Influence of the Burn Wound Responses to In jury
on
Local and Systemic
DOUGLAS W. WILMORE, M.D., LOUIS H. AULICK, PH.D., MAJOR M.S.C., ARTHUR D. MASON, JR., M.D., BASIL A. PRUITT, JR., M.D., COLONEL, M.C.
Total resting leg blood flow, measured by venous occlusion plethysmography; leg oxygen consumption; substrate turnover; and leg surface temperature were determined in 21 nonseptic burn patients and four normals. The patients studied during the second to third week postinjury sustained total body surface injuries averaging 45% (range 12-86%) and leg injuries of 35% total leg surface (0-82.5%). To integrate the peripheral metabolic and circulatory events with the systemic responses to injury, total body oxygen consumption, cardiac output, rectal and mean skin temperatures were also measured. Leg blood flow and leg surface temperature generally increased with total burn size but did not correlate with cardiac output, total body oxygen consumption, or body temperature. However, leg blood flow was closely related to the extent of the leg burn (r' = 0.73). To evaluate the metabolic determinants of the wound blood flow, patients were matched for burn size (40.5% total body surface in one group vs. 42%), resulting in similar systemic responses to injury (cardiac index 7.8 + 0.7 L/min m2 vs. 7.5 + 0.8, VO2 204 + 12 ml/min m2 vs. 241 + 22, rectal temperature 38.5 + 0.30 vs. 38.3 + 0.30, NS). One group (n = 7) had extensive leg burns (58% of the leg surface), the other (n = 9) minimal leg injuries (9.5%). Leg oxygen consumption was similar in the two groups (0.24 + 0.01 ml/100 ml leg mmn vs. 0.19 ± 0.04, NS), although leg blood flow was markedly increased in the injured extremities (8.0 ± 0.5 ml/100 ml leg min vs. 4.2 + 0.4, p < 0.001). Glucose uptake and lactate production were enhanced in the burned extremities (glucose 0.34 + 0.08 mg/100 ml leg mmn vs. 0.04 + 0.03, p < 0.01, lactate 0.30 + 0.08 mg/100 ml leg min vs. 0.06 + 0.06, p < 0.05) and related in a general manner with size of the leg burn. Increased peripheral blood flow following injury is directed to the wound and unrelated to aerobic metabolic demands of the extremity. The selectively perfused wound consumes glucose and produces lactate. The increased systemic cardiovascular and metabolic responses to thermal injury are essential for the enhanced circulatory and anaerobic demands of the healing wound.
Presented at the Annual Meeting of the American Surgical Association. Boca Raton, Florida, March 23-25, 1977. Reprint requests: Douglas W. Wilmore, M.D., United States Army Institute of Surgical Research, Brooke Army Medical Center, Fort Sam Houston, Texas, 78234. The opinions or assertions contained herein are the private views of the authors and are not to be construed as official or as reflecting the views of the Department of the Army or the Department of Defense.
From the United States Army Institute of Surgical Research, Brooke Army Medical Center, Fort Sam Houston, Texas
CIRCULATORY
AND
METABOLIC
ALTERATIONS
characterize the compensatory adjustments which occur following major injury. After successful resuscitation, cardiac output rises and body temperature and ventilation increase, reflecting heightened energy demands on the body. Weight loss and increased urinary excretion of nitrogen, potassium, phosphorus, and other intracellular constituents, reflect the accelerated catabolism which occurs following trauma. During the hypercatabolic, reparative, or "flow" phase of injury, these general systemic events occur as if in response to tissue inflammation and in support of wound repair.10 With healing of the wound, the systemic responses abate and convalescent anabolism begins, as characterized by an increased appetite and activity and a rebuilding of body mass. Clinical studies over the past half century have quantitated and interrelated these systemic adjustments to injury. The initial observations of Cuthbertson, describing the post-traumatic responses following long bone fracture,9 were confirmed and extended by Howard,'7 Moore,23 and others. Although high caloric diets diminished loss of body tissue following injury,26 the systemic hemodynamic and metabolic responses were not blunted by increased food intake.29 The interrelationship between loss of protein economy and hypermetabolism was established by Kinney20 and associates" in a variety of surgical patients. The increase in cardiac output paralleled the rise in oxygen consumption in patients with various hypermetabolic disease processes.'4 Increased gluconeogenesis occurs in infected and injured patients,22 and the rate of hepatic glucose production was closely related to the extent of injury.3' Finally, the hormonal mediators of these systemic responses to injury were recognized33 and the
444
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BURN WOUND INFLUENCES
445
tween the seventh and twenty-second postburn
central role of the sympathetic nervous system as orchestrator of the homeostatic events following major injury was established.30 Although the various sytemic circulatory and metabolic alterations following injury have been quantified, it has been difficult to interrelate physiologic and biochemical events to each other and to the healing wound. In this study, associated systemic and regional hemodynamic and metabolic events were monitored in the thermally injured patient. The influence of the wound on these integrated physiologic responses was evaluated.
day, with the mean day of study being the thirteenth day following injury. All patients were: 1) normotensive and hemodynamically stable after an uneventful resuscitation, 2) in a normal state of hydration, with a hematocrit greater than 33, and without abnormalities in serum electrolyte concentration, osmolality, or pH, 3) free of systemic infection as determined by clinical symptoms and signs, chest x-rays, and daily blood cultures, and 4) alert, cooperative, and able to participate
Materials and Methods
Four normal subjects served as controls. All were thoroughly accustomed to the techniques of respiratory, circulatory, and metabolic testing.
in the study.
Subjects Twenty-one noninfected burn patients were selected to represent a wide range of total body surface and leg injuries; all were male, and none had known pre-existing diseases (Table 1). The patients were studied be-
All subjects were studied in the early morning. Normal individuals fasted for at least ten hours before the
TABLE 1. Characteristics of Subjects Studied
Subjects
Estimated* Total Leg Volume (L)
Total Body Burn (Per Cent)
Per Cent Third Degree
Total Leg Burn (Per Cent)
Per Cent Third Degree Leg
Age (Year)
Weight (kg)
Body Surface Area (m2)
35 24 29 28
77.3 75.0 84.1 63.6
2.06 1.98 2.04 1.72
11.081 12.442 12.437 9.602
0 0 0 0
0 0 0 0
0 0 0 0
0 0 0 0
50 50 36 29 29 20 32
1.72 1.72 1.99 2.06 2.06 2.06 2.05 1.92 1.91 1.71 2.10
7.877 7.544 12.042 12.500 10.567 15.274 13.146 10.056 9.306 9.089 13.229
12 12 12 24.5 24.5 28 29 29.5 35 43 45
6 6 1 0 0 0 5 0 1.5 2 24
2.5 57.5 0 20 20
45 17.5
2.5 27.5 0 0 0 0 0 0 0 0 5
10 10 10 11 18 7 9 12 11 9 12
Burn
Postburn Day Studied
Individual Variations
During Study
Controls 1 2 3 4 Patients la lb 2 3a 3b 4 5 6 7 8 9
54 18 33 40
58.6 58.6 80.8 83.5 83.5 83.7 89.4 76.3 69.6 63.4 88.0
lOa
22
67.2
1.72
9.389
46.5
43
17.5
17.5
8
lOb 11 12 13 14
22 19 26 18 28
57.5 72.8 73.2 80.3 77.2
1.63 1.92 1.93 2.07 1.97
7.730 10.022 10.752 12.799 10.769
46.5 48 50 50 50
43 2 31 40 14.5
17.5 12.5 0 82.5 52.5
17.5 0 0 82.5 15
19 12 17 22 21
15 16 17
20 17 19
59.1 82.5 68.2
1.70 2.05 1.91
10.427 13.570 8.635
50.5 57.5 61.5
5 12 28
37.5 15 60
2.5 0 57.5
10 14 21
18 19 20a 20b 21
19 21 24 24 22
64.4 67.2 61.1 53.4 79.5
1.73 1.78 1.70 1.61 2.10
9.242 10.930 9.873 6.622 10.728
67 73 78 78 86
0 2.5 0 0 57
65 45 80 80 82.5
0 0 0 0 82.5
11 15 11 20 8
*
70 2.5 0 10
Measurement of left leg Measurement of right leg
Dressing on left hand
Small venectomy wound left lower leg; upper extremities in dressings Dressings over trunk, both upper arms, and right thigh
Dressings on right leg Dressings on left upper
extremity
Volume of leg inside the plethysmograph (by displacement) plus volume outside.
