Veterinary Surgery, 21, 1,20-24, 1992
Treatment of Dogs in Hemorrhagic Shock by lntraosseous Infusion of Hypertonic Saline and Dextran E. B. OKRASINSKI, DVM, D. J. KRAHWINKEL, MS, DVM, Diplomate ACVS, and W. L. SANDERS, PhD Under isoflurane anesthesia, 50% of the calculated blood volume was removed from 11 dogs. After 30 minutes, five dogs were treated with hypertonic saline and dextran (HSD) (5 mL/kg) followed by isotonic saline solution (2 mL/kg) intraosseously. Six dogs (controls) received isotonic saline (7 mL/kg) intraosseously. All treatments were administered through the medullary cavity of the tibia over a 30-minute period. Cardiac output, mean arterial pressure, central venous pressure, packed cell volume, total protein, and blood gases were monitored for 4 hours. Cardiac output, mean arterial pressure, and circulating volume (indicated by packed cell volume and total protein) were significantly improved after administration of HSD. We conclude that intraosseous infusion of HSD is efficacious in treating hemorrhagic shock and believe the technique may prove to be useful in clinical situations when intravenous lines cannot be established rapidly.
the blood loss, HSD restored cardiac output and mean arterial pressure.I2 Hypertonic saline and dextran may be given via peripheral or central venous lines with equal efficacy.I3 The use of HSD by intraosseous infusion has not been reported. The purpose of this study was to investigate the use of intraosseous infusions of HSD in dogs as a method for resuscitation of hemorrhagic shock.
is critical in the treatment of R animals with hemorrhagic shock. Intravenous catheters may be difficult or impossible to place in young or APID VENOUS ACCESS
obese animals in shock. Intraosseous infusions can be started rapidly regardless of the patient's cardiovascular status, and they have been shown to be safe and reliable for emergency use.'.' Epinephrine, dopamine, atropine, sodium bicarbonate, dextrose, phenobarbital, and diazepam were as effective in emergencies when administered intraosseously as they were by central IV Crystalloids and blood can also be administered intraosseously. In studies with immature dogs, the maximum intraosseous flow rate for infusion of crystalloids was 29 mL/min, which was too slow for treatment of hemorrhagic shock.' Results were similar in small swine and calve^.^,^ For these reasons, it would be appealing to treat hemorrhagic shock with a solution that could be given intraosseously in smaller volumes. Intravenous administration of hypertonic saline and dextran (HSD) has been shown to improve cardiovascular parameters and survival in experimental shock models. 'O-" The beneficial effects of HSD have been shown to be superior to either hypertonic saline or dextran alone." When administered in volumes equal to 10% of
Materials and Methods Eleven conditioned adult beagles weighing 8.6 to 12 kg were determined to be normal by physical examination. Complete blood cell counts, serum chemistries, and electrolytes were measured, The dogs were fasted for 12 hours. The dogs were anesthetized by chamber induction with isoflurane.* After tracheal intubation, anesthesia was maintained with isoflurane. No other drugs were administered. Anesthetic levels were determined with end-tidal infrared spectrophotometry.t Isoflurane levels were maintained at 1.0 to 1.5 times the reported canine min* Anaquest, Madison. Wisconsin.
t Datex, Helsinki. Finland.
From the Department of Urban Practice, College of Veterinary Medicine (Okrasinski, Krahwinkel)and the Department of Statistics,Agricultural Experiment Station (Sanders), University of Tennessee, Knoxville, Tennessee. American College of Veterinary Surgeons, New Orleans, Louisiana. Presented at the 25th Annual Meeting (1990), Funded by the University of Tennessee College of Veterinary Medicine Venture Grant. No reprints available.
