OF THE OFTHE TOTHE FLUID AND ISOF FLUID Theamounts of fluid injected into the veins of each of the...

17
INTRAVENOUS INJECTIONS A STUDY OF THE COMPOSITION OF THE BLOOD DURING CONTINUOUS TRAUMA TO THE INTESTINES WHEN No FLUID IS INJECTED AND WHEN FLUID IS INJECTED CONTINUOUSLY By J. W. BEARD AND ALFRED BLALOCK (From the Department of Surgery, Vanderbilt University, Nashville) (Received for publication September 3, 1931) It is well known that the volume of circulating blood is reduced in shock. If the reduction is so great that the loss cannot be compensated for by further vasoconstriction, a decline in the arterial blood pressure results. There are two methods by which the blood pressure may be raised. First, drugs that cause the arterioles to constrict may be injected. The pressure in the larger arteries rises but the effect on the blood supply to an organ may be decreased by the constriction of the arterioles in that organ. Since an increase in the supply of blood to the tissues and not a high blood pressure is the primary object in view, the use of vasocon- strictor drugs is usually unsatisfactory. Second, fluids may be injected intravenously in an effort to increase both the blood volume and the blood pressure. Solutions of widely varied physical and chemical characteristics have been used in the treatment of shock. The results obtained by the intravenous administration of fluids, other than whole blood or possibly gum acacia, have not been encouraging. Cannon (1) states, "All the evidence, both clinical and experimental, indicates that the intravenous injection of normal salt solution or Ringer's solution has only a temporary effect. The injected fluid promptly passes into the tissue spaces and within a brief period the pressure is as low as before, if not lower." The rapid loss of solutions of crystalloids from the blood stream explains the transitory beneficial effects of the injection but does not explain why the condition of the patient should often be worse shortly after the adminis- tration of fluid than it was before. The experiments described in this paper were undertaken for the purpose of finding an explanation for this observation. The studies have been extended to a comparison of the effects of the administration of various fluids that are commonly used in the treatment of shock. The studies consisted in the main of repeated determinations of the amount and composition of the plasma in the blood stream under the various conditions. Alterations in the content in protein of the blood 249

Transcript of OF THE OFTHE TOTHE FLUID AND ISOF FLUID Theamounts of fluid injected into the veins of each of the...

Page 1: OF THE OFTHE TOTHE FLUID AND ISOF FLUID Theamounts of fluid injected into the veins of each of the animals in these experiments were excessive. However, determinations were performed

INTRAVENOUSINJECTIONS

A STUDYOF THE COMPOSITIONOF THE BLOODDURINGCONTINUOUSTRAUMATO THE INTESTINES WHENNo FLUID IS INJECTED AND

WHENFLUID IS INJECTED CONTINUOUSLY

By J. W. BEARDAND ALFRED BLALOCK

(From the Department of Surgery, Vanderbilt University, Nashville)

(Received for publication September 3, 1931)

It is well known that the volume of circulating blood is reduced inshock. If the reduction is so great that the loss cannot be compensatedfor by further vasoconstriction, a decline in the arterial blood pressureresults. There are two methods by which the blood pressure may beraised. First, drugs that cause the arterioles to constrict may be injected.The pressure in the larger arteries rises but the effect on the blood supplyto an organ may be decreased by the constriction of the arterioles in thatorgan. Since an increase in the supply of blood to the tissues and not ahigh blood pressure is the primary object in view, the use of vasocon-strictor drugs is usually unsatisfactory. Second, fluids may be injectedintravenously in an effort to increase both the blood volume and theblood pressure.

Solutions of widely varied physical and chemical characteristics havebeen used in the treatment of shock. The results obtained by theintravenous administration of fluids, other than whole blood or possiblygum acacia, have not been encouraging. Cannon (1) states, "All theevidence, both clinical and experimental, indicates that the intravenousinjection of normal salt solution or Ringer's solution has only a temporaryeffect. The injected fluid promptly passes into the tissue spaces andwithin a brief period the pressure is as low as before, if not lower." Therapid loss of solutions of crystalloids from the blood stream explains thetransitory beneficial effects of the injection but does not explain why thecondition of the patient should often be worse shortly after the adminis-tration of fluid than it was before. The experiments described in thispaper were undertaken for the purpose of finding an explanation for thisobservation. The studies have been extended to a comparison of theeffects of the administration of various fluids that are commonly used inthe treatment of shock.

