and ven- In 1942, Wile and Schamberg identified large fat tricle, the upper pole of the right kidney and globules within the pulmonary arterioles of five the cerebral vessels. Cerebral arterial air embo- out of seven rabbits that received IO infusions of lism has been reported in a child with patent mapharsen in 5% dextrose solution. Although no foramen ovale and atrial septal defect (van Rijn other marrow components or fragments of bone et al., 2008). were found within the lungs, they concluded that these fat globules must have embolized from the IO Pain space (Wile and Schamberg, 1942). More recent studies have shown that increases in IOP as low Pain with IO insertion comes from both the as 37 mmHg can embolize marrow contents somatic pain fibres of the skin and periosteum, (Whitenack and Hausberger, 1971), occurring in as well as visceral pain fibres scattered through- 89–100% of IO infusions (Orlowski et al., 1989a). out the medullary cavity and trabecular bone. However, these emboli do not seem to cause any These visceral fibres produce vague, referred clinical effect unless the patient has an intracardiac sensation of pain in response to inflammation, shunt allowing embolization into the brain and ischaemia or distension (Ross et al., 1995; other vital organs via the arterial system Laroche, 2002). Consequently, control of pain (Orlowski et al., 1989a). The number of fat in IO access must address both superficial emboli found on autopsy does not appear to be (somatic) and deep (visceral) pain. The infu- significantly altered by increasing the rate of infu- sion of hypertonic substances (Meyer and sion, infusion pressure or the total volume of fluid Perlmutter, 1943; Heinild et al., 1947), high infu- infused (Orlowski et al., 1989a; Hasan et al., 2001). sion pressures (Philbeck et al., 2009) and high Fiallos and colleagues demonstrated in a swine infusion rates (Tocantins et al., 1941b) have all model that there was no increase in fat embolism been found to increase pain with IO infusion. with IO administration of epinephrine, normal Infusion at the humeral site has been reported saline or sodium bicarbonate infusion during to be less painful than infusion at the tibial site CPR. They found the same number of fat globules in adults (Miller, 2010a). in the pulmonary vasculature of pigs that under- Pain perception with IO needle insertion and went CPR using IV access as were found in pigs infusion is highly variable. In one study, 30% of that underwent CPR using IO access (Fiallos et al., patients reported no pain with infusion, while 1997). In humans, fatal fat embolism following 23% of patients reported 10/10 pain on a intraosseous venography has been reported visual analog scale (Davidoff et al., 2005). (Gildenhorn et al., 1960; Thomas and Tighe, 1973). In another study, significant infusion pain was Embolization of air is also a consideration only reported in 3 of 26 patients (Cooper et al., with IO infusions, just as with PIV and CVC 2008). In general, needle insertion appears to infusion (Wald et al., 2003). Anatomic studies be far less painful than infusion through the by Tarrow showed that air emboli are usually same device (Davidoff et al., 2005; Fowler caught in the capillaries of the sternum during et al., 2008; Miller and Morissette, 2010a; sternal infusion. In the tibia, however, the rel- Sheehan et al., 2011). atively larger nutrient vein allows air emboli to Lidocaine is the local anaesthetic most com- pass more easily into the general circulation monly used with IO needle insertions, although (Tarrow et al., 1952). Hillewig and colleagues 1% procaine hydrochloride (NovocainÕ) has also reported a case in which intravascular gas was been used for subperiosteal anaesthesia prior to found on CT scan and autopsy following IO IO insertion in the past (Bailey, 1944; Gimson, infusion, presumably due to air injection 1944; Tarrow et al., 1952). The standard dose of along with medication or failure to properly 2% preservative-free lidocaine is 0.5 mg/kg in Paxton 217 patients from 3 to 39 kg, and 20–40 mg in patients adults to their staff (Lavis, 2000). Hayden and >39 kg (Miller et al., 2005; Davidoff et al., 2005). Panacek found that the mean number of IO However, pain may not be adequately controlled lines placed by graduates of accredited emergency even with higher doses of lidocaine (Frascone medicine residencies in the United States was 2 et al., 2007; Miller, 2010a). A first dose of (range 1–6) during their entire residency. This lidocaine should be injected into the IO space at number did not appear to be affected by annual least 30 s prior to initiating infusion, followed by a emergency department volume (Hayden and rapid normal saline syringe flush of at least Panacek, 1999). 