Intraosseous Administration Research Articles

Recovery of fibrinogen concentrate after intraosseous application is equivalent to the intravenous route in a porcine model of hemodilution

BACKGROUNDFibrinogen concentrate is increasingly considered as a hemostatic agent for trauma patients experiencing bleeding. Placing a venous access is sometimes challenging during severe hemorrhage. Intraosseous access may be considered instead. Studies of intraosseous infusion of coagulation factor concentrates are limited. We investigated in vivo recovery following intraosseous administration of fibrinogen concentrate and compared the results with intravenous administration.METHODSThis study was performed on 12 pigs (mean [SD] body weight, 34.1 [2.8] kg). Following controlled blood loss (35 mL/kg) and fluid replacement with balanced crystalloid solution, intraosseous (n = 6) administration of fibrinogen concentrate (80 mg per kilogram of bodyweight) in the proximal tibia was compared with intravenous (n = 6) administration of the same dose (fibrinogen infusion time approximately 5 minutes in both groups). The following laboratory parameters were assessed: blood cell count, prothrombin time index, activated partial thromboplastin time, and plasma fibrinogen concentration (Clauss assay). Coagulation status was also assessed by thromboelastometry.RESULTSAll tested laboratory parameters were comparable between the intraosseous and intravenous groups at baseline, hemodilution, and 30 minutes after fibrinogen concentrate administration. In vivo recovery of fibrinogen was also similar in the two groups (89% [23%] and 91% [22%], respectively). There were no significant between-group differences in any of the thromboelastometric parameters. Histologic examination indicated no adverse effects on the tissue surrounding the intraosseous administration site.CONCLUSIONThis study suggests that intraosseous administration of fibrinogen concentrate results in a recovery of fibrinogen similar to that of intravenous administration. The intraosseous route of fibrinogen concentrate could be a valuable alternative in situations where intravenous access is not feasible or would be time consuming.LEVEL OF EVIDENCEProspective, randomized, therapeutic feasibility study in an animal model, level V.

Onset and Duration of Intravenous and Intraosseous Rocuronium in Swine

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

Coronary Perfusion Pressure Response to High-Dose Intraosseous versus Standard-Dose Intravenous Epinephrine Administration after Prolonged Cardiac Arrest

Background: This study was done to compare coronary perfusion pressure (CPP) prior to the first rescue shock (RS) among a group of animals that received intraosseous (IO) epinephrine 0.1 mg/ kg (high-dose epinephrine [HDE]) with a group that received intravenous (IV) epinephrine 0.01 mg/kg (standard-dose epinephrine [SDE]) during cardiac arrest resuscitation using a swine model of prolonged out-of-hospital ventricular fibrillation (VF) cardiac arrest. Methods: This was a secondary analysis of prospectively collected data from two IACUC approved protocols. Seventy-nine Yorkshire swine (25 - 35 kg) were surgically instrumented under anesthesia and VF was electrically induced. After 10 minutes of untreated VF in the IO study (n = 26) and 12 minutes of untreated VF in the IV study (n = 53), resuscitation commenced with closed chest compressions (CCC). A single dose of epinephrine (HDE IO or SDE IV, respectively) was given and flushed with saline. The CCC and RS attempts were standardized for all animals. The CPP was defined as aortic diastolic pressure minus right atrial diastolic pressure measured 2.5 minutes after medication delivery. Descriptive statistics were used to analyze the data. Results: Baseline group characteristics were mathematically the same. Just prior to the first RS, HDE IO resulted in a mean CPP of 33.2 mmHg (95%CI: 26.6, 39.9), while SDE IV resulted in a mean CPP of 25.0 mmHg (95%CI: 20.5, 29.4). Conclusion: This observation study reaffirms the assertion that HDE IO may be required to generate CPP values similar to SDE IV during resuscitation of prolonged VF.

