J

July 1944, vol.51 PUGSLEY AND FARQUHARSON: INTRAVENOUS INFUSIONS 5

Acting on the directions given them from drip method in common use. Fig. 1 illustrates
time to time, your representative bodies have the apparatus usually used. The graduated
endeavoured to aid in the progress of the plans burette, of 250 c.e. capacity, contained the in-
for the betterment of the health services. A fusion fluid. It was placed at a height of about
great responsibility has been placed upon them three feet above the level of the vein selected
by the Association, but if at any time the pro- for the injection. A cannula or needle of large
posals are considered to be progressing along bore (usually 18 gauge) was always used. Dur-
lines which are contrary to the principles laid ing all the observations the clamp on the rubber
down by General Council, then that body tubing was- widely open.
should be called together to further advise upon
a suitable course of action. Apparatus Used for
As a profession we are interested in the m5 Intravenous Infusiorls
development of the best type of health service
and it is only by the provisioin of that service
that we can look forward to a healthier and
more robust national life.
.uGtraduated
9 burette.
-~ Verti cal
1390 Sherbrooke St. West. height
1~3 to 4
Clamp -
3et
vrwide open.
FACTORS INFLUENCING THE RATE OF
FLOW OF INTRAVENOUS INFUSIONS` 18 gauge needle,
(With Special Reference to Venoconstriction Drup
Drlpk
bub \
or cannula in vein
of forearm-or long
Induced by Serum) saphenous vein at
ankle.
By H. E. Pugsley, M.D. and 3 feet of
R. F. Farquharson, M.B., F.R.C.P.(C) tubing
coiled
IN the treatment of shock due to hsemorrhage between 25 >
or loss of plasma it is important that the hot water C
bags -or ~-
blood volume be restored as quickly as possible. ice bags.
The difficulties often experienced in giving in- Thermometer
fusions of blood, serum or other fluids at a
rapid rate to patients in shock led to a study of Fig. 1
the factors that influence the rate of flow of The rate of flow was recorded either in c.c.
fluids administered intravenously. per five-minute period as measured in the
The following factors were found to have an burette or by counting the number of drops per
important influence on the rate of flow of intra- minute flowing through the drip bulb. The
venous infusions: temperature of the fluid, as it entered the vein,
1. The size of the vein at the site of the was recorded by a Fahrenheit thermometer en-
infusion. closed in a glass tube connecting the tubing with
2. The temperature of the infusion fluid as the cannula. The infusion fluid was given at
it enters the vein. room temperature (70 to 740 F.) unless other-
3. The nature of the infusion fluid (some wise stated. When it was desired to lower the
fluids induce venoconstriction). temperature of the solution, about three feet
4. The pressure of the fluid. of the rubber tubing* close to the vein was
TECHNIQUE AND METHODS coiled between two uncovered ice bags. By this
The infusions were all given by the gravity- procedure the temperature of the solution, as
it entered the vein, could be lowered to between
* From the Departments of Medicine and Thera- 42 and 560 F. depending on the rate of flow.
peutics, University of Toronto, and the Medical Service,
Toronto General Hospital. Similarly the temperature of the solution could
This work was undertaken as part of the investiga-
tion of the Subcommittee on Shock and Blood Substitutes *
The rubber tubing used had an outer diameter of
of the National Research Council, Canada. 5 mm.
6 PUGSLEY AND FARQUHARSON: INTRAVENOUS INFUSIONS
be raised to between 90 and 105° F. by placing
the coiled tubing between two uncovered hot
water bags; the temperature of the water in the
bags was about 1300 F.
Under the above conditions and before intro-
duction of the needle into the vein, all the fluids
used in the experiment would flow through the
apparatus in a continuous stream. Serum at
room temperature (720 F.) flowed at a rate of
248 c.c. in five minutes; at 540 F. the rate was
226 c.c. and at 1020 F. the rate was 276 c.e.
When it was desired to raise the pressure of
the fluid such measures as raising the height
of the burette to six feet, "milking the tubing"
or injection by syringe were tried. In some
cases the infusion fluid was placed in a closed
jar with an air inlet and a positive pressure of
100 to 115 mm. of mercury was established in
the jar by the use of a rubber bulb, valve and
manometer attached to the air inlet.
The fluids were infused into the long saphe-
nous vein at the ankle or one of the superficial
veins of the cubital fossa, forearm, or dorsum
of the hand. The veins were classified as small
in size if their outer diameter measured ap-
proximately two to four mm. in diameter, and
large if the diameter was five mm. or greater.
