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THE METABOLIC RESPONSE TO BURNS
By ERIC REISS,1 ELINOR PEARSON, AND CURTIS P. ARTZ WITH THE ASSISTANCEt OF BERNARD BALIKOV (From the Surgical Research Unit, Brooke Army Medical Center, Fort Sam Houston, Texas)
(Submitted for publication January 3, 1955; accepted September 1, 1955)
Since Cuthbertson first published his important
investigations, the metabolic response to trauma
has been the subject of continuous study in many
disciplines of medicine (1-8). An impressive
body of knowledge has been accumulated with
respect to changes in plasma electrolyte concen-
trations, urinary electrolyte excretion, body com-
position, and adrenocortical activity.
There is general agreement that injury is ac-
companied by an increased excretion of nonpro-
tein nitrogenous products, but the importance of
this phenomenon, its interpretation in terms of
body economy, and its therapeutic implications
remain the subject of controversy (4, 5, 7). On
the basis of the nitrogen-sulfur and nitrogen-phos-
phorus ratios in the urine of rats with fractures,
Cuthbertson (^) concluded in his earlier (^) studies that
the increased excretion of nitrogen after fractures
results chiefly from muscle catabolism (1). How-
ard and Mason, on the other hand, were unable to
correlate nitrogen balance with that of potassium
or (^) phosphorus in (^) postoperative patients (8). In
burned rats, Braasch, Bell, and Levenson noted
only transiently increased excretion of potassium
and phosphorus while nitrogen excretion remained
high for longer periods of time (9). Cope, Na-
thanson, Rourke, and Wilson (10) and Moore and
Ball (^) (7) recorded early negative nitrogen and
positive potassium balance in burned patients.
In the present study, the balances of nitrogen,
calcium, phosphorus, magnesium, potassium, so-
dium, and chloride were measured in burned pa-
tients for long periods of time. Information was
sought about 1 ) the relative rates of mineral losses,
and 2) changes in body composition.
METHODS
The data on five adults, four men and one womian, are
included in^ this report. All^ were in^ good health^ be-
' (^) Present Address: (^) Departmnent of Medicine, Wash-
ington University School of Medicine, St. Louis, Mis- souri.
fore injury. Metabolic studies were begun immediately after injury. The length of individual studies varied from 60 to 180 days. The early fluid therapy given, the rationale for its use, and the details of local care have been discussed in previous publications (11, 12).
I. Metabolic ward regimen Facilities were available for complete studies on two patients at any one time. The patients were cared for in (^) special cubicles or in the air-conditioned side-rooms of a research ward. Air-conditioning was provided in order to minimize the losses of electrolytes through sweat. One of the authors was responsible for all as- pects of treatment. Four nurses who were especially
trained in metabolic technics were responsible for nurs-
ing care and collection of all specimens. The patients
were weighed daily for the first two postburn weeks and
twice a^ week^ thereafter.^ A^ Toledo scale^ was^ used^ with a special attachment for^ weighing patients on^ Stryker frames. This^ scale registers weights to^ within^114 gm. The reproducibility of weighing a^ patient, with or
without a frame, was repeatedly tested and found to be
satisfactory. When possible, allowance for weight change due to a dressing change was made by weighing patients both before and after a dressing change.
II. Dietary regimen All of the food was prepared in and served from a
special diet kitchen under the supervision of the research
dietitian. Three menus were served in rotation, each menu supplying approximately 2000 calories, 100 gm. of
protein, 250 gm. of carbohydrate, 60 gm. of fat, 50 mEq.