20
OKRASINSKI, KRAHWINKEL, AND SANDERS imum alveolar concentration^.'^ Ventilation was maintained with a mechanical ventilator delivering 2 1% F,02 at a rate of 12 breaths per minute and a tidal volume of 22 mL/kg body weight. The left femoral artery and left jugular vein were cannulated for sampling and pressure measurements. The right jugular vein was exposed and a 5F Swan-Ganz catheter$ was advanced to the pulmonary artery for cardiac output determination. The medial aspect of the proximal end of the tibia was infiltrated with 3 mL of 2% lidocaine and an 18-gauge bone marrow needle was inserted into the medullary cavity. The dogs were heparinized (100 IU/ kg IV) (Fig. 1). Mean arterial pressures, central venous pressures, and pulmonary artery pressures were measured by pressure transducers attached to a multichannel physiologic recorder.(ill With the dogs in dorsal recumbency, the transducers were positioned at the level of the thoracic inlet and readjusted to read 0 mm Hg when opened to the atmosphere. Cardiac output was measured with a cardiac output computer7 and a thermodilution technique with 5 mL iced injectates. Each cardiac output was determined by averaging three measurements. Arterial gases were determined with an automated blood gas analyzer.# Packed cell volume and total protein were measured with microcapillary tubes and a light refractometer. After a 1-hour stabilization period, cardiac output, mean arterial pressure, central venous pressure, packed cell volume, total protein, heart rate, and arterial blood gases were recorded every 30 minutes. During the first 30 minutes, 50%of each dog’s calculated blood volume (45 mL/kg) was removed. Thirty minutes after exsanguination, the animals were treated by intraosseous infusion into the tibia over a 30-minute period. Six dogs (controls) were treated with isotonic saline solution (7 mL/kg). Five dogs received 7.5% NaCl and 6% dextran 70 (HSD) (5 mL/kg), followed by isotonic saline (2 mL/kg). HSD was prepared by adding medical grade NaCl to 6% dextran in saline in quantities sufficient to create a 7.5% NaCl SOlution. The response to treatment was recorded for 3 hours. At the completion of the study, the catheters were removed and anesthesia was ended. The animals were monitored for 2 days. Packed cell volume, total protein, and degree of lameness were recorded daily. Statistical analysis was performed by calculating best fit asymptotic curve to the posttreatment response data.I5 Differences between treatments were ascertained by testing the hypothesis of no differencebetween curves. Differences were considered significant at p < .05. $. American Edwards Lab, Anasco, Puerto Rico. p Statham Instruments, Oxnard, California. (1 Could, Dayton, Ohio. 7American Edwards Lab, Anasco, Puerto Rico. # Corning Medical, Medfield, Massachusetts.
21
F,0,21% 1 .O-I.5 MAC lsoflurane
TREATMENT : Group 1-0 9 % NaCl Group 11.-7 5% HSD
Arterial Blood Gases
\\\ \\
Fig. 1. Schematic representation of the anesthesia instrumentation and monitoring of animals in this study.
Results
Cardiac output and mean arterial pressure dropped profoundly in all dogs after blood loss. These values returned to near baseline within 30 minutes of treatment with HSD and were maintained for the 3-hour observation period. Cardiac output and mean arterial pressure of control animals slowly increased after exsanguination but remained significantly lower than the treatment group (p < .05) (Figs. 2A, B). There was a slight increase in packed cell volume during exsanguination of all dogs. After treatment, there was a significant decrease in the packed cell volume of animals treated with HSD. Packed cell volume of the controls decreased slightly but remained above baseline values (Fig. 2C). Total protein in all dogs declined throughout the study. This decline was significantly greater in animals treated with HSD (Fig. 2D).
22
INTRAOSSEOUS INFUSION FOR SHOCK 80
2.0 1.9 1.8 1.7 c .- 1.6 E 1.5 1.4 4 1.3 ,a 1.2 1.1 0 1.0 0.9 0.8 0.7 0.6 0.5 0.4
,
'I
-
i HSD
r E
3
m
E 60 m
Control
2
3 70
50
?
P
5 3
._ 40 5 30
z
I
=
20 10
1
0
2
3
B
Time (hr)
A
Fig. 2A. The effect of intraosseous infusions on cardiac output (L/rnin).
38
-d
m 36
E
3
s 6
P 5m
!:
5.0 4.9 4.8 4.7 4.6 c 4.5 ._ 2 4.4 2 4.3 a - 4.2 4.1
I 35
33 32
.
a 31
0
1
C
2
. 1
2 Time (hr)
3
Fig. 26. The effect of intraosseous infusions on mean arterial pressure (mm Hg).
39
37
i 0
4
$
4.0 3.9
3.8 3.7 3.6 3.5
HSD B
B
3
I 4
Time (hr)
Fig. 2C. The effect of intraosseous infusions on packed cell volume.
D
Time (hr)
Fig. 2D. The effect of intraosseous infusions on total protein (g/dL).
150 140
m
Z 130
Fig. 2. The effect of intraosseous infusion of hypertonic saline and dextran (HSD) or saline (controls) following blood loss. Blood loss began at T = 0 and ended at T = 30 minutes. Treatments were administered by intraosseous infusion from T = 1 hour until T = 1.5 hours.