The studies consisted in the main of repeated determinations of theamount and composition of the plasma in the blood stream under thevarious conditions. Alterations in the content in protein of the blood

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BLOODCHANGESWITH INTESTINAL TRAUMA

serum will be particularly emphasized. Trauma to the intestines waschosen as the method of producing shock because the trauma could becontinuous and fluid could be recovered from the peritoneal cavity asfrequently as desired for study.

METHODDogs were used in all experiments. They were profoundly anesthetized by

sodium barbital (0.3 gram per kilogram of body weight administered in-travenously) and gave no evidence of pain during the experiments, at the com-pletion of which they were killed. After making a long midline abdominalincision, the intestines were traumatized (2) by passing them continuouslybetween the fingers. The trauma resulted in a copious weeping of fluid fromthe peritoneal surfaces. The intestines were not withdrawn from the peritonealcavity during the traumatization and the fluid that accumulated there wascollected frequently for study.

The blood pressure was determined by placing in the carotid artery a can-nula that was connected to a mercury manometer. Blood for the variousanalyses was withdrawn from one of the femoral veins and it was replaced byan equal quantity of blood that was obtained from a normal dog. Samples ofblood were obtained before the trauma was begun and at approximately oneand one-half hour intervals thereafter until the blood pressure had declined toa low level with the exception of experiment T 17. Urine was collected, atthe same time that the samples of blood were withdrawn, through a catheterthat was placed in the bladder. The animal was kept warm by the use of aheating pan.

The nitrogen content of the blood serum, the peritoneal fluid and the urinewas determined. In the studies on the blood serum and the peritoneal fluid,the nitrogen was partitioned in most of the experiments. The nonproteinnitrogen was estimated by the method of Folin and Wu (3) except in thoseexperiments in which the effects of concentrated solutions of glucose or gumacacia were being studied; in these the macro-Kjeldahl method was used.Albumin and globulin were separated by the use of 22.2 per cent sodium sul-phate as recommended by Howe (4). Two cc. samples of serum and fluid wereanalyzed instead of 0.5 cc. samples and the dilutions with the sodium sulphatesolutions were proportionately the same. Fifty of the resulting 62 cc. werechosen as the aliquot parts. The nitrogen of the albumin and of the totalprotein were determined by the Gunning (5) modification of the Kjeldahlmethod. The total nitrogen of the urine was also determined by this method.In all the tables the nitrogen is expressed as protein.

Van Allen tubes were used in the hematocrit determinations. The methodof Cohen and Smith (6) was employed for the estimation of the hemoglobin.The initial blood volume of the animal was assumed to be 10 per cent of thebody weight and on this basis the original volumes of red blood cells and plasmawere calculated by the use of the hematocrit readings. In some experimentsboth hemoglobin and hematocrit determinations were performed, while inothers the hemoglobin was not determined. If the hemoglobin and red bloodcell count were both determined, the alterations in the total blood volume wereassumed to vary in an inverse ratio to the changes in the percentage of hemo-globin. Having determined the alteration in the total blood volume, thevolumes of red blood cells and plasma were calculated from the hematocritreadings. When only hematocrit determinations were performed, it wasassumed that the volume of red blood cells remained constant throughout

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J. W. BEARDAND ALFRED BLALOCK

the experiments and the alterations in the volume of plasma were computedfrom the changes in hematocrit readings. The figures for the entire amount ofprotein were obtained by multiplying the percentage of protein per unit volumeof serum by the total amount of plasma. No attempt was made to determinethe alterations in the blood volume and in the entire amount of protein in theexperiments in which the whole blood was injected. It is realized that themethods of calculation are only relatively accurate. The main error is intro-duced by the fact that the volume of red blood cells did not remain constantsince some red blood cells escaped with the plasma into the peritoneal cavityand others accumulated in the traumatized area.

In the experiments in which fluid was introduced intravenously, it wasinjected at body temperature at a constant rate into either the external jugularor femoral vein. The amount of fluid that was given was approximately 10 cc.per kilogram of body weight per hour. The following fluids were used in thedifferent experiments: (1) 0.9 per cent salt solution, (2) 3.0 per cent salt solution,(3) 6.0 per cent glucose, (4) 20 per cent glucose, (5) 6.0 per cent gum acacia, (6)Evans' solution of 6.0 per cent gum acacia and 20 per cent glucose in 0.9 percent salt solution, (7) blood serum and (8) whole blood.