Dressings on left hand Two weeks post-excision; dressings on right leg
Dressings on arms and right leg
446
WILMORE AND OTHERS
study, and all patients were fasted after midnight. Those patients requiring intravenous fluid to maintain a normal state of hydration received 0.04 molar nutrientfree sodium chloride infusions for six hours before and throughout the study. While routine clinical care continued, patient manipulation was minimized for at least six hours before the study. Patients who were unable to rest during this period were not studied. The burn wounds were treated by a variety of techniques. The majority of patients were treated by the exposure method, utilizing silver sulfadiazene cream (Silvadeneg) applied to the injured surface, but some patients were treated with 1 1% mafenide acetate topical antibiotic (Sulfamylong cream). Some wounds were covered with dressings soaked in saline, five per cent mafenide, or 0.5% silver nitrate. While the treatments themselves have no known direct effect on blood flow or leg metabolism, they do require manipulation of the patient, resulting in patient discomfort. To insure that each patient was well rested and unstimulated before the study, wound treatment was also minimized for at least eight hours prior to the study. In the patients treated by the closed technique, dressings were removed only from the left legjust prior to the study. Routine clinical care and monitoring were maintained throughout all phases of the study.
Study Design All studies took place in an environmental chamber previousy described.35 The ambient temperature was maintained at 300, and relative humidity ranged between 40-50%. Control subjects wore light cotton shorts, and patients were draped with a light cotton towel. The postabsorptive subjects were moved to the study room between 5:00 and 6:00 A.M. and placed supine in bed. Nine copper-constantan thermocouples were attached to the skin at the same sites in all subjects (dorsum of the foot, lateral and posterior calf, posterior and anterior thigh, dorsum of the hand, forearm, abdomen, and low back). Leg skin temperatures were monitored from both legs, using five additional thermocouples, in patients with asymmetrical leg burns. In those patients treated in dressings, the thermocouples were placed on the wound, under the dressing, except for the fully exposed leg under study. A rectal probe was inserted to a depth of ten centimeters from the external anal sphincter. All temperatures were recorded at five-minute intervals on a Leeds and Northrup Numatron scanning facility and recorder. If not already present, an intravenous catheter was placed in a large caliber vein and patency maintained with a constant infusion of 0.04 molar sodium chloride solution. A plastic catheter (#25 or #21) was placed percutane-
Ann. Surg. * October 1977
ously in an accessible extremity artery (femoral, dorsalis pedis, or radial) not in the leg under study and positioned to insure free flow of arterial blood. Patency of the catheter was maintained by slow infusion of 0.04 molar sodium chloride solution by syringe pump. Following the initial preparation phase, the patients were allowed to rest for at least an hour in the semidark, quiet room and then repositioned to the side of the bed. The left leg* was inserted in a large, soft, pliable, water-impermeable boot and then placed in a full-length plethysmograph. Water was added to the plethysmograph at a temperature equal to the mean leg skin temperature and maintained at that temperature throughout the remainder of the study. At the end of a 30-minute period of equilibration with the water in the plethysmograph, the subject's cardiac output was determined by the dye dilution technique. This was followed by measurement of leg blood flow and calibration of the plethysmograph. A canopy hood was then placed over the patient's head, and continuous oxygen consumption was measured over 15-20 minutes. Following this, blood was then drawn from the femoral vein and, simultaneously, from the arterial line for determination of arterial and venous substrate concentration of the limb under study. Water was then drained from the plethysmograph and the patient's leg removed from the instrument. In preliminary investigations, the order of these measurements was varied. These trials demonstrated that the study results were unaffected by the measurement sequence as long as adequate time was allowed for the patient to return to the resting state following each manipulation. Puncture of the vasculature of the limb under study always followed measurement of limb blood flow. Total time for the study, including periods for equilibration, was three to four hours. The patients usually slept throughout this period of time. As patient comfort was a basic prerequisite in this study, whenever it could not be achieved, the study was discontinued. To achieve near basal conditions, conversation was minimized and hand signals were used between the investigators during the study.
Study Methods Leg blood flow was determined by use of a fulllength, water filled, venous occlusion plethysmograph as previously described.5 Briefly, this plethysmograph is a rigid, rectangular box made of clear plexiglass. To facilitate its use in injured limbs, it can be disassembled into three sections, a thigh plate and attached boot, a trough section with mesh sling to support the leg, and *
Both legs were studied on Patient 1.
Vol. 186 * No. 4
BURN WOUND INFLUENCES
a full-length top. The patient's leg was slipped through a tailor made opening in the thigh plate and into a large, loose fitting, polyvinyl boot. The boot served to form a freely expandable, watertight seal between the limb and the plethysmograph, preventing fluid exchange across the burn wound and minimizing contamination. The boot and thigh plate were advanced to the proximal thigh and the leg placed in the mesh sling of the plethysmograph. The three sections of the plethysmograph were then locked together and the box filled with water equal to the mean skin temperature of the leg under study. Venous occlusion was accomplished by rapid inflation of a ten centimeter wide tourinquet cuff placed as high on the upper thigh as possible. Occlusion pressure was varied for each subject to obtain a maximal rate of limb swelling. In some patients with burns on the thigh, a topical anesthetic (two per cent viscous lidocaine) was applied to the area under the tourniquet cuff to reduce pain resulting from inflation. With venous occlusion, the limb swells; and the change in limb volume caused water to rise in a chimney located on the top of the plethysmograph. The increase in column hydrostatic pressure was converted to an electrical signal, amplified and recorded. In order to avoid the initial inflation artifact, the rate of leg volume change between four to ten seconds following venous occlusion was used to determine blood flow. In the majority of measurements, the response was linear during this time
period. The plethysmograph was calibrated periodically with the leg in place. The volume of the limb within the plethysmograph was determined by subtracting the volume of water in the plethysmograph from its known capacity. The eight to ten flow measurements were averaged and leg blood flow expressed in ml/100 ml leg volume per minute. In order to relate peripheral measurements with systemic events in the same patient, the volume of the entire leg was estimated. The approximate volume of the leg outside the plethysmograph was calculated from measurements of the circumference of the exposed thigh and the distance from the symphysis pubis to the plethysmograph. Total leg volume estimates were used only in the comparison of total body and leg oxygen consumption; all other results reported in 100 ml units of leg volume utilized only the portion of the leg within the plethysmograph. The validity of including the proximal portion of the leg not within the plethysmograph in the total leg measurements was demonstrated by studies in normal subjects. Withdrawing the leg from the plethysmograph had no effect on leg blood flow per 100 ml leg volume until the instrument was below the mid-thigh level. Cardiac output was performed by rapidly injecting
447
a one milliliter bolus of indocyanine green dye (10 mg/ml) into a large bore vein and monitoring the arterial dilution with a Waters DCR-702 densitometer, strip chart recorder, and cardiac output computer. Each reported cardiac output was the mean of three to five determinations. Prior to each experiment, known concentrations of green dye were mixed with the subject's venous blood, and the densitometer and recorder system were calibrated. The results obtained from the cardiac output computer were routinely verified by manual integration of the recorded curves. These dye dilution cardiac output results compared favorably with those obtained by the Fick and thermal dilution
techniques. Oxygen consumption of the patient was measured using a modification of the open circuit technique. The patient placed his head in a clear plexiglass canopy hood, fitted with a pliable loose-fitting neck seal. Forty to 70 liters of room air were pulled through the box by an exhaust fan, insuring that all expired air exited through the exhaust opening. Due to individual differences in ventilation, flow rate was adjusted for each subject by altering the size of the exhaust port. Optimizing flow rate for each subject prevented accumulation of carbon dioxide within the head box while providing the necessary differential between input and exit gas concentrations for accurate determination. A bidirectional, low resistance turbine flowmeter* continuously measured exit flow. Concentrations of carbon dioxide and oxygen in the exhaust gas were monitored continuously and inflow gas concentrations measured at discrete time intervals by a Perkin-Elmer mass spectrometer (Model MGA-1 100). Analog signals from the flowmeter and mass spectrometer were continuously fed to a dedicated computer housed within the metabolic room. The temperature and humidity of the exhaust gas were determined through the use of wet and dry bulb thermometers placed in the exhaust air stream. These measurements and barometric pressure were entered into a program of the dedicated computer, which continuously integrated flow rate and gas concentrations and corrected gas volume to standard conditions. This data retrieval and analysis system provided serial determinations of the patient's oxygen consumption, carbon dioxide production, respiratory exchange ratio, and metabolic rate. The time interval for these computations was set between two to five minutes. Multiple on-line metabolic determinations provided by this system clearly established the development of a steady * Quantum Flowmeter, Quantum Dynamics, Inc., Tarzana, California. Calibration of this flowmeter was performed at the University of Colorado Engineering Laboratory, Boulder, Colorado.