Murine Hemophilia A With Or Without Pre-Existing Anti-Factor VIII Inhibitors Is Partially Corrected By Factor VIII Stored In Platelets After Intraosseous Infusion Of Lentiviral Vectors Into Bone Marrow Without Preconditioning

IntroductionPlatelets may comprise an ideal vehicle for delivering FVIII in hemophilia A (HemA) as FVIII stored in platelet α-granules is protected from neutralization by inhibitory antibodies and, during bleeding, activated platelets locally excrete their contents to promote clot formation. In order to avoid specific challenges posed by ex vivo gene delivery including, in particular, the requirement to pre-condition the subject, we evaluated intraosseous (IO) infusion of self-inactivating lentiviral vectors (LV) for in situ gene transfer into bone marrow cells. In previous studies, we confirmed that hematopoietic stem cells (HSCs) can be efficiently transduced to express GFP after IO administration of LV driven by a MND promoter (M-GFP-LV). MethodsIn the current study, we aimed at limiting transgene expression to the megakaryocyte lineages using IO delivery of 20 µL LV containing either GFP (G-GFP-LV) or a B-domain variant human FVIII (G-F8-LV) gene under the control of megakaryocyte strictly specific promoter glycoprotein 1bα (Gp1bα). ResultsIn M-GFP-LV treated control mice, GFP was detected in 6.4% of HSCs, 3.4% of B220+, and 9.0% of CD11c+ bone marrow cells on day 29. In contrast, in G-GFP-LV (6.0E+08 TU/mL) treated mice, GFP was undetectable in bone marrow HSCs, B220+, CD11c+ or CD11b+ cells. GFP expression level in platelets of G-GFP-LV treated mice was ten folds of that in M-GFP-LV treated mice (0.1% vs 0.01%). It indicated that in platelets, the activity of Gp1bα was stronger than that of MND. More importantly, GFP expression levels were stable over 100 days, suggesting that platelets containing the transgene products did not elicit transgene-specific immune responses. Next, we treated HemA mice with G-F8-LV (6.0 E+07 TU/mL). There was no detectable hFVIII expression in bone marrow HSCs on day 8 or in blood cells (CD3ε+, B220+, CD11c+ or CD11b+) on day 35. However, up to 3% platelets express hFVIII on day 91. These results suggested that HSCs in HemA mice were successfully transduced by G-F8-LV after IO infusion, and in the long term, FVIII was synthesized in megakaryocytes and stored in platelet α-granules. In treated mice, the average percentage of platelets expressing hFVIII was stable at 1-2% from day 27 to day 160. The average FVIII antigen level in platelets on day 112 was 1 mU per 1 × 108 platelets, which was comparable with platelet FVIII in transgenic and ex vivo gene therapy treated mice. We also evaluated LV-treated HemA animals for phenotypic correction of bleeding diathesis by tail clip assay. The blood loss was 41% (n=7), 48% (n=5) and 33% (n=5) compared with control HemA (normalized to 100%), mock treated HemA (∼100%), and wild-type (2.5%) mice on days 35, 118 and 160, respectively. Additionally, there was neither detectable FVIII activity nor anti-FVIII antibodies in blood on day 160, which indicated that there was insignificant leaky expression of FVIII in other cells. Finally, we also infused G-F8-LV into HemA inhibitor mice. Inhibitors were induced by repeated injection of 3U recombinant hFVIII. The average antibody level was 80 Bethesda Unit before IO infusion of the vectors. In G-F8-LV treated mice, the average hFVIII antigen level on day 27 was 0.74 mU per 1 x 108 platelets (n=5). Bleeding assay was performed on day 160. The blood loss of treated mice was significantly reduced compared with untreated HemA mice, indicating that IO infusion of G-F8-LV can overcome anti-FVIII antibodies and correct hemophilia phenotype. ConclusionWe have successfully transduced HSCs in situ by a single infusion of LVs into bone marrow to correct hemophilia A. Gp1bα promoter in lentiviral vectors can specifically direct the transgene expression in mouse platelets. Following IO infusion of G-F8-LV, FVIII stored in platelets can persistently and partially correct the HemA phenotype for at least five months (experimental duration) in mice with and without pre-existing inhibitors. Overall, direct transduction of bone marrow cells targeting platelet-specific FVIII expression may provide an effective therapy to treat severe hemophilia A patients with high-titer inhibitors. Disclosures:No relevant conflicts of interest to declare.

