Comparison of intraosseous, central, and peripheral routes of sodium bicarbonate administration during CPR in pigs

ORIGINAL CONTRIBUTION CPR, sodium bicarbonate, routes of administration, comparison sodium bicarbonate, administration, comparison of routes

Comparison of Intraosseous, Central, and Peripheral Routes of Sodium Bicarbonate Administration During CPR in Pigs Obtaining venous access continues to be one of the m o s t difficult problems faced by a physician caring for the pediatric patient in cardiac arrest. Our study examined the use of the intraosseous route (through the bone) to obtain venous access for sodium bicarbonate administration in a cardiac arrest model. Ventricular fibrillation was induced in 23 domestic swine. Cardiopulmonary resuscitation was performed for five m i n u t e s and sodium bicarbonate (1 mEq/kg) was administered through a peripheral IV line (n = 6), a central IV line (n = 5), or intraosseously (n = 6). Controls (n = 6) did not receive bicarbonate. Blood p H was sampled every two minutes for 30 minutes from the right ventricle, left ventricle, and femoral artery. A n analysis of variance revealed that the central and intraosseous routes were significantly different (P < .05) from the peripheral group, and that all three groups were significantly different (P < .05) from the control. Pathology studies revealed only minor damage to bone when sodium bicarbonate was administered intraosseously. These data demonstrate that the intraosseous route is a rapid and effective alternative for venous access in a cardiac arrest model. [Spivey WH, Lathers CM, Malone DR, Unger liD, Bhat S, McNamara RN, Schoffstall J, 7hrner N: Comparison of intraosseous, central, and peripheral routes of sodium bicarbonate administration during CPR in pigs. A n n Emerg Med December 1985;14:1135-1140.]

William H Spivey, MD* Claire M Lathers, PhDt Daniel R Malone, MD* Henry D Unger, MD* Sheela Bhat, MD* Robert N McNamara, MD* John Schoffstall, MD* Nihal Tumer, PhDt Philadelphia, Pennsylvania

INTRODUCTION Despite improvements in technique and equipment for obtaining venous access during a cardiac arrest, it is not always possible to secure a peripheral or central IV line as expeditiously as desired. This is especially true of pediatric patients in w h o m the increase in body fat, the anatomical variation from adults, the small vasculature, and the pofential for a septic hip joint secondary to a femoral stick compound the difficult task of establishing venous access in cardiac arrest. In 1940 Tocantins 1 described a simple and reliable method of obtaining venous access. By inserting a needle into the medullary cavity of long bones and infusing fluid or drugs into the bone, access to the circulatory system was obtained rapidly. This method has been examined by numerous investigators 2-9 and has been found to be safe and efficient for the infusion of saline, DsW, plasma, blood, dopamine, and other drugs in patients with a normally functioning cardiovascular system. Recent studies have advocated the intraosseous route in infant and pediatric cardiac arrest as a viable alternative when venous access is not readily available.lO, ll N o studies to date, however, have examined blood flow or drug absorption by this route in a cardiac arrest model. One purpose of our study was to examine the absorption of sodium bicarbonate from the medullary cavity of bone in a cardiac arrest model and compare it with absorption of bicarbonate administered through the central or peripheral IV routes. A second purpose was to examine changes in the pH of blood in the right and left ventricles of the heart as bicarbonate was administered by the intraosseous, central, or peripheral routes.

Address for reprints: William H Spivey, MD, The Department of Emergency Medicine, Medical College of Pennsylvania, 3300 Henry Avenue, Philadelphia, Pennsylvania 19129.

From the Departments of Emergency Medicine* and Pharmacologyt, The Medical College of Pennsylvania, Philadelphia, Pennsylvania. Received for publication June 3, 1985. Accepted for publication July 25, 1985. Presented at the University Association for Emergency Medicine Annual Meeting in Kansas City, Missouri, May 1985.