The saphenous vein at the ankle and the super-
ficial veins in the dorsum of the hand and mid-
forearm were usually small and the veins at the
cubital fossa, large in size. Frequently, however,
large veins were found in the forearm.
The fluids infused were physiological saline,
5%o dextrose solution, human serum, citrated
plasma, citrated whole blood and various modifi-
cations of the latter three fluids.
The whole blood used was citrated either by
the addition of 500 c.c. of blood to 50 e.c. of
a 2.5% solution of sodium citrate or by mixing
equal parts of blood and a solution of dextrose
2%o, sodium citrate 0.8%o and sodium chloride
0.42%o. Plasma was obtained from both types
of citrated blood. Some lots of citrated blood
were administered while fresh; others after
storage in the refrigerator (4 to 50 C.) for
periods varying up to eleven days. Plasma was
used either fresh or after varying periods of
storage in the frozen state. The stored plasma
was that obtained by citration with the dextrose-
citrate-saline mixture. A commercial prepara-
tion of dried plasma was also used.
Most of the serum used was supplied for
investigational purposes by the Connaught
ECan. M. A. J.
LJuly1944, vol. 51
Laboratories. The various modifications of
serum infused are described in the relevant
section of the paper. Serum, when stored, was
kept at room temperature. Reconstituted serum,
plasma, and citrated whole blood were always
filtered through several layers of gauze before
being infused to insure that no particulate
matter gained access to the intravenous ap-
paratus. The infusions were usually given to
patients immediately following an operation;
most patients were not in a state of shock.
Contraction of the vein, induced by insertion
of the needle, did not appear to be a significant
factor in any of this work.
RESULTS
1. Effect of the size of the vein.-The rate of
flow of any of the infusion fluids, at any tem-
perature, was rapid when introduced into a
large vein.
When a small vein was used some fluids
(saline, glucose solution, fresh' citratQd whole
blood and fresh citrated plasma) flowed in
relatively rapidly at room temperature and
others (serum and reconstituted dried plasma)
very slowly. Serum and reconstituted dried
plasma appeared to induce contraction of the
veins resulting in a marked slowing or even a
complete arrest of the flow. For example, in
one patient stored plasma flowed at the rate
of 20 c.c. per five minutes when infused into a
small cephalic vein in the mid-forearm and at
the rate of 150 c.c. per five minutes when intro-
duced into a large cubital vein. In another
patient the rate of flow of serum into the above
mentioned veins was 15 c.c. in five minutes and
70 c.c. in five minutes respectively.
The effect of the size of the vein on the rate
of flow of serum infusions given at room tem-
TABLE 1.
THE EFFECT OF THE SIZE OF THE VEIN ON THE RATE OF
FLOW OF SERUM INFUSIONS GIVEN AT ROOM
TEMPERATURE
Average
No. rate of
of in- flow c.c.
fusions per 5
Size of vein Site of infusion min.
1. Sma ll. Long saphenous
vein at ankle* 22 9
2. Usually small; Vein of dorsum of
some large... hand or forearm 11 28
3. Large..... Cubital vein 4 77
*One exceptional case, in which the long saphenous
vein was large in size, is not included in the series; the rate
of flow was 126 c.c. per five minutes.
Can. M. A.J.
July 1944, vol. 51 J PUGSLEY AND FARQUHARSON: INTRAVENOUS INFUSIONS 7

perature is illustrated in Table I. It is ap- could also be induced by placing a light ice
parent that serum flowed very slowly when in- pack on the skin of the limb just proximal to
fused into small veins. Physiological saline or the needle. Similar application of a hot water
5%a dextrose solution, given into the same veins, bottle to the skin, however, resulted in little or
flowed rapidly. In seven such cases, in all of no increase in the rate of flow above that of the
which the long saphenous vein at the ankle was infusion at room temperature.
used, the flow was completely arrested on It should be pointed out that warming or
changing from saline to serum. In the remain- cooling the fluid in the intravenous jar may
ing twenty infusions into small veins, the rate have little or no effect on the rate of flow, as
of flow of serum varied from 2 c.e. to 38 c.c. the temperature of the fluid may then have ap-
per five minute period. It is possible that the proached that of the room before it enters the
flow into a long, small vein is slower than into vein.
a shorter vein of the same calibre. During the infusion of serum, while the tub-
When serum was infused into a large vein ing was coiled between hot water bottles, there
the rate was much more rapid but was still was noted a peculiar marked variation in the
slower than that of physiological saline, 5%b rate of flow from moment to moment. That
dextrose or fresh citrated whole blood. such variation was related to corresponding
When any of the infusion fluids were intro- changes in the temperature of the serum as it
duced at a low temperature into a small vein entered the vein is shown in Chart 1. There
the rate of flow was usually slow.
