EDITORIALS
the patient's decision to seek care in the ED or to a d d r e s s t h e l i m i t e d availability of alternative sources of care. Society m u s t begin to address the difficult ethical and moral issues of equitable h e a l t h care delivery. Congress m u s t take appropriate steps to provide a m e c h a n i s m for our citizens to access appropriate h e a l t h care, including emergency and p r i m a r y care, especially for the increasing n u m b e r s of individuals who have no access to health insurance because of their emp l o y e r s ' e c o n o m i c woes. A m e r i c a n c i t i z e n s s h o u l d n o t a c c e p t an increase in the level of u n c o m p e n s a t e d care b e c a u s e of o u r n a t i o n a l econ o m i c recession. M a n y of the solutions to alleviating both the access to care issue and t h e ED o v e r c r o w d i n g p r o b l e m are contained in the ACEP policy statem e n t on hospital and ED overcrowding: 3 • Provide a basic level of h e a l t h insurance for all citizens; • Remove financial disincentives to h o s p i t a l s for p r o v i d i n g e m e r g e n c y care; • Where needed, increase the capacity to provide critical care, inpatient, and nursing h o m e services; and
• S u p p o r t access to p r i m a r y care services and encourage initiatives des i g n e d to p r e v e n t s e r i o u s i l l n e s s e s and injuries. We m u s t reaffirm our c o m m i t m e n t to w o r k w i t h Congress and the adm i n i s t r a t i o n to achieve e n a c t m e n t of legislation to solve the access to care challenge, while assuring that emergency physicians receive equitable r e i m b u r s e m e n t for services rendered. We applaud the efforts of Pane et al and other researchers in the field, and we concur w i t h the concluding statem e n t c o n t a i n e d in t h e A c c e s s to H e a l t h Care Coalition document: " . . . in order to m e e t the i m m e d i a t e c h a l l e n g e of t h e u n i n sured population, and the longer t e r m challenge of a better h e a l t h care s y s t e m for all Americans, the medical profession m u s t recognize its responsibility to w o r k w i t h others to assure quality care is delivered in a cost efficient manner. We can do no less. T h e h e a l t h of t h e n a t i o n is r e f l e c t e d in t h e h e a l t h of its people." The individual physician will impact the s y s t e m far less t h a n those w h o are organized in a c h i e v i n g t h e
s o c i a l goal of u n i v e r s a l a c c e s s to h e a l t h care. 4 The t i m e has come for emergency physicians to u n i t e on behalf of our patients, our colleagues in emergency medicine, and our fellow physicians in other specialties by advocating h e a l t h care reform embodying p r i n c i p l e s of access to care and appropriate r e i m b u r s e m e n t .
E Jackson Allison, ]r, MD/MPH, FACEP Department of Emergency Medicine East Carolina University School of Medicine Greenville, North Carolina Kenneth L DeHart, MD, FACEP Departmer~t of Emergency Medicine Grand Strand General Hospital North Myrtle Beach, South Carolina 1. American College of Emergency Physicians: Longrange plan and e n v i r o n m e n t a l a s s e s s m e n t 1990-9[: ACEP statement of direction: Value statements. Dallas, American College of Emergency Physicians, approved, board iff directors, March 10, [990. 2. American College of Emergency Physicians: Survey studies characteristics of ACEP incmbcrs. ACEP New~ 1986;5:7. 3. American College of Emergency Physicians: Measures to deal with emergency department overcrowding, Arm Emerg Med [990;19:944-945. 4. Kieinman EC: Health care m crisis: A proposed role fl~r the individual physician as adw~cate. ]AMA 199l; [5:1991-1992.