In most of the experiments in which fluid was injected, the water contentof the blood and of skeletal muscle was determined by drying the tissue at 105° C.to a constant weight. Blood was collected from the femoral vein. Skeletalmuscle was obtained from the pectoral and one of the flexor muscles of thethigh at the beginning of the experiments and from symmetrical sites on theopposite side of the body at the completion.

RESULTS

I. CONTINUOUSTRAUMATO THE INTESTINES. NO FLUID INJECTED

When the intestines were traumatized continuously the animalsusually lived six or seven hours. The decline in blood pressure was morerapid towards the end of the experiment than at the beginning. Thehematocrit determinations showed a progressive increase in the propor-tion of red blood cells to plasma throughout the experiments. Thecalculated volume of plasma decreased until at the completion of theexperiments it was approximately one-half of its original value. Thecalculated total protein content of the blood serum remained approxi-mately the same throughout the experiments and the correspondingfluid from the peritoneal cavity on analysis showed a content in proteinvery nearly the same as that of the serum. The percentages of albuminand of globulin in the blood serum were altered very little during thecourse of the experiments. The content in albumin of the peritonealfluid was greater than that of the blood serum, whereas the content inglobulin of the peritoneal fluid was usually less than that of the serum-Since the volume of plasma was greatly diminished, the absolute amountsof total protein, albumin and globulin in the blood stream were consider-ably reduced.

The results of three typical experiments are given in Table I.

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II. CONTINUOUSTRAUMATO THE INTESTINES. CONTINUOUSINJECTION

OF FLUID

The amounts of fluid injected into the veins of each of the animalsin these experiments were excessive. However, determinations wereperformed frequently during the experiments and the effects of small aswell as large amounts of fluid are to be seen in the results in the tables.The average survival period of the animals in these experiments wasapproximately the same as that in the experiments in which the intestineswere traumatized and no fluid was introduced. The type of fluid thatwas injected in these experiments did not seem to alter considerably thelength of life of the animals. The longest survival period was encounteredin dog T 17 in which the intestines were traumatized and whole bloodwas injected for seven and one-half hours. At the end of this time theblood pressure was essentially normal, but the animal died three hourslater. The alterations in the percentage of hemoglobin paralleled fairlyclosely the changes in the hematocrit readings. In many experiments adilution of the blood occurred just before death. In all experiments inwhich the nitrogen of the control specimen of urine was determined as wellas that obtained later, it was found that the urine collected during thecontrol period had the higher total protein equivalent. In most of theexperiments the amount of nitrogen that was lost in the urine was verysmall. In all of these experiments the intestines were traumatized con-tinuously.

The effects of the different solutions employed were briefly as follows.The detailed results of one experiment in each group are given in Table II.Because of lack of space, the others are not included.

1. The injection of 0.9 per cent salt solutionFour experiments of this type were performed. Associated with

the trauma and the injection of large amounts of salt solution there wasan increase in the proportion of red blood cells to plasma in all of the ex-periments. The calculated total volume of blood plasma decreased.The percentage of protein per unit volume of serum decreased markedlyin all experiments except T 48, in which there was very little alteration.The calculated entire amount of protein in the blood stream at the com-pletion of the experiments was approximately one-half of the originalvalues. There was a decrease in the concentration of albumin andglobulin. The content in albumin of the peritoneal fluid was greaterthan that of the blood serum while the globulin content of the serum wasgreater than that of the fluid.

2. The injection of 3.0 per cent salt solutionIn three of the four experiments, the injection of 3.0 per cent salt

solution while the intestines were being traumatized was associated with

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an increase in the concentration of red blood cells. The calculated vol-ume of plasma decreased in three of the four experiments. In all experi-ments there was a decrease in the percentage of total protein, of albuminand of globulin with a diminution in the calculated entire amount of eachin the blood stream. The content in albumin of the peritoneal fluid wasslightly greater than that of the blood serum, while the globulin contentof the serum was greater than that of the fluid.

3. The injection of 6.0 per cent glucose solutionIn three of the four experiments there was an increase in the propor-

tion of red blood cells to plasma. In one experiment the volume ofplasma increased and in three it decreased. In all experiments there wasa decrease in the percentage and in the calculated entire amount of totalprotein, albumin and globulin. The albumin content of the peritonealfluid was usually greater than that of the blood serum, while the globulincontent of the serum was greater.