10 mL, and another 20 mg of lidocaine (Miller Providers trained in PALS techniques are et al., 2010a; Philbeck et al., 2010). Additional nearly twice as successful at obtaining IO access dosing and flushing may be required. as non-PALS trained providers, due to the imple- Other local IO anaesthetics, such as etido- mentation of IO training into the PALS course caine (Stabile et al., 2000) and 3% mepivacaine (Baker et al., 2009). Furthermore, providers (Replogle et al., 1999; Gallatin et al., 2000) have who are trained in IO vascular access are also been used with some success in dental applica- more likely to want to use this approach when tions, but have not yet been evaluated for use leading resuscitations (Lo and Reynolds, 2009). with IO vascular access. The intraosseous regio- Different methods of simulation have been used nal anaesthesia technique using IO lidocaine with varying success in teaching providers about has been employed with orthopaedic surgeries, IO placement techniques. Chicken legs (Walter but requires the application of a tourniquet and Clark, 1990), turkey legs (Fuchs et al., 1991), (inflated to 250–300 mmHg in the arm and pork ribs (Ota et al., 2003), human cadaveric 350–400 mmHg in the leg) to prevent rapid studies (Tabas et al., 2005; Levitan et al., 2009), escape of lidocaine from the medullary space telesimulation models (Mikrogianakis et al., (Waisman et al., 1995). 2011), plastic mannequins (Miller et al., 2005) and even a candy bar wrapped in plaster to simu- Training late bone (Bateman and Bateman, 2010) have been used to successfully train providers in IO insertion Although the intraosseous route is a well-known techniques. approach to rapid vascular access, it is generally Difficulties in obtaining rapid vascular access underutilized by most providers. In one recent under hazardous material (Haz-Mat) conditions survey of healthcare professionals, 23.5% had have led many researchers to examine the utility experienced a medical incident in which they of the IO approach. Several studies have believed that IO was indicated but had not shown that providers can place IO needles attempted it. Not surprisingly, the most more easily than PIV catheters while wearing common reasons for not using IO infusion were personal protective equipment (PPE) (Suyama lack of equipment (48.3% of respondents) and et al., 2007; Lamhaut et al., 2010; Mitchell lack of adequate training (32.6%). Most of these et al., 2010). There also seems to be little differ- respondents had attended a lecture (96.7%) or ence in time required to place IO needles participated in bedside teaching (61.8%) on the between providers wearing PPE and those not subject, but only 5.6% had actually participated wearing PPE (Ben-Abraham et al., 2003; in a hands-on workshop (Hallas et al., 2010). Lamhaut et al., 2010). Lavis and colleagues found that 74% of respon- dents to a questionnaire on IO infusion knew that Future research IO technology could be used in adults, but only 7% had actually used it themselves. All were Despite the tremendous growth of research into involved in training medical staff, but only 11% IO vascular access over the last two decades, said that they taught techniques for IO infusion in many questions remain unanswered. One of the 218 Trauma 14(3) most important barriers to increasing the popu- Although it is impossible to ascertain the pre- larity of IO access is the lingering doubt in many cise number of IO devices that have been placed providers’ minds about the safety of this method. over the last 90 years, the number is likely in the Historical data on complications such as osteo- many tens of thousands (Vidacare, 2011). myelitis and fat embolism are both reassuring Unfortunately, this wealth of experience with and a cause for concern. Although the rate of IO catheter placement and complications is not osteomyelitis has been assumed to be only fully reflected in the medical literature. Myriad 0.6%, this is based on a meta-analysis of the reasons for this discrepancy may be found. In reported IO insertions prior to 1985 (Rosetti the past, IO devices were inserted and closely et al., 1985). Much has changed since the first monitored in the inpatient setting. This allowed cases of IO infusion were reported in the 1940s. for earlier detection of both immediate and sub- Full sterile technique including drapes and gown sequent complications. IO devices are now typi- is commonly used today for CVC insertion, but cally placed by prehospital or emergency not for peripheral IV insertion. Although medicine providers, which can lead to disconti- modern IO needles are sterilized and intended nuity of care in regards to detecting potential for only a single use, manufacturers recommend non-immediate complications