2. Effect of the temperature of the infusion
fluid.-Alarked changes in the temperature of
the fluids as they entered the vein, usually had
a striking effect on the rate of flow into small
veins; warming the fluid increased the rate of
flow and cooling the fluid decreased the rate.
This was particularly notable in the case of
serum or reconstituted dried plasma. It was
definite also when fresh citrated whole blood
or saline were infused (see Table II). In some
instances cooling of serum resulted in complete
arrest of the flow. Marked slowing of the rate TIME IN MINUTES
Chart 1
TABLE IT.
was very little increase in the rate of flow as
THE EFFECT OF THE TEMPERATURE OF INFUSION (SERUM,
CITRATED WHOLE BLOOD AND SALINE SOLUTION) ON the temperature of the serum rose from room
THE RATE OF FLOW INTO SMALL VEINS t.emnrn.tltnre to 900 F. but there was a striking
tt111PW1~~L am JL .1M U ,CAV'lA V V CA - .1 . . .^. . CsusAs

increase when the temperature had risen to

Temperature of fluid
as it entered the vein
________________________________
Rate of flow in Cc. about 100 F. The serum would then flow so
per 5 minmustes
rapidly through the tubing coiled between hot
Whole water bottles that the temperature of the serum
Serurrrt * blood Physalilnocal
avera~ ge average average would fall to about 900 F. and when this cooler
of 6 caLses of 4 cases of 3 cases
fluid entered the vein the rate of flow would

1. Room temperature 102 again become slow. With slow flow through
(70°-74° F.)......... 10 102
2. Temperature 42°-
the tubing the temperature of the serum would
560 F. (tubing coiled 21 rise again and the rate of flow increase once
between two ice bags) 3 50
more.
3. Temperature 90°-
105° F. (tubing coiled 3. Effect of the nature of the infusion fluid.-
between tWO not 135 When physiological saline solution, stored
water bags) 74 170
pooled serum and citrated whole blood (fresh
*In fourteen other cases the rate of flowr of serum or or stored one to four days) were infused in
reconstituted plasma was measured in droj ps. Atminute.
room
succession into a small vein, a striking differ-
temperature the average rate was 66 drops sperthe aver- ence in the rate of flow was observed (see
On heating the fluid to between 900 and 10 50F.
age rate rose to over 200 drops per minuite and often
Table III). The citrated whole blood and
flowed too fast to be counted.
8 PUGSLEY AND
saline solution flowed at a rapid rate but stored
serum flowed slowly. The order in wrhich the
fluids wsrere infused was varied in difterent
cases with no essential differenee in the results.
The citrated blood used in the first three
cases of Table III consisted of ten parts of
TABLE III.
THE RATE OF FLOW OF SALINE SOLUTION, STORED SERUM
AND CITRATED WHOLE BLOOD (FRESH OR STORED 1-4
DAYS) INFUSED IN SUCCESSION AT ROOM TEMPERATUIRE,
INTO A SMALL VEIN
Rate of flow in c.c.
FARQUHARSON: INTRAVENOUS INFUSIONS ECan. M. A. J.
[July 1944, vol. 51
serum was infused into a small vein the rate
of flow was invariably slow, whereas the rate
of flow of physiological saline, 5%o dextrose
solution or fresh citrated blood into the same
vein, was relatively rapid. Even when a large
vein was used and the rate of flow of serum
was correspondingly more rapid, it was still
slower than that of the other fluids. For in-
stance, in one case when whole blood had been
flowing into a large vein at a rate of 400 e.e.
per five minute period, changing to seruim
resulted in a slowing of the rate to 125 per c.c.

per O minutes
five minutes.