448
Ann. Surg.
WILMORE AND OTHERS
October 1977
TABLE 2. Systemic and Peripheral Responses to Injury
Systemic Responses
Subjects Controls 1 2 3 4 Patients la
lb 2 3a 3b 4 5 6 7 8 9 10a 10b 11 12 13 14 15 16 17 18 19 20a 20b 21
Peripheral Responses Mean Skin Temp.
Mean Leg Surface Temperature
(OC)
37.1 37.0 36.8 36.9 36.7 36.7 37.9 38.7 37.7 38.6 38.0 39.4 37.8 38.2 38.1 39.4 39.3 39.6 38.3 38.3 38.3 38.7 39.0 39.6 37.2 38.7 38.7 38.5 37.5
Cardiac Index (L/m2* min)
Oxygen Consumption (mIIm2* min)
Rectal Temp. (OC)
2.92 3.52 3.99 3.29
127 130 130 119
3.80 3.80 5.30 7.43 5.59 7.00 7.87 9.86 7.34 8.63 6.43 11.69 8.04 8.95 7.84 5.92 7.68 8.93 8.38 10.24 7.64 10.50 11.18 8.06 5.94
144 144 161* 184* 184* 296 207 188 170 217* 197 226 177 226* 230* 211 230* 279 258 309 204 247 345 227 265
Leg Glucoset Turnover (mg/100 ml
Leg Lactatet Turnover (mg/100 ml
leg- min)
leg- min)
0.065 0.162 0.063 0.205
0.040 0.057 0.200 0.124
0.129 0.014 -0.058 -0.152
0.077 0.255 0.144 0.155 0.215 0.219 0.341 0.193 0.077 0.230 0.185 0.322 0.062 0.128 0.307 0.200 0.230 0.265 0.186 0.279 0.144 0.350 0.541 0.231 0.373
0.118 0.171 0.157
0.003 -0.128 0.050
0.374 -0.092 0.044 0.018 0.516 0.081 0.000 -0.097 0.202 0.000 0.484 0.000 0.254 0.099 0.554 0.000 0.000 0.500 -0.107 0.148
-0.090 0.009 0.022 -0.032 -0.430 -0.428
(OC)
Leg Blood Flow (mlV100 ml leg- min)
Leg Oxygen Consumption (ml/100 ml leg- min)
34.3 34.7 34.3 34.3
32.6 33.7 33.9 33.8
2.02 2.84 2.50 3.10
35.2 35.2 34.9 36.6 35.8 36.2 36.2 37.1 35.7 36.3 35.7 37.1 37.0 35.7 36.0 36.0 36.3 36.3 36.7 36.5 35.8 35.7 36.5 36.8 33.8
34.0 34.6 33.8 36.1 35.2 35.9 36.2 35.3 34.2 36.4 33.9 36.8 35.8 35.7 34.8 34.7 35.7 35.9 35.3 35.2 35.8 36.2 35.9 36.1 31.6
2.95 8.53 2.61 8.39 7.05 7.48 4.60 4.42 3.50 8.60 4.04 7.07 3.24 4.48 3.17 9.68 6.24 6.36 4.93 9.24 12.21 6.82 8.33 10.71 5.94
* Oxygen consumption predicted from burn size; t positive values ,indicate uptake, concentrations and individual A-V differences.)
state respiratory gas exchange and permitted convenient basal metabolic measurements in patients with facial burns or subjects who were asleep. Analysis of exhaust air collected in Douglas bags yielded results within +3% of the volume and gas concentrations obtained by the canopy hood system. At the end of the study, blood was drawn from the femoral vein of the leg under study through a 19 gauge needle. Simultaneously, arterial blood was sampled from the arterial catheter. Heparinized arterial and venous blood was analyzed for pH and oxygen concentrations using a Corning 165 Blood Gas Analyzer. Simultaneous Co-oximeterg measurements of oxygen content were performed in over one-half of the samples and yielded comparable results. Whole blood glucose was measured by the glucose oxidase method16 and lactate by an enzymatic technique.12 Hematocrit and hemoglobin concentrations were determined on all samples. All samples were measured in triplicate and the average value reported.
-
-0.003 -0.108 0.051 -0.455 -0.056 -0.407 0.025 -0.527 0.073 -0.142 -0.418 -0.030
indicates production. (See Appendix for arterial
Calculations
Total body mean skin temperature (T,k) was calculated by appropriately weighting nine skin temperatures according to the estimated surface area being represented: TSk = 0.143 T anterior thigh + 0.081 T posterior thigh + 0.168 T lateral calf + 0.105 T low back + 0.140 T forearm + 0.050 T dorsum of hand + 0.315 T abdomen. Mean leg skin temperature (Tskl) was calculated in a similar manner from five leg skin temperatures: TSkl = 0.365 T anterior thigh + 0.122 T posterior thigh + 0.250 T lateral calf + 0.083 T posterior calf + 0.179 T foot. Leg substrate turnover and oxygen uptake were calculated: Turnover = flow x (arterial concentration femoral vein concentration). -
Results Systemic Response to Injury Cardiac output, total body oxygen consumption, rectal and mean skin temperature all increase in a gen-
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449
BURN WOUND INFLUENCES
TABLE 3. The Effect of Total Body Surface Burn on the Systemic Responses to Injury (Mean and Range or S.E.M.) Per Cent Total Body Surface Burn
4
Number of subjects Number of studies Age (years)*
Weight (kg) Body surface area (m2) Per cent total body burn
Age and
8
10
4
5
38
9 30
11 21
(24-35)
(29-50)
(18-54)
(17-28)
75.0
76.6
74.2
69.6
(63.6-84.1)
(58.6-83.5)
(57.5-89.4)
(53.4-82.5)
1.95
1.96
1.89
1.87
(1.72-2.06)
(1.72-2.06)
(1.63-2.10)
(1.61-2.10)
Postburn day studied
*
3
29
0
Cardiac index (L/m2 min) Oxygen consumption (ml/m2 min) Rectal temperature (°C) Mean skin temperature (°C)
>49
25-49
50
6
32 (17-54) 75.4 (58.6-89.4) 1.94 (1.72-2.05)
0
16-50
± 0.81 ± 0.92
± 0.035
± 3 83 ± 1 2 0.068 ± 0.033 17.8 ± 3.3 0.2 ± 0.5 0.002 ± 0.018
6.45 15.54 3.49 0.223
± 0.67 ± 0.54
± 0.45 ± 0.033
± 14 101 ± 1 2 0.126 ± 0.092 16.9 ± 2.4 -5.5 ± 2.2
-0.317 ± 0.105
35.1
± 0.5
8.71 14.37 3.42 0.275 85
± 0.68
3
± 0.37 ± 0.61 ± 0.039
± 5 ± 1
0.236 ± 0.083 15.8 ± 2.9 -2.2 ± 0.7 -0.197 ± 0.071
* Arterial-Femoral Vein. t Positive values indicate uptake; - indicates production.