of their placement only local skin cleansing prior to IO insertion, or use. Hospital providers may also be unaware and not full sterile draping techniques (Pyng of unsuccessful attempts at IO access made by Medical Corporation, 2011; Vidacare, 2011; pre-hospital personnel. WaisMed Ltd., 2011). It remains to be seen Long-term follow-up is shockingly rare in the whether this confidence in the historically low modern IO literature. Most of the modern liter- rate of osteomyelitis will be borne out with ature on IO devices focuses on time needed to increased use of the IO approach. Fungal osteo- obtain access, rates of successful placement, ease myelitis has only recently been reported as a of use, device failures and immediate complica- complication of IO catheterization (Platt et al., tions. Today, only case reports and animal stud- 1993; Dog˘ an et al., 2004). Consequently, the ies seem to address the occurrence of delayed incidence and potential severity of this complica- complications, although reporting on such tion are not yet known. With increasing antibi- delayed complications was a primary objective otic resistance in the modern age, one can only of the earliest literature on the subject. speculate about the effect that resistant strains Consequently, it may be exceedingly difficult to such as methicillin-resistant Staphylococcus detect a significant shift in the incidence of aureus and vancomycin-resistant Enterococcus delayed complications from the earlier literature will have on the severity of IO-associated osteo- to the modern era. myelitis. The questions of local needle care (e.g. Information is also needed to help IO practi- appropriate dressings and needle hygiene), tioners predict the appropriate depth of inser- acceptable dwell times (12 vs. 24 or 72 h) and tion, maximal safe rate of infusion at various prophylactic antibiotics to prevent infection sites and dosage of intramedullary anaesthetic must ultimately be addressed in large, case-con- (e.g. lidocaine) needed. Current manufacturer trol studies. Unfortunately, most of the current recommendations on estimating insertion depth data is anecdotal. Fat embolism, virtually and needle length are based on binary distribu- unheard of in early studies outside of the tions of patient weight (e.g. <40 kg and >40 kg) animal model, may become more common with and age (e.g. <12 years, >12 years), but anthro- the higher infusion rates used today, compared pomorphic studies have not yet been done to to the meagre flow rates used by most early prac- determine whether better metrics might exist to titioners. The current evidence on this subject is correlate readily available patient characteristics mixed (Whitenack and Hausberger, 1971; to the predicted depth of insertion at various Orlowski et al., 1989a; Hasan et al., 2001). anatomic insertion sites. Characteristics such as Paxton 219 body mass index, height, waist circumference or is not equivalent to proving that they are effica- circumference of the limb might be appropriate cious in the same doses used for PIV adminis- starting-off points. tration. If practitioners are to continue Studies are beginning to show that the issue administering medications via the IO route, of extravasation is not merely related to catheter appropriate IO doses must be confirmed with dislodgement, but may also be significantly studies examining serum levels, volume of distri- affected by fluid infusion rates or pressures bution, time to peak effect and other physiolog- (Gunal, 1996; Alam et al., 2002). Furthermore, ical effects. The popular conception is that IO the effects of infusion rate and pressure on administration is equivalent to PIV administra- extravasation seem to be dependent on the rela- tion, so differences should not exist. However, tive size of the target bone and surrounding many drugs have already been shown to have compartments to the volume of fluid infused, different bioavailability when given by the IO suggesting that scala may be established to pre- route compared to the PIV route (Jaimovich, dict a safe maximum rate and pressure of infu- 1989; Jaimovich and Kecskes, 1991; Pollack, sion for individual patients (Gunz and Dean, 1991; Spivey, 1992; Butt, 2001; Chastagner, 1945; Schoffstall, 1989; Gunal, 1996). 