BRIEF REPORT intraosseous infusion; vascular access
Bone Marrow Aspirate as an A c c e s s i b l e and Reliable Source for Critical Laboratory Studies Study objective: To determine whether laboratory studies performed on bone marrow aspirate can be used to predict values in the peripheral blood of human beings. Design: Prospective correlative study. Setting: Tertiary care pediatric hospital. Type of participants: Fifteen patients from the hematology-oncology division of Children's Hospital, Oakland, California, were studied during routine diagnostic bone marrow aspirations. Interventions: Aliquots of serum and bone marrow obtained as part of routine diagnostic studies were analyzed. M e a s u r e m e n t s and m a i n results: Venous and bone marrow samples were analyzed for blood gas values, hemoglobin, and serum chemistries. Bone marrow specimens were found to reliably predict venous values of pH, bicarbonate, base excess, Pco 2, hematocrit, sodium, chloride, and glucose. Bone marrow was not predictive of blood oxygenation, potassium, or ionized calcium. Conclusion: This study demonstrates in human beings what has previously been shown in animals - that the bone marrow is an alternative source of blood for a variety of laboratory studies. [Grisham J, Hastings C: Bone marrow aspirate as an accessible and reliable source for critical laboratory studies. Ann Emerg Med October 1991;20:1121-1124.]
Jonathan Grisham, MD* Caroline Hastings, MDt Oakland, California From the Departments of Emergency Medicine* and Hematology, t Children's Hospital, Oakland, California. Received for publication January 8, 1991. Revision received May 6, 1991. Accepted for publication June 10, 1991. Financial support for this study was provided in part by Cook Critical Care, Inc. Address for reprints: Jonathan Grisham, MD, Department of Emergency Medicine, Children's Hospital, Oakland, 747 52nd Street, Oakland, California 94609.
INTRODUCTION Establishing rapid vascular access in critically ill children is often the most t i m e c o n s u m i n g and f r u s t r a t i n g aspect of the r e s u s c i t a t i o n effort. The use of intraosseous (IO) infusions in these patients has undergone a relatively recent resurgence of p o p u l a r i t y 1-5 after a long period of quiescence since first introduced in the early part of this century.6, 7 A great deal of research has been done on w h a t can be infused into the IO space and at w h a t rate it can be infused. However, u n t i l recently, no one has examined w h e t h e r a small aspirate of m a r r o w blood obtained upon p l a c e m e n t of the IO needle might be useful for d e t e r m i n i n g certain laboratory values. As w i t h obtaining vascular access, procuring blood for critical studies by arterial or venous p u n c t u r e is often e x t r e m e l y difficult in shock or arrested states. Recent w o r k in a n i m a l s suggests that m a r r o w blood m a y have values for a wide variety of laboratory studies very similar to those of venous and arterial blood. 8-10 Orlowski et al compared these three sites in dogs for electrolytes, c h e m i s t r i e s , blood gases, and h e m o g l o b i n and found t h a t values were generally similar. 8 Unger et al found that electrolytes, calcium, glucose, blood urea nitrogen, and creatinine were not different in bone m a r r o w and venous blood in swine. 1° The purpose of our study was to d e t e r m i n e if a similar correlation exists in h u m a n beings.
MATERIALS A N D M E T H O D S Fifteen p a t i e n t s from the h e m a t o l o g y - o n c o l o g y d i v i s i o n of C h i l d r e n ' s Hospital, Oakland, California, were studied. These patients ranged from 10 months to 17 years old w i t h a m e a n of 9.5 years; l l patients were less than 10 years old. T h e y were selected because the specific target population of critically ill children would be very difficult or impossible to study and
20:10 October 1991
Annals of Emergency Medicine
1121/101
BONE
MARROW
Grisham
ASPIRATE
& Hastings
FIGURE. Scatterplots of correlation
coefficients for each variable. b e c a u s e t h e s e p a t i e n t s all r e c e i v e r o u t i n e bone m a r r o w aspirates and peripheral blood sampling as part of their standard care. Diagnoses for the patients were primarily oncologic; the majority had acute leukemia. O t h e r diagnoses i n c l u d e d H o d g k i n ' s disease, i m m u n e deficiency, congenital neutropenia, and aplastic anemia. N i n e of t h e p a t i e n t s w e r e s t u d i e d while under m i l d conscious sedation; six were studied under general anesthesia. All were cardiovascularly stable. This study was approved by the Research C o m m i t t e e and the Investigational Review Board at Children's Hospital, Oakland. All bone m a r r o w samples were obtained from the anterior or posterior iliac crest w i t h a 20-mL syringe and e i t h e r a 16-gauge d i s p o s a b l e b o n e m a r r o w needle or a 16-gauge IO needle. O n e m i l l i l i t e r each of v e n o u s blood and bone m a r r o w aspirate was o b t a i n e d after r o u t i n e studies were p e r f o r m e d . Bone m a r r o w was aspirated into a heparin-coated syringe to p r e v e n t clotting. Venous blood was obtained either by peripheral phlebot o m y or from a central venous catheter. The m e a n t i m e between phlebot o m y and bone m a r r o w aspirate was 11.5 minutes, w i t h a range of five to 30 minutes. Blood gas analysis was p e r f o r m e d using an AVL 945 a u t o m a t e d blood gas a n a l y z e r (AVL S c i e n t i f i c Corp, R o s w e l l , Georgia). S p u n c a p i l l a r y tube h e m a t o c r i t s were performed on the m i c r o t a i n e r samples, and s e r u m was then analyzed for a "stat panel" with a STAT Profile 6 machine (NOVA Biomedical, W a l t h a m , Massachusetts). C o m p a r a t i v e samples of h e p a r i n i z e d and n o n h e p a r i n i z e d ser u m were run and showed no difference in results by the STAT Profile 6 machine. Pearson's correlation coefficients w e r e c a l c u l a t e d for e a c h v a r i a b l e measured, and levels of significance were d e t e r m i n e d using the standard t distribution. Parameters w i t h P > .05 were considered to not have a significant correlation. A standard statistical program was used to calculate all values by computer.