LT
e
mm 120 I 110 100 90
0
E
1
2 Time (hr)
3
4
Fig. 2E. The effect of intraosseous infusions on heart rate.
All heart rates increased gradually over the 3-hour penod. This increase was higher in animals treated with HSD (p < .05) (Fig. 2E). Blood gases, pH, and central venous pressures were not significantly different between treatment groups. Packed cell volume and total protein at 24 and 48 hours were similar regardless of treatment.
Dogs in the control group had no signs of lameness after the study. There was moderate to marked lameness on day 1 that resolved within 48 hours in the dogs treated with HSD.
Discussion Similar studies of hemorrhagic shock have been performed with dogs under barbiturate anesthesia, which re-
OKRASINSKI, KRAHWINKEL, AND SANDERS quired repeated administration of the drug. I 2 , l 6 As a result, anesthetic levels varied. Isoflurane allowed consistent anesthetic levels to be maintained throughout the current study, and it had minimal effects on the cardiovascular system.14 It has been stated that blood loss greater than 48% is fata1.I7-I8All control animals in this study survived despite a 50% blood loss. We believe that the use of isoflurane anesthesia may have been responsible. It has been reported that substances injected intraosseously quickly reach the central c i r ~ u l a t i o nData . ~ ~ ~from ~ this study confirm that observation. Cardiac output and mean arterial pressure returned to baseline levels within 30 minutes of infusing HSD intraosseously. This was significantly above the response to isotonic saline solution. The beneficial effects of HSD were primarily the result ofa rapid fluid shift to the intravascular space. The marked decreases in packed cell volume and total protein gave evidence of that fluid shift, which was induced by an increased osmotic gradient.” The controls had a very slight decrease in packed cell volume after treatment. This observation reiterated the inaccuracy of hematocrit values in reflecting acute blood loss. Other reported benefits of treatment with HSD include improved cardiac performance and visceral arterial dilat i ~ n . ” - ’ The ~ increase in cardiac output after HSD was the result of increased stroke volume and heart rate. The determinants of stroke volume are preload and contractility. Central venous pressure is often used as a measure of preload. Central venous pressure did not differ between controls and animals treated with HSD. An increase in stroke volume without increased central venous pressure may be a reflection of increased contractility in the animals treated with HSD. Elevation of mean arterial pressure is a reflection of the increase in cardiac output. Change in peripheral resistance may have contributed to an increased mean arterial pressure, but peripheral resistance was not measured. All animals in this study developed metabolic acidosis as a result of tissue hypoperfusion. Compensation for metabolic acidosis depends on increased loss of carbon dioxide by hyperventilation. Since all the dogs were ventilated mechanically, respiratory compensation could not occur. Therefore, there was no difference between treatment groups. Mechanical ventilation maintained similar blood gases in both groups. Despite profound hypotension after exsanguination, changes in heart rates occurred slowly over the 3-hour observation period and never exceeded 160 beats per minute. There are two possible explanations for the absence of a reflex tachycardia. First, the animals were anesthetized with isoflurane. Isoflurane has been shown to interfere with baroreceptor response to h y p ~ t e n s i o nThis .~~ interference has been shown to occur at 2.6% inspired isoflurane, but not at 1.3%. Since animals in this study
23
never exceeded 1.7% inspired isoflurane, this seems an unlikely cause. The second possible explanation is the presence of a cardiac depressor reflex that originates from vagal afferent C fibers originating in the left ventricle. This reflex elicits a slower heart rate during hypotension when inadequate ventricular filling is o ~ c u r r i n g . ~ ~ , ’ ~ The use of HSD raises some hypothetical concerns about iatrogenic hypernatremia, increased hemorrhage, and the possibility of coagulopathy or anaphylaxis associated with dextran. In more than 300 studies in which HSD was used to treat hemorrhagic shock, there were no reports of adverse effects associated with h~pernatremia.’~ Increased hemorrhage has been reported after the administration of HSD in an uncontrolled hemorrhage This would seem logical because of the effects of HSD on cardiac output and mean arterial pressure. The authors advocated the use of HSD as adjunctive therapy to improve cardiovascular parameters while definitive measures were taken to stop hemorrhage. The adverse effects of dextran on platelet function are well d ~ c u m e n t e dThe .~~ effects tend to be offset by increasing peripheral perfusion during hypotension. The incidence of anaphylaxis to dextran in domestic animals has not been reported. The use of hypertonic agents for intraosseous infusions has been reported in laboratory investigations and in clinIn a review of 982 intraosseous infuical sions in children in 1947, there were four cases of osteomyelitis. Three of those children had received hypertonic In reviews conducted after 1977, there have been no reports of osteomyelitis associated with intraosseous infusions. This is probably related to the improved use of aseptic technique and the decreased use of prolonged intraosseous infusions.32 The local effect of one hypertonic solution, sodium bicarbonate, has been closely examined. Only minimal histopathologic changes were noted immediately or 1 month after intraosseous i n f ~ s i o n . ’ . ~There ’ ’ ~ ~ was no long-term effect on development of immature bones after intraosseous infusion of sodium bicarbonate. Five percent sodium chloride (NaCl) causes necrosis of the marrow and some endosteal damage when administered intraosseously. Dextran 70 causes minimal disruption of the medullary cavity.** The long-term consequences of intraosseous infusions of HSD are unknown. The risk of damage to the medullary cavity must be weighed against the potential benefits of intraosseous infusion of HSD in an emergency situation. In conclusion, the results of this study add to the list of emergency applications of intraosseous infusions. By using small volumes of HSD, the intraosseous route may be used to substantially improve cardiovascular param-