Intraosseous Administration of Thrombolytics for Pulmonary Embolism

BackgroundMassive pulmonary embolism is associated with cardiac dysfunction and ischemia, hemodynamic collapse, and significant potential for death. The American College of Chest Physicians and American College of Emergency Physicians each supports thrombolytic administration to hemodynamically unstable patients with acute pulmonary embolism. ObjectivesIn the resuscitation of patients with massive pulmonary embolism and obstructive shock, difficulty with vascular access can hinder care. Alternative options may facilitate delivery of thrombolytics and enhance patient management. Case ReportThe case presented is a 36-year-old woman with massive pulmonary embolism associated with hemodynamic instability. She was treated with thrombolytics through a tibial intraosseous line. ConclusionsTo the best of our knowledge, this is the first identified case of a patient not in cardiac arrest in whom thrombolytics were administered via an intraosseous line. Similarly, we believe this is also the first reported case of thrombolytics delivered via an intraosseous line for massive pulmonary embolism in the United States.

Intraoperative Anaphylaxis Secondary to Intraosseous Gelatin Administration

FloSeal and SurgiFlo Hemostatic Matrices are commonly used in surgical procedures to promote coagulation and minimize blood loss. They are composed of bovine and porcine gelatin matrix, respectively, that can be injected into pedicles to stop osseous bleeding during pedicle screw insertion. This report details 2 pediatric spinal deformity reconstructive surgery patients who experienced intraoperative cardiovascular events after the intraosseous administration of animal-derived gelatin. Case #1 is an 11-year-old female with adolescent idiopathic scoliosis who was undergoing routine posterior spinal instrumentation and fusion. During placement of the fourth pedicle screw, the patient developed profound hypotension, tachycardia, and elevated airway pressures requiring intravenous epinephrine and phenylephrine for hemodynamic support. Surgery was aborted. Postoperative work-up demonstrated a positive ImmunoCAP study for bovine gelatin. Surgery was repeated 1 week later, without the use of FloSeal, and no episodes of hemodynamic instability. Case #2 was a 9-year-old female with juvenile idiopathic scoliosis who was undergoing a growing spine construct. As in Case #1, SurgiFlo was placed into 2 pedicle tracts after which there was profound hypotension, tachycardia, and elevated airway pressures. Resuscitative efforts included intravenous atropine and epinephrine with resolution. Surgery was aborted. Surgery was repeated 2 weeks later, without the use of SurgiFlo, with no episodes of hemodynamic instability. Given that the patient's symptoms were classic for anaphylaxis, and that the timing of the anaphylaxis immediately followed the administration of FloSeal and SurgiFlo we believe that FloSeal and SurgiFlo were the causes of the reactions. These are the first known reported cases of intraoperative anaphylaxis associated with FloSeal and SurgiFlo. On the basis of our experience, in order to avoid intraoperative cardiovascular events, we obtain preoperative ImmunoCAP testing and eliciting a thorough preoperative history about bovine-derived and porcine-derived gelatin products.

253 Intraosseous Administration of CT Contrast in a Porcine Model: A Feasibility Study

Study Objectives: Obtaining rapid intravenous (IV) access is often difficult in patients who have sustained injuries due to major trauma. Intraosseous (IO) access is a safe and reliable alternative when peripheral IV access cannot be obtained quickly. For many trauma patients, contrast-enhanced computed tomography imaging is an important element of the initial diagnostic evaluation performed in the emergency department (ED). However, minimal information has been published regarding the injection of contrast material using IO access for the purpose of obtaining a contrast-enhanced computed tomography scan. This study was performed to evaluate IO administration of contrast material for a trauma-protocol computed tomography scan in an adult mini-swine model. Methods: Skeletally mature mini-swine were anesthetized and had peripheral IV and IO access established. IO access was obtained in the proximal humerus with fluoroscopic confirmation of correct needle placement. Each animal underwent contrast-enhanced trauma-protocol computed tomography scans using both routes of contrast administration. Contrast was administered using a MedRad® computerized power-injection system. computed tomography confirmation of contrast arterial phase wash-out between studies was established prior to administration of the second contrast injection. The order for route of administration (IV or IO) was randomized for each animal using block randomization. Images were evaluated for adequacy of vascular opacification by 2 board-certified radiologists. Results: All images obtained with both IV and IO contrast administration were judged to be adequately opacified to meet diagnostic criteria. One animal had partial extravasation of contrast after IO administration despite proper needle placement. Conclusion: In this swine model, injection of contrast material through a proximal humerus IO site resulted in adequate opacification of trauma-protocol computed tomography images in all animals. Our results suggest that intraosseous administration of contrast material may be a viable alternative in trauma patients when attempts at obtaining other vascular access are unsuccessful or would lead to unacceptable delays in diagnostic evaluation. Further study is warranted in human subjects to investigate the effectiveness of this methodology as well as the incidence and significance of contrast extravasation.