burn (Table 4). Leg blood flow (LBF) increased in a curvilinear manner with the per cent of leg burn (% LB): LBF, ml/100 ml leg-min = 2.990 + 0.1576 %LB 0.0011 %LB2, (r2 = 0.73). Leg blood flow was also curvilinearly related to the mean leg skin temperature of the extremity (r2 = 0.58). Although leg oxygen consumption increased with the size of the leg burn, extremity blood flow correlated poorly with leg oxygen consumption (r2 = 0. 16). The uptake of glucose and production of lactate were not significantly related to the oxygen consumption of the extremity.
(r2 = 0.33), cardiac index (X2 = 0.18), total body oxygen consumption (r2 = 0.33), rectal or total body mean skin temperatures (r2 = 0.08 and 0.19). Leg oxygen consumption also correlated poorly with the body temperatures (r2 = 0.13 for rectal and 0.04 for mean skin) and cardiac index (r2 = 0.28) of the patients, but maintained a fairly constant relationship with total body oxygen consumption; the oxygen uptake of one leg accounted for approximately 6% of the total body oxygen consumption over the wide range of measurements (Fig. 2).
The Relationship Between Systemic and Local Responses to Injury With the increase in the size of total body surface burn, there is a general increase in the size of the leg burn (r2 = 0.43). The increase in leg blood flow, however, was poorly related to total body surface burn
Local Factors Which Influence Peripheral Circulation and Metabolism To standardize the systemic influences on peripheral events and thereby identify the local factors which influence leg blood flow, the patients were matched for age, weight, total body surface injury, and the associated systemic responses to injury (Table 5). One
-
Vol. 186 . No. 4
451
BURN WOUND INFLUENCES 50-
x
E 40-
x x
x
FIG. 2. The consumption of oxygen by the whole leg is related to total body oxygen consumption of the normals and hypermetabolic bum patients.
30-
x x
x
'it
20x
1 x 10-
xx
x
y
=
-9.0568 + 0.0802
x
r2 =0.5899
x
x
200
250
300 350 400 450 500 550 TOTAL BODY OXYGEN CONSUMPTION ml /min
had major leg burns (58% LB) and the other had minimal or no leg burns (9.5% LB). The systemic responses to injury were comparable in both groups, as reflected by similar body temperatures, cardiac index, and total body oxygen consumption. Leg blood flow, however, was increased significantly by the local presence of the burn wound. The increased leg blood flow was not associated with a comparable rise in limb oxygen consumption, indicating that the extra blood flow was not in response to increased aerobic metabolic demands of the limb. Glucose uptake and lactate production were higher in the more extensively injured limbs. In general, increases in glucose consumption and lactate production in the injured limbs were a function of both the increased leg blood flow and increased arteriovenous differences of these substances across the limbs. group
Discussion Previous indirect evidence suggests that much of the extra blood flow in the burn patient is directed to peripheral tissues. Gump and associates15 found that splanchnic blood flow represented a smaller proportion of the total cardiac output in three burn patients than it did in normal individuals or patients with postoperative infection. Studies of body heat transfer in burn patients suggested that much of the peripheral blood flow was directed toward the surface.35 High superficial blood flow was apparent as burn patients maintained above normal surface temperatures in spite of increased evaporative cooling of the burn wound. In addition, the coefficient of core-to-skin heat conductance, an index of surface blood flow, was twice normal
600
.
650
in burn patients studied in a variety of thermal environments.
Since this data and the results of previous studies4'5 demonstrate that increased leg blood flow in the burn patient is closely related to the extent of local injury on that particular extremity and not found in uninjured legs, the increased peripheral blood flow appears to be directed primarily to the burn wound. Wound blood flow is considered a major component of the hyperdynamic circulatory response to thermal injury. The increase in cardiac output is related to the extent of total body surface injury in a manner similar to the relationship between the size of limb injury and blood flow (Fig. 3). Serial blood flow measurements in patients with third degree wounds of the lower extremities further support the concept that this extra peripheral blood flow is wound directed. Two to three days after a fullthickness injury, which causes thrombosis of superficial vessels, leg blood flow is near control levels. With time, flow increases and, by the end of the first week, reaches levels predicted for the size of the leg burn. This increase is associated with the formation of a richly vascularized wound bed. In contrast, partialthickness injury does not ablate the superficial vascular bed, and blood flow is elevated in those legs with second degree burns as soon as circulatory volume is restored. In addition, excision of a vascularized fullthickness wound to fascia results in a prompt decrease in leg blood flow.5 Blood flow in these limbs is restored to elevated levels with formation of a granulation bed which will accept a skin graft. Under normal physiologic conditions, blood flow to the extremity responds to variations in the oxygen de-
452
WILMORE AND OTHERS
TABLE 5. Comparison of Patients With SmallI and Large Leg Bums (Mean and Range of S.E. M.)
Large Leg Bumsn"
Small Leg Bums§ Patient Characteristics Number of subjects
7
8
Number of studies
7
9
Age (years)
(18(128 50)
28
(17-50)
Weight (kg)
70.1 (58.6-83.7)
73.2
(57.5-89.4)
Body surface area (m2)
1.88
1.89
(1.63-2.10)
Per cent total body face burn
sur-
42 (12-61.5) 58.0
40.5
(12-57.5)
Per cent total leg burn
9.5
(37.5-82.5) 14 (7-22)
(0-17.5)
Postburn day studied
12
(8-19)
Systemic Responses Cardiac index
(L/
m2 * min) Oxygen consumption (mum2 min) Rectal temperature
(OC) Mean skin temperature (°C)
Peripheral Responses Mean leg skin temperature (°C) Leg blood flow (ml/100 ml leg-min) Arterial oxygen concentration (ml/ 100 ml) A-FV¶ oxygen difference (ml/100 ml) Leg oxygen consump-
tion
+ 0.70 ±
12
Arterial lactate concentration (mg/ 100 ml) A-FV lactate difference (mg/100 ml) Leg lactate turnover (mg/100 ml leg- min)
+
0.81
241 ± 22 38.3 ± 0.3 36.1 ± 0.2
38.5
±
0.3
36.1
±
0.2
35.2
±
0.3
4.22
±
0.43
35.5 ± 0.3 8.02 + 0.51k
15.08
±
0.40
15.29 ± 0.72
4.40
±
0.87
3.08
0.187
±
0.037
0.240 ± 0.010
(mlV100 ml
leg- min) Arterial glucose concentration (mg/ 100 ml) A-FV glucose difference (mg/100 ml) Leg glucose turnover (mg/100 ml leg- min)
7.46
± 0.26
10
81
±
1
4
±
0.033
17.2
±
3.4
17.6 ± 3.6
-1.4
±
1.4
-3.6 ± 0.9
-0.060
±
0.055
-0.299 ± 0.075*
89 1
0.037
±
± 4
± 1* 0.336 ± 0.077t
p
on
Local and Systemic
DOUGLAS W. WILMORE, M.D., LOUIS H. AULICK, PH.D., MAJOR M.S.C., ARTHUR D. MASON, JR., M.D., BASIL A. PRUITT, JR., M.D., COLONEL, M.C.