** Okrasinski EB, Patton CS, Krahwinkel DJ. Unpublished data.
INTRAOSSEOUS INFUSION FOR SHOCK
eters. This would enable emergency clinicians more time to establish intravenous catheters and to institute definitive therapeutic measures.
References I. Brunette DD, Fischer R. lntravascular access in pediatric cardiac
arrest. Am J Emerg Med 1988;6:577-579. 2. Glaeser PW. Losek JD, Nelson DB, et al. Pediatric intraosseous infusion: impact on vascular access time. Am J Emerg Med 1988;6:33 1-333. 3. Shoor PM. Berryhill RE. Benumof JL. Intraosseous infusion: pressure flow relationship and pharmacokinetics. J Trauma 1979;9:772774. 4. Neish SR. Macon MG, Moore JW, Graeber GM. lntraosseous infusion of hypertonic glucose and dopamine. Am J Dis Child 1988: 1422378-880. 5. Brickman KR, Rega P, Guincess M. A comparative study of intraosseous versus peripheral intravenous infusion of diazepam and phenobarbital in dogs. Ann of Emerg Med 1987; 16:11411 144. 6. Prete MR, Hannan CJ. Burkle FM. Plasma atropine concentration via the intravenous endotracheal and intraosseous routes of administration. Ann Emerg Med 1987;5:101-104. 7. Spivey WH, Lathers CM, Malone DR, et al. Comparison of intraosseous, central, and peripheral routes of sodium bicarbonate administration during CPR in pigs. Ann Emerg Med 1985; 14:I 135I 139. 8. Hodge D, Paredes CD, Fleisher G. lntraosseous infusion flow rates in hypovolemic “pediatric” dogs. Ann Emerg Med 1987; 16:305307. 9. Schoffstall JM. Spivey WH, Davidheiser S, et al. Intraosseous crystalloid and blood infusion in a swine model. J Trauma 1989;29: 384-387. 10. Velasco IT, Rocha E Silva M, Oliviera MA, et al. Hypertonic and hyperoncotic resuscitation from severe hemorrhage shock in dogs: a comparative study. Crit Care Med 1989; 17:26 1-264. II. Mullins RJ, Hudgen RW. Hypertonic saline resuscitates dogs in endotoxic shock. J Surg Res 1987;43:37-44. 12. Velasco IT, Pontieri V, Rocha E Silva M, Loper OU. Hyperosmotic NaCl and severe hemorrhagic shock. Am J Physiol 1980;239: H664-H673. 13. Hand R, Holcoft JW. Perion PR, Kramer GC. Comparison of peripheral and central infusions of 7.5% NaC1/6% dextran 70. Surgery 1988: 103:684-689. 14. Egger El. IsoJltrrune, u Compendium and Rrlfrrence. Airco Inc., Madison, WI. 1981:12, 32-49. 15. SAS Institute Inc., “SAS/STAT’”” Guide for Personal Computers. Version 6 Edition. Cary, NC, SAS Institute Inc. 198755 1.