Comparison of time to loss of consciousness and maintenance of anesthesia following intraosseous and intravenous administration of propofol in rabbits

To compare time to loss of consciousness (LOC) and effective maintenance of anesthesia following intraosseous (IO) and IV administration of propofol in rabbits. Evaluation study. 24 New Zealand White rabbits. Rabbits were selected to receive IO (n = 6) or IV (6) bolus administration of 1% propofol (12.5 mg/kg [5.67 mg/lb]) only or an identical bolus of propofol IO (6) or IV (6) followed by a constant rate infusion (CRI; 1 mg/kg/min [0.45 mg/lb/min]) by the same route for 30 minutes. Physiologic variables were monitored at predetermined time points; time to LOC and durations of anesthesia and recovery were recorded. Following IO and IV bolus administration, mean time to LOC was 11.50 and 7.83 seconds, respectively; changes in heart rate, respiratory rate, oxygen saturation (as measured by pulse oximetry), and mean arterial blood pressure values were evident, but findings did not differ between groups. For the IO- and IV-CRI groups, propofol-associated changes in heart rate, oxygen saturation, and mean arterial blood pressure values were similar, and although mean arterial blood pressure decreased significantly from baseline, values remained > 60 mm Hg; respiratory rate decreased significantly during CRI in both groups, but remained higher in the IO-CRI group. Anesthesia and recovery time did not differ between the IO- and IV-CRI groups. In all evaluated aspects of anesthesia, IO administration of propofol was as effective as IV administration in rabbits. Results suggested that total IO anesthesia can be performed in rabbits with limited vascular access.

Rapid and Complete Bioavailability of Antidotes for Organophosphorus Nerve Agent and Cyanide Poisoning in Minipigs After Intraosseous Administration

Management of chemical weapon casualties includes the timely administration of antidotes without contamination of rescuers. Personal protective equipment makes intravenous access difficult but does not prevent intraosseous drug administration. We therefore measured the systemic bioavailability of antidotes for organophosphorus nerve agent and cyanide poisoning when administered by the intraosseous, intravenous, and intramuscular routes in a small study of Göttingen minipigs. Animals were randomly allocated to sequentially receive atropine (0.12 mg/kg by rapid injection), pralidoxime (25 mg/kg by injection during 2 minutes), and hydroxocobalamin (75 mg/kg during 10 minutes) by the intravenous or intraosseous route, or atropine and pralidoxime by the intramuscular route. Plasma concentrations were measured for 6 hours to characterize the antidote concentration-time profiles for each route. Maximum plasma concentrations of atropine and pralidoxime occurred within 2 minutes when administered by the intraosseous route compared with 8 minutes by the intramuscular route. Maximum plasma hydroxocobalamin concentration occurred at the end of the infusion when administered by the intraosseous route. The mean area under the concentration-time curve by the intraosseous route was similar to the intravenous route for all 3 drugs and similar to the intramuscular route for atropine and pralidoxime. This study showed rapid and substantial antidote bioavailability after intraosseous administration that appeared similar to that of the intravenous route. The intraosseous route of antidote administration should be considered when intravenous access is difficult.

Pharmacokinetics of intraosseous and central venous drug delivery during cardiopulmonary resuscitation

We compared the pharmacokinetics of intraosseous (IO) drug delivery via tibia or sternum, with central venous (CV) drug delivery during cardiopulmonary resuscitation (CPR). MethodsCPR of anesthetized KCl arrest swine was initiated 8min post arrest. Evans blue and indocyanine green, each were simultaneously injected as a bolus with adrenaline through IO sternal and tibial needles, respectively, n=7. In second group (n=6) simultaneous IO sternal and IV central venous (CV) injections were made. ResultsPeak arterial blood concentrations were achieved faster for sternal IO vs. tibial IO administration (53±11s vs. 107±27s, p=0.03). Tibial IO dose delivered was 65% of sternal administration (p=0.003). Time to peak blood concentration was similar for sternal IO and CV administration (97±17s vs. 70±12s, respectively; p=0.17) with total dose delivered of sternal being 86% of the dose delivered via CV (p=0.22). ConclusionsIO drug administrations via either the sternum or tibia were effective during CPR in anesthetized swine. However, IO drug administration via the sternum was significantly faster and delivered a larger dose.