From the Laboratory to the Bedside: When? The article by Pollack et al, "Intraosseous A d m i n i s t r a t i o n of A n t i b i otics: S a m e - D o s e C o m p a r i s o n W i t h I n t r a v e n o u s A d m i n i s t r a t i o n in t h e Weanling Pig," in this issue of Annals raises an i m p o r t a n t q u e s t i o n : When s h o u l d a c l i n i c i a n t a k e basic science data and apply it to clinical situations? In their study, Pollack et al compared intraosseous and IV adm i n i s t r a t i o n of different a n t i b i o t i c s , each in four pigs, and from this extrapolated clinical r e c o m m e n d a t i o n s for intraosseous a n t i b i o t i c a d m i n i s tration in children. T h e gap b e t w e e n their laboratory data and the septic pediatric patient is a large one and requires careful thought before the jump is made. There are f u n d a m e n t a l differences between animals and h u m a n beings 172/821
that m u s t be considered w h e n evaluating animal data and animal models. 1. A n i m a l s m a y differ among species and from h u m a n beings in the rate of drug absorption, distribution, m e t a b o l i s m , and excretion. Enzymes that m e t a b o l i z e drugs in the kidney, liver, and lung vary a m o n g a n i m a l species. Proteins that bind drugs are different among species and m a y lead to d i f f e r e n c e s in a v a i l a b l e d r u g . T h e r e m a y be a n a t o m i c differences such as p e r c e n t a g e of body fat t h a t change a b s o r p t i o n and d i s t r i b u t i o n . C o n s e q u e n t l y , s i m i l a r i t i e s or differe n c e s in p h a r m a c o k i n e t i c s in one species m a y not be the same in other species or in h u m a n beings. W h e n ever possible, m o r e than one species s h o u l d be s t u d i e d and result~ cornAnnals of Emergency Medicine
pared for similarities and differences. 2. A n i m a l s a r e r a r e l y p e r f e c t models for h u m a n disease. The m o r e dissimilar the a n i m a l m o d e l and the h u m a n disease, the less likely the results will have clinical relevance. T h e response of a' h e a l t h y a n e s t h e tized a n i m a l to a drug is likely to be q u i t e different from t h a t of an una n e s t h e t i z e d h u m a n in a d i s e a s e d state. For instance, during sepsis, a change in h e m o d y n a m i c s leads to a change in absorption. Tissue permea b i l i t y c h a n g e s , as s e e n w i t h t h e m e n i n g e s during m e n i n g i t i s , w h i c h m a y lead to a different d i s t r i b u t i o n pattern. Finally, enzyme function m a y change, leading to a difference in m e t a b o l i s m and excretion. 3. A n i m a l m o d e l s of disease are often o v e r s i m p l i f i c a t i o n s of a specific 20:7 July 1991
EDITORIALS
p r o b l e m . For e x a m p l e , to p r o d u c e a hypertensive a n i m a l model, a k i d n e y is wrapped tightly, producing changes in the renin angiotensin regu l a t i o n of blood pressure, thus leading to h y p e r t e n s i o n . However, this o c c u r s o v e r w e e k s as o p p o s e d to years or decades as seen in h u m a n disease. I n f o r m a t i o n from studies of a n t i h y p e r t e n s i v e agents in these anim a l m o d e l s is useful b u t is n o t always the answer to h u m a n hypertension. Interpretation of data, even in a good a n i m a l m o d e l of disease, m u s t be d o n e c a u t i o u s l y . A l l t o o o f t e n there is an over-generalization of the r e s u l t s and a t e n d e n c y to correlate t h e m w i t h clinical information prematurely. See related article, p 772. Despite their limitations, animal m o d e l s do provide e x t r e m e l y valuable i n f o r m a t i o n a b o u t disease processes and intervention. M u c h of this i n f o r m a t i o n does not come from single studies, but rather from m u l t i p l e studies using different species and techniques. C h a n g i n g c l i n i c a l practice or trying a n e w therapy based on one a n i m a l s t u d y is n o t j u s t i f i e d . However, if m u l t i p l e , w e l l - d e s i g n e d studies s h o w a t r e n d or c o n s i s t e n t pattern, then clinical study or appli-
20:7: July 1991