Total resting leg blood flow, measured by venous occlusion plethysmography; leg oxygen consumption; substrate turnover; and leg surface temperature were determined in 21 nonseptic burn patients and four normals. The patients studied during the second to third week postinjury sustained total body surface injuries averaging 45% (range 12-86%) and leg injuries of 35% total leg surface (0-82.5%). To integrate the peripheral metabolic and circulatory events with the systemic responses to injury, total body oxygen consumption, cardiac output, rectal and mean skin temperatures were also measured. Leg blood flow and leg surface temperature generally increased with total burn size but did not correlate with cardiac output, total body oxygen consumption, or body temperature. However, leg blood flow was closely related to the extent of the leg burn (r' = 0.73). To evaluate the metabolic determinants of the wound blood flow, patients were matched for burn size (40.5% total body surface in one group vs. 42%), resulting in similar systemic responses to injury (cardiac index 7.8 + 0.7 L/min m2 vs. 7.5 + 0.8, VO2 204 + 12 ml/min m2 vs. 241 + 22, rectal temperature 38.5 + 0.30 vs. 38.3 + 0.30, NS). One group (n = 7) had extensive leg burns (58% of the leg surface), the other (n = 9) minimal leg injuries (9.5%). Leg oxygen consumption was similar in the two groups (0.24 + 0.01 ml/100 ml leg mmn vs. 0.19 ± 0.04, NS), although leg blood flow was markedly increased in the injured extremities (8.0 ± 0.5 ml/100 ml leg min vs. 4.2 + 0.4, p < 0.001). Glucose uptake and lactate production were enhanced in the burned extremities (glucose 0.34 + 0.08 mg/100 ml leg mmn vs. 0.04 + 0.03, p < 0.01, lactate 0.30 + 0.08 mg/100 ml leg min vs. 0.06 + 0.06, p < 0.05) and related in a general manner with size of the leg burn. Increased peripheral blood flow following injury is directed to the wound and unrelated to aerobic metabolic demands of the extremity. The selectively perfused wound consumes glucose and produces lactate. The increased systemic cardiovascular and metabolic responses to thermal injury are essential for the enhanced circulatory and anaerobic demands of the healing wound.
Presented at the Annual Meeting of the American Surgical Association. Boca Raton, Florida, March 23-25, 1977. Reprint requests: Douglas W. Wilmore, M.D., United States Army Institute of Surgical Research, Brooke Army Medical Center, Fort Sam Houston, Texas, 78234. The opinions or assertions contained herein are the private views of the authors and are not to be construed as official or as reflecting the views of the Department of the Army or the Department of Defense.
From the United States Army Institute of Surgical Research, Brooke Army Medical Center, Fort Sam Houston, Texas
CIRCULATORY
AND
METABOLIC
ALTERATIONS
characterize the compensatory adjustments which occur following major injury. After successful resuscitation, cardiac output rises and body temperature and ventilation increase, reflecting heightened energy demands on the body. Weight loss and increased urinary excretion of nitrogen, potassium, phosphorus, and other intracellular constituents, reflect the accelerated catabolism which occurs following trauma. During the hypercatabolic, reparative, or "flow" phase of injury, these general systemic events occur as if in response to tissue inflammation and in support of wound repair.10 With healing of the wound, the systemic responses abate and convalescent anabolism begins, as characterized by an increased appetite and activity and a rebuilding of body mass. Clinical studies over the past half century have quantitated and interrelated these systemic adjustments to injury. The initial observations of Cuthbertson, describing the post-traumatic responses following long bone fracture,9 were confirmed and extended by Howard,'7 Moore,23 and others. Although high caloric diets diminished loss of body tissue following injury,26 the systemic hemodynamic and metabolic responses were not blunted by increased food intake.29 The interrelationship between loss of protein economy and hypermetabolism was established by Kinney20 and associates" in a variety of surgical patients. The increase in cardiac output paralleled the rise in oxygen consumption in patients with various hypermetabolic disease processes.'4 Increased gluconeogenesis occurs in infected and injured patients,22 and the rate of hepatic glucose production was closely related to the extent of injury.3' Finally, the hormonal mediators of these systemic responses to injury were recognized33 and the
444
Vol. 186 * No. 4
BURN WOUND INFLUENCES
445
tween the seventh and twenty-second postburn
central role of the sympathetic nervous system as orchestrator of the homeostatic events following major injury was established.30 Although the various sytemic circulatory and metabolic alterations following injury have been quantified, it has been difficult to interrelate physiologic and biochemical events to each other and to the healing wound. In this study, associated systemic and regional hemodynamic and metabolic events were monitored in the thermally injured patient. The influence of the wound on these integrated physiologic responses was evaluated.
day, with the mean day of study being the thirteenth day following injury. All patients were: 1) normotensive and hemodynamically stable after an uneventful resuscitation, 2) in a normal state of hydration, with a hematocrit greater than 33, and without abnormalities in serum electrolyte concentration, osmolality, or pH, 3) free of systemic infection as determined by clinical symptoms and signs, chest x-rays, and daily blood cultures, and 4) alert, cooperative, and able to participate
Materials and Methods
Four normal subjects served as controls. All were thoroughly accustomed to the techniques of respiratory, circulatory, and metabolic testing.
in the study.
Subjects Twenty-one noninfected burn patients were selected to represent a wide range of total body surface and leg injuries; all were male, and none had known pre-existing diseases (Table 1). The patients were studied be-
All subjects were studied in the early morning. Normal individuals fasted for at least ten hours before the
TABLE 1. Characteristics of Subjects Studied
Subjects
Estimated* Total Leg Volume (L)
Total Body Burn (Per Cent)
Per Cent Third Degree
Total Leg Burn (Per Cent)
Per Cent Third Degree Leg
Age (Year)
Weight (kg)
Body Surface Area (m2)
35 24 29 28
77.3 75.0 84.1 63.6
2.06 1.98 2.04 1.72
11.081 12.442 12.437 9.602
0 0 0 0
0 0 0 0
0 0 0 0
0 0 0 0
50 50 36 29 29 20 32
1.72 1.72 1.99 2.06 2.06 2.06 2.05 1.92 1.91 1.71 2.10
7.877 7.544 12.042 12.500 10.567 15.274 13.146 10.056 9.306 9.089 13.229
12 12 12 24.5 24.5 28 29 29.5 35 43 45
6 6 1 0 0 0 5 0 1.5 2 24
2.5 57.5 0 20 20
45 17.5
2.5 27.5 0 0 0 0 0 0 0 0 5
10 10 10 11 18 7 9 12 11 9 12
Burn
Postburn Day Studied
Individual Variations
During Study
Controls 1 2 3 4 Patients la lb 2 3a 3b 4 5 6 7 8 9
54 18 33 40
58.6 58.6 80.8 83.5 83.5 83.7 89.4 76.3 69.6 63.4 88.0
lOa
22
67.2
1.72
9.389
46.5
43
17.5
17.5
8
lOb 11 12 13 14
22 19 26 18 28
57.5 72.8 73.2 80.3 77.2
1.63 1.92 1.93 2.07 1.97
7.730 10.022 10.752 12.799 10.769
46.5 48 50 50 50
43 2 31 40 14.5
17.5 12.5 0 82.5 52.5
17.5 0 0 82.5 15
19 12 17 22 21
15 16 17
20 17 19
59.1 82.5 68.2
1.70 2.05 1.91
10.427 13.570 8.635
50.5 57.5 61.5
5 12 28
37.5 15 60
2.5 0 57.5
10 14 21
18 19 20a 20b 21
19 21 24 24 22
64.4 67.2 61.1 53.4 79.5
1.73 1.78 1.70 1.61 2.10
9.242 10.930 9.873 6.622 10.728
67 73 78 78 86
0 2.5 0 0 57
65 45 80 80 82.5
0 0 0 0 82.5
11 15 11 20 8
*
70 2.5 0 10
Measurement of left leg Measurement of right leg
Dressing on left hand
Small venectomy wound left lower leg; upper extremities in dressings Dressings over trunk, both upper arms, and right thigh
Dressings on right leg Dressings on left upper
extremity
Volume of leg inside the plethysmograph (by displacement) plus volume outside.