16. Markov AK, Jeny J , Thomas 2, et al. Increasing survival of dogs subjected to hemorrhagic shock by the administration of fructose 1-6 diphosphate. Surgery 1987; 1025 15-527. 17. Pascoe PJ. Emergency care medicine. In: Short CE, ed. Principles und Prucfice ~f Veterinary Anesthesia. Baltimore: Williams and Wilkins. 1987:567. 18. Nelson AW. Hypovolemic shock. Vet Clin North Am 1976;6:187. 19. Tocantis LM. Rapid absorption of substances injected into the bone marrow. SOCExp Biol Med 1940;45:292-296. 20. Smith GJ, Kramer GC. Perron P. et al. A comparison of several hypertonic solutions for resuscitation of bled sheep. J Surg Res 1985;39:517-528. 2 I. Rowe GG.McKenna DH. Corliss RJ,Sialer S. Hemodynamic effects of hypertonic sodium chloride. J Applied Physiol 1972: 32: 182184. 22. Rocha E Silva M, Negraes GA. Soares MA. Hypertonic saline resuscitation from severe hemorrhagic shock: patterns of regional blood flow. Circ Shock 1986; 19: 165. 23. Maningas PA. Resuscitation with 7.5% NaCl in 6% Dextran 70 during hemorrhagic shock in swine: effects on organ blood flow. CritCare Med 1987:15:1121-1126. 24. Seagard JL, Elegbe EO. Hopp FA. et al. Effects of isoflurane on the baroreceptor reflex. Anesthesiology 1983:59:5 I1-520. 25. Sander-Jensen K. Mehlsen J. Stadeager C, et al. Heart rate during hypotension central hypovolemia before and after atropine in man. First Vienna Shock Forum, Part A. 1987:629-632. 26. Oberg B, White S. The role of vagal cardiac nerves and atrial baroreceptors on circulatory adjustments to hemorrhage in cats. Acta Physiol Scand 1970; 80:395-403. 27. Maningas PA, Mattox KL, Pepe PE, et al. Hypertonic saline for the prehospital management of traumatic hypotension. Am J Surg 1989; 157528-533. 28. Gross D, Landau EH, Baruch K, Krausz MM. Quantitative measurements of bleeding following hypertonic saline therapy in uncontrolled hemorrhagic shock. J Trauma 1989;29:79-83. 29. Raffe MR. Fluid therapy, electrolyte and acid-base balance, and blood replacement. In: Short CE, ed. Principles and fraciice oJ‘ Veferinarj Anes/he.c.iu. Baltimore: Williams and Wilkins. 1987: 489-490. 30. Heinald S, Sondergaard T, Tudvad F. Bone marrow infusions in childhood: experience from a thousand infusions. J Pediatr 1947; 30:400-4 I1. 3 I. Lathers CM, Kim JF, High WB. et al. An investigation ofthe pathological and physiological effects on intraosseous sodium bicarbonate in pigs. J Clin Pharmacol 1989;29:354-359. 32. Brillman JC. Intraosseous infusions for emergency intravascular access. J Emerg Med 1988: 10:75-80. 33. Brickman KR, Rega P, Koltz M, Guinness M. Analysis of growth plate abnormalities following intraosseous infusions through the proximal tibia1 epiphysis in pigs. Ann Emerg Med 1988; I 7: 12 I123.
Treatment of Dogs in Hemorrhagic Shock by lntraosseous Infusion of Hypertonic Saline and Dextran E. B. OKRASINSKI, DVM, D. J. KRAHWINKEL, MS, DVM, Diplomate ACVS, and W. L. SANDERS, PhD Under isoflurane anesthesia, 50% of the calculated blood volume was removed from 11 dogs. After 30 minutes, five dogs were treated with hypertonic saline and dextran (HSD) (5 mL/kg) followed by isotonic saline solution (2 mL/kg) intraosseously. Six dogs (controls) received isotonic saline (7 mL/kg) intraosseously. All treatments were administered through the medullary cavity of the tibia over a 30-minute period. Cardiac output, mean arterial pressure, central venous pressure, packed cell volume, total protein, and blood gases were monitored for 4 hours. Cardiac output, mean arterial pressure, and circulating volume (indicated by packed cell volume and total protein) were significantly improved after administration of HSD. We conclude that intraosseous infusion of HSD is efficacious in treating hemorrhagic shock and believe the technique may prove to be useful in clinical situations when intravenous lines cannot be established rapidly.
the blood loss, HSD restored cardiac output and mean arterial pressure.I2 Hypertonic saline and dextran may be given via peripheral or central venous lines with equal efficacy.I3 The use of HSD by intraosseous infusion has not been reported. The purpose of this study was to investigate the use of intraosseous infusions of HSD in dogs as a method for resuscitation of hemorrhagic shock.