Surgical Enucleation of the Right Eye Following Traumatic Injury in an Eastern Screech–owl (Megascops asio)

Surgical enucleation using a transaural approach was successfully performed following traumatic globe injury in an Eastern screech–owl (Megascops asio). Initial stabilization of this patient consisted of intraosseous administration of crystalloids and hypertonic saline, anti–inflammatory drugs, and broad–spectrum antibiotics. At surgery, general anesthesia was achieved using butorphanol as a premedicant and isofluorane in oxygen as an induction and maintenance anesthetic agent. Postoperative care included meloxicam for 7 days, trimethoprim/sulfadiazine for 14 days, and topical wound management. The surgical site healed in an uncomplicated manner. The bird was successfully flight tested and eventually released back into its natural habitat. Considerations for release and permanent captive placement in raptors with unilateral vision impediments are discussed.

Recommendations for the Use of Intraosseous Vascular Access for Emergent and Nonemergent Situations in Various Healthcare Settings: A Consensus Paper

In recognition of the value of intraosseous (IO) vascular access in patient resuscitation and stabilization, leading national and international organizations have published position papers that have served to change the standard of care for emergency vascular access. Among them are the American Heart Association (AHA), addressing vascular access in cardiac arrest patients, 1 American Heart Association American Heart Association guidelines for cardiopulmonary resuscitation and emergency cardiovascular care: management of cardiac arrest. Circulation. 2005; : IV-58–IV-66 Google Scholar the International Committee on Resuscitation (ILCOR), 2 International Liaison Committee on Resuscitation (ILCOR) International consensus of cardiopulmonary resuscitation and emergency cardiovascular care science with treatment recommendations: advanced life support. Resuscitation. 2005; 67: 213-247 PubMed Google Scholar the European Resuscitation Council, 3 European Resuscitation Council European resuscitation guidelines. Resuscitation. 2005; 6751 (Accessed July 3, 2010): 51-52http://www.erc.edu/index.php Google Scholar the Infusion Nurses Society (INS), 4 Infusion Nurses Society [position paper] The role of the registered nurse in the insertion of intraosseous access devices. J Infus Nurs. 2009; 32: 187-188 Crossref PubMed Scopus (11) Google Scholar the National Association of EMS Physicians (NAEMSP), 5 Fowler R Gallagher JD Isaacs MS et al. [resource document to the NAEMSP position statement]. The role of intraosseous vascular access in the out-of-hospital environment. Prehosp Emerg Care. 2007; 11: 63-66 Crossref PubMed Scopus (92) Google Scholar with the Emergency Nurses Association (ENA) and the American Association of Critical-Care Nurses (AACN) endorsing the INS position paper. 6 Emergency Nurses Association ENA-supported statements. http://www.ena.org Google Scholar , 7 American Association of Critical-Care Nurses American Association of Critical-Care Nurses endorses nurses’ expanded role in use of IO access devices. http://www.aacn.org/WD/PressRoom Google Scholar These professional societies recognized that IO access may provide significant time savings that could benefit patients in emergent situations by decreasing the time required to achieve access and the time required to administer necessary fluids and medications. The AHA concluded that intravenous (IV) and IO administration have equal, predictable drug delivery and pharmacologic effects. Both AHA and European Resuscitation Council guidelines state that IO access should be the first alternative to failed IV access. 1 American Heart Association American Heart Association guidelines for cardiopulmonary resuscitation and emergency cardiovascular care: management of cardiac arrest. Circulation. 2005; : IV-58–IV-66 Google Scholar , 2 International Liaison Committee on Resuscitation (ILCOR) International consensus of cardiopulmonary resuscitation and emergency cardiovascular care science with treatment recommendations: advanced life support. Resuscitation. 2005; 67: 213-247 PubMed Google Scholar Lynn Phillips, Infusion Nurses Society and Consortium Chair. Lucinda Brown, Society of Pediatric Nurses. Teri Campbell, Air and Transport Nurses Association. Julie Miller, American Association of Critical-Care Nurses. Jean Proehl, Emergency Nurses Association. Barbara Youngberg, Visiting Professor of Health Law and Policy, Beazley Institute for Health Law and Policy, Loyola University Chicago College of Law.