RESULTS Raw data are displayed in graphic form w i t h correlation coefficients for 102/1122
y 7.20
7.30
7.40
pH r ~
30
40
50
60
70
40
pCO 2 r = .78
,86
60
80
pO 2 r =
100
.35
o
i
8 O3
o
.Z. 20
22 24
26 28
HCO 3 r =
30
.76
•
-6
-4
-2
0
2
4
60
Base Excess r = .90
%0 2
130
3.5
70
80
Satr
=
90
! O0
.52
(D eGL
"tO_
20
25
30
35
40
Hematocrit r =
95
1(}0
105
Chloride r =
45
.87
110
134
138
Sodium r =
115
,79
0.9
1.o
142
1.1
4.5
Potassium r =
.73
12
Calcium r = .24
loo
5.5 .09
15o 200 250
Glucose r = .96
Bone Marrow
each variable (Figure). One set of Po 2 values was not included in the analysis; the s e r u m s p e c i m e n was an arterial sample from a patient under general anesthesia. In addition, two sets of h e m a t o c r i t values were e l i m i n a t e d b e c a u s e of s a m p l e c l o t t i n g a n d heparin c o n t a m i n a t i o n . Each p a r a m e t e r studied, its correlation coefficient, and its level of sign i f i c a n c e are l i s t e d (Table). T h e r e was a significant correlation b e t w e e n venous and bone m a r r o w samples for pH, Pco2, HCO3, base excess, hematocrit, sodium, chloride, and glucose. T h e r e was no p r e d i c t a b l e r e l a t i o n ship for o x y g e n a t i o n (Po~ and %O~ saturation), p o t a s s i u m , and i o n i z e d calcium. Despite the absence of a sigA n n a l s of E m e r g e n c y M e d i c i n e
n i f i c a n t c o r r e l a t i o n b e t w e e n venous a n d b o n e m a r r o w v a l u e s for potassium, the bone marrow values were u n i f o r m l y higher by an average of 1.0 mEq/L. Ionized c a l c i u m was higher in the peripheral blood specim e n s in all but one patient.