Dressings on left hand Two weeks post-excision; dressings on right leg
Dressings on arms and right leg
446
WILMORE AND OTHERS
study, and all patients were fasted after midnight. Those patients requiring intravenous fluid to maintain a normal state of hydration received 0.04 molar nutrientfree sodium chloride infusions for six hours before and throughout the study. While routine clinical care continued, patient manipulation was minimized for at least six hours before the study. Patients who were unable to rest during this period were not studied. The burn wounds were treated by a variety of techniques. The majority of patients were treated by the exposure method, utilizing silver sulfadiazene cream (Silvadeneg) applied to the injured surface, but some patients were treated with 1 1% mafenide acetate topical antibiotic (Sulfamylong cream). Some wounds were covered with dressings soaked in saline, five per cent mafenide, or 0.5% silver nitrate. While the treatments themselves have no known direct effect on blood flow or leg metabolism, they do require manipulation of the patient, resulting in patient discomfort. To insure that each patient was well rested and unstimulated before the study, wound treatment was also minimized for at least eight hours prior to the study. In the patients treated by the closed technique, dressings were removed only from the left legjust prior to the study. Routine clinical care and monitoring were maintained throughout all phases of the study.
Study Design All studies took place in an environmental chamber previousy described.35 The ambient temperature was maintained at 300, and relative humidity ranged between 40-50%. Control subjects wore light cotton shorts, and patients were draped with a light cotton towel. The postabsorptive subjects were moved to the study room between 5:00 and 6:00 A.M. and placed supine in bed. Nine copper-constantan thermocouples were attached to the skin at the same sites in all subjects (dorsum of the foot, lateral and posterior calf, posterior and anterior thigh, dorsum of the hand, forearm, abdomen, and low back). Leg skin temperatures were monitored from both legs, using five additional thermocouples, in patients with asymmetrical leg burns. In those patients treated in dressings, the thermocouples were placed on the wound, under the dressing, except for the fully exposed leg under study. A rectal probe was inserted to a depth of ten centimeters from the external anal sphincter. All temperatures were recorded at five-minute intervals on a Leeds and Northrup Numatron scanning facility and recorder. If not already present, an intravenous catheter was placed in a large caliber vein and patency maintained with a constant infusion of 0.04 molar sodium chloride solution. A plastic catheter (#25 or #21) was placed percutane-
Ann. Surg. * October 1977
ously in an accessible extremity artery (femoral, dorsalis pedis, or radial) not in the leg under study and positioned to insure free flow of arterial blood. Patency of the catheter was maintained by slow infusion of 0.04 molar sodium chloride solution by syringe pump. Following the initial preparation phase, the patients were allowed to rest for at least an hour in the semidark, quiet room and then repositioned to the side of the bed. The left leg* was inserted in a large, soft, pliable, water-impermeable boot and then placed in a full-length plethysmograph. Water was added to the plethysmograph at a temperature equal to the mean leg skin temperature and maintained at that temperature throughout the remainder of the study. At the end of a 30-minute period of equilibration with the water in the plethysmograph, the subject's cardiac output was determined by the dye dilution technique. This was followed by measurement of leg blood flow and calibration of the plethysmograph. A canopy hood was then placed over the patient's head, and continuous oxygen consumption was measured over 15-20 minutes. Following this, blood was then drawn from the femoral vein and, simultaneously, from the arterial line for determination of arterial and venous substrate concentration of the limb under study. Water was then drained from the plethysmograph and the patient's leg removed from the instrument. In preliminary investigations, the order of these measurements was varied. These trials demonstrated that the study results were unaffected by the measurement sequence as long as adequate time was allowed for the patient to return to the resting state following each manipulation. Puncture of the vasculature of the limb under study always followed measurement of limb blood flow. Total time for the study, including periods for equilibration, was three to four hours. The patients usually slept throughout this period of time. As patient comfort was a basic prerequisite in this study, whenever it could not be achieved, the study was discontinued. To achieve near basal conditions, conversation was minimized and hand signals were used between the investigators during the study.
Study Methods Leg blood flow was determined by use of a fulllength, water filled, venous occlusion plethysmograph as previously described.5 Briefly, this plethysmograph is a rigid, rectangular box made of clear plexiglass. To facilitate its use in injured limbs, it can be disassembled into three sections, a thigh plate and attached boot, a trough section with mesh sling to support the leg, and *
Both legs were studied on Patient 1.
Vol. 186 * No. 4
BURN WOUND INFLUENCES
a full-length top. The patient's leg was slipped through a tailor made opening in the thigh plate and into a large, loose fitting, polyvinyl boot. The boot served to form a freely expandable, watertight seal between the limb and the plethysmograph, preventing fluid exchange across the burn wound and minimizing contamination. The boot and thigh plate were advanced to the proximal thigh and the leg placed in the mesh sling of the plethysmograph. The three sections of the plethysmograph were then locked together and the box filled with water equal to the mean skin temperature of the leg under study. Venous occlusion was accomplished by rapid inflation of a ten centimeter wide tourinquet cuff placed as high on the upper thigh as possible. Occlusion pressure was varied for each subject to obtain a maximal rate of limb swelling. In some patients with burns on the thigh, a topical anesthetic (two per cent viscous lidocaine) was applied to the area under the tourniquet cuff to reduce pain resulting from inflation. With venous occlusion, the limb swells; and the change in limb volume caused water to rise in a chimney located on the top of the plethysmograph. The increase in column hydrostatic pressure was converted to an electrical signal, amplified and recorded. In order to avoid the initial inflation artifact, the rate of leg volume change between four to ten seconds following venous occlusion was used to determine blood flow. In the majority of measurements, the response was linear during this time
period. The plethysmograph was calibrated periodically with the leg in place. The volume of the limb within the plethysmograph was determined by subtracting the volume of water in the plethysmograph from its known capacity. The eight to ten flow measurements were averaged and leg blood flow expressed in ml/100 ml leg volume per minute. In order to relate peripheral measurements with systemic events in the same patient, the volume of the entire leg was estimated. The approximate volume of the leg outside the plethysmograph was calculated from measurements of the circumference of the exposed thigh and the distance from the symphysis pubis to the plethysmograph. Total leg volume estimates were used only in the comparison of total body and leg oxygen consumption; all other results reported in 100 ml units of leg volume utilized only the portion of the leg within the plethysmograph. The validity of including the proximal portion of the leg not within the plethysmograph in the total leg measurements was demonstrated by studies in normal subjects. Withdrawing the leg from the plethysmograph had no effect on leg blood flow per 100 ml leg volume until the instrument was below the mid-thigh level. Cardiac output was performed by rapidly injecting
447
a one milliliter bolus of indocyanine green dye (10 mg/ml) into a large bore vein and monitoring the arterial dilution with a Waters DCR-702 densitometer, strip chart recorder, and cardiac output computer. Each reported cardiac output was the mean of three to five determinations. Prior to each experiment, known concentrations of green dye were mixed with the subject's venous blood, and the densitometer and recorder system were calibrated. The results obtained from the cardiac output computer were routinely verified by manual integration of the recorded curves. These dye dilution cardiac output results compared favorably with those obtained by the Fick and thermal dilution
techniques. Oxygen consumption of the patient was measured using a modification of the open circuit technique. The patient placed his head in a clear plexiglass canopy hood, fitted with a pliable loose-fitting neck seal. Forty to 70 liters of room air were pulled through the box by an exhaust fan, insuring that all expired air exited through the exhaust opening. Due to individual differences in ventilation, flow rate was adjusted for each subject by altering the size of the exhaust port. Optimizing flow rate for each subject prevented accumulation of carbon dioxide within the head box while providing the necessary differential between input and exit gas concentrations for accurate determination. A bidirectional, low resistance turbine flowmeter* continuously measured exit flow. Concentrations of carbon dioxide and oxygen in the exhaust gas were monitored continuously and inflow gas concentrations measured at discrete time intervals by a Perkin-Elmer mass spectrometer (Model MGA-1 100). Analog signals from the flowmeter and mass spectrometer were continuously fed to a dedicated computer housed within the metabolic room. The temperature and humidity of the exhaust gas were determined through the use of wet and dry bulb thermometers placed in the exhaust air stream. These measurements and barometric pressure were entered into a program of the dedicated computer, which continuously integrated flow rate and gas concentrations and corrected gas volume to standard conditions. This data retrieval and analysis system provided serial determinations of the patient's oxygen consumption, carbon dioxide production, respiratory exchange ratio, and metabolic rate. The time interval for these computations was set between two to five minutes. Multiple on-line metabolic determinations provided by this system clearly established the development of a steady * Quantum Flowmeter, Quantum Dynamics, Inc., Tarzana, California. Calibration of this flowmeter was performed at the University of Colorado Engineering Laboratory, Boulder, Colorado.