cation m a y be warranted. T h e quality of a research study (design, m e t h o d o l o g y , d a t a c o l l e c t i o n ) and relevance of the a n i m a l m o d e l to the disease process being studied are essential c o m p o n e n t s for any meaningful c o n c l u s i o n s . It is i n c u m b e n t on investigators w h o use animals for r e s e a r c h to c a r e f u l l y p l a n e x p e r i m e n t s and extract as m u c h information as possible from each animal. As a research fellow, I r e m e m b e r a mentor telling m e that if I was going to sacrifice an a n i m a l ' s life, then I was obligated to get every bit of information possible from the study. All too often physicians conduct " q u i c k and dirty" studies using a m i n i m a l n u m ber of animals and address only one issue. M u c h of the w o r k in areas such as i n t r a o s s e o u s and e n d o t r a c h e a l drug a d m i n i s t r a t i o n is typical of this problem. A single drug dose is administered, a few blood levels are d r a w n and assayed, and the investigator writes a paper. Rarely are issues such as tissue deposition of the drug, detailed pharmacokinetics, effect of the d r u g on t h e d i s e a s e p r o c e s s , a n d pathologic changes of the drug on the bone or lung addressed. This is valuable information that is lost. To obtain it, m o r e animals m u s t be sacrificed. In their paper, P o l l a c k et al have
Annals of Emergency Medicine
provided us w i t h useful information about the intraosseous administration of antibiotics that was not available previously. This is the first paper to address antibiotic administration by this route, and their data are consistent with other studies that have shown that the intraosseous route is similar but not identical to a peripheral venous site. This is a helpful first step, b u t m u c h m o r e w o r k a n d i n f o r m a t i o n are n e e d e d before we can feel as confident about giving intraosseous antibiotics to the septic child as we do giving IV antibiotics. We are often willing to accept and try new ideas in an emergency w h e n traditional resources have failed us, but before we accept a n e w c o n c e p t or new i n f o r m a t i o n as part of our routine practice, it m u s t be very clear that there is a proven benefit. W h e n should the clinician take ani m a l data to the bedside? There is obv i o u s l y no c l e a r - c u t a n s w e r to this question. However, before this step is taken, the clinician m u s t have welldesigned, thorough studies that provide clear evidence that a change in c l i n i c a l p r a c t i c e is l i k e l y to be safe and advantageous to the patient.
William H Spivey, MD, FACEP Department of Emergency Medicine Medical College of Pennsylvania Philadelphia
822/t73
the patient's decision to seek care in the ED or to a d d r e s s t h e l i m i t e d availability of alternative sources of care. Society m u s t begin to address the difficult ethical and moral issues of equitable h e a l t h care delivery. Congress m u s t take appropriate steps to provide a m e c h a n i s m for our citizens to access appropriate h e a l t h care, including emergency and p r i m a r y care, especially for the increasing n u m b e r s of individuals who have no access to health insurance because of their emp l o y e r s ' e c o n o m i c woes. A m e r i c a n c i t i z e n s s h o u l d n o t a c c e p t an increase in the level of u n c o m p e n s a t e d care b e c a u s e of o u r n a t i o n a l econ o m i c recession. M a n y of the solutions to alleviating both the access to care issue and t h e ED o v e r c r o w d i n g p r o b l e m are contained in the ACEP policy statem e n t on hospital and ED overcrowding: 3 • Provide a basic level of h e a l t h insurance for all citizens; • Remove financial disincentives to h o s p i t a l s for p r o v i d i n g e m e r g e n c y care; • Where needed, increase the capacity to provide critical care, inpatient, and nursing h o m e services; and
• S u p p o r t access to p r i m a r y care services and encourage initiatives des i g n e d to p r e v e n t s e r i o u s i l l n e s s e s and injuries. We m u s t reaffirm our c o m m i t m e n t to w o r k w i t h Congress and the adm i n i s t r a t i o n to achieve e n a c t m e n t of legislation to solve the access to care challenge, while assuring that emergency physicians receive equitable r e i m b u r s e m e n t for services rendered. We applaud the efforts of Pane et al and other researchers in the field, and we concur w i t h the concluding statem e n t c o n t a i n e d in t h e A c c e s s to H e a l t h Care Coalition document: " . . . in order to m e e t the i m m e d i a t e c h a l l e n g e of t h e u n i n sured population, and the longer t e r m challenge of a better h e a l t h care s y s t e m for all Americans, the medical profession m u s t recognize its responsibility to w o r k w i t h others to assure quality care is delivered in a cost efficient manner. We can do no less. T h e h e a l t h of t h e n a t i o n is r e f l e c t e d in t h e h e a l t h of its people." The individual physician will impact the s y s t e m far less t h a n those w h o are organized in a c h i e v i n g t h e
s o c i a l goal of u n i v e r s a l a c c e s s to h e a l t h care. 4 The t i m e has come for emergency physicians to u n i t e on behalf of our patients, our colleagues in emergency medicine, and our fellow physicians in other specialties by advocating h e a l t h care reform embodying p r i n c i p l e s of access to care and appropriate r e i m b u r s e m e n t .