MATERIALS A N D METHODS Twenty-three domestic swine of either sex weighing 15.6 kg to 26.0 kg were anesthetized with ketamine 25 mg/kg intramuscularly and alpha chlo14:12 December 1985

Annals of Emergency Medicine

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SODIUM BICARBONATE ADMINISTRATION Spivey et al

ralose 20 mg/kg IV. Gallamine 2 mg/ kg IV was used to prevent muscle fasciculations. T h e swine u n d e r w e n t a tracheostomy and were ventilated mechanically w i t h a Harvard respirator on 28% 0 2. A lead II ECG was recorded t h r o u g h o u t t h e e x p e r i m e n t . T h e left f e m o r a l a r t e r y was cannulated distally w i t h a 10-cm catheter for t h e r e c o r d i n g of m e a n a r t e r i a l blood p r e s s u r e and s a m p l i n g of arterial blood gases. A Swan-Ganz catheter was introduced through the left femoral vein into the right ventrid e . This was done under continuous monitoring of pressure wave forms as r e c o r d e d on a p o l y g r a p h . A p i g t a i l catheter was introduced similarly into the left ventricle through the distal left carotid artery. The positions of the pigtail and Swan-Ganz catheters were c o n f i r m e d by t h o r a c o t o m y and card i o m y o t o m y at the end of each experiment. All catheters were found to be in t h e c o r r e c t p o s i t i o n . A l l t h r e e c a t h e t e r s were a t t a c h e d to p r e s s u r e t r a n s d u c e r s for r e c o r d i n g of b l o o d p r e s s u r e on a polygraph. T h e y also were used to draw blood samples simultaneously for blood gas measurements. Prior to the induction of ventricular fibrillation (VF), animals were assigned to one of four groups: control, central, peripheral, or intraosseous. The control group (n=6) received no further cannulization. The central group (n=5) had a 12-cm 18-gauge catheter inserted through the left internal jugular v e i n i n t o t h e s u p e r i o r vena cava for administration of bicarbonate at a later time. The catheter position was confirmed to be correct in all five a n i m a l s at autopsy. A 20-gauge angiocath was inserted into a dorsal vein of the distal right forelimb in the peripheral group (n=6), and an 18-gauge spinal needle was introduced into the medullary cavity of the proximal right tibia in the intraosseous group (n = 6). The technique used to insert a needle into the bone was identical to that used in our ED. After skin preparation an 18-gauge spinal needle with stylet was inserted into the broad, flat, anteromedial surface of the tibia 1 crn below the tibial tuberosity. It was ins e r t e d e i t h e r p e r p e n d i c u l a r to t h e bone or in a slightly caudal direction. This was done to prevent injection of fluid or drugs i n t o t h e e p i p h y s e a l plate. Once resistance of cortex was overcome, the n e e d l e was a d v a n c e d easily into the marrow. The stylet was 20/1136

removed and the position of the needle was confirmed by free aspiration of blood and such m a r r o w contents as fat and bone spicules. A Grass S-88 stimulator (Grass Instrument Company, Quincy, Massachusetts) was used to induce VF by stimulating the right ventricle w i t h a pacing w i r e i n t r o d u c e d t h r o u g h the left jugular vein. Initial stimulator settings were 100 V, 200 impulses/s, 1-ms delay, and 10-ms duration. These parameters were increased until VF was induced. Two animals proved to be refractory to this m e t h o d ; VF was induced in these animals w i t h a 60-Hz transthoracic s t i m u l u s w i t h o u t difficulty. After the i n d u c t i o n of anesthesia, blood samples were t a k e n from the left femoral artery and arterial pH was measured on a 213 pH/blood gas anal y z e r ( I n s t r u m e n t a t i o n Laboratories, Edison, N e w Jerseyl. T h e r e s p i r a t o r was adjusted to m a i n t a i n a control pH of 7.40. To obtain control pH values just prior to the induction of VI:, 0.6mL aliquots of blood were drawn sim u l t a n e o u s l y i n t o h e p a r i n i z e d syringes f r o m t h e right v e n t r i c l e , left ventricle, and left femoral artery of each animal. Blood pH was measured in this m a n n e r f r o m all t h r e e sites every two m i n u t e s for the duration of the e x p e r i m e n t {30 minutes}. A t the onset of VF the animals were disconnected from the respirator and no respiratory or circulatory a u g m e n t a t i o n was performed until five m i n u t e s post arrest, w h e n resuscitation w i t h a mechanical resuscitator was begun. The s t e r n u m was compressed two inches with 60 to 70 lb of force and the animals were ventilated every fifth compression w i t h 18 cm H 2 0 of oxygen. Ten m i n u t e s post arrest, sodium bicarbonate 1 mEq/kg [1 mEq/1 mL I was adm i n i s t e r e d t h r o u g h t h e central, peripheral, or intraosseous routes. The c o n t r o l a n i m a l s did n o t r e c e i v e sod i u m bicarbonate. The sodium bicarbonate was followed by a 20-mL saline flush in the peripheral, intraosseous, and central groups. There was no further pharmacologic intervention until the end of the experiment. Tibias from three of the animals receiving intraosseous s o d i u m bicarbonate were removed at the conclusion of t h e e x p e r i m e n t w i t h t h e i n t r a osseous needle in place and were preserved in 10% buffered formalin. They then were decalcified, sectioned transversely, and stained with h e m a t o x y l i n Annals of Emergency Medicine