DISCUSSION This study confirms in h u m a n beings w h a t has previously been shown in dogs and swine 8-1o - that the bone m a r r o w m a y provide an a l t e r n a t i v e source of blood for certain laboratory studies in children in w h o m venous and arterial access is difficult or impossible. We chose to compare bone m a r r o w a n d v e n o u s s a m p l e s for blood gases, hematocrit, and a "star 20:10 O c t o b e r 1991
BONE M A R R O W ASPIRATE Grisham & Hastings
TABLE. Correlation coefficients and P values Parameter
r
P
pH
.86
< .001
PCO2
.78
< .001
PC2
.35
NS
HCO3
.76
< .05
Base excess
.90
< .001
%02 saturation
.52
NS
Hematocrit
.87
< .005
Sodium
.73
< .005
Potassium
.09
NS
Chloride
.79
< O01
Calcium
.24
NS
Glucose
.96
< .001
panel" because these tests encompass the m o s t often n e e d e d laboratory s t u d i e s in e m e r g e n t l y ill children. For the m a j o r i t y of the values studied, the bone m a r r o w accurately predicts venous levels. A significant refationst~ip was found for pH, Pco2, HCOd, base excess, h e m a t o c r i t , sod i u m , chloride, and glucose. In a previous study, the bone marrow appeared to represent a vascular c o m p a r t m e n t similar to the capillary bed for b l o o d gas a n a l y s i s . 8 In our study, we found that blood gas values, except measures of oxygenation, w e r e v e r y s i m i l a r to v e n o u s samples. This m a y be of significant value b e c a u s e in c h i l d r e n w i t h cardiovascular collapse, a venous blood gas m o r e a c c u r a t e l y r e f l e c t s t i s s u e p e r f u s i o n - o x y g e n a t i o n t h a n do arterial blood gas values. Potassium values were consistently higher in the bone marrow, alt h o u g h n o t to a p r e d i c t a b l e degree. We believe this is a result of the traum a t i c nature of s p e c i m e n collection and the high negative pressure generated in aspirating m a r r o w that leads to hemolysis. This hypothesis is supported by a previous study in w h i c h e l e v a t e d l e v e l s of l a c t a t e d e h y d r o genase were found in aspirated marrow c o m p a r e d w i t h v e n o u s blood, possibly due to t r a u m a to the bone. s Ionized c a l c i u m levels were higher in the peripheral blood in all except one p a t i e n t for u n k n o w n r e a s o n s , although c a l c i u m binding w i t h osseous e l e m e n t s in the m a r r o w space could lead to a decrease in i o n i z e d (free)
values. It is unfortunate that we were unable to confirm the results of earlier 20:10 October 1991
studies by O r l o w s k i et al and Unger et al that suggested that there was no difference b e t w e e n bone m a r r o w and venous values of p o t a s s i u m and calcium, b e c a u s e these ions are often i m p o r t a n t in the etiology and recovery of cardiac arrest. The different res u l t s m a y be due to d i f f e r e n c e s in e q u i p m e n t and s t a t i s t i c a l a n a l y s i s r a t h e r t h a n to a true difference bet w e e n a n i m a l and h u m a n subjects. Both authors m e a s u r e d total calcium, a value that m a y be less susceptible t h a n i o n i z e d c a l c i u m to b i n d i n g by e l e m e n t s of bone, as suggested above. T h e 2 0 - m L s y r i n g e s u s e d in o u r study probably generate considerably greater negative pressure (and hemolysis) t h a n the 3-mL and 10-mL syringes used in previous studies, w h i c h m a y a c c o u n t for our h i g h e r bone m a r r o w values for potassium. Finally, previous studies have used a comparison of the m e a n values of laboratory tests of bone m a r r o w and peripheral blood to d e t e r m i n e if a sign i f i c a n t r e l a t i o n s h i p exists. We believe that correlation coefficients are m o r e useful than a comparison of the m e a n s w h e n trying to use one variable to predict another. A possible weakness of this study is the fact that the subjects were all in a n o r m a l cardiovascular state, and it is n o t k n o w n if t h e r e w o u l d be greater differences in laboratory values in the arrested or low blood flow state. However, patients in our study w h o were e x a m i n e d under general a n e s t h e s i a t e n d e d to be m o r e acidotic than those under conscious sedation, and this was reflected accurately in the bone marrow. In addition, an earlier study in dogs demonstrated that w i t h severe hypoventilation, IO pH and P c o 2 changed along w i t h (and were no different from) the venous and arterial values. 9 W h e t h e r the characteristics of the bone marrow change s i g n i f i c a n t l y in the noflow s i t u a t i o n remains to be seen. All bone marrow aspirates were obtained from the iliac crest in this study, w h e r e a s in c l i n i c a l p r a c t i c e the long bones of the leg are the m o s t often used sites for IO infusion. Evalu a t i o n of bone m a r r o w cellularity is not dependent on the site of collection, and we have no reason to believe t h a t the p a r a m e t e r s m e a s u r e d in this s t u d y w o u l d be different at different sites. However, if it proved m o r e difficult to aspirate blood from t h e t i b i a l site, one c o u l d e x p e c t a Annals of Emergency Medicine