2001). It is also clear that some medications Pain perception also remains highly variable have local effects on the bone marrow and among patients, with the same protocol for lido- local vascular tone, but only a handful of med- caine dosing leading to complete pain control in ications have been examined for such effects some patients and virtually no pain control in (Brickman et al., 1996; Johnson et al., 1999; others (Davidoff et al., 2005; Frascone et al., Voelckel et al., 2001; Alam et al., 2002). A 2007; Cooper et al., 2008; Philbeck et al., 2010; more complete understanding of how different Miller et al., 2010a). Lidocaine has been used IO medications affect not only their own distri- with most IO insertions to date, but there is a bution, but subsequent administrations of med- great paucity of IO literature studying whether ications is essential. The use of hypertonic other anaesthetics may be more effective. The solutions for IO resuscitation is compelling due dental literature has provided some candidates to the lower volumes of fluid needed to obtain a for alternative agents (Replogle et al., 1999; physiological effect, but animal studies have Gallatin et al., 2000; Stabile et al., 2000), but shown very mixed results in regards to their providing local IO anaesthesia in the context safety and the adverse outcomes associated of ongoing fluid infusion may prove to be chal- with their extravasation into the soft tissues lenging. The key appears to be providing a (Pillar, 1954; Spivey, 1987; Alam et al., 2002). period of time after the slow infusion of local New sites for IO access will undoubtedly be anaesthetic during which no infusion occurs, explored in the coming decades, including many allowing the anaesthetic to have its effect prior that are until now only theoretical or minimally to be washed away by infusing fluid. Studies are described. These include the clavicle, calcaneus, needed to determine not only the optimal type radius, ulna and potentially any bone in the and dose of anaesthetic, but also the optimal human body. Of course, the risks and benefits time between anaesthetic injection and the initi- of cannulating specific bones may be modified ation of infusion. by factors such as the size of the surrounding Most medications that can be infused via PIV soft tissue compartment, the proximity of have been infused via the IO route, but only a vital structures that could be inadvertently few have been studied to determine whether the injured and the local degree of vascularity. serum levels or appropriate therapeutic end- Bone growth and remodelling abnormalities points are reached in an equivalent fashion (e.g. osteogenesis imperfecta, osteoporosis, etc.) through both routes. Proving that medications may also prove to be less imposing obstacles in can be safely administered via IO vascular access the future, as newer devices or techniques are 220 Trauma 14(3) developed to reduce the cortical and trabecular considers the potential complications, time shear stresses associated with IO infusion. Some required to obtain access and other factors cases have already been reported in the literature that may contraindicate its use. in which patients with these conditions were Indirect vascular access via the intraosseous resuscitated with current IO needles without route offers an effective alternative to direct vas- complications (Davidoff et al., 2005). Future cular access methods that has already proven its IO needles may also be composed of other sub- life-saving potential in thousands of reported stances such as ceramic, silicone or plastic, cases to date. IO access may not be appropriate rather than the current stainless steel needles. for all patients, but it deserves a place in the More flexible IO catheter materials may be less modern provider’s armamentarium. It can be prone to dislodgement with manipulation, especially valuable when other alternatives for although they could present problems with cath- vascular access are impossible or could compro- eter removal. Antibiotic- or anticoagulant- mise patient safety due to prolonged time to impregnated needles could theoretically prove obtaining access or other complications of cath- useful in preventing the complications of local eter placement. However, IO cannulation and infection or needle clotting. Auto-injectors for infusion is not without its own complications, one-time infusion of medications into the IO and this potential for complications must be space may also have significant advantages weighed carefully against the many potential over oral, intramuscular or subcutaneous benefits of its use. routes in regards to speed of reaching the central circulation. Long-term implantable infusion Disclosures devices of the future may employ IO vascular access for the administration of antibiotics, che- None. motherapy, insulin or other drugs. In short, the future of indirect vascular access via the IO Funding route may only be limited by our own imagina- This research received no specific grant from any tion and the relative safety and utility of this funding agency in the public, commercial, or not- approach as compared to direct venous access. for-profit sectors.

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