is critical in the treatment of R animals with hemorrhagic shock. Intravenous catheters may be difficult or impossible to place in young or APID VENOUS ACCESS
obese animals in shock. Intraosseous infusions can be started rapidly regardless of the patient's cardiovascular status, and they have been shown to be safe and reliable for emergency use.'.' Epinephrine, dopamine, atropine, sodium bicarbonate, dextrose, phenobarbital, and diazepam were as effective in emergencies when administered intraosseously as they were by central IV Crystalloids and blood can also be administered intraosseously. In studies with immature dogs, the maximum intraosseous flow rate for infusion of crystalloids was 29 mL/min, which was too slow for treatment of hemorrhagic shock.' Results were similar in small swine and calve^.^,^ For these reasons, it would be appealing to treat hemorrhagic shock with a solution that could be given intraosseously in smaller volumes. Intravenous administration of hypertonic saline and dextran (HSD) has been shown to improve cardiovascular parameters and survival in experimental shock models. 'O-" The beneficial effects of HSD have been shown to be superior to either hypertonic saline or dextran alone." When administered in volumes equal to 10% of
Materials and Methods Eleven conditioned adult beagles weighing 8.6 to 12 kg were determined to be normal by physical examination. Complete blood cell counts, serum chemistries, and electrolytes were measured, The dogs were fasted for 12 hours. The dogs were anesthetized by chamber induction with isoflurane.* After tracheal intubation, anesthesia was maintained with isoflurane. No other drugs were administered. Anesthetic levels were determined with end-tidal infrared spectrophotometry.t Isoflurane levels were maintained at 1.0 to 1.5 times the reported canine min* Anaquest, Madison. Wisconsin.
t Datex, Helsinki. Finland.
From the Department of Urban Practice, College of Veterinary Medicine (Okrasinski, Krahwinkel)and the Department of Statistics,Agricultural Experiment Station (Sanders), University of Tennessee, Knoxville, Tennessee. American College of Veterinary Surgeons, New Orleans, Louisiana. Presented at the 25th Annual Meeting (1990), Funded by the University of Tennessee College of Veterinary Medicine Venture Grant. No reprints available.
20
OKRASINSKI, KRAHWINKEL, AND SANDERS imum alveolar concentration^.'^ Ventilation was maintained with a mechanical ventilator delivering 2 1% F,02 at a rate of 12 breaths per minute and a tidal volume of 22 mL/kg body weight. The left femoral artery and left jugular vein were cannulated for sampling and pressure measurements. The right jugular vein was exposed and a 5F Swan-Ganz catheter$ was advanced to the pulmonary artery for cardiac output determination. The medial aspect of the proximal end of the tibia was infiltrated with 3 mL of 2% lidocaine and an 18-gauge bone marrow needle was inserted into the medullary cavity. The dogs were heparinized (100 IU/ kg IV) (Fig. 1). Mean arterial pressures, central venous pressures, and pulmonary artery pressures were measured by pressure transducers attached to a multichannel physiologic recorder.(ill With the dogs in dorsal recumbency, the transducers were positioned at the level of the thoracic inlet and readjusted to read 0 mm Hg when opened to the atmosphere. Cardiac output was measured with a cardiac output computer7 and a thermodilution technique with 5 mL iced injectates. Each cardiac output was determined by averaging three measurements. Arterial gases were determined with an automated blood gas analyzer.# Packed cell volume and total protein were measured with microcapillary tubes and a light refractometer. After a 1-hour stabilization period, cardiac output, mean arterial pressure, central venous pressure, packed cell volume, total protein, heart rate, and arterial blood gases were recorded every 30 minutes. During the first 30 minutes, 50%of each dog’s calculated blood volume (45 mL/kg) was removed. Thirty minutes after exsanguination, the animals were treated by intraosseous infusion into the tibia over a 30-minute period. Six dogs (controls) were treated with isotonic saline solution (7 mL/kg). Five dogs received 7.5% NaCl and 6% dextran 70 (HSD) (5 mL/kg), followed by isotonic saline (2 mL/kg). HSD was prepared by adding medical grade NaCl to 6% dextran in saline in quantities sufficient to create a 7.5% NaCl SOlution. The response to treatment was recorded for 3 hours. At the completion of the study, the catheters were removed and anesthesia was ended. The animals were monitored for 2 days. Packed cell volume, total protein, and degree of lameness were recorded daily. Statistical analysis was performed by calculating best fit asymptotic curve to the posttreatment response data.I5 Differences between treatments were ascertained by testing the hypothesis of no differencebetween curves. Differences were considered significant at p < .05. $. American Edwards Lab, Anasco, Puerto Rico. p Statham Instruments, Oxnard, California. (1 Could, Dayton, Ohio. 7American Edwards Lab, Anasco, Puerto Rico. # Corning Medical, Medfield, Massachusetts.