eosin stain for microscopic examination. Each sample was examined by a pathologist for evidence of damage to the cells or supporting structures. In order to analyze the data using an analysis of variance, the m e a n p H for each t i m e (every two m i n u t e s for 30 minutes} was paired w i t h its adjacent mean. Thus eight pairs rather than 16 individual means were analyzed, makhag the data m o r e manageable. Data for all our groups were analyzed using a two-way analysis of variance w i t h repeated measures on time. A simple effect a n a l y s i s of v a r i a n c e was performed across groups. W h e n significance was found, a N e u m a n Keuls post hoc test was applied. All data reported significant had P value < .05. RESULTS Baseline heart rate and blood pressure (mean --- SE) values for the four groups were as follows: control, 202 + 42 beats/min and 117 + 41 m m Hg; peripheral, 187 _+ 32 b e a t s / m i n and 130 - 24 m m Hg; intraosseous, 165 + 47 b e a t s / m i n and 125 + 27 m m Hg; and central, 163 + 16 beats/min and 120 _+ 24 m m Hg. There was no difference in both parameters (P < .05) among the groups. The pH (mean -+ SE) of blood from the femoral artery i m m e d i a t e l y prior to cardiac arrest was as follows: control, 7.41 _+ 0.02; peripheral, 7.42 _+ 0.02; intraosseous, 7.40 -+ 0.01; and central, 7.42 + 0.01. There was no difference among the groups. After card i a c a r r e s t all f o u r g r o u p s d e m o n strated a respiratory acidosis that was reversed w h e n thoracic compressions and ventilations were initiated at five m i n u t e s w i t h t h e m e c h a n i c a l resuscitator (Figure 1). One m i n u t e after resuscitation began the pH was norm a l i z e d to a p p r o x i m a t e l y 7.4 in all groups. A respiratory alkalosis was evident during the next four minutes. The p H peaked at 7.48 + 0.03 in the control group at ten m i n u t e s post arrest, and gradually declined to 7.07 + 0.07 after 30 m i n u t e s of cardiac arrest (25 m i n u t e s of mechanical resuscitation). Within two m i n u t e s of the administration of s o d i u m bicarbonate, the peripheral, intraosseous, and central routes showed increases in p H above control levels (P < .05). The increase was the greatest in the central group, 7.77 -+ 0.09. The intraosseous and peripheral groups d e m o n s t r a t e d p H of 7.66 -+ 0.03 and 7.65 -+ 0.06, respec14:12 December 1985

Fig. l. The effect of sodium bicarbonate on the pH (mean +_ SE) of blood from the femoral artery. Data from the four experimental groups, control (n = 6), peripheral (n = 6), intraosseous (n = 6), and central (n = 5), are graphed as a function of time. The arrows on the abscissa indicate the time of VF, initiation of mechanical resuscitation, and administration of sodium bicarbonate (1 mEq/kg), respectively, from left to right.

8.0 7.9 f

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Ventricular Mechanical NaHCO 3 Fibrillation Resuscitator tively. T h e pH in the intraosseous group, however, continued to increase, and peaked at 7.71 + 0.06 at 18 minutes post arrest (eight minutes post sodium bicarbonate administration); the peripheral group demonstrated a gradual decline during the next 20 minutes. An analysis of variance did not reveal a significant difference between the intraosseous and central groups; however, they were significantly different than the peripheral and control groups. The peripheral group was significantly different than the control group. There was no significant difference in the pH of the peripheral, 14:12 December 1985

2 intraosseous, and central routes two minutes after the infusion of sodium bicarbonate. They were significantly different than the control. Four minutes p o s t s o d i u m b i c a r b o n a t e administration, however, a significant difference was evident w h e n the peripheral group was compared to the intraosseous and central groups. This difference was present throughout the remainder of the experiment. Baseline pH of blood from the left ventricle obtained in the four experimental groups was as follows: control, 7.39 + 0.01; peripheral, 7.41 _+ 0.01; intraosseous, 7.39 + 0.01; and central, 7.41 - 0.01. A pattern of acidosis folAnnals of Emergency Medicine