E Jackson Allison, ]r, MD/MPH, FACEP Department of Emergency Medicine East Carolina University School of Medicine Greenville, North Carolina Kenneth L DeHart, MD, FACEP Departmer~t of Emergency Medicine Grand Strand General Hospital North Myrtle Beach, South Carolina 1. American College of Emergency Physicians: Longrange plan and e n v i r o n m e n t a l a s s e s s m e n t 1990-9[: ACEP statement of direction: Value statements. Dallas, American College of Emergency Physicians, approved, board iff directors, March 10, [990. 2. American College of Emergency Physicians: Survey studies characteristics of ACEP incmbcrs. ACEP New~ 1986;5:7. 3. American College of Emergency Physicians: Measures to deal with emergency department overcrowding, Arm Emerg Med [990;19:944-945. 4. Kieinman EC: Health care m crisis: A proposed role fl~r the individual physician as adw~cate. ]AMA 199l; [5:1991-1992.
From the Laboratory to the Bedside: When? The article by Pollack et al, "Intraosseous A d m i n i s t r a t i o n of A n t i b i otics: S a m e - D o s e C o m p a r i s o n W i t h I n t r a v e n o u s A d m i n i s t r a t i o n in t h e Weanling Pig," in this issue of Annals raises an i m p o r t a n t q u e s t i o n : When s h o u l d a c l i n i c i a n t a k e basic science data and apply it to clinical situations? In their study, Pollack et al compared intraosseous and IV adm i n i s t r a t i o n of different a n t i b i o t i c s , each in four pigs, and from this extrapolated clinical r e c o m m e n d a t i o n s for intraosseous a n t i b i o t i c a d m i n i s tration in children. T h e gap b e t w e e n their laboratory data and the septic pediatric patient is a large one and requires careful thought before the jump is made. There are f u n d a m e n t a l differences between animals and h u m a n beings 172/821
that m u s t be considered w h e n evaluating animal data and animal models. 1. A n i m a l s m a y differ among species and from h u m a n beings in the rate of drug absorption, distribution, m e t a b o l i s m , and excretion. Enzymes that m e t a b o l i z e drugs in the kidney, liver, and lung vary a m o n g a n i m a l species. Proteins that bind drugs are different among species and m a y lead to d i f f e r e n c e s in a v a i l a b l e d r u g . T h e r e m a y be a n a t o m i c differences such as p e r c e n t a g e of body fat t h a t change a b s o r p t i o n and d i s t r i b u t i o n . C o n s e q u e n t l y , s i m i l a r i t i e s or differe n c e s in p h a r m a c o k i n e t i c s in one species m a y not be the same in other species or in h u m a n beings. W h e n ever possible, m o r e than one species s h o u l d be s t u d i e d and result~ cornAnnals of Emergency Medicine
pared for similarities and differences. 2. A n i m a l s a r e r a r e l y p e r f e c t models for h u m a n disease. The m o r e dissimilar the a n i m a l m o d e l and the h u m a n disease, the less likely the results will have clinical relevance. T h e response of a' h e a l t h y a n e s t h e tized a n i m a l to a drug is likely to be q u i t e different from t h a t of an una n e s t h e t i z e d h u m a n in a d i s e a s e d state. For instance, during sepsis, a change in h e m o d y n a m i c s leads to a change in absorption. Tissue permea b i l i t y c h a n g e s , as s e e n w i t h t h e m e n i n g e s during m e n i n g i t i s , w h i c h m a y lead to a different d i s t r i b u t i o n pattern. Finally, enzyme function m a y change, leading to a difference in m e t a b o l i s m and excretion. 3. A n i m a l m o d e l s of disease are often o v e r s i m p l i f i c a t i o n s of a specific 20:7 July 1991
EDITORIALS