It appeared that stored, pooled seruim con-
Physio-
logical Stored tained a factor which induced a strong, and
Case saline serum sustainied contraction of the vein through
which it was being infused resulting in a re-
1. Mr. J. B. No. B37500.. 245 9 duction of the rate of flow.
2. Miss J. Y. No. B37639.. 155 18
3. Mrs. M. No. B35921... 50 0 In an attempt to discover the niatuire of this
4. Mrs. E. No. B42720.... 197 11 venoconstrictor factor presenit in stored, pooled
5. Mrs. A. No. B43561.... 220 38
6. Mr. D. D. No. B36030.. stream * 5 serum the following modifications of serumii
7. Mr..J. McG. No. A27723 126 0
weve tested: fresh serum, serum froni a donor
Average rate......... 166 12 of the same blood group as the recipient;
serum pooled from many donors of difterent
*Rate of flow not measured in cc. balt the fluiid flowed blood groups, dried serum reconstituted by the
through the drip bulb in a stream.
addition of distilled water (final pH 9.3), dried
TABLE IV. serum reconstituted with 0.15%c citric acid
THE VISCOSITY OF THE INFUTSION FLUIDS AS MEASURED
BY OSTWALD'S VISCOMETER solution (final pH 7.3), a mixture of teni parts
of serum and one part solution of 2.5%o sodiuim
iscosity C.ar.S. units citrate and lastly, fresh serum obtained from
Fluid 't 21.1 °C. at 37.00 C. fresh citrated plasma made to coagulate by the
addition of a small amount of calcium chloride
1. Citrateea whole blood (10 parts soltution. All of these modifications of serum
blood + 1 part 2.5% solution
of sodium citrate)........... .0529 .0299
2. Citrated whole blood (equjal TABLE V.
parts whole blood and glu-
eose-citrate-saline solution)... .0182 .0123 THE RATE OF FLOW OF SALINE SOLUTION, FRESH SERUM
3. Plasma obtained from citrated AND CITRATED PLASMA (FRESH OR STORED 1-2 DAYS)
whole blood (10 parts blood INFUSED IN SUCCESSION, AT ROOM TEMPERATURE, INTO
+ 1 part citrate solution) .0170 01 9n THE LONG SAPHENOUS VEIN AT THE ANKLE
4. Normal human serum........ .0166 .0117
5. Physiological saline ......... .0098 .0071
6. Water...................... .0098 Rate of flowv in c.c.
per 5 minutes
Citrated
blood plus onie part of 2.5%o solution of sodiumn plasma
citrate. In the remaining four cases the cit- Physio- (fresh or
logical Fresh stored
rated blood consisted of equal parts of whole Case saline serum 1-2 days)
blood and glucose-citrate-saline solutioni. There 1. Miss R. A. No. B46461. 100 0 87
was no significant difference in the rate of flow 2. Mr. H. MeK.
of these two preparationis of citrated blood. No. B43889 . 115 0 132
3. Mr. L. F. No. B5969 205 5 360*
The slower flowiing of serum, as conmpared with 4. Mrs. M. G. No. 041832. 200 0 not given
whole blood, was not due to a differeniee in 5. Mrs. M. A. No. B43561. 220 notgiven 118
6. Mr. F. McC. No. B42622 128 0 not given
viscosity, as whole blood is more viscous thaan
serum (see Table IV). Average rates .161 1 174
A total of thirty-seven infusions of serui
was given -to 27 patienits (see Table I). When
*Actually 72 c.c. in one minute. Estimated rate of
360c.c. per five minutes.
Can. M. A. J. l PUGSLEY AND FARQUHARSON: INTRAVENOUS INFUSIONS
July 1944, vol. 51 1

flowed as slowly into small 'veins as did the
stored, pooled serum.
As a further step in the investigation various
modifications of plasma were tested. When
citrated plasma, fresh or stored one to two
days, was infused into small veins it flowed
rapidly like fresh citrated whole blood (Table
V). When reconstituted dried plasma was
used under the same circumstances, however,
the rate of flow was invariably slow. Citrated
plasma, stored in the frozeni state for several
weeks, gave variable results; some lots flowed
rapidly, some slowly.
The effect of storage oin the rate of fiow of
citrated whole blood was then observed (Table
VI). It was founid that blood stored for eight
TAR3LE VI.
THE RATE OF FLOW'' OF SALINE SOLUTION, STORED SERUM,
AND CITRATED WHOLE BILOOD (STORED 8-1.1 DAYS)
INFUSED IN SUCCESSION AT Room TEMPERATURE, INTO
A SMALL VEIN
Rate of flow in c.c.
per 5 minutes
Citrated
Physto- whole blood
logical Stored (stored
Case saline serum 8-11 days)
1. Mrs. D. No. A60595.... 172 12 52
i.
3.
Mr. McC. No. B42622'
Mr. F. No. B5969 ......
128
205
0
2
40
17
4. Mr. McK. No. B43889.. 115 0 32
5. Mis- E. S. No. 4995 120 30 35
Average rates .148 9 35
to eleven days flowed definiitely miiore slowly
than did the fresher preparations.