g r e a t e r effect of h e m o l y s i s on the p o t a s s i u m level. A l t h o u g h m a n y of o u r p a t i e n t s were o n c o l o g y patients, we do n o t believe that their underlying pathology affected values of the parameters studied in the bone marrow. N o n e of the patients had e x t r e m e l y elevated W B C c o u n t s to a c c o u n t for t h e h i g h e r p o t a s s i u m seen in the bone m a r r o w . M o s t of t h e o n c o l o g y patients were stable w i t h n o r m a l RBC and WBC counts, and some of the hematology patients had depressed blood cell counts. Future investigation in this area is n e c e s s a r y to d e t e r m i n e w h e t h e r a s i m i l a r r e l a t i o n s h i p exists b e t w e e n the bone marrow and peripheral blood in low-flow or no-flow states; one m i g h t expect a greater difference w i t h the p e r i p h e r a l p o o l i n g seen in these situations. It m a y also be useful to k n o w if certain drug levels (eg, a n t i c o n v u l s a n t s , t h e o p h y l l i n e ) are s i m i l a r in v e n o u s b l o o d and b o n e m a r r o w aspirate. In addition, various bone m a r r o w sites s h o u l d be compared to d e t e r m i n e if there are differences in t h e a b i l i t y to get a good blood return and w h e t h e r there is an equal c o r r e l a t i o n b e t w e e n m a r r o w and blood at different sites. Based on the results of this study, we r e c o m m e n d that on p l a c e m e n t of an IO needle a brief a t t e m p t be made to o b t a i n a s m a l l a s p i r a t e of b o n e m a r r o w . M a n y a u t h o r i t i e s suggest t h i s m a n e u v e r to c o n f i r m p r o p e r p l a c e m e n t of the needle. If the att e m p t at aspiration is successful and blood cannot be obtained by arterial or venous puncture, the sample should be sent for laboratory analysis (as s u p p o r t e d b y t h i s a n d o t h e r studiesS-t°). P r o l o n g e d a t t e m p t s to o b t a i n an a s p i r a t e s h o u l d n o t be m a d e as they m a y delay the administration of life-saving therapy. Heparin i z a t i o n of the syringe is necessary to p r e v e n t c l o t t i n g ; t h e s a m p l e s h o u l d be s p u n d o w n , a n d s e r u m s h o u l d be u s e d for t h e c h e m i s t r y panel to prevent clotting in the STAT Profile 6 machine. U n t i l comparisons are m a d e t h a t s h o w a good correlation between m a r r o w and peripheral b l o o d in t h e n o - f l o w state, s e r u m f r o m a r t e r i a l or v e n o u s p u n c t u r e (when o b t a i n a b l e ) w i l l r e m a i n the first choice for laboratory analysis.
CONCLUSION O u r s t u d y supports the idea t h a t 1123/103
BONE MARROW ASPIRATE Grisham & Hastings
bone marrow aspirate can be used for blood gas and stat c h e m i s t r y panel analysis, w i t h the e x c e p t i o n of potassium and ionized c a l c i u m values and m e a s u r e s of o x y g e n a t i o n . Human bone marrow has been s h o w n to be an a l t e r n a t i v e s o u r c e of blood samples as well as an excellent route of drug and fluid a d m i n i s t r a t i o n in children w i t h difficult vascular access. Correlation of bone marrow aspirate and v e n o u s values in the lowflow and no-flow states has yet to be determined. W h e n blood cannot be o b t a i n e d from a v e n o u s or arterial site, bone marrow aspirate m a y be used to predict serum values of certain critical laboratory studies.
104/1124
T h e a u t h o r s t h a n k Elliot Vichinsky, MD, a n d J a m e s F e u s n e r , M D , for t h e i r h e l p reviewing this manuscript; Haiganoush Preisler, Joseph Telfair, MSW, M P H , a n d L y n n e N e u m a y r , M D , for s t a t i s t i c a l a n a l ysis; t h e blood gas a n d clinical laborator i e s a t C h i l d r e n ' s H o s p i t a l for t h e i r s u p port and assistance; and Cook Critical C a r e I n c for t h e i r f i n a n c i a l a n d m a t e r i a l support.
osseous infusion: An alternative route of pediatric intravascular access. Ann Emerg Med 1985;14:885-888.
REFERENCES L Glaeser PW, Losek JD: Emergency intraosseous infu sions in children. A m J Emerg Med 1986;4:34 36.
8. Orlowski JP, Porembka DT, Gallagher JM, et ah The bone marrow as a source of laboratory studies. Ann Emerg Med 1989;18:1348-135L
2. Orlowski JP, Porembka DT, Gallagher JM, et al: Comparison study of intraosseous, central intravenous, and peripheral intravenous infusions of emergency drugs. Am J Dis Child 1990;144:112-117.
9. Brickman K, Rega P, Guinness M: A comparative study of intraosseous, intravenous and intra-arterial pH changes during hypoventilation in dogs. Ann Emerg Med 1987;I6:510.
3. Pratt JL: Intraosseous infusion. Int Pediatr 1989; 4:19-23.
10. Unger H, 8pivey WH, McNamara RM, et al: Comparison of intraosseous and intravenous CBC and ASTRA 8 in swine (abstract). Ann Emerg Med 1986~ 15:647.
4. Rosetti VA, Thompson BM, Miller J, et al: Intra-
Annals of Emergency Medicine
5. Spivey WH: Intraosseous infusions, f Pediatr 1987; 111:639 643. 6. Heinlid S, Sondergaard T, Tudvad F: Bone marrow infusion in childhood: Experience from a thousand infusions. ] Pediatr 1947;30:400-411. 7. Tocantins LM, O'Neill JF, Price AH: Infusions of blood and other fluids via the bone marrow in traumatic shock and other forms of peripheral circulatory failure. Ann Surg 1941;114:1085-1092.