p r o b l e m . For e x a m p l e , to p r o d u c e a hypertensive a n i m a l model, a k i d n e y is wrapped tightly, producing changes in the renin angiotensin regu l a t i o n of blood pressure, thus leading to h y p e r t e n s i o n . However, this o c c u r s o v e r w e e k s as o p p o s e d to years or decades as seen in h u m a n disease. I n f o r m a t i o n from studies of a n t i h y p e r t e n s i v e agents in these anim a l m o d e l s is useful b u t is n o t always the answer to h u m a n hypertension. Interpretation of data, even in a good a n i m a l m o d e l of disease, m u s t be d o n e c a u t i o u s l y . A l l t o o o f t e n there is an over-generalization of the r e s u l t s and a t e n d e n c y to correlate t h e m w i t h clinical information prematurely. See related article, p 772. Despite their limitations, animal m o d e l s do provide e x t r e m e l y valuable i n f o r m a t i o n a b o u t disease processes and intervention. M u c h of this i n f o r m a t i o n does not come from single studies, but rather from m u l t i p l e studies using different species and techniques. C h a n g i n g c l i n i c a l practice or trying a n e w therapy based on one a n i m a l s t u d y is n o t j u s t i f i e d . However, if m u l t i p l e , w e l l - d e s i g n e d studies s h o w a t r e n d or c o n s i s t e n t pattern, then clinical study or appli-
20:7: July 1991
cation m a y be warranted. T h e quality of a research study (design, m e t h o d o l o g y , d a t a c o l l e c t i o n ) and relevance of the a n i m a l m o d e l to the disease process being studied are essential c o m p o n e n t s for any meaningful c o n c l u s i o n s . It is i n c u m b e n t on investigators w h o use animals for r e s e a r c h to c a r e f u l l y p l a n e x p e r i m e n t s and extract as m u c h information as possible from each animal. As a research fellow, I r e m e m b e r a mentor telling m e that if I was going to sacrifice an a n i m a l ' s life, then I was obligated to get every bit of information possible from the study. All too often physicians conduct " q u i c k and dirty" studies using a m i n i m a l n u m ber of animals and address only one issue. M u c h of the w o r k in areas such as i n t r a o s s e o u s and e n d o t r a c h e a l drug a d m i n i s t r a t i o n is typical of this problem. A single drug dose is administered, a few blood levels are d r a w n and assayed, and the investigator writes a paper. Rarely are issues such as tissue deposition of the drug, detailed pharmacokinetics, effect of the d r u g on t h e d i s e a s e p r o c e s s , a n d pathologic changes of the drug on the bone or lung addressed. This is valuable information that is lost. To obtain it, m o r e animals m u s t be sacrificed. In their paper, P o l l a c k et al have
Annals of Emergency Medicine
provided us w i t h useful information about the intraosseous administration of antibiotics that was not available previously. This is the first paper to address antibiotic administration by this route, and their data are consistent with other studies that have shown that the intraosseous route is similar but not identical to a peripheral venous site. This is a helpful first step, b u t m u c h m o r e w o r k a n d i n f o r m a t i o n are n e e d e d before we can feel as confident about giving intraosseous antibiotics to the septic child as we do giving IV antibiotics. We are often willing to accept and try new ideas in an emergency w h e n traditional resources have failed us, but before we accept a n e w c o n c e p t or new i n f o r m a t i o n as part of our routine practice, it m u s t be very clear that there is a proven benefit. W h e n should the clinician take ani m a l data to the bedside? There is obv i o u s l y no c l e a r - c u t a n s w e r to this question. However, before this step is taken, the clinician m u s t have welldesigned, thorough studies that provide clear evidence that a change in c l i n i c a l p r a c t i c e is l i k e l y to be safe and advantageous to the patient.
William H Spivey, MD, FACEP Department of Emergency Medicine Medical College of Pennsylvania Philadelphia
822/t73