The venoconstrictor factor that causes slow-
ing of the rate of flow appears to be present
invariably in serum. It may be demoiistrated
at once in serum formed by sponitaneous clot-
ting of fresh blood and also in serum obtained
when fresh citrated plasmna is made to clot by
the addition of calciuin chloride. It develops
in blood and plasma on standing; it is present
in moderate degree in blood stored eight to
eleven days and in plasma stored in the frozen
state for many weeks. Large amounts are
always present in reconstituted dried plasma.
In serum and dried plasma this factor is
stable. It seems to be uinaffected by long
storage at roonm temperature, by drying, by
wide variations in temperature and by varia-
tion in pH between 7.3 and 9.3.
4. Effect of the pressure of the fluids.-The
effect of pressure on the rate of flow was great-
ly miodified by the degree of resistance resulting
from venoconstriction. If there was complete
arrest of flow because of strong contraction of
the vein, increasing the pressure usually failed
to induce a flow. For example, in the case of
seven serum infusions administered to five
patients there was coinplete arrest of flow as
soon as the serum entered the vein. The long
saphenous vein at the ankle was used in all
instances. Increasing the pressure by such
measures as "milking the tubing" or applyinig
force with a syringe caused very little serum to
enter the vein and induced pain in the leg and
ankle near the site of the infusion. That this
arrest of flow was not due to such factors as
thrombosis was indicated by the following ob-
servations: (1) if the temperature of the serum
as it entered the vein was raised to abotut 1000
F. a rapid flow was established (the warmed
serum had to be forced into the veini at first by
"mriilking the tubing"), (2) if the serumii in the
apparatus and tubiing was replaced by saline
solution a rapid flow of saline wras slowly re-
established (the saline had to be forced into
the vein at first).
When there was moderate contraction of the
vein with reduction of flow to a slow drip an
increase in pressure gave rise to somne increase
ill the rate but usually failed to iniduce a rapid
flow. For example, in a severely shocked
patient with cold extremities, a 5% solutioni of
dextrose in saline flowed into the contracted
long saphenous vein at a slow drip w^hich was
not materially altered when the reservoir was
raised to a height of six feet above the veini.
Similarly, in another case, serum in a closed
jar three feet above the level of the vein, flowed
at a rate of 8 drops per minute. Establish-
ment of a positive pressure' of 115 mm. of nmer-
cury in the jar caused ani inerease in the rate of
flow only to 66 drops per miinute (about 14 e.c.
per five minutes). Warming the serumii, with-
out an increase in pressure, inereased. the r.ate
to 190 drops per minute (about 40 e.e. per five
minutes). The combiined effect of wiarmlLilng the
serum and increasing the pressure resulted in
the serum flowing through the drip bulb in a
steady stream.
When the vein offered slight resistance to the
flow of the infusion, increasing the pressure
greatly increased the rate. For instance, stored
citrated blood flowed at the rate of 35 e.e. per
five minutes when the jar was three feet above
the level of the vein. Raising the pressure in
10 PUGSLEY AND FARQUHARSON: INTRAVENOUS INFUSIONS ECan. M. A. J.
[July 1944, vol. 5t
the jar to 100 mm. of mercury nature of the plasma. In other patients con-
increased the
rate to 105 c.c. per five minutes. stricting pressure bandages or theoretically ele-
vated venous pressure due to extensive pul-
DISCUSSION monary burns were blamed for this phenome-
In severe cases of shock fluids should be in- non ". Lang and Schweigh,7 reporting on a
fused rapidly to replace the depleted blood trial of stored serum and plasma in the German
volume. That many workers have found it army on the Russian front, remarked that the
difficult to give infusions at a rapid rate is fluid was not warmed before transfusion. The
indicated by the increasing use of appliances only disadvantage of not warming it, they state,
designed to increase the rate of flow by raising may be the production of spasm in the veins
the pressure. (National Research Council, with consequent slowing of the rate of flow. In
Washington;' Raven ;2 Willcutt ;3 Lundy and a study of reactions following the administra-
Rogers4). Unfortunately it has been our ex- tion of reconstituted serum Major A. L. Chute'0
perience that a great increase in pressure may noted venospasm frequently. It was manifested
fail to induce a rapid flow when infusions are by marked slowing of the flow of the infusion
given into strongly contracted small peripheral and pressure was often required to maintain
veins. Such a strong sustained contraction of the rate of flow. In one or two cases there was
a small vein may be induced in a normal sub-
pain or tingling along the course of the vein.