20:10 October 1991
Bone Marrow Aspirate as an A c c e s s i b l e and Reliable Source for Critical Laboratory Studies Study objective: To determine whether laboratory studies performed on bone marrow aspirate can be used to predict values in the peripheral blood of human beings. Design: Prospective correlative study. Setting: Tertiary care pediatric hospital. Type of participants: Fifteen patients from the hematology-oncology division of Children's Hospital, Oakland, California, were studied during routine diagnostic bone marrow aspirations. Interventions: Aliquots of serum and bone marrow obtained as part of routine diagnostic studies were analyzed. M e a s u r e m e n t s and m a i n results: Venous and bone marrow samples were analyzed for blood gas values, hemoglobin, and serum chemistries. Bone marrow specimens were found to reliably predict venous values of pH, bicarbonate, base excess, Pco 2, hematocrit, sodium, chloride, and glucose. Bone marrow was not predictive of blood oxygenation, potassium, or ionized calcium. Conclusion: This study demonstrates in human beings what has previously been shown in animals - that the bone marrow is an alternative source of blood for a variety of laboratory studies. [Grisham J, Hastings C: Bone marrow aspirate as an accessible and reliable source for critical laboratory studies. Ann Emerg Med October 1991;20:1121-1124.]
Jonathan Grisham, MD* Caroline Hastings, MDt Oakland, California From the Departments of Emergency Medicine* and Hematology, t Children's Hospital, Oakland, California. Received for publication January 8, 1991. Revision received May 6, 1991. Accepted for publication June 10, 1991. Financial support for this study was provided in part by Cook Critical Care, Inc. Address for reprints: Jonathan Grisham, MD, Department of Emergency Medicine, Children's Hospital, Oakland, 747 52nd Street, Oakland, California 94609.
INTRODUCTION Establishing rapid vascular access in critically ill children is often the most t i m e c o n s u m i n g and f r u s t r a t i n g aspect of the r e s u s c i t a t i o n effort. The use of intraosseous (IO) infusions in these patients has undergone a relatively recent resurgence of p o p u l a r i t y 1-5 after a long period of quiescence since first introduced in the early part of this century.6, 7 A great deal of research has been done on w h a t can be infused into the IO space and at w h a t rate it can be infused. However, u n t i l recently, no one has examined w h e t h e r a small aspirate of m a r r o w blood obtained upon p l a c e m e n t of the IO needle might be useful for d e t e r m i n i n g certain laboratory values. As w i t h obtaining vascular access, procuring blood for critical studies by arterial or venous p u n c t u r e is often e x t r e m e l y difficult in shock or arrested states. Recent w o r k in a n i m a l s suggests that m a r r o w blood m a y have values for a wide variety of laboratory studies very similar to those of venous and arterial blood. 8-10 Orlowski et al compared these three sites in dogs for electrolytes, c h e m i s t r i e s , blood gases, and h e m o g l o b i n and found t h a t values were generally similar. 8 Unger et al found that electrolytes, calcium, glucose, blood urea nitrogen, and creatinine were not different in bone m a r r o w and venous blood in swine. 1° The purpose of our study was to d e t e r m i n e if a similar correlation exists in h u m a n beings.
MATERIALS A N D M E T H O D S Fifteen p a t i e n t s from the h e m a t o l o g y - o n c o l o g y d i v i s i o n of C h i l d r e n ' s Hospital, Oakland, California, were studied. These patients ranged from 10 months to 17 years old w i t h a m e a n of 9.5 years; l l patients were less than 10 years old. T h e y were selected because the specific target population of critically ill children would be very difficult or impossible to study and
20:10 October 1991
Annals of Emergency Medicine
1121/101
BONE
MARROW
Grisham
ASPIRATE
& Hastings
FIGURE. Scatterplots of correlation
coefficients for each variable. b e c a u s e t h e s e p a t i e n t s all r e c e i v e r o u t i n e bone m a r r o w aspirates and peripheral blood sampling as part of their standard care. Diagnoses for the patients were primarily oncologic; the majority had acute leukemia. O t h e r diagnoses i n c l u d e d H o d g k i n ' s disease, i m m u n e deficiency, congenital neutropenia, and aplastic anemia. N i n e of t h e p a t i e n t s w e r e s t u d i e d while under m i l d conscious sedation; six were studied under general anesthesia. All were cardiovascularly stable. This study was approved by the Research C o m m i t t e e and the Investigational Review Board at Children's Hospital, Oakland. All bone m a r r o w samples were obtained from the anterior or posterior iliac crest w i t h a 20-mL syringe and e i t h e r a 16-gauge d i s p o s a b l e b o n e m a r r o w needle or a 16-gauge IO needle. O n e m i l l i l i t e r each of v e n o u s blood and bone m a r r o w aspirate was o b t a i n e d after r o u t i n e studies were p e r f o r m e d . Bone m a r r o w was aspirated into a heparin-coated syringe to p r e v e n t clotting. Venous blood was obtained either by peripheral phlebot o m y or from a central venous catheter. The m e a n t i m e between phlebot o m y and bone m a r r o w aspirate was 11.5 minutes, w i t h a range of five to 30 minutes. Blood gas analysis was p e r f o r m e d using an AVL 945 a u t o m a t e d blood gas a n a l y z e r (AVL S c i e n t i f i c Corp, R o s w e l l , Georgia). S p u n c a p i l l a r y tube h e m a t o c r i t s were performed on the m i c r o t a i n e r samples, and s e r u m was then analyzed for a "stat panel" with a STAT Profile 6 machine (NOVA Biomedical, W a l t h a m , Massachusetts). C o m p a r a t i v e samples of h e p a r i n i z e d and n o n h e p a r i n i z e d ser u m were run and showed no difference in results by the STAT Profile 6 machine. Pearson's correlation coefficients w e r e c a l c u l a t e d for e a c h v a r i a b l e measured, and levels of significance were d e t e r m i n e d using the standard t distribution. Parameters w i t h P > .05 were considered to not have a significant correlation. A standard statistical program was used to calculate all values by computer.