4. The injection of 20 per cent glucose solutionA concentration of the blood occurred during the early part of the

three experiments. During the later stages of two of the experiments,a dilution of the blood took place. There was a marked diminution inthe concentration of total protein, albumin and globulin in all instancesand the calculated entire amount of each in the blood stream was greatlydecreased. There was a higher percentage of albumin and a lower per-centage of globulin in the blood serum than in the peritoneal fluid.

5. The injection of 6.0 per cent gum acacia solutionIf six per cent gum acacia in normal salt solution was injected during

the trauma, there was an increase in the concentration of the blood at theend of an hour and a half in two of the three experiments. Later obser-vations showed a definite dilution of the blood. There was a markeddecrease in the total protein, albumin and globulin per unit volume ofserum. Even though there was an increase in the calculated total volumeof plasma in most of the experiments the total amount of the proteinconstituents in the blood stream was markedly diminished. The amountof gum acacia that remained in the circulation was not determined.

6. The injection of 6.0 per cent gum acacia and 20.0 per cent glucose in 0.9per cent normal salt solution

In all experiments there was a marked dilution of the red blood cellsand a large increase in the volume of plasma in the blood stream. Thepercentages of total protein, of albumin, and of globulin per unit volumeof serum and the calculated entire amounts of each in the blood streamwere decreased in all experiments. The concentration of albumin in the

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BLOODCHANGESWITH INTESTINAL TRAUMA

peritoneal fluid was greater and the concentration of globulin was lessthan in the blood serum.

7. The injection of blood serumEven though blood serum was injected continuously, the concentra-

tion of red blood cells increased in two of the three experiments. Thecontent of total protein, of albumin, and of globulin in the blood serumremained approximately the same throughout the course of the experi-ments. In two of the three experiments there was a decrease in thecalculated entire amount of protein in the blood stream. Since proteinwas present in the blood serum that was being injected, the true loss ofprotein was greater than the apparent loss. For example, in experimentT 27, the calculated entire amount of protein in the blood stream beforethe trauma was instituted was 52 grams. Five and one-half hours laterit was 34 grams, indicating a loss of 18 grams. But during this time 46grams of protein had been injected so that the true loss was 64 gramsrather than 18.

8. The injection of whole bloodThe concentration of the red blood cells increased tremendously in the

three experiments in which whole blood was injected. No attempt wasmade to estimate the alterations in the volume of circulating blood butwe can be quite certain that the volume of plasma was reduced eventhough whole blood was injected. The concentration of total protein,albumin and globulin in the blood serum either remained the same orincreased slightly during the course of the studies. The results of theseexperiments differ from those obtained after the injection of blood serum.There was a much more decided increase in the concentration of the redblood cells.

WATERCONTENTOF BLOODAND MUSCLE

As has been stated previously, the water contents of blood and ofskeletal muscles were determined in experiments in which the intestineswere traumatized and various fluids were injected. The effects of intes-tinal trauma alone had been determined in previous experiments byHarris and Blalock (7). In the experiments in which normal salt solutionwas introduced there was a slight decrease in the water content of theblood. In those in which gum acacia solutions were used there was adefinite increase in the water content of the blood and in those in whichwhole blood was injected there was a rather large decrease. The altera-tions that were found in the experiments in which 3.0 per cent salt solu-tion, 6.0 per cent glucose, 20.0 per cent glucose and blood serum were in-jected were negligible. In the experiments in which the solution of gumacacia and glucose was injected a definite increase in the water content ofmuscle was found. When 20.0 per cent glucose was injected, a slight

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J. W. BEARDAND ALFRED BLALOCK

decrease resulted. With these two exceptions the alterations in the watercontent of skeletal muscle were of too small magnitude to be of impor-tance.

The results of the determinations on the water content of blood andmuscle in the various experiments are given in Table III.