ject by any of the following conditions: (1)
For many years it has been known that per-
the application of an ice pack to the skin over-
lying the vein; (2) the infusion of a cold fluid fusion of isolated tissues with defibrinated blood
(temperature 42 to 560 F.) into the vein, and or serum leads to intense constriction of the
(3) the infusion of such fluids as serum or re- arteries and slowing of the rate of flow of the
constituted plasma which contain a venocon- perfusion fluid. This experimental work was
strictor substance. A similar venoconstriction well reviewed by Janeway, Richardson and
is often found in patients in a state of severe Park8 in 1918. Using an isolated strip 6f ox
shock with cold extremities. carotid they found that a vasoconstrictor sub-
Such venoconstriction in shock has been noted stance was present in serum and defibrinated
by McMichael.5 In describing a severe case that blood but not in uncoagulated blood. It was
followed crushing injuries he stated that, "the their conclusion that the "vasoconstrictor sub-
final irreversible state which was reached after stance though present in coagulated blood is
the operation was accompanied by a consider- not dependent on the actual formation of the
able spasm of the veins which made transfusion blood clot nor is it related to any of the factors
of blood slow and difficult. This venospasm is concerned in coagulation with the possible ex-
not infrequently encountered in severe collapse ception of thromboplastin."
and it may be impossible to force blood into More recently Landis, Wood and Guerrantg
the veins even under pressure". We are in have demonstrated that perfusion of defibrinated
agreement with this statement but we believe blood and serum induced marked vasoconstric-
that if a large vein is used for the infusion a tion in the surviving ear of the rabbit. Like
rapid flow will be readilv obtained. other investigators they did not determine the
The difficulty of administering infusions at a nature of the vasoconstrictor substance which
rapid rate to patients in shock has been greatly appears very quickly when blood or plasma is
augmented by the introduction of serum, stored permitted to clot.
-plasma and stored citrated whole blood as re-
placement fluids. IUsually no explanation is It is probable that the venoconstrictor factor
given for the slowing of the flow of these latter which we have found to be present in human

fluids. In treating burn cases Soutter6 noted serum, dried-plasma, and citrated blood that has
that plasma that had been stored in the frozen been stored for many days, is similar to the
state flowed slowly in many instances. The fol- vasoconstrictor substance noted in perfusion ex-
lowing is a quotation from his paper: "this was periments in animals. It is possible that this
usually in leg veins which were small and substance plays a part in the arrest of hsemor-
tortuous. We blamed this slow flowing, when rhage. The nature of this substance is, as yet,
dextrose ran well, upon the relative gummy undetermined.
Can. 1 A.5J. WAUGH AND RUDDICK: STUDIES
SUMMARY AND CONCLUSIONS
1. Intravenous infusions of citrated whole
blood, citrated plasma, serum, physiological
saline and glucose solution were given by the
gravity-drip method and the rate of flow under
various conditions was measured.
2. The following factors were found to have
an important influence on the rate of flow of
these infusions: (1) the size of the vein at the
site of the infusion, (2) the temperature of the
fluid as it enters the vein, (3) the nature of the
fluid (some fluids induce venoconstriction) and
(4) the pressure of the fluid.
3. Infusions given into large veins, such as
the median cubital, always flowed rapidly; the
temperature and nature of the, fluid had little
effect on the rate of flow.
4. When infusions were given into small
veins, however, such as the long saphenous
vein at the ankle, the temperature of the fluid,
as it entered the vein, had a pronounced effect
on the rate of flow. Cooling the fluid caused
contraction of the vein and marked slowing of
the rate. Increase in temperature gave rise to
venodilatation and increase of flow.
5. Similarly, the nature of the fluid had a
striking effect on the rate of flow into small
veins. Human serum and reconstituted dried
.plasma were found to contain a factor which
caused strong sustained contraction of the vein
with resultant slowing of the flow. Such a
factor was not demonstrated in fresh citrated
whole blood, fresh citrated plasma, physiologi-
cal saline or 5% dextrose solution.
The nature of this venoconstrictor substance
was not determined. It could be demonstrated
at once in serum obtained by coagulation of
fresh whole blood or plasma. It seemed to
develop gradually in citrated whole blood or
plasma on prolonged storage. It was not re-
lated to the blood group of the donor or to the
pH of the fluid.
6. Increasing the pressure resulted in a
marked increase in the rate of flow when the
vein offered little resistance to the flow of the
infusion. When, on the other