448
Ann. Surg.
WILMORE AND OTHERS
October 1977
TABLE 2. Systemic and Peripheral Responses to Injury
Systemic Responses
Subjects Controls 1 2 3 4 Patients la
lb 2 3a 3b 4 5 6 7 8 9 10a 10b 11 12 13 14 15 16 17 18 19 20a 20b 21
Peripheral Responses Mean Skin Temp.
Mean Leg Surface Temperature
(OC)
37.1 37.0 36.8 36.9 36.7 36.7 37.9 38.7 37.7 38.6 38.0 39.4 37.8 38.2 38.1 39.4 39.3 39.6 38.3 38.3 38.3 38.7 39.0 39.6 37.2 38.7 38.7 38.5 37.5
Cardiac Index (L/m2* min)
Oxygen Consumption (mIIm2* min)
Rectal Temp. (OC)
2.92 3.52 3.99 3.29
127 130 130 119
3.80 3.80 5.30 7.43 5.59 7.00 7.87 9.86 7.34 8.63 6.43 11.69 8.04 8.95 7.84 5.92 7.68 8.93 8.38 10.24 7.64 10.50 11.18 8.06 5.94
144 144 161* 184* 184* 296 207 188 170 217* 197 226 177 226* 230* 211 230* 279 258 309 204 247 345 227 265
Leg Glucoset Turnover (mg/100 ml
Leg Lactatet Turnover (mg/100 ml
leg- min)
leg- min)
0.065 0.162 0.063 0.205
0.040 0.057 0.200 0.124
0.129 0.014 -0.058 -0.152
0.077 0.255 0.144 0.155 0.215 0.219 0.341 0.193 0.077 0.230 0.185 0.322 0.062 0.128 0.307 0.200 0.230 0.265 0.186 0.279 0.144 0.350 0.541 0.231 0.373
0.118 0.171 0.157
0.003 -0.128 0.050
0.374 -0.092 0.044 0.018 0.516 0.081 0.000 -0.097 0.202 0.000 0.484 0.000 0.254 0.099 0.554 0.000 0.000 0.500 -0.107 0.148
-0.090 0.009 0.022 -0.032 -0.430 -0.428
(OC)
Leg Blood Flow (mlV100 ml leg- min)
Leg Oxygen Consumption (ml/100 ml leg- min)
34.3 34.7 34.3 34.3
32.6 33.7 33.9 33.8
2.02 2.84 2.50 3.10
35.2 35.2 34.9 36.6 35.8 36.2 36.2 37.1 35.7 36.3 35.7 37.1 37.0 35.7 36.0 36.0 36.3 36.3 36.7 36.5 35.8 35.7 36.5 36.8 33.8
34.0 34.6 33.8 36.1 35.2 35.9 36.2 35.3 34.2 36.4 33.9 36.8 35.8 35.7 34.8 34.7 35.7 35.9 35.3 35.2 35.8 36.2 35.9 36.1 31.6
2.95 8.53 2.61 8.39 7.05 7.48 4.60 4.42 3.50 8.60 4.04 7.07 3.24 4.48 3.17 9.68 6.24 6.36 4.93 9.24 12.21 6.82 8.33 10.71 5.94
* Oxygen consumption predicted from burn size; t positive values ,indicate uptake, concentrations and individual A-V differences.)
state respiratory gas exchange and permitted convenient basal metabolic measurements in patients with facial burns or subjects who were asleep. Analysis of exhaust air collected in Douglas bags yielded results within +3% of the volume and gas concentrations obtained by the canopy hood system. At the end of the study, blood was drawn from the femoral vein of the leg under study through a 19 gauge needle. Simultaneously, arterial blood was sampled from the arterial catheter. Heparinized arterial and venous blood was analyzed for pH and oxygen concentrations using a Corning 165 Blood Gas Analyzer. Simultaneous Co-oximeterg measurements of oxygen content were performed in over one-half of the samples and yielded comparable results. Whole blood glucose was measured by the glucose oxidase method16 and lactate by an enzymatic technique.12 Hematocrit and hemoglobin concentrations were determined on all samples. All samples were measured in triplicate and the average value reported.
-
-0.003 -0.108 0.051 -0.455 -0.056 -0.407 0.025 -0.527 0.073 -0.142 -0.418 -0.030
indicates production. (See Appendix for arterial
Calculations
Total body mean skin temperature (T,k) was calculated by appropriately weighting nine skin temperatures according to the estimated surface area being represented: TSk = 0.143 T anterior thigh + 0.081 T posterior thigh + 0.168 T lateral calf + 0.105 T low back + 0.140 T forearm + 0.050 T dorsum of hand + 0.315 T abdomen. Mean leg skin temperature (Tskl) was calculated in a similar manner from five leg skin temperatures: TSkl = 0.365 T anterior thigh + 0.122 T posterior thigh + 0.250 T lateral calf + 0.083 T posterior calf + 0.179 T foot. Leg substrate turnover and oxygen uptake were calculated: Turnover = flow x (arterial concentration femoral vein concentration). -
Results Systemic Response to Injury Cardiac output, total body oxygen consumption, rectal and mean skin temperature all increase in a gen-
Vol. 186 . No. 4
449
BURN WOUND INFLUENCES
TABLE 3. The Effect of Total Body Surface Burn on the Systemic Responses to Injury (Mean and Range or S.E.M.) Per Cent Total Body Surface Burn
4
Number of subjects Number of studies Age (years)*
Weight (kg) Body surface area (m2) Per cent total body burn
Age and
8
10
4
5
38
9 30
11 21
(24-35)
(29-50)
(18-54)
(17-28)
75.0
76.6
74.2
69.6
(63.6-84.1)
(58.6-83.5)
(57.5-89.4)
(53.4-82.5)
1.95
1.96
1.89
1.87
(1.72-2.06)
(1.72-2.06)
(1.63-2.10)
(1.61-2.10)
Postburn day studied
*
3
29
0
Cardiac index (L/m2 min) Oxygen consumption (ml/m2 min) Rectal temperature (°C) Mean skin temperature (°C)
>49
25-49
50
6
32 (17-54) 75.4 (58.6-89.4) 1.94 (1.72-2.05)
0
16-50
± 0.81 ± 0.92
± 0.035
± 3 83 ± 1 2 0.068 ± 0.033 17.8 ± 3.3 0.2 ± 0.5 0.002 ± 0.018
6.45 15.54 3.49 0.223
± 0.67 ± 0.54
± 0.45 ± 0.033
± 14 101 ± 1 2 0.126 ± 0.092 16.9 ± 2.4 -5.5 ± 2.2
-0.317 ± 0.105
35.1
± 0.5
8.71 14.37 3.42 0.275 85
± 0.68
3
± 0.37 ± 0.61 ± 0.039
± 5 ± 1
0.236 ± 0.083 15.8 ± 2.9 -2.2 ± 0.7 -0.197 ± 0.071
* Arterial-Femoral Vein. t Positive values indicate uptake; - indicates production.