lowed by alkalosis similar to that of the femoral artery blood was evident in all experimental groups (Figure 2). After sodium bicarbonate administration the peripheral group pH peaked at 7.60 + 0.06 two minutes post sodium bicarbonate administration and gradually decreased. The pH in the intraosseous group, 7.69 + 0.04, did not peak until four minutes after sodium bicarbonate administration; the pH in the central group peaked after two minutes at 7.72 + 0.06. A n analysis of variance revealed that the three groups receiving sodium bicarbonate were significantly different from control, and the central and intraosseous groups differed significantly from the peripheral group. There was no significant difference in the pH of the peripheral, intraosseous, and central routes two minutes after the administration of sodium bicarbonate. They were significantly different from the control. Four minutes post sodium bicarbonate administration, however, a significant difference was evident w h e n the peripheral group was compared to the intraosseous and central groups. This difference was present throughout the remainder of the experiment. Baseline pH of blood obtained from the right ventricle for each group was as follows: control, 7.39 - 0.03; peripheral, 7.40 + 0.01; intraosseous, 7.36 -+ 0.01; and central, 7.38 -+ 0.02. The pH of all four groups was similar for the first ten minutes (P > .05) (Figure 3). After the administration of sodium bicarbonate the pH of all three groups peaked within two minutes at the following levels: peripheral, 7.33 1137/21

SODIUM BICARBONATE ADMINISTRATION Spivey et al

Fig. 3. The effect of sodium bicarbonate on the p H (mean +_ SE) of blood from the right ventricle. The routes of a d m i n i s t r a t i o n , arrows, a n d the n u m b e r of animals are the s a m e as in Figure 1. + 0.03; i n t r a o s s e o u s , 7.33 + 0.03; and central, 7.35 _+ 0.03. A n analysis of variance revealed a significant difference between the control and the three groups receiving sodium bicarbonate. There was not, however, a significant difference among the three routes of administration. The pathologist's gross examination of the three tibias after intraosseous b i c a r b o n a t e a d m i n i s t r a t i o n revealed loss of cells only at the site of injection. A cavity measuring approximately V2 x V2 cm was present at the tip of the needle. Microscopic exami n a t i o n c o n f i r m e d d i s p l a c e m e n t of cells in the center of the marrow and demonstrated some disruption of the n o r m a l c e l l u l a r p a t t e r n in t h e cells i m m e d i a t e l y a d j a c e n t to the cavity. There also was an increase in inflammatory cells in this area; however, the majority of bone marrow and cells surr o u n d i n g t h e site of i n j e c t i o n were normal.

DISCUSSION In recent years several authors have .advocated the intraosseous route as an alternative to venous cannnlation during cardiac arrest.to, u It was not clear, however," whether sodium bicarbonate administered by the intraosseous route would enter the central circulation effectively and raise the blood pH because of a low flow state during card i o p u h n o n a r y resuscitation, a preferential m o v e m e n t of blood flow to the head and upper extremities,12,13 and the flow d y n a m i c s for bone, w h i c h have never been investigated during resuscitation, it also was not clear ff there is a difference in the ability of s o d i u m b i c a r b o n a t e to e l e v a t e t h e blood pH when administered by different routes, or if different routes adversely affect the p H in t h e heart. This is of particular concern with the central route, in w h i c h case a large bolus of sodium bicarbonate is delivered to the right a t r i u m and subsequently to the coronary arteries with little time for dilution. In our study d o m e s t i c swine were s e l e c t e d as a m o d e l b e c a u s e of t h e similarity of their cardiovascular sys22/1138

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I I I I I I I I I I i I I I ~1 0 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 l l l Time (min) Ventricular Mechanical NaHCO 3 Fibrillation Resuscitator

t e m to that of h u m a n beings and because the weight of swine is similar to that of infants or small children. The anesthetic agent alpha chloralose was used because it maintains cardiac reflexes during anesthesia and does not cause venous dilation or a decrease in arterial blood pressure.14 With this anesthetic it was possible to m a i n t a i n a good vascular tone prior to arrest and to m i n i m i z e t h e cardiac d e p r e s s i o n and t h e v e n o u s d i l a t i o n seen w i t h some other anesthetics. In order to facilitate flow from the bone to the central c i r c u l a t i o n , s o d i u m b i c a r b o n a t e was followed i m m e d i a t e l y by a 20-mL flush of saline. This also was done for the peripheral and central routes to maintain a consistent experimental design. The data revealed t h a t in all four groups there was a brief acidosis post arrest that was reversed w i t h hyperventilation by the mechanical resuscitation. At ten m i n u t e s post arrest this rise in pH was reversed as the animals d e v e l o p e d an i n c r e a s i n g m e t a b o l i c acidosis. Bicarbonate administered through a peripheral IV produced an increase in pH, but this did not continue after 12 minutes. Both central and intraosseous administration of bicarbonate produced an increase in pH that remained throughout the experiment. Our data demonstrate that sodium b i c a r b o n a t e r e a c h e s t h e c e n t r a l circ u l a t i o n w i t h i n t w o m i n u t e s regardless of t h e r o u t e of a d m i n i s t r a tion. It does not, however, appear to Annals of Emergency Medicine