Hemodynamics after intraosseous administration of hydroxocobalamin or normal saline in a goat model

Study Objective Hydroxocobalamin may be lifesaving in cyanide (CN) poisoning, but personal protective equipment (PPE) wear, rescue, and decontamination may delay intravenous administration. Intraosseous (IO) lines may be rapidly placed even when wearing PPE. We assessed the hemodynamics of hydroxocobalamin (OHCo) and normal saline (NS) by the IO route. Methods Twelve anesthetized Spanish goats underwent arterial line catheterization. Operators in PPE placed IO lines. After placement confirmation by fluoroscopy, animals randomly received hydroxocobalamin 75 mg/kg (3 mL/kg) (n = 6) or normal saline (NS) 3 mL/kg (n = 6) IO over approximately 7.5 minutes. Blood pressures and heart rates were monitored for 240 minutes after infusion initiation. Results In the OHCo group, mean systolic and diastolic pressures peaked at 120 minutes, with mean increases of 14% and 17%, respectively, relative to infusion start, returning to near preinfusion values at 240 minutes. Heart rate changes were virtually nil. In the NS group, mean systolic pressures peaked at 60 minutes, with a mean increase of 36%, whereas diastolic pressures peaked at about 110 minutes, increasing 42%, returning to near preinfusion values at 240 minutes. Heart rate changes were minimal. Conclusion Hemodynamic effects of OHCo given by the IO route in non–CN-poisoned goats are mild and well tolerated. Increases in mean blood pressure at peak after baseline were greater in the NS group, but the mean values over time were not significantly different from those observed in the OHCo group. Hemodynamic effects would likely differ somewhat in a CN-poisoned goat. Intraosseous OHCo administration warrants additional investigation.

Intraosseous administration of hydroxocobalamin in the acute treatment of cyanide poisoning

Intraosseous administration of hydroxocobalamin in the acute treatment of cyanide poisoning

Intraossäre Fehlpunktion

In cases of emergency it can sometimes be difficult or even impossible to achieve peripheral venous access. However, intraosseous (IO) devices enable vascular access even under adverse conditions due to the abundant, non-collapsible intramedullary vessels which are able to rapidly transport drugs and infusions to the central circulation. Therefore, the current European Resuscitation Council (ERC) guidelines favour IO access even in adults if rapid peripheral venous catheterization is not possible.Appropriate training in homologous IO devices is imperative for successfully achieving vascular access. Lacking or insufficient training may lead to complications. The present article describes a case of incorrect IO device application on a severely injured patient in the resuscitation room. Flawed patient positioning and incorrect handling of the IO device led to displacement of the device. Therefore, the intraosseous administration of drugs or infusions was not possible.

172: Hemodynamics Following Intraosseous Administration of Hydroxocobalamin in the Goat

172: Hemodynamics Following Intraosseous Administration of Hydroxocobalamin in the Goat

The intraosseous and intravenous administration of morphine is bioequivalent,

The intraosseous and intravenous administration of morphine is bioequivalent,

Intraosseous Drug Administration in Children and Adults During Cardiopulmonary Resuscitation

To review and assess the available literature on the use of intraosseous (IO) drug administration during cardiopulmonary resuscitation, addressing the benefits and risks of using this method of drug delivery in children and adults. The MEDLINE (1950-July 2007) database was searched for pertinent abstracts, using the key term intraosseous infusions. Additional references were obtained from the bibliographies of the articles reviewed. Manufacturer Web sites were used to obtain information about IO insertion devices. All available English-language clinical trials, retrospective studies, and review articles describing IO drug administration were reviewed. Studies conducted in animal models to evaluate the effectiveness and safety of IO drug administration were also included. IO access uses the highly vascularized bone marrow to deliver fluids and medications during cardiopulmonary resuscitation. This route, developed in the 1940s, has been revived in the past decade as a means of achieving rapid vascular access when intravenous access cannot be obtained. The primary advantage of IO access is the high success rate (approximately 80%). Most trained providers can place an IO line within 1-2 minutes. A number of small-scale studies and retrospective reviews have established the usefulness of this route for the delivery of many commonly used resuscitation drugs. In addition, animal models have demonstrated rapid drug delivery to the systemic circulation. While all resuscitation drugs can be given by the IO route, administration of ceftriaxone, chloramphenicol, phenytoin, tobramycin, and vancomycin may result in lower peak serum concentrations. The most common adverse effect seen with IO use, extravasation, has been reported in 12% of patients. Compartment syndrome, osteomyelitis, and tibial fracture are rare, but have also been reported. IO administration is a safe and effective method for delivering drugs during cardiopulmonary resuscitation. It should be considered whenever intravenous access cannot be rapidly obtained.