DISCUSSION

When the intestines are passed continuously between the fingers, acopious weeping of fluid from the peritoneal surfaces results. In a pre-vious communication (8) studies of the composition of this fluid werereported. It was found among other things that the protein contentof the fluid was approximately the same as that of the blood plasma.Those studies did not include determinations of the albumin and globulincontent of the fluid. It has been found in this study that the albumincontent of the peritoneal fluid was greater than that of the blood serumwhile the globulin content of the fluid was less than that of blood serum.When fluids were injected continuously while the intestines were beingtraumatized, usually this same relationship between the blood serum andthe peritoneal fluid was found. It is doubtful if the high percentage ofalbumin in the fluid was due entirely to concentration as a result ofevaporation. Possibly trauma resulted in the loss of some of the pro-teins of the fixed tissues into the fluid. If it is assumed that the osmoticpressure in the capillaries and in the tissue spaces of the injured intestineswere the same, then it is apparent that there would be no force resistingthe filtration pressure in the vessels of the damaged area and that largeamounts of fluid would be expressed.

It is of particular interest in these experiments that the percentage ofprotein, albumin and globulin per unit volume of serum remained prac-tically constant throughout the period in which the intestines were trau-matized and no fluid was injected and that it decreased considerably inmost of the experiments in which fluids other than blood and serum wereintroduced. A careful review of the literature did not reveal any experi-ments closely similar to the present studies. White and Erlanger (9)determined in three experiments the effects of the injection of a stronglyhypertonic solution of gum acacia and glucose into animals in shock as aresult of partial occlusion of the inferior vena cava. In their experimentsthe injection was not continuous and the effects of only one solution weredetermined. In summarizing their results, they state, "The bloodvolume, markedly diminished in shock, is increased to above its normallevel by the injection and then falls to or below its normal level. . . . Theabsolute amount of plasma protein is markedly diminished in shock, isincreased by the injection and the increase continues for some time afterthe injection. It is believed that at least a part of the increase in plasmaprotein following the injection in shock is due to a passage of protein inthrough the vessel walls."

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260 BLOODCHANGESWITH INTESTINAL TRAUMA

TABLE III

The effects of continuous intestinal trauma and the continuous administration of fluids onthe water content of blood and muscles

WaterAmount Blo Hea-

Fluid given Time of fluid | Hemato|given pressure crit Pectoral ThighBlood muscle muscle

per cent cc. mm. Hg per cent per cent per cent per cent

0.9 Saline ........... Control 0 145 44.5 80.40 74.05 73.1560 45' 1013 30 54.5 77.50 75.40 72.60

0.9 Saline ........... Control 0 156 51.2 79.20 75.40 74.3530 15' 488 48 53.0 77.60 75.20 74.00

0.9 Saline ........... Control 0 130 50.5 77.80 76.30 74.5570 30' 1260 78 62.3 76.20 75.80 74.20

0.9 Saline ........... Control 0 160 52.4 76.40 70.60 68.9570 1386 22 60.7 75.30 75.25 67.40

Average ........ Control 148 49.65 78.45 74.09 72.75Later 45 57.63 76.65 75.41 72.05

3.0 Saline ........... Control 0 156 52.0 77.20 73.35 73.0060 50' 975 44 53.0 79.42 75.60 72.00

3.0 Saline ........... Control 0 136 33.0 83.00 77.18 75.0550 750 30 30.4 85.30 78.70 78.25

3.0 Saline ........... Control 0 128 49.3 78.90 77.55 74.9570 1148 0 54.2 79.10 74.30 74.60

3.0 Saline ........... Control 0 160 53.9 76.20 70.7070 30' 1095 105 61.3 75.90 69.50

Average ........ Control 145 47.0 78.83 76.03 73.43Later 45 49.7 79.93 76.30 73.59

6.0 Glucose Control 0 140 40.5 80.50 63.1580 1200 40 35.0 84.30 67.20

6.0 Glucose Control 0 100 33.2 83.30 78.30 75.5840 600 35 37.5 83.05 76.58 76.62

6.0 Glucose Control 0 130 41.7 80.95 75.60 73.5560 40' 707 21 38.0 83.00 76.10 75.00

6.0 Glucose.Control 0 152 45.4 79.50 76.40 74.8070 896 100 54.0 78.10 75.00 73.70

Average . Control 131 40.2 81.06 76.77 71.77Later 49 41.1 82.11 75.89 73.13

20.0 Glucose. Control 0 130 43.2 78.90 73.90 72.6570 30' 1125 40 59.0 75.45 73.20 72.60

20.0 Glucose Control 0 164 44.5 79.00 75.62 73.8870 15' 1088 0 35.5 81.75 74.30 72.10

20.0 Glucose . Control 0 130 48.8 78.25 75.55 74.6070 30' 848 62 36.8 80.30 71.20 69.65

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J. W. BEARDAND ALFRED BLALOCK