reach t h e c e n t r a l c i r c u l a t i o n in t h e same concentration. Centrally administered sodium bicarbonate maintains an elevated pH throughout the experiment, suggesting that a greater concentration is circulating in the central circulation to buffer hydrogen ions. A similar pattern is present for the intraosseous route. The p H takes longer to peak by this route; however, it maintains an elevated pH as does the central route. Sodium bicarbonate, when administered peripherally, elevates the pH w i t h i n two minutes, but does not m a i n t a i n a h i g h pH. T h i s suggests that not as m u c h of the sodium bicarbonate reaches the central circulation. It m a y be that m u c h of the bicarbonate is expended buffering hydrogen ions in the periphery. A n alternative possibility is that the lack of a sustained increase in pH simply m a y reflect a sluggish blood flow in the periphery that does not transport drugs well. The latter concept is supported by the work of Hedges and c o w o r k e r s 15 a n d K u h n and a s s o c i ates, 16 who have demonstrated a decrease in the peak of radioisotopes and indocyanine green w h e n these were a d m i n i s t e r e d by the peripheral route as opposed to the central route. In our study the change in blood pH was monitored after sodium bicarbonate administration at various points in the circulatory system. Changes in the p H in t h e right v e n t r i c l e were m i n o r in all groups. Once the blood passed through the lungs and the carbon dioxide content decreased, how-

14:12 December 1985

ever, dramatic changes in pH were evident. All three routes d e m o n s t r a t e d an increase in the pH of left ventricle blood within two m i n u t e s of administration; however, this increase was not statistically different a m o n g the various routes. This makes it difficult to draw a n y c o n c l u s i o n s r e g a r d i n g possible adverse effects or superiority of one route versus the other during the early m i n u t e s of bicabonate administration. It m a y be that more frequent sampling is necessary to detect significant changes in the p H in response to sodium bicarbonate administration.by different routes. Absorption of drugs administered by the intraosseous route was investigated as early as 1940 by Tocantins. 17 He demonstrated t h a t congo red dye injected into the tibia of rabbits could be aspirated from the heart w i t h i n ten seconds. Later, Papper18 compared circulation t i m e from the s t e r n u m and an antecubital vein in seven patients and f o u n d no s i g n i f i c a n t difference between these routes. Intraosseous epinephrine was compared w i t h the W, intramuscular, and subcutaneous routes by Macht. 8 He demonstrated a similar t i m e to onset and magnitude of change in blood pressure for the intraosseous and IV routes. Intramuscular and subcutaneous a d m i n i s t r a t i o n of epinephrine produced a m i n i m a l response in b l o o d pressure. M o s t recently, Shoor and colleagues 9 demonstrated that the infusion of saline was 600 m L / h r w h e n a d m i n i s t e r e d i n t o the medial malleolus of sheep. To date, all studies of intraosseous fluid or drug administration, including the studies cited above, have examined the route in animals or patients with a normal cardiovascular system, not in arrest or during CPR. Based on the low blood flow during cardiopulm o n a r y r e s u s c i t a t i o n , e s p e c i a l l y in the lower extremities, it was predicted that intraosseous sodium bicarbonate would not be effective during cardiac arrest. The data, however, show this to be a very effective route. This m a y be explained by several possibilities. First, by f o l l o w i n g t h e b o l u s of sod i u m b i c a r b o n a t e w i t h a f l u s h of saline, the bicarbonate m a y have been forced o u t of t h e m e d u l l a r y c a v i t y rapidly i n t o t h e c e n t r a l c i r c u l a t i o n . This w o u l d not require active blood flow through the marrow cavity, but would i n s t e a d be d e p e n d e n t on circulation in the femoral and popliteal vessels. A second explanation is that 14:12 December 1985