21
F,0,21% 1 .O-I.5 MAC lsoflurane
TREATMENT : Group 1-0 9 % NaCl Group 11.-7 5% HSD
Arterial Blood Gases
\\\ \\
Fig. 1. Schematic representation of the anesthesia instrumentation and monitoring of animals in this study.
Results
Cardiac output and mean arterial pressure dropped profoundly in all dogs after blood loss. These values returned to near baseline within 30 minutes of treatment with HSD and were maintained for the 3-hour observation period. Cardiac output and mean arterial pressure of control animals slowly increased after exsanguination but remained significantly lower than the treatment group (p < .05) (Figs. 2A, B). There was a slight increase in packed cell volume during exsanguination of all dogs. After treatment, there was a significant decrease in the packed cell volume of animals treated with HSD. Packed cell volume of the controls decreased slightly but remained above baseline values (Fig. 2C). Total protein in all dogs declined throughout the study. This decline was significantly greater in animals treated with HSD (Fig. 2D).
22
INTRAOSSEOUS INFUSION FOR SHOCK 80
2.0 1.9 1.8 1.7 c .- 1.6 E 1.5 1.4 4 1.3 ,a 1.2 1.1 0 1.0 0.9 0.8 0.7 0.6 0.5 0.4
,
'I
-
i HSD
r E
3
m
E 60 m
Control
2
3 70
50
?
P
5 3
._ 40 5 30
z
I
=
20 10
1
0
2
3
B
Time (hr)
A
Fig. 2A. The effect of intraosseous infusions on cardiac output (L/rnin).
38
-d
m 36
E
3
s 6
P 5m
!:
5.0 4.9 4.8 4.7 4.6 c 4.5 ._ 2 4.4 2 4.3 a - 4.2 4.1
I 35
33 32
.
a 31
0
1
C
2
. 1
2 Time (hr)
3
Fig. 26. The effect of intraosseous infusions on mean arterial pressure (mm Hg).
39
37
i 0
4
$
4.0 3.9
3.8 3.7 3.6 3.5
HSD B
B
3
I 4
Time (hr)
Fig. 2C. The effect of intraosseous infusions on packed cell volume.
D
Time (hr)
Fig. 2D. The effect of intraosseous infusions on total protein (g/dL).
150 140
m
Z 130
Fig. 2. The effect of intraosseous infusion of hypertonic saline and dextran (HSD) or saline (controls) following blood loss. Blood loss began at T = 0 and ended at T = 30 minutes. Treatments were administered by intraosseous infusion from T = 1 hour until T = 1.5 hours.
LT
e
mm 120 I 110 100 90
0
E
1
2 Time (hr)
3
4
Fig. 2E. The effect of intraosseous infusions on heart rate.
All heart rates increased gradually over the 3-hour penod. This increase was higher in animals treated with HSD (p < .05) (Fig. 2E). Blood gases, pH, and central venous pressures were not significantly different between treatment groups. Packed cell volume and total protein at 24 and 48 hours were similar regardless of treatment.
Dogs in the control group had no signs of lameness after the study. There was moderate to marked lameness on day 1 that resolved within 48 hours in the dogs treated with HSD.