TABLE III (continued)

WaterAmount Blood Hemato-Fluid given Time Of fluidprsue ctgiven ~~~~Blood Pectoral Thighmuscle muscle

Per cent CC. mm. Hg per cent per cent per cent per centAverage ........ Control 141 45.5 78.72 75.02 73.71

Later 34 43.8 79.17 72.90 71.45

6.0 Acacia . Control 0 124 40.8 80.90 78.25 77.2560 20' 950 50 33.0 83.30 78.30 77.62

6.0 Acacia .. Control 0 150 39.8 80.10 75.55 70.3050 15' 788 0 36.0 82.70 76.60 64.90

6.0 Acacia .. Control 0 140 38.8 80.00 75.80 74.8570 30' 975 90 31.7 83.80 77.75 75.00

Average ........ Control 138 39.8 80.33 76.53 74.13Later 47 33.6 83.27 77.55 72.51

Acacia, glucose, saline Control 0 154 53.0 77.70 75.45 74.8560 15' 938 0 25.5 84.00 71.78 71.70

Acacia, glucose, saline Control 0 144 43.0 79.50 70.15 72.0060 45' 1013 0 30.2 82.23 66.15 68.80

Acacia, glucose, saline Control 0 150 42.8 80.75 77.60 73.5870 30' 840 38 30.0 83.75 75.20 69.90

Acacia, glucose, saline Control 0 130 43.0 79.95 75.20 74.2570 742 63 33.3 82.45 75.50 70.60

Average ........ Control 145 45.5 79.48 74.60 73.67Later 25 29.8 83.36 72.16 70.25

Blood plasma ....... Control 0 160 43.7 79.10 77.40 74.4050 35' 838 15 52.6 77.50 76.30 73.35

Blood plasma ....... Control 0 123 42.2 80.50 75.20 72.4050 25' 444 73 40.0 81.05 75.00 72.40

Blood plasma ..... . Control 0 133 45.1 79.70 76.5 74.2040 45' 427 0 47.0 79.40 76.2 72.50

Average ........ Control 139 43.7 79.77 76.37 73.67Later 29 46.5 79.32 75.83 72.75

Whole blood .. . Control 0 146 39.3 82.20 70.20 69.1540 5' 613 0 59.0 77.10 74.90 67.30

Whole blood .. Control 0 168 44.0 79.30 76.10 74.8570 35' 1138 136 76.5 71.10 75.60 73.10

Whole blood ........ Control 0 150 47.3 79.35 77.15 74.8060 25' 412 0 67.5 74.50 75.40 73.15

Average ........ Control 155 42.9 80.28 74.48 72.93Later 45 67.7 74.23 75.30 71.18

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6 BLOODCHANGESWITH INTESTINAL TRAUMA

It is rather surprising in the experiments in which solutions of salt or ofglucose were injected and in which there was a decrease in the amount oftotal protein, albumin and globulin per unit volume of serum that therewas usually at the same time a decrease in the volume of plasma in theblood stream. The smallest alterations in the plasma volume were asso-ciated with the giving of 20 per cent glucose solution. Since the plasmavolume was usually reduced, the decrease in the percentage of proteinwas not due to simple dilution by the injected fluid. As both the per-centage of protein and the volume of plasma were usually both reduced,the entire amount of protein in the blood stream was greatly diminished.In the experiments in which the six per cent gum acacia or the gumacacia-glucose solutions were injected, the findings were different in thatthey were usually associated with an increase in the plasma volume andthe decrease in the percentage of protein was greater than that usuallyfound if salt or glucose solutions were used. The gum acacia-glucosesolution produced a greater increase in the volume of plasma than did thesix per cent gum acacia. Even though the plasma volume was greatlyincreased in some of these experiments, there was always a decrease inthe entire amount of protein. The nitrogen content of the gum acaciathat was used was found to be negligible. The values for protein in theseexperiments are misleading in that they do not give a true estimate of theosmotic pressure that the serum was capable of exerting since six per centgum acacia has an osmotic pressure approximately the same as that ofblood serum. The gum acacia that was present in the blood stream atany given time was not determined.