RESULTS Raw data are displayed in graphic form w i t h correlation coefficients for 102/1122
y 7.20
7.30
7.40
pH r ~
30
40
50
60
70
40
pCO 2 r = .78
,86
60
80
pO 2 r =
100
.35
o
i
8 O3
o
.Z. 20
22 24
26 28
HCO 3 r =
30
.76
•
-6
-4
-2
0
2
4
60
Base Excess r = .90
%0 2
130
3.5
70
80
Satr
=
90
! O0
.52
(D eGL
"tO_
20
25
30
35
40
Hematocrit r =
95
1(}0
105
Chloride r =
45
.87
110
134
138
Sodium r =
115
,79
0.9
1.o
142
1.1
4.5
Potassium r =
.73
12
Calcium r = .24
loo
5.5 .09
15o 200 250
Glucose r = .96
Bone Marrow
each variable (Figure). One set of Po 2 values was not included in the analysis; the s e r u m s p e c i m e n was an arterial sample from a patient under general anesthesia. In addition, two sets of h e m a t o c r i t values were e l i m i n a t e d b e c a u s e of s a m p l e c l o t t i n g a n d heparin c o n t a m i n a t i o n . Each p a r a m e t e r studied, its correlation coefficient, and its level of sign i f i c a n c e are l i s t e d (Table). T h e r e was a significant correlation b e t w e e n venous and bone m a r r o w samples for pH, Pco2, HCO3, base excess, hematocrit, sodium, chloride, and glucose. T h e r e was no p r e d i c t a b l e r e l a t i o n ship for o x y g e n a t i o n (Po~ and %O~ saturation), p o t a s s i u m , and i o n i z e d calcium. Despite the absence of a sigA n n a l s of E m e r g e n c y M e d i c i n e
n i f i c a n t c o r r e l a t i o n b e t w e e n venous a n d b o n e m a r r o w v a l u e s for potassium, the bone marrow values were u n i f o r m l y higher by an average of 1.0 mEq/L. Ionized c a l c i u m was higher in the peripheral blood specim e n s in all but one patient.
DISCUSSION This study confirms in h u m a n beings w h a t has previously been shown in dogs and swine 8-1o - that the bone m a r r o w m a y provide an a l t e r n a t i v e source of blood for certain laboratory studies in children in w h o m venous and arterial access is difficult or impossible. We chose to compare bone m a r r o w a n d v e n o u s s a m p l e s for blood gases, hematocrit, and a "star 20:10 O c t o b e r 1991
BONE M A R R O W ASPIRATE Grisham & Hastings
TABLE. Correlation coefficients and P values Parameter
r
P
pH
.86
< .001
PCO2
.78
< .001
PC2
.35
NS
HCO3
.76
< .05
Base excess
.90
< .001
%02 saturation
.52
NS
Hematocrit
.87
< .005
Sodium
.73
< .005
Potassium
.09
NS
Chloride
.79
< O01
Calcium
.24
NS
Glucose
.96
< .001
panel" because these tests encompass the m o s t often n e e d e d laboratory s t u d i e s in e m e r g e n t l y ill children. For the m a j o r i t y of the values studied, the bone m a r r o w accurately predicts venous levels. A significant refationst~ip was found for pH, Pco2, HCOd, base excess, h e m a t o c r i t , sod i u m , chloride, and glucose. In a previous study, the bone marrow appeared to represent a vascular c o m p a r t m e n t similar to the capillary bed for b l o o d gas a n a l y s i s . 8 In our study, we found that blood gas values, except measures of oxygenation, w e r e v e r y s i m i l a r to v e n o u s samples. This m a y be of significant value b e c a u s e in c h i l d r e n w i t h cardiovascular collapse, a venous blood gas m o r e a c c u r a t e l y r e f l e c t s t i s s u e p e r f u s i o n - o x y g e n a t i o n t h a n do arterial blood gas values. Potassium values were consistently higher in the bone marrow, alt h o u g h n o t to a p r e d i c t a b l e degree. We believe this is a result of the traum a t i c nature of s p e c i m e n collection and the high negative pressure generated in aspirating m a r r o w that leads to hemolysis. This hypothesis is supported by a previous study in w h i c h e l e v a t e d l e v e l s of l a c t a t e d e h y d r o genase were found in aspirated marrow c o m p a r e d w i t h v e n o u s blood, possibly due to t r a u m a to the bone. s Ionized c a l c i u m levels were higher in the peripheral blood in all except one p a t i e n t for u n k n o w n r e a s o n s , although c a l c i u m binding w i t h osseous e l e m e n t s in the m a r r o w space could lead to a decrease in i o n i z e d (free)