of sodium, 75 mEq. of potassium, 22 mEq. of magnesium,
(^45) mEq. of (^) chloride, 1.3 (^) gm. of (^) calcium, and 1.5 (^) gm. of phosphorus. The menus consisted only of foods that can be stored or (^) preserved in the frozen state. A (^) dietary supplement was given in the form of a formula con- sisting of eggs, dried whole and skim milk, Dextri- Maltose®, and a flavoring agent. The supplement pro- vided an additional 2700 calories, 100 gm.. of protein, 473 gm. of carbohydrate, 85 gm. of fat, 130 mEq. of
sodium, 120 mEq. of^ potassium, 135 mEq. of chloride, 22
mEq. of^ magnesium, 2.4^ gm. of^ calcium, and^ 2.7^ gm. of
phosphorus. If^ a^ patient ingested all^ of the^ menu^ and
the supplement, he received approximately 4700 calories
and 200 gn. of protein. The following vitamins were
given in capsule form: ascorbic acid-1000 mg.; thiamin hydrochloride-60 mg.; riboflavin-40 mg.; nicotinamide
-200 mg.; and calcium pantothenate-40 mg. A serious
attempt to^ achieve^ constancy of^ intake^ was not^ made
THE METABOLIC RESPONSE TO BURNS
because of the critical nature of the patients' illness. The patients were encouraged to eat as much of the total diet as possible. The supplement was given between meals during the^ day and^ at^ intervals^ during the^ night. The intakes that^ were^ achieved^ can^ therefore^ be^ con- sidered a reflection of^ appetite, a^ variable that^ may be interpreted in^ terms of the^ natural^ history of^ convales- cence from a severe burn. A (^) detailed report on food (^) analyses has been presented elsewhere (13). Storage facilities^ for food^ were^ avail- able for studies of 6 to 8 weeks' duration.^ Sample diets, prepared and cooked in^ the same^ manner^ in^ which^ they were served to patients, were analyzed periodically. Each of the menus was analyzed three to six times from each lot of food. Since it was demonstrated that the mineral content was significantly different in various lots of food, the mean of the analyses of a particular lot was used for calculation of the intake during the time when this lot was served. The composition of the formula was de- termined from the mean of repeated analyses. The vol- ume of formula ingested was carefully measured. Un- eaten foods (^) (rejects) were (^) pooled for individual meta- bolic periods and then^ analyzed. Salt was^ not^ used^ for^ cooking, and^ the^ patients salted their own^ food from^ a^ salt shaker^ containing a carefully weighed amount^ of^ anhydrous sodium^ chloride. Food^ was served under close supervision of a member of the staff to avoid careless spillage of salt.
III. Collection, preparation, and analysis of specimen The intake and urinary excretion of all minerals were measured in 24-hour metabolic periods for the first 2 to 3 weeks and in 5-day metabolic periods thereafter. Stools were pooled in 10-day periods from the beginning of the study. Dressings were pooled in convenient periods, the length of which was determined by the exigency of treatment in particular patients. During the early parts of a study, an effort was made to time dressing changes according to metabolic periods, but this practice proved too cumbersome and therefore had to be abandoned. Glacial acetic acid, 50 ml., was added to the urine col- lection bottles at (^) the beginning of each 24-hour collec- tion (^) period. Carmine was used as a marker for stool col- lection (^) periods. Cascara tablets or enemas were used at the end of stool collection periods, and a distinct sepa- ration of stools into periods was usually possible. For unknown reasons, recovery of the carmine proved diffi- cult in the early postburn period even though large quan- tities of carmine (^) were given. When distinct stool sepa- rations were not feasible, the first stool collection period was (^) extended to (^20) days and occasionally even longer. The dressings were thoroughly washed in large washing machines, and^ aliquots of the^ washings were^ analyzed. All samples were prepared and analyzed by methods that have been previously described (13). To test (^) the adequacy of the metabolic regimen in gen- eral, three normal subjects were observed for four 5-day periods each.^ They were^ found^ to be essentially in equilibrium with respect to all constituents studied.
IV. Computation of balances and method of charting
Balances were computed from all sources of intake and (^) output. Electrolyte solutions, which were given
in large volumes during the early postburn period, were
not analyzed, and the composition as given by the manu- facturer (volume and^ concentration) was^ used in cal-
culating the intake from^ this^ source.^ Since^ plasma pro-
teins enter the metabolic pool more rapidly than eryth- rocyte protein, nitrogen intake derived from whole^ blood transfusions was computed on the basis of the^ plasma protein content only; erythrocyte nitrogen was not counted as part of the intake. For estimating the min- eral content of the plasma portion of whole blood, aver- age values were used (7). Lyophilized plasma was given only rarely. The amount of whole blood given to the various patients is recorded^ on^ the^ metabolic^ cor- relation charts and in the Appendix. Since erythrocytes were not included in the intake, any dressings contain- ing appreciable amounts of blood were discarded. This practice resulted in failure to measure some of the plasma proteins and minerals lost with the blood into the dress- ings. No allowance was made for 20 to 30 ml. of blood that were drawn daily in the first 2 to 3 weeks for a study of plasma electrolyte concentration changes. These studies will be reported separately. For ease of interpretation, all of the data were charted on an average per day basis. The same grouping of data is used for all patients in order that a time-corre- lated comparison of their respective metabolic adjust- ment can be made visually. The day of injury is "day zero," the day after injury is the first postburn day, and so forth. The first 10 days of study are divided into a zero through second day period and a third through ninth day period. Thereafter, the balances are charted in 10-day intervals. The pooling of balances into arbitrary periods is^ a^ matter^ of^ convenience for graphic^ presenta- tion. It obscures (^) some important details, but these can be obtained from the original data.2 Nitrogen, potassium, magnesium, and phosphorus are charted approximately in the relative proportions in which these minerals are believed to be present in normal muscle. Calcium and phosphorus are charted in a ratio that approximates the calcium-phosphorus ratio of^ bone. Sodium^ and chloride are charted^ separately. The intake is^ charted from the zero line up and the output from the top of the intake line down. Solid black areas indicate negative balance below the zero line and positive balance above it The cross-hatched areas represent exudate contribution to the output. The relative contributions of urine and feces to the output are not shown. Four ordinate scales are applicable to the five minerals charted on the upper part of the charts. One gram of nitrogen is charted as equivalent to 3.3 mEq. of potas- sium and us^ gm. of phosphorus. Calcium and phos- phorus are charted in a ratio of 2: 1. For charting pur- poses, these ratios are convenient approximations to the 2Detailed data are available to the reader on request:
Lt. Col. Curtis P. Artz, Surgical Research Unit, Brooke
Army Medical Center, Fort Sam Houston, Texas.