Retention, Distribution, and Effects of Intraosseously Administered Ibandronate in the Infarcted Femoral Head

The local distribution, retention, and effects of intraosseous administration of ibandronate in the infarcted femoral heads were studied. Intraosseous administration effectively delivered and distributed ibandronate in the infarcted femoral heads and decreased the femoral head deformity in a large animal model of Legg-Calve-Perthes disease. Bisphosphonate therapy has gained significant attention for the treatment of ischemic osteonecrosis of the femoral head (IOFH) because of its ability to inhibit osteoclastic bone resorption, which has been shown to contribute to the pathogenesis of femoral head deformity. Because IOFH is a localized condition, there is a need to explore the therapeutic potential of local, intraosseous administration of bisphosphonate to prevent the femoral head deformity. The purpose of this study was to investigate the distribution, retention, and effects of intraosseous administration of ibandronate in the infarcted head. IOFH was surgically induced in the right femoral head of 27 piglets. One week later, a second operation was performed to inject (14)C-labeled or unlabeled ibandronate directly into the infarcted head. (14)C-ibandronate injected heads were assessed after 48 h, 3 weeks, or 7 weeks later to determine the distribution and retention of the drug using autoradiography and liquid scintillation analysis. Femoral heads injected with unlabeled ibandronate were assessed at 7 weeks to determine the degree of deformity using radiography and histomorphometry. Autoradiography showed that (14)C-Ibandronate was widely distributed in three of the four heads examined at 48 h after the injection. Liquid scintillation analysis showed that most of the drug was retained in the injected head, and almost negligible amount of radioactivity was present in the bone and organs elsewhere at 48 h. At 3 and 7 weeks, 50% and 30% of the (14)C-drug were found to be retained in the infarcted heads, respectively. Radiographic and histomorphometric assessments showed significantly better preservation of the infarcted heads treated with intraosseous administration of ibandronate compared with saline (p < 0.001). This study provides for the first time the evidence that local intraosseous administration is an effective route to deliver and distribute ibandronate in the infarcted femoral head to preserve the femoral head structure after ischemic osteonecrosis. In a localized ischemic condition such as IOFH, local administration of bisphosphonate may be preferable to oral or systemic administration because it minimizes the distribution of the drug to the rest of the skeleton and bypasses the need for having a restored blood flow to the infarcted head for the delivery of the drug.

The use of skin allograft with donor-specific tolerance in a rabbit model of full-thickness burn

Previous studies in our laboratory demonstrated that portal vein or intraosseous administration of donor bone marrow cells for modulation of the central immune system is likely to be beneficial for allograft tolerance induction in rabbits. We recently reported that the severity of host conditioning for donor-specific tolerance induction was reduced without loss of efficacy by using a single intraosseous injection of donor bone marrow cells without immunosuppressive agent administration or T cell depletion. We now further investigated the feasibility and effectiveness of skin allografting using donor-specific tolerance to treat full-thickness burns. Materials and methods Dutch rabbits were used as recipients, and Japanese white rabbits were used as donors. Three experimental groups of burned rabbits were studied. Group I, allograft control; group II, allograft plus total-body irradiation; group III, allograft plus total-body irradiation and bone marrow infusion. Allograft survival times were determined by macroscopic and histopathologic examinations. Results Mean (S.D.) skin allograft survival was as follows: group I, 13.2 (4.1) days; group II, 15.2 (3.7) days; group III, 108.4 (14.3) days. Conclusion We have shown the potential to perform long-term skin allografts by the induction of donor-specific tolerance in a rabbit model of burn.