values. It is unfortunate that we were unable to confirm the results of earlier 20:10 October 1991
studies by O r l o w s k i et al and Unger et al that suggested that there was no difference b e t w e e n bone m a r r o w and venous values of p o t a s s i u m and calcium, b e c a u s e these ions are often i m p o r t a n t in the etiology and recovery of cardiac arrest. The different res u l t s m a y be due to d i f f e r e n c e s in e q u i p m e n t and s t a t i s t i c a l a n a l y s i s r a t h e r t h a n to a true difference bet w e e n a n i m a l and h u m a n subjects. Both authors m e a s u r e d total calcium, a value that m a y be less susceptible t h a n i o n i z e d c a l c i u m to b i n d i n g by e l e m e n t s of bone, as suggested above. T h e 2 0 - m L s y r i n g e s u s e d in o u r study probably generate considerably greater negative pressure (and hemolysis) t h a n the 3-mL and 10-mL syringes used in previous studies, w h i c h m a y a c c o u n t for our h i g h e r bone m a r r o w values for potassium. Finally, previous studies have used a comparison of the m e a n values of laboratory tests of bone m a r r o w and peripheral blood to d e t e r m i n e if a sign i f i c a n t r e l a t i o n s h i p exists. We believe that correlation coefficients are m o r e useful than a comparison of the m e a n s w h e n trying to use one variable to predict another. A possible weakness of this study is the fact that the subjects were all in a n o r m a l cardiovascular state, and it is n o t k n o w n if t h e r e w o u l d be greater differences in laboratory values in the arrested or low blood flow state. However, patients in our study w h o were e x a m i n e d under general a n e s t h e s i a t e n d e d to be m o r e acidotic than those under conscious sedation, and this was reflected accurately in the bone marrow. In addition, an earlier study in dogs demonstrated that w i t h severe hypoventilation, IO pH and P c o 2 changed along w i t h (and were no different from) the venous and arterial values. 9 W h e t h e r the characteristics of the bone marrow change s i g n i f i c a n t l y in the noflow s i t u a t i o n remains to be seen. All bone marrow aspirates were obtained from the iliac crest in this study, w h e r e a s in c l i n i c a l p r a c t i c e the long bones of the leg are the m o s t often used sites for IO infusion. Evalu a t i o n of bone m a r r o w cellularity is not dependent on the site of collection, and we have no reason to believe t h a t the p a r a m e t e r s m e a s u r e d in this s t u d y w o u l d be different at different sites. However, if it proved m o r e difficult to aspirate blood from t h e t i b i a l site, one c o u l d e x p e c t a Annals of Emergency Medicine
g r e a t e r effect of h e m o l y s i s on the p o t a s s i u m level. A l t h o u g h m a n y of o u r p a t i e n t s were o n c o l o g y patients, we do n o t believe that their underlying pathology affected values of the parameters studied in the bone marrow. N o n e of the patients had e x t r e m e l y elevated W B C c o u n t s to a c c o u n t for t h e h i g h e r p o t a s s i u m seen in the bone m a r r o w . M o s t of t h e o n c o l o g y patients were stable w i t h n o r m a l RBC and WBC counts, and some of the hematology patients had depressed blood cell counts. Future investigation in this area is n e c e s s a r y to d e t e r m i n e w h e t h e r a s i m i l a r r e l a t i o n s h i p exists b e t w e e n the bone marrow and peripheral blood in low-flow or no-flow states; one m i g h t expect a greater difference w i t h the p e r i p h e r a l p o o l i n g seen in these situations. It m a y also be useful to k n o w if certain drug levels (eg, a n t i c o n v u l s a n t s , t h e o p h y l l i n e ) are s i m i l a r in v e n o u s b l o o d and b o n e m a r r o w aspirate. In addition, various bone m a r r o w sites s h o u l d be compared to d e t e r m i n e if there are differences in t h e a b i l i t y to get a good blood return and w h e t h e r there