63
THE METABOLIC RESPONSE TO BURNS
RESULTS
I. Balances^ and^ Correlations
Nitrogen balance
In patients 1 through 5, the (^) duration of nega-
tive nitrogen balance (catabolic phase) was 28,
36, 31, 30, and 15 days, respectively (Figures
1-6). Negative nitrogen balance resulted from
the (^) very large excretion of (^) urinary nitrogen as
well as from a low dietary intake. The urinary ni-
trogen was much higher in the four men than in
the woman (patient 4). There were large fluc-
tuations from day to day in the amount of urinary
nitrogen excreted, and the (^) excretion rate (^) tended toward a maximum at the end of the first post- burn week. As the nitrogen balance approached equilibrium and became positive, the urinary ni- trogen was generally low and, occasionally, ex- ceptionally low. In patient 4, for example, the average urinary nitrogen was 5.9 gm. on an in- take of (^) 10.3 gm. 45 to (^49) days after injury. The greatest urinary nitrogen loss on any one (^) day oc- curred in patient 5, who excreted 36.9 gm. of nitrogen on the seventh postburn day on an in- take of 18.8 (^) gm. of (^) nitrogen. Urinary nitrogen excretion of 25 to 30 gm. per (^) day was (^) commonly
PATIENT.^2 0C 24 YEARS
201 3- 45 TOTAL BURN
I
0-2 3-9^3 10-19-
0 G) (^) (9D a 20-29 30-39 40- POSTBURN DAYS
S
50-
aC (D aI 60-69 (^) ?0-?9m
I a 3 4 6 7 6 9
so 69.4 61.3 57.9 56 57.5 .4 56. 55 so 50 45 40 35
30 I5- 0- li15- I (^10) z h (^) 5. 0 I~- 0-!
0 10'
.
t 190 10 1? ISO 150 140 130 120- 110 100- 90- so.- 70- tO. so.- 5I0-
4 0. iL 30- 20-
0O lo- 10-
0, 0 -to 30 - c (^) 40- E (^) 5so-
WEIGHT IN KG,
76. 7no
I
)I-
0
Is
0 E L E 0 0
hi
z 0
N
6o
3;. M 3O
LO 1.6 Z O.@ a
O ;s
-0*
7FI rI
I' I (^) ; 18 E
I..
JD
IA
|s
PERIODS
FIG. 2A. METABOLIC CORRELATION CHART, 6 To 79 DAYS, PATIENT 2
ERIC REISS, ELINOR PEARSON, AND CURTIS P. ARTZ
PATIENT *2 0' 24 YEARS 20% 3 45% TOTAL (^) BURN
_i.1 6ao (^) 87.6 P.S ISA 6053 0.6 61.6 (^) .3 63.
F 1 I 1 a 1 F ii 1 1
4 I 4 I
-o
"A o^ PIP r al cm Cs us~~~ ~ ~~~~~s-
us
O-~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~- no U,
w m m rw JL u
00- QD 90-06 100-
B 110-119 (^) 120-129 (^) 130- POSTBURN DAYS
(D
140-149 150-1S9^ ID
10 11 1t 13 14 Io 16 17 Is (^1)
*0-169 (^) 170-IT
PERIODS FIG. 2B. METABOLIC CORRELATION (^) CHART, 80 TO (^179) DAYS, PATIENT 2
observed in the first (^) postburn week at a time when
intakes were (^) generally low.
The magnitude of positive nitrogen balance dur-
ing the anabolic phase (period of (^) predominantly
positive nitrogen (^) balance) varied (^) greatly. The
highest rate of nitrogen (^) storage occurred in (^) pa-
tient 1 whose average nitrogen retention was 20
gm. per day between the 46th and 55th (^) postburn
days.