The results obtained in the studies of the effects of the injection ofblood serum and whole blood differed from the others mainly in that theconcentration of protein in the serum of the blood stream did not decrease.In two of the three experiments in which blood serum was introducedthere was a decrease in the plasma volume and in the entire amount ofserum protein, although enormous amounts of serum had been injected.In the experiments in which whole blood was administered, there was atremendous increase in the concentration of the red blood cells andprobably a decrease in the plasma volume.

It has been known for a long time that solutions of crystalloids leavethe blood stream shortly after having been injected. That the injectionof these solutions in the presence of gross capillary injury following traumawould result in a great decrease in the protein content of the blood plasmaas well as in the volume of plasma has not been appreciated. Since theosmotic pressure in the vessels is maintained largely by the protein, thesignificance of the alterations is apparent. If the blood pressure and theplasma volume were the same in two animals one of which had and one ofwhich had not received injections of solutions of crystalloids in largequantities, it is believed that the chances of recovery would be greater in

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J. W. BEARDAND ALFRED BLALOCK

the animal that had not received the fluid since the protein content ofthe serum would not be decreased. This point could not be determinedin these experiments as all of the animals died as a result of the long dura-tion of the trauma and the depth of the anesthesia. Very little if anydifference in the rapidity of the fall of the blood pressure was observed inthe experiments on intestinal trauma alone and those in which bothtrauma and the injection of fluid were carried out. Perhaps the survivalperiod of the latter group was a little longer but the difference was notgreat. In an animal in which the intestines had been traumatized for along period, if the injection of crystalloid solutions was stopped, we havethe distinct impression that the blood pressure declined more rapidlythan in an animal in a similar condition in which no fluid had been intro-duced. Wedo not mean to imply if a patient is in shock as the result ofan injury and no donor is obtainable that saline or similar solutions shouldnot be injected. However, in the absence of a favorable response in theblood pressure after a considerable amount of solution had been injected,almost certainly the further administration of the same fluid intraven-ously would diminish the chances of recovery.

As has been stated previously, the total quantity of fluid injected inmost of the experiments was quite large but frequent analyses were per-formed and in this way the effects of small amounts were also determined.There seems to be a tendency at the present time to use very large quan-tities of fluids intravenously in treating patients. In reporting theirresults with the use of normal salt solution in treating shock, MacFeeand Baldridge (10) recently stated, "The solution has been given intra-venously in amounts ranging from 2000 cc. to 8000 cc. at a single injec-tion."

The gum acacia solutions that were injected presented the distinctadvantage over the solutions of crystalloids in that they were associatedwith an increase in plasma volume rather than a decrease. It is quitetrue that the protein content of the serum was decreased to a lower valuein these experiments than in any others, but the functions of the proteinin maintaining the osmotic pressure of the circulating blood were probablytaken over at least partially by the gumacacia which is a colloid and henceexerts an osmotic pressure. Wedo not know how much gum acacia wasin the circulation at any one time or how long it remained there. Con-cerning the fate of gum acacia, Bayliss (11) states, " I have obtained thepentose test in the blood twenty-four hours after injection, but it haddisappeared in three weeks. If eliminated in the urine, the process is veryslow, since the urine collected for six hours after injection gave no reac-tion, even when concentrated."

When whole blood was injected continuously while the intestineswere being traumatized, there was a tremendous increase in the concen-tration of the red blood cells. This was to be expected since the loss of

18

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BLOODCHANGESWITH INTESTINAL TRAUMA

red blood cells at the site of the trauma was small as compared with theloss of plasma. The effects that may result when the blood becomesgreatly concentrated have been described by Underhill in numerouspublications.

The injection of blood serum was associated with the smallest altera-tions in the composition of the blood. The percentage of protein perunit volume of serum and the plasma volume were not changed greatlyin these experiments. There was a large loss of protein in the fluid thatescaped but due to the fact that serum was being injected, the lost proteinof the blood serum was replaced.

The greatest part of the fluid that was lost from the circulation escapedthrough the capillaries of the injured area. Determinations of the watercontent of skeletal muscle showed that it did not escape into them. Inmost instances in which 3.0 per cent salt solution was injected, the dogspassed fluid from the rectum. The amount of fluid and of nitrogen thatescaped in the urine was not very great in most of the experiments.Edema of the lungs was noted several times at autopsy.