is an equal c o r r e l a t i o n b e t w e e n m a r r o w and blood at different sites. Based on the results of this study, we r e c o m m e n d that on p l a c e m e n t of an IO needle a brief a t t e m p t be made to o b t a i n a s m a l l a s p i r a t e of b o n e m a r r o w . M a n y a u t h o r i t i e s suggest t h i s m a n e u v e r to c o n f i r m p r o p e r p l a c e m e n t of the needle. If the att e m p t at aspiration is successful and blood cannot be obtained by arterial or venous puncture, the sample should be sent for laboratory analysis (as s u p p o r t e d b y t h i s a n d o t h e r studiesS-t°). P r o l o n g e d a t t e m p t s to o b t a i n an a s p i r a t e s h o u l d n o t be m a d e as they m a y delay the administration of life-saving therapy. Heparin i z a t i o n of the syringe is necessary to p r e v e n t c l o t t i n g ; t h e s a m p l e s h o u l d be s p u n d o w n , a n d s e r u m s h o u l d be u s e d for t h e c h e m i s t r y panel to prevent clotting in the STAT Profile 6 machine. U n t i l comparisons are m a d e t h a t s h o w a good correlation between m a r r o w and peripheral b l o o d in t h e n o - f l o w state, s e r u m f r o m a r t e r i a l or v e n o u s p u n c t u r e (when o b t a i n a b l e ) w i l l r e m a i n the first choice for laboratory analysis.
CONCLUSION O u r s t u d y supports the idea t h a t 1123/103
BONE MARROW ASPIRATE Grisham & Hastings
bone marrow aspirate can be used for blood gas and stat c h e m i s t r y panel analysis, w i t h the e x c e p t i o n of potassium and ionized c a l c i u m values and m e a s u r e s of o x y g e n a t i o n . Human bone marrow has been s h o w n to be an a l t e r n a t i v e s o u r c e of blood samples as well as an excellent route of drug and fluid a d m i n i s t r a t i o n in children w i t h difficult vascular access. Correlation of bone marrow aspirate and v e n o u s values in the lowflow and no-flow states has yet to be determined. W h e n blood cannot be o b t a i n e d from a v e n o u s or arterial site, bone marrow aspirate m a y be used to predict serum values of certain critical laboratory studies.
104/1124
T h e a u t h o r s t h a n k Elliot Vichinsky, MD, a n d J a m e s F e u s n e r , M D , for t h e i r h e l p reviewing this manuscript; Haiganoush Preisler, Joseph Telfair, MSW, M P H , a n d L y n n e N e u m a y r , M D , for s t a t i s t i c a l a n a l ysis; t h e blood gas a n d clinical laborator i e s a t C h i l d r e n ' s H o s p i t a l for t h e i r s u p port and assistance; and Cook Critical C a r e I n c for t h e i r f i n a n c i a l a n d m a t e r i a l support.
osseous infusion: An alternative route of pediatric intravascular access. Ann Emerg Med 1985;14:885-888.
REFERENCES L Glaeser PW, Losek JD: Emergency intraosseous infu sions in children. A m J Emerg Med 1986;4:34 36.
8. Orlowski JP, Porembka DT, Gallagher JM, et ah The bone marrow as a source of laboratory studies. Ann Emerg Med 1989;18:1348-135L
2. Orlowski JP, Porembka DT, Gallagher JM, et al: Comparison study of intraosseous, central intravenous, and peripheral intravenous infusions of emergency drugs. Am J Dis Child 1990;144:112-117.
9. Brickman K, Rega P, Guinness M: A comparative study of intraosseous, intravenous and intra-arterial pH changes during hypoventilation in dogs. Ann Emerg Med 1987;I6:510.
3. Pratt JL: Intraosseous infusion. Int Pediatr 1989; 4:19-23.
10. Unger H, 8pivey WH, McNamara RM, et al: Comparison of intraosseous and intravenous CBC and ASTRA 8 in swine (abstract). Ann Emerg Med 1986~ 15:647.
4. Rosetti VA, Thompson BM, Miller J, et al: Intra-
Annals of Emergency Medicine
5. Spivey WH: Intraosseous infusions, f Pediatr 1987; 111:639 643. 6. Heinlid S, Sondergaard T, Tudvad F: Bone marrow infusion in childhood: Experience from a thousand infusions. ] Pediatr 1947;30:400-411. 7. Tocantins LM, O'Neill JF, Price AH: Infusions of blood and other fluids via the bone marrow in traumatic shock and other forms of peripheral circulatory failure. Ann Surg 1941;114:1085-1092.
20:10 October 1991