There was a significant positive correlation be-
tween (^) nitrogen intake and fecal nitrogen (^) (r =
0.58; P < 0.001). However, the (^) regression co-
efficient was low (^) (0.05), and the fecal (^) nitrogen
(^8) The blood nonprotein nitrogen concentration was measured at (^) frequent intervals in (^) all patients. Azo-
temia was not observed at any time.
was rarely outside the (^) range of 1 to (^2) gm. per day. The exudate (^) nitrogen, on the other (^) hand, was highly variable and contributed a substantial frac- tion to the total output. Exudate (^) nitrogen de- creased as wound closure was achieved. The wounds of patient 4 deteriorated (^) progressively, and this was reflected by a high (^) nitrogen content in (^) the exudate. On several occasions, the exu- date (^) nitrogen accounted for (^) more than 50 per cent of the total (^) nitrogen output.
Potassium-nitrogen correlation.
In the immediate (^) postburn period, potassium balance was (^) negative in all (^) patients, and the potas- sium-nitrogen ratio of the balances (^) approximated the value expected (^) by whole tissue catabolism.
22o- 210 too- 100 1e ISo 160 ISO 140 130 120 Ito too- 90 so
60 -
li40- 30 - o =' 10 _R-
60-^ SS 655 560 45- 40- 35 30-
IS
hOi 0s-
to X 10 a
zC 105
oH 0
|5e b (^1) 0,
-1I I .'C.
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-5.
- sit
- (^) 2t.
- (^).
- (^) 2.
- (^) 1. 8.t -ot a -0.
-0 a -l 0 --t h. 0 --2e.O^ E --t.
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gi (^20)
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h
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ot
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in
ERIC REISS, ELINOR PEARSON, AND CURTIS P. (^) ARTZ
PATIENT (^) .3 0' (^20) YEARS 23 % 3° 25% TOTAL BURN
FIG. 3B.
- (^) 3.
- (^) 2.8>.
- 2.6 a
- 2.4 z
- 2.2^ CL
- 2.0 , -1. (^8 0) a:r 1.6 x 0L 1.4 ) 0 1.2 x 1.0 IL 0 -0.8 (^9)
- 0.6^0 0.4 o Q2 o 0 x --0. -0. -0.6 (^) X -0.8 Z
--1.2 uL 0 E-
-1.6 (^0)
, 4E
I I IuIL
ID 04
80-89 (^) 90-99 100-109 110- POSTBURN DAYS , 10 I I 12 13 PERIODS
METABOLIC CORRELATION CHART, 80 TO 115 DAYS, PATIENT 3
was associated with a^ high potassium content of
the exudate, and on several occasions as much
as 40 per cent of the total potassium excretion
occurred via the exudate.
Correlation of calcium, phosphorus, and other
mineral balances
A rapid, approximate estimate of the theoreti-
cal phosphorus balance based on calcium and ni-
trogen can^ be^ obtained^ visually from the charts
by adding the observed nitrogen and calcium bal-
ances in an algebraic manner. Similarly, the
theoretical nitrogen balance based on calcium
and phosphorus can be obtained by algebraically
subtracting the observed calcium from the ob-
served phosphorus balance. The theoretical po-
tassium balance based on calcium and phosphorus
equals the theoretical nitrogen balance based on
these constituents.
68
45 -
40 -
35 -
30 -
25 -
20 -
lS-
a (^10)
I 5
z 0- 0 I- 5 z
0
-10-
4
0.^ Cc
Z -j
IL 0
0D
-4.
0 --0. -0. --1. --I.6. -2. -2. -2. L (^) -3.
-ri I- 4 I a-
IAw
r,
001,
THE METABOLIC RESPONSE TO BURNS
In the early postburn period, the theoretical
phosphorus balance based on calcium and nitro-
gen consistently deviated from the observed phos-
phorus balance, so that the observed phosphorus
loss was smaller than that predicted on the basis of the nitrogen and calcium balances. During the same interval, the theoretical potassium balance based on nitrogen deviated^ markedly and^ con- sistently from the observed potassium balance so that the observed potassium excretion was less than that predicted on the basis of the nitrogen balance. Thus, the deviations from the^ expected values of both the phosphorus and potassium balances coincided in time as well as direction. In subsequent periods, there was, in general,
Patient *4^9 27 Years 45% (^) 3° 55% (^) Total burn
40 130 WEIGHT IN KG. 35 ~^ ltl to t 74 65 61 110- 30 100
- (^60) )20 70- so -
hi (^40) ~ 20
o (^) O1-
d. 't
0 E^30 040 .IS (^) -50 K
agreement between the theoretical^ and^ observed phosphorus balances, both^ at^ times^ when^ nitrogen balance was^ positive and^ when^ it^ was^ negative. During many of the^ study periods, the theoretical phosphorus balance was^ in^ better^ agreement^ with the observed potassium balance than with the ob- served nitrogen balance.