burn (Table 4). Leg blood flow (LBF) increased in a curvilinear manner with the per cent of leg burn (% LB): LBF, ml/100 ml leg-min = 2.990 + 0.1576 %LB 0.0011 %LB2, (r2 = 0.73). Leg blood flow was also curvilinearly related to the mean leg skin temperature of the extremity (r2 = 0.58). Although leg oxygen consumption increased with the size of the leg burn, extremity blood flow correlated poorly with leg oxygen consumption (r2 = 0. 16). The uptake of glucose and production of lactate were not significantly related to the oxygen consumption of the extremity.
(r2 = 0.33), cardiac index (X2 = 0.18), total body oxygen consumption (r2 = 0.33), rectal or total body mean skin temperatures (r2 = 0.08 and 0.19). Leg oxygen consumption also correlated poorly with the body temperatures (r2 = 0.13 for rectal and 0.04 for mean skin) and cardiac index (r2 = 0.28) of the patients, but maintained a fairly constant relationship with total body oxygen consumption; the oxygen uptake of one leg accounted for approximately 6% of the total body oxygen consumption over the wide range of measurements (Fig. 2).
The Relationship Between Systemic and Local Responses to Injury With the increase in the size of total body surface burn, there is a general increase in the size of the leg burn (r2 = 0.43). The increase in leg blood flow, however, was poorly related to total body surface burn
Local Factors Which Influence Peripheral Circulation and Metabolism To standardize the systemic influences on peripheral events and thereby identify the local factors which influence leg blood flow, the patients were matched for age, weight, total body surface injury, and the associated systemic responses to injury (Table 5). One
-
Vol. 186 . No. 4
451
BURN WOUND INFLUENCES 50-
x
E 40-
x x
x
FIG. 2. The consumption of oxygen by the whole leg is related to total body oxygen consumption of the normals and hypermetabolic bum patients.
30-
x x
x
'it
20x
1 x 10-
xx
x
y
=
-9.0568 + 0.0802
x
r2 =0.5899
x
x
200
250
300 350 400 450 500 550 TOTAL BODY OXYGEN CONSUMPTION ml /min
had major leg burns (58% LB) and the other had minimal or no leg burns (9.5% LB). The systemic responses to injury were comparable in both groups, as reflected by similar body temperatures, cardiac index, and total body oxygen consumption. Leg blood flow, however, was increased significantly by the local presence of the burn wound. The increased leg blood flow was not associated with a comparable rise in limb oxygen consumption, indicating that the extra blood flow was not in response to increased aerobic metabolic demands of the limb. Glucose uptake and lactate production were higher in the more extensively injured limbs. In general, increases in glucose consumption and lactate production in the injured limbs were a function of both the increased leg blood flow and increased arteriovenous differences of these substances across the limbs. group
Discussion Previous indirect evidence suggests that much of the extra blood flow in the burn patient is directed to peripheral tissues. Gump and associates15 found that splanchnic blood flow represented a smaller proportion of the total cardiac output in three burn patients than it did in normal individuals or patients with postoperative infection. Studies of body heat transfer in burn patients suggested that much of the peripheral blood flow was directed toward the surface.35 High superficial blood flow was apparent as burn patients maintained above normal surface temperatures in spite of increased evaporative cooling of the burn wound. In addition, the coefficient of core-to-skin heat conductance, an index of surface blood flow, was twice normal
600
.
650
in burn patients studied in a variety of thermal environments.
Since this data and the results of previous studies4'5 demonstrate that increased leg blood flow in the burn patient is closely related to the extent of local injury on that particular extremity and not found in uninjured legs, the increased peripheral blood flow appears to be directed primarily to the burn wound. Wound blood flow is considered a major component of the hyperdynamic circulatory response to thermal injury. The increase in cardiac output is related to the extent of total body surface injury in a manner similar to the relationship between the size of limb injury and blood flow (Fig. 3). Serial blood flow measurements in patients with third degree wounds of the lower extremities further support the concept that this extra peripheral blood flow is wound directed. Two to three days after a fullthickness injury, which causes thrombosis of superficial vessels, leg blood flow is near control levels. With time, flow increases and, by the end of the first week, reaches levels predicted for the size of the leg burn. This increase is associated with the formation of a richly vascularized wound bed. In contrast, partialthickness injury does not ablate the superficial vascular bed, and blood flow is elevated in those legs with second degree burns as soon as circulatory volume is restored. In addition, excision of a vascularized fullthickness wound to fascia results in a prompt decrease in leg blood flow.5 Blood flow in these limbs is restored to elevated levels with formation of a granulation bed which will accept a skin graft. Under normal physiologic conditions, blood flow to the extremity responds to variations in the oxygen de-
452
WILMORE AND OTHERS
TABLE 5. Comparison of Patients With SmallI and Large Leg Bums (Mean and Range of S.E. M.)
Large Leg Bumsn"
Small Leg Bums§ Patient Characteristics Number of subjects
7
8
Number of studies
7
9
Age (years)
(18(128 50)
28
(17-50)
Weight (kg)
70.1 (58.6-83.7)
73.2
(57.5-89.4)
Body surface area (m2)
1.88
1.89
(1.63-2.10)
Per cent total body face burn
sur-
42 (12-61.5) 58.0
40.5
(12-57.5)
Per cent total leg burn
9.5
(37.5-82.5) 14 (7-22)
(0-17.5)
Postburn day studied
12
(8-19)
Systemic Responses Cardiac index
(L/
m2 * min) Oxygen consumption (mum2 min) Rectal temperature
(OC) Mean skin temperature (°C)
Peripheral Responses Mean leg skin temperature (°C) Leg blood flow (ml/100 ml leg-min) Arterial oxygen concentration (ml/ 100 ml) A-FV¶ oxygen difference (ml/100 ml) Leg oxygen consump-
tion
+ 0.70 ±
12
Arterial lactate concentration (mg/ 100 ml) A-FV lactate difference (mg/100 ml) Leg lactate turnover (mg/100 ml leg- min)
+
0.81
241 ± 22 38.3 ± 0.3 36.1 ± 0.2
38.5
±
0.3
36.1
±
0.2
35.2
±
0.3
4.22
±
0.43
35.5 ± 0.3 8.02 + 0.51k
15.08
±
0.40
15.29 ± 0.72
4.40
±
0.87
3.08
0.187
±
0.037
0.240 ± 0.010
(mlV100 ml
leg- min) Arterial glucose concentration (mg/ 100 ml) A-FV glucose difference (mg/100 ml) Leg glucose turnover (mg/100 ml leg- min)
7.46
± 0.26
10
81
±
1
4
±
0.033
17.2
±
3.4
17.6 ± 3.6
-1.4
±
1.4
-3.6 ± 0.9
-0.060
±
0.055
-0.299 ± 0.075*
89 1
0.037
±
± 4
± 1* 0.336 ± 0.077t
p