Discussion Similar studies of hemorrhagic shock have been performed with dogs under barbiturate anesthesia, which re-
OKRASINSKI, KRAHWINKEL, AND SANDERS quired repeated administration of the drug. I 2 , l 6 As a result, anesthetic levels varied. Isoflurane allowed consistent anesthetic levels to be maintained throughout the current study, and it had minimal effects on the cardiovascular system.14 It has been stated that blood loss greater than 48% is fata1.I7-I8All control animals in this study survived despite a 50% blood loss. We believe that the use of isoflurane anesthesia may have been responsible. It has been reported that substances injected intraosseously quickly reach the central c i r ~ u l a t i o nData . ~ ~ ~from ~ this study confirm that observation. Cardiac output and mean arterial pressure returned to baseline levels within 30 minutes of infusing HSD intraosseously. This was significantly above the response to isotonic saline solution. The beneficial effects of HSD were primarily the result ofa rapid fluid shift to the intravascular space. The marked decreases in packed cell volume and total protein gave evidence of that fluid shift, which was induced by an increased osmotic gradient.” The controls had a very slight decrease in packed cell volume after treatment. This observation reiterated the inaccuracy of hematocrit values in reflecting acute blood loss. Other reported benefits of treatment with HSD include improved cardiac performance and visceral arterial dilat i ~ n . ” - ’ The ~ increase in cardiac output after HSD was the result of increased stroke volume and heart rate. The determinants of stroke volume are preload and contractility. Central venous pressure is often used as a measure of preload. Central venous pressure did not differ between controls and animals treated with HSD. An increase in stroke volume without increased central venous pressure may be a reflection of increased contractility in the animals treated with HSD. Elevation of mean arterial pressure is a reflection of the increase in cardiac output. Change in peripheral resistance may have contributed to an increased mean arterial pressure, but peripheral resistance was not measured. All animals in this study developed metabolic acidosis as a result of tissue hypoperfusion. Compensation for metabolic acidosis depends on increased loss of carbon dioxide by hyperventilation. Since all the dogs were ventilated mechanically, respiratory compensation could not occur. Therefore, there was no difference between treatment groups. Mechanical ventilation maintained similar blood gases in both groups. Despite profound hypotension after exsanguination, changes in heart rates occurred slowly over the 3-hour observation period and never exceeded 160 beats per minute. There are two possible explanations for the absence of a reflex tachycardia. First, the animals were anesthetized with isoflurane. Isoflurane has been shown to interfere with baroreceptor response to h y p ~ t e n s i o nThis .~~ interference has been shown to occur at 2.6% inspired isoflurane, but not at 1.3%. Since animals in this study
23
never exceeded 1.7% inspired isoflurane, this seems an unlikely cause. The second possible explanation is the presence of a cardiac depressor reflex that originates from vagal afferent C fibers originating in the left ventricle. This reflex elicits a slower heart rate during hypotension when inadequate ventricular filling is o ~ c u r r i n g . ~ ~ , ’ ~ The use of HSD raises some hypothetical concerns about iatrogenic hypernatremia, increased hemorrhage, and the possibility of coagulopathy or anaphylaxis associated with dextran. In more than 300 studies in which HSD was used to treat hemorrhagic shock, there were no reports of adverse effects associated with h~pernatremia.’~ Increased hemorrhage has been reported after the administration of HSD in an uncontrolled hemorrhage This would seem logical because of the effects of HSD on cardiac output and mean arterial pressure. The authors advocated the use of HSD as adjunctive therapy to improve cardiovascular parameters while definitive measures were taken to stop hemorrhage. The adverse effects of dextran on platelet function are well d ~ c u m e n t e dThe .~~ effects tend to be offset by increasing peripheral perfusion during hypotension. The incidence of anaphylaxis to dextran in domestic animals has not been reported. The use of hypertonic agents for intraosseous infusions has been reported in laboratory investigations and in clinIn a review of 982 intraosseous infuical sions in children in 1947, there were four cases of osteomyelitis. Three of those children had received hypertonic In reviews conducted after 1977, there have been no reports of osteomyelitis associated with intraosseous infusions. This is probably related to the improved use of aseptic technique and the decreased use of prolonged intraosseous infusions.32 The local effect of one hypertonic solution, sodium bicarbonate, has been closely examined. Only minimal histopathologic changes were noted immediately or 1 month after intraosseous i n f ~ s i o n . ’ . ~There ’ ’ ~ ~ was no long-term effect on development of immature bones after intraosseous infusion of sodium bicarbonate. Five percent sodium chloride (NaCl) causes necrosis of the marrow and some endosteal damage when administered intraosseously. Dextran 70 causes minimal disruption of the medullary cavity.** The long-term consequences of intraosseous infusions of HSD are unknown. The risk of damage to the medullary cavity must be weighed against the potential benefits of intraosseous infusion of HSD in an emergency situation. In conclusion, the results of this study add to the list of emergency applications of intraosseous infusions. By using small volumes of HSD, the intraosseous route may be used to substantially improve cardiovascular param-
** Okrasinski EB, Patton CS, Krahwinkel DJ. Unpublished data.
INTRAOSSEOUS INFUSION FOR SHOCK
eters. This would enable emergency clinicians more time to establish intravenous catheters and to institute definitive therapeutic measures.
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