Magnesium balance and correlation
In order to establish a baseline for comparison, three normal subjects were^ studied^ for^ four^ 5-day metabolic periods each. The^ intake^ was^ constant at approximately 26 mEq. of magnesium per day. On the average, 25 per cent of the ingested mag- nesium was excreted in the urine, the remainder
2.6 04
-2.4 - -L a
-Io 1. IL
0 -LO 0.4 a
Q 0
0 ro
SQwol o -1^ 2~.0. .ILS
.
4..
(^32) a. L4 (^) C
1.2 a
043 -o (^) Z; -a4g _,,l --0L -LO
a
I
iI
I 2. 3 4 5 6 7 - S
PERIODS FIG. 4. METABoLIC CO^ TION CHART, PATIENT 4
THE METABOLIC RESPONSE TO BURNS
tive balances are a result of the large amounts of
these ions given in^ an^ effort to keep pace with the
obligatory edema that is characteristic^ of^ recent
burns. The exudate always contributed^ a^ large
and important fraction of the total sodium and
chloride output during this early period, and fail-
ure to take account of this important route of elec-
trolyte excretion would result in^ paradoxically
large positive balances. The loss of these electro-
lytes through the sweat was large in all of the
patients. Burned patients are more comfortable in
warm than in moderately cool surroundings. Air-
t.gm.
o
conditioning, which was available, was poorly tolerated and could be used only rarely.
II. Changes in Body Composition
Whole tissue
If the early negative nitrogen balance is a re- flection of whole tissue catabolism, the magnitude of whole tissue^ loss^ was^ very great in^ some^ of^ the patients. If 1 gm. of nitrogen is considered equivalent to 30 gm. of tissue, the patients lost between 8.2 kg. and 11.7 kg. of lean body tissue
-ACTUAL N^ BALANCE
--- (^) THEORETICAL N BALANCE BASED ON P BALANCE CORRECTED FOR Ca.
ACTUAL N^ BALANCE
THEORETICAL N^ BALANCE BASED ON Mg BALANCE
I j.,a a^ LJ (^) *_p. * * I' I 2 a (^) _ a a (^) a * 0 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 32 34 36 38 40 42 44 46 48 5052 54 56 58 60 TIME IN DAYS
FIG. 6. COMPARISON BETWEEN THE OBSERVED THEORETICAL NITROGEN BALANCES BASED ON THE BALANCES OF POTAS- SIUM, PHOSPHORUS AND CALCIUM, AND MAGNESIUM (PATIENT 1) Note the early, relative retention of potassium and phosphorus.
ACTUAL N BALANCE
---THEORETICAL N BALANCE BASED ON K BALANCE
71
ERIC REISS, ELINOR PEARSON, AND CURTIS P. ARTZ
TABLE I Cumulative observed and theoretical nitrogen bakances during catabolic and anabolic phases
Potassium (^) Phosphorus Proto- Dura- Cumula- Cumula- * (^) t Cumula- Cumula- Proto- plasm I (^) II tion of tive N tive K K/N Theoretical Dis- tive P tive Ca plasm P P/N Theoretical Dis- Patient phase (^) balance balance ratio N balance crepance balance balance balance ratio N balance crepance
days gm. mEq. mEq./gm. gm. gm. gm. gm. gm. gm. gm. Catabolic Phase 1 28 -390 - 830 2.1 -277 113 -13.4 - 6.4 -10.5 1:37 -158 232 (^2 36) -341 - 660 1.9 -220 121 - 7.2 + 3.8 - 8.9 1:38 -134 207 3 31 -383 -1010 2.6 -337 46 -18.6 -18.6 -10.3 1:37 -154 229 4 30 -275 - 290 1.0 - 97 178 - 7.1 -2.7 - 5.9 1:47 - 88 187 5 15 -322 - 440 1.4 -147 175 - 7.2 + 3.9 - 8.9 1:36 -134 188 Mean 1.8 126 1:39 209
Anabolic Phase 1 33 +415 +1000 2.4 +333 (82) +34.1 + 3.4 +32.6 1:13 +489 74 2 144 +335 +1760 5.2 +587 252 +13.6 -54.1 +37.9 1:9 +568 233 3 85 +293 +1020 3.5 +340 47 + 2.5 -18.2 +10.7 1:27 +160 (133) 4 58 +108 + 730 6.8 +243 135 +12.1 +16.4 + 4.7 1:23 + (^70) ( 38) 5 65 +347 +1720 5.0 +573 226 +19.8 -24.3 +30.7 1:11 +460 133 Mean 4.6 1:
- (^) Cumulative K balance divided by 3 (1 gm. N = (^3) mEq. K).
t Difference^ between^ cumulative^ N^ balance^ and theoretical N balance^ based^ on^ K^ balance.