SUMMARYAll of the experiments were performed on dogs that were deeply

anesthetized by sodium barbital. Shock was produced by continuouslypassing the intestines between the fingers. Blood serum and the fluidthat escaped into the peritoneal cavity were collected frequently for thestudies.

In the first group of experiments studies were performed on the bloodserum and the peritoneal fluid during continuous trauma to the intestines.No fluid was administered. Among the findings were the following. (1)There was a great diminution in the volume of plasma in the circulation.(2) The protein content per unit volume of serum remained approximatelythe same throughout the experiments. (3) The total protein content ofthe blood serum and the peritoneal fluid were approximately the same inall instances. (4) The content in albumin of the peritoneal fluid wasusually greater than that of the blood serum and the content in globulinwas less.

In the second group of experiments various solutions were injectedintravenously at a constant speed while the intestines were being trau-matized. The solutions included (1) 0.9 per cent saline, (2) 3.0 per centsaline, (3) 6.0 per cent glucose, (4) 20.0 per cent glucose, (5) 6.0 per centgum acacia, (6) a solution of 6.0 per cent gum acacia and 20.0 per centglucose in normal saline, (7) blood serum and (8) whole blood. Amongthe findings were the following. (1) The total protein content of theblood serum and the peritoneal fluid that were collected simultaneouslywas approximately the same in all experiments. (2) The albumin con-tent of the peritoneal fluid was usually greater than that of the blood

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J. W. BEARDAND ALFRED BLALOCK

serum while the globulin content was less. (3) The injection of the solu-tions of salt and glucose was usually associated with a decrease in thepercentage of protein per unit volume of serum, a diminution of the vol-ume of plasma in the circulation and a great decrease in the absoluteplasma protein. (4) When the solutions of gum acacia were injected,there was a decrease in the percentage of protein, an increase in the plasmavolume and a decrease in the absolute amount of plasma protein. (5)The injection of blood serum was associated usually with comparativelysmall alterations in the percentage of protein, the volume of plasma andthe absolute amount of plasma protein. (6) When whole blood was in-jected, there was very little alteration in the percentage of protein in theblood serum. Since there was a tremendous increase in the concentra-tion of the blood, there was probably a rather large reduction in theplasma volume and in the absolute amount of plasma protein.

BIBLIOGRAPHY

1. Cannon, W. B., Traumatic Shock. D. Appleton & Co., New York, 1923,p. 177.

2. Blalock, Alfred, Arch. Surg., 1931, xxii, 314. Trauma to the Intestines.The Importance of the Local Loss of Fluid in the Production of the LowBlood Pressure.

3. Folin, O., and Wu, Hsien, J. Biol. Chem., 1919, xxxviii, 81. A System ofBlood Analysis.

4. Howe, P. E., J. Biol. Chem., 1921, xlix, 109. The Determination of theProteins in Blood-A Micro Method.

5. Gunning, J. W., Ztschr. f. Anal. Chem., 1889, xxviii, 188. Ueber eineModification der Kjeldahl-Methode.

6. Cohen, B., and Smith, A. H., J. Biol. Chem., 1919, xxxix, 489. TheColorimetric Determination of Hemoglobin.

7. Harris, P. N., and Blalock, Alfred, Arch. Surg., 1931, xxii, 638. Experi-mental Shock. X. Observations on the Water Content of the Tissuesof the Body After Trauma and After Hemorrhage.

8. Beard, J. W., and Blalock, Alfred, Arch. Surg., 1931, xxii, 617. Experi-mental Shock. VIII. The Composition of the Fluid that Escapes fromthe Blood Stream After Mild Trauma to an Extremity, After Traumato the Intestines and After Burns.

9. White, H. L., and Erlanger, J., Am. J. Physiol., 1920, liv, 1. The Effecton the Composition of the Blood of Maintaining an Increased BloodVolume by the Intravenous Injection of a Hypertonic Solution of GumAcacia and Glucose in Normal, Asphyxiated and Shocked Dogs.

10. MacFee, W. F., and Baldridge, R. R., Ann. Surg., 1930, xci, 329. Post-operative Shock and Shock-Like Conditions. Treatment by Infusionin Large Volume.

11. Bayliss, W. M., Report of Shock Committee, Medical Research Committee,Report I, 1918, p. 13. Intravenous Injections to Replace Blood.

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