blood may, in fact, be circulated actively through the bone during cardiop u l m o n a r y resuscitation. The bone is a noncollapsible structure with a rich n e t w o r k of a r t e r i e s and large veins that pierce the cortex. 19 This w o u l d a l l o w t h e c i r c u l a t i o n of blood w i t h less resistance than that occurring in such other tissues as muscle, fat, and skin. Finally, metabolic demands and changes in the p H of b l o o d in t h e m e d u l l a r y c a v i t y of bone have n o t been investigated in cardiac arrest and cadiopulmonary resuscitation. The medullary blood may not become acidotic as rapidly as blood in the per i p h e r a l tissues, so less b i c a r b o n a t e m a y be used buffering hydrogen ions at t h e s i t e of i n j e c t i o n a n d conseq u e n t l y m o r e m a y reach the central circulation. We hope that future studies in our laboratory will answer these questions. A major concern w i t h any route of drug administration is long-term complications. If intraosseous administration of a drug will compromise significantly the bone or limb later, then it m a y not be an acceptable route. Several authors have addressed this probl e m . H e i n i l d a n d c o l l e a g u e s 2o described h i s t o l o g i c a l e x a m i n a t i o n of the tibia in 11 patients who had died w i t h i n two weeks of intraosseous infusion of blood. The deaths were not related to the infusion. H e i n i l d said, "The o n l y m a c r o s c o p i c f i n d i n g was the site of the insertion of the needle, about as thick as a pin. In every speci m e n the epiphyseal line was found to be perfectly n o r m a l microscopically." He also examined the tibia of 72 children w h o h a d r e c e i v e d i n t r o s s e o u s transfusions with roentgenographs w i t h i n two years of the infusion. O n l y m i n o r calcium deposits at the. site of injection were noted during the first six months. After one year there were no roentgenologic abnormalities. T h e s e d a t a agree w i t h t h o s e of Arbeiter and Greengard 21 and Elston and c o w o r k e r s . 2~ T h e y f o l l o w e d up patients receiving intraosseous infusion of b l o o d or c r y s t a l l o i d w i t h r o e n t genographs and found no bony changes after six months. Because of the hypertonicity of sod i u m bicarbonate and the potential for sclerosing tissues, our study addressed the cellular damage incurred by infusing bicarbonate into bone. In all three tibias examined there was evidence of mechanical displacement of cells that Annals of Emergency Medicine

o c c u r r e d w h e n b i c a r b o n a t e was injected into the bone marrow. However, only m i n i m a l damage was evident in the cells surrounding the site of injection. Cells and supporting b o n y matrix elsewhere appeared normal. We did not address the long-term effect of this m i n o r damage. It m a y be surm i s e d that the damaged cells w o u l d be p h a g o c y t i z e d a n d n e w t i s s u e organized rapidly w i t h o u t adverse effects because the area involved was so small. CONCLUSION Based on our study data and a careful review of the literature, we believe that the intraosseous route is an excellent alternative for venous access in c a r d i a c a r r e s t w h e n c e n t r a l or peripheral venous c a n n u l i z a t i o n is n o t readily available. Although our data suggest that the intraosseous route actually m a y be superior to a peripheral IV in cardiac arrest, we do not recomm e n d it as a first l i n e of access in h u m a n beings until more information is available.

The authors thank Valerie Farris, Larry Pratt, and Todd O'Hara for technical assistance; Ed Gracely for statistical analysis; John Someberg, MD, for advice and technical expertise; and Ursula LaBrusciano for assistance in preparation of this manuscript.

REFERENCES 1. Tocantins LM, O'Neil JF. Infusion of blood and other fluids into the circulation via the bone marrow. Proc Soc Exp Biol Med 1940;45:782-783. 2. Farrow AB, Turkel H, Thompson S: Infusions via the bone marrow and biopsy of the bone and bone marrow. Anesthesiology 1952;13:501-509. 3. Tocantins LM, Oneil JF: Complications of intraosseous therapy. A n n Surg 1945;2:266-277. 4. Rogers 8N, Benumof JL: Intraosseous infusions, in Roberts JR, Hedges JR (eds): Clinical Procedures in Emergency Medicine. Philadelphia, WB Saunders, 1985, pp

339-343. 5. Meola F: Bone marrow infusions as a routine procedure in children. J Pediatr 1944;25:13-16. 6. Valdes MM: Intraosseous fluid administration in emergencies. Lancet 1977;1: 1235-1236. 7. Berg RA: Emergency infusion of catecholamines into bone marrow. A m J Dis Child 1984; 138:810-811. 1139/23

SODIUM BICARBONATE ADMINISTRATION Spivey et al

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