(Cumulative Ca balance
Cumulative P balance- 2.23 /
§ Protoplasm P balance times 15. Difference between cumulative N balance and theoretical N balance based on P and Ca balances. Figures in parentheses indicate that the expected nitrogen retention was approximated. See text for details.
during the catabolic^ phase. In^ the^ first^10 days, the mean (^) nitrogen loss was 18 gm. per day, which would be equivalent to 540 gm. of whole tissue loss per day. During the entire catabolic phase, the potassium- nitrogen ratios of the losses were 2.1, 1.9, 2.6, 1.0, and 1.4 mEq. per gm., (^) respectively, and, during the same (^) period, the (^) phosphorus-nitrogen ratios (corrected for^ calcium) were^ 1:^ 37, 1:^ 38, 1:^ 37, 1: 47, and 1: 36, respectively (Table I). Whole tissue catabolism alone would be expected to yield a potassium-nitrogen ratio of approximately 3. mEq. per gm. and a phosphorus-nitrogen ratio of 1: 15. If the nitrogen losses are considered to be derived from^ whole tissue catabolism on one hand and catabolism (^) of tissues containing nitrogen but neither potassium nor phosphorus on the other, the theoretical (^) potassium and (^) phosphorus-free ni- trogen losses can be estimated (Table I). In some of the patients, these estimates based on (^) potassium and on (^) phosphorus were in (^) good agreement (pa- tients 4 and 5), while in others the agreement was
poor.
In the anabolic phase, the mineral ratios could
be (^) expected to approximate those observed in the catabolic phase. For the anabolic phase taken as a whole, potassium-nitrogen ratios were 2.4, 5.2, 3.5, 6.8, and 5.0, respectively, and the phosphorus- nitrogen ratios (corrected for calcium) were 1: 13, 1: 9, 1: 27, 1: 23, and 1: 11, respectively. The expected anabolic ratio was approximated only in patients 3 and 4, with respect to phosphorus and (^) nitrogen; the (^) phosphorus-nitrogen ratio in patients 1, 2, and^ 5, as^ well as the potassium-ni- trogen ratio in patients 2 through 5 were the reverse of the expected.
Fat
Changes in fat stores were estimated for the catabolic and anabolic phases by comparing the observed weight changes with the weight changes predicted on^ the basis of the nitrogen balance.
The electrolyte balances were not used as a meas-
ure of (^) changes in (^) the body fluid (^) compartments be- cause of the (^) inaccuracy of (^) the sodium and (^) chlo- ride balances that resulted from^ sweat^ loss.^ In order to avoid the cumulative errors in^ the electro- lyte balance, the two weights used for calculating
ERIC REISS, ELINOR PEARSON, AND CURTIS P. ARTZ
mation.5 (^) Although the incidence of renal cal-
culi appears to be small, the advisability of giving
diets with a high calcium and phosphorus content
is open to question in view of the findings pre-
sented here. Changes in^ the^ magnesium balance^ reflected,^ to a (^) large extent, changes in fecal magnesium ex-
cretion. The latter was distinctly influenced by
the level of magnesium intake. It was of interest
that, in several study periods, the fecal magnesium
was greater than the magnesium intake. This in-
dicates either that magnesium was excreted into
the gastrointestinal tract or that fecal excretion of
previously ingested magnesium was greatly de-
layed. Strongly positive magnesium balance was
observed only in patient 1 during the latter part
of the study. This resulted from a slightly de-
creased fecal magnesium excretion that was associ-
ated with a greatly increased magnesium intake.
Correlations and changes in body composition
The most striking and consistent change in the balances was the failure of the early potassium and phosphorus balances to correlate^ with^ the nitrogen balance. When the entire catabolic phase is considered, the catabolized tissue contained less potassium and phosphorus in relationship to ni- trogen than normal protoplasm. This may be ex- plained as the loss of a relatively nitrogen-rich tissue or as loss of (^) protoplasm with (^) deposition of potassium and^ phosphorus, either in^ intracellular fluid or with glycogen. Since collagen and skin contain a large amount of nitrogen in relation to potassium, lysis of large amounts of these tissues may account for part of the nitrogen lost in excess of that (^) expected by the (^) potassium balance. Ca- tabolism of plasma proteins, liver proteins, and other reserve protein stores may explain part of
(^5) In a review of (^650) burned patients, most of whom were immobilized for at least three months and (^) frequently much (^) longer, there was one (^) patient who had bilateral re- nal calculi, two patients who had a bladder calculi, and two patients in whom renal calculus formation was suspected clinically but not confirmed roentgenologically. The in- cidence of asymptomatic calculus formation in the geni- to-urinary tract is not known. Nearly all patients were given diets with high calcium and phosphorus contents similar to those used in^ the present study. The calcium and (^) phosphorus contents of the diets are (^) high because milk and milk products are used as supplements to the regular diet.
the large nitrogen losses in excess of potassium and phosphorus during the early catabolic phase. The ratio of nitrogen to other intracellular con- stituents during the anabolic phase would be ex- pected to^ be the same as that during the catabolic phase. Actually, these ratios were often the re- verse of the expected during the anabolic phase. This may be explained partly by the fact that the catabolic phase was studied in its entirety while the anabolic phase certainly extended far beyond the completion of these studies.^ None^ of^ the pa- tients had achieved nitrogen equilibrium by the time the studies ended. When patients 1 and 5 were discharged from the hospital, the nitrogen losses incurred after injury had been replaced in both patients so that the cumulative nitrogen bal- ance from the time of injury^ to discharge ap- proached zero. Two months after discharge, addi- tional studies were performed in these patients for four 5-day metabolic periods. At that late date, both patients were still in significantly positive nitrogen, potassium, phosphorus,^ calcium,^ and magnesium balances. Thus, convalescence in^ these patients was characterized by mineral retention in excess of the amounts present in the body be- fore (^) injury. This is most surprising since the capacity for^ mineral^ storage of healthy adults^ is quite limited.
Clinical data
During the catabolic phase, areas of^ partial- thickness skin loss healed satisfactorily in^ all^ pa- tients, and skin grafts took well in patients 2, 3, and 5, who were grafted during this period. Dur- ing the anabolic phase, clinical correlations be- tween nitrogen balance^ and^ a^ good healing capac- ity could not always be established. Positive ni-
trogen balance^ per se^ does^ not^ appear to^ insure
proper healing, and other factors, such as degree of depletion of body proteins and fat stores, en- docrine changes, and changes in the wound itself, probably play dominant roles in the healing
process.
SUMMARY
- The balances^ of^ nitrogen, potassium, phos- phorus, calcium, magnesium, sodium, and^ chloride were measured^ in^ five^ severely burned^ patients from the time of (^) injury to (^) complete healing.
74
THE METABOLIC RESPONSE TO BURNS
Individual studies varied in^ length from 60^ to 180
days.
2. The nitrogen losses incurred during the cata-
bolic phase could not be accounted for on the
basis of whole tissue dissolution: the negative ni-
trogen balance was greater than could be ex-
plained by either the potassium balance or the
phosphorus balance corrected for calcium.
3. In general, magnesium balance paralleled
the nitrogen balance in direction, but the^ nitrogen-
magnesium ratio of catabolized tissue and ana-
bolized tissue varied greatly.
4. Body fat losses, estimated^ from^ nitrogen
balance and weight changes, appeared to^ occur^ in
all patients during both the catabolic and the
anabolic phases.
ACKNOWLEDGMENT
We wish to (^) express our (^) gratitude to Drs. (^) Harry S. Soroff, Benjamin A. (^) Barnes, Melvin S. (^) Schwartz, C. F.
Liedberg, and Irving Gray for their help and advice.
Captains Helen Donnelly, Rebecca^ Holland, Violet^ Green,
Margaret Maher, and Edith^ Bonnet^ and^ Lieutenant^ Alice
Edelen were responsible for^ carrying out^ an^ exacting
metabolic routine. Mr. William Creech and^ Mr.^ Emil Shaw gave valuable technical assistance. We are^ par-
ticularly indebted to Dr. William H. Amspacher, form-
erly Commanding Officer of the Surgical Research Unit,
whose sustained support and encouragement made these studies possible.
APPENDIX
Patient 1. This 32-year-old Negro airman received
partial-thickness (second degree) burns of 70 per cent
of the body surface when a relative attempted to kill him
by pouring boiling water^ over^ him^ while he^ was^ sleeping
in the nude. Before^ injury, the^ patient had been^ in^ ex-
cellent health.
Physical examination revealed^ a^ well-developed, well-
nourished man^ who^ had burns^ involving the^ face, both
upper extremities, portions of^ the^ anterior^ and^ posterior
aspects of^ the^ trunk, and^ both^ thighs. Local^ care^ con-
sisted of^ superficial debridement^ and^ cleansing of^ all
burned areas, and the^ application of^ compression dress-
ings over all areas except the face and the anterior as-
pect of the trunk; these were treated by the exposure
method. During the first 48 hours after burning, the
patient was given intravenously 1500 ml. of blood, 1500
ml. of plasma, 1000 ml. of 0.9 per cent saline, 9000 ml. of
lactated-Ringer's solution, and 1000 ml. of^5 per cent
dextrose in^ water. On this^ regimen, the^ urinary output
was maintained at approximately 50 ml. per hour, and
signs and^ symptoms of^ circulatory collapse were^ not
observed. Swelling of the^ wounds^ began immediately
after injury and increased progressively until the 8th post-
75
burn day. Until this time, the patient's clinical course was characterized by progressive deterioration as evi- denced by periods of disorientation, (^) abdominal distention,
and increasing fever (1040 F. on fifth postburn day). On
the 8th postburn day, a diuresis occurred, the urine vol- umes being 5180 ml., 5140 ml., 3600 ml., 5160 ml., and 6440 ml. on the 8th, 9th, 10th, 11th, and 12th postburn days, respectively. Concomitantly, the sensorium cleared, abdominal distention ceased, and the temperature be- came normal. Thereafter, the patient felt well and in- gested increasing quantities of food. The wounds healed satisfactorily so that most burned areas were epithelized within 3 weeks. Complete heal- ing was noted on the 33rd postburn day. Convalescence was complicated on the 22nd postburn day by what was believed to be phlebothrombosis of the leg veins and a small pulmonary infarct. Heparin treatment was given. The patient was ambulatory on the 35th postburn day. He returned to the hospital for follow-up studies 106 days after injury. At that time, his (^) weight had returned to preburn levels. Patient 2. This (^) 24-year-old white airman received ex- tensive burns when a kerosene stove exploded in his trailer. The patient's wife was fatally burned in the same accident. Before injury, the patient had been in good health except for minor psychiatric difficulties. Physical examination revealed a well-developed, well- nourished man who had burns (^) extending over 45 per cent of (^) the body surface. Full-thickness (third degree) burns were noted on the face, the scalp, and both up- per extremities, a total of 20 per cent of the body sur- face. Partial-thickness burns involved the trunk and the anterior aspect of the thighs. Local care consisted
of superficial debridement and cleansing of all burned
areas, exposure treatment of the face, and compression dressings over^ the other burned areas. A tracheotomy was performed a few hours after injury. Supportive therapy during the first 48 hours consisted
of 750 ml. of plasma, 1300 ml. of 0.9 per cent saline, 5000
ml. of lactated-Ringer's solution, and 1000 ml. of 5 per
cent dextrose in water. On this regimen, the urinary
output was maintained at approximately 40 ml. per hour,
and signs and symptoms of circulatory collapse did not
develop. Fever (1050 F.) became evident on the 5th day
postburn, and on the 9th postburn day, a diagnosis of sep- ticemia caused by Micrococcus-pyogenes, var. aureus, coagulase positive, was established by blood culture.
Therapy consisted of Chloramphenicol intravenously.
The temperature gradually receded to between 100° F.
and 101° F., and the last positive blood culture was ob-
tained on the 12th postburn day.
The patient was disoriented immediately after injury and had episodes of disorientation and hallucinations for the first month. It was believed that these were caused
by his inability to see (edema of lids and, later, tarsor-
rhaphy) and his concern about his wife's death and his disfigurement, which accentuated psychiatric difficulties that were (^) present before (^) injury.
The partial-thickness burns^ were healed within a
month after injury. Many skin grafts failed to take ow-
THE METABOLIC RESPONSE TO BURNS
cent). Local care consisted of (^) superficial debridement and cleansing of all burned (^) surfaces, and the (^) application of (^) compression dressings over all (^) burned areas (^) except the face, which was treated (^) by the (^) exposure method. Supportive therapy during the first 48 hours con- sisted of 3400 ml. of blood, 1500 ml. of (^) lactated-Ringer's solution, 1000 ml. of 10 per cent invert (^) sugar, and 300 ml. of 5 per cent dextrose in water. On this (^) regimen, the urine flow was 75 ml. per hour on the (^) average. Cir- culatory failure did^ not^ develop, but the patient was dis-
oriented and^ restless^ during the^ first^ seven^ postburn
days. On the fifth postburn day, fever of 1050 F. sug- gested the presence of septicemia, but several blood cul-
tures failed to establish this diagnosis. The tempera-
ture receded to 1010 F. by the 7th postburn day. Con- comitantly, the patient became oriented and cooperative. The subsequent clinical course was uneventful ex- cept for wound (^) suppuration and poor graft takes as a
result of colonization of the wounds by Group A beta
hemolytic streptococci. This^ accounts^ for^ the^ protracted course. The partial-thickness burns were well healed
by the 25th postburn day, and nearly complete skin
coverage was^ achieved^ by the^ 50th^ postburn day. Skin
grafts: 43rd and 70th postburn days. Dressing changes under anesthesia: 10th, 13th, 29th, 34th, 37th, and 40th postburn (^) days. Blood (^) transfusion: 43rd (^) postburn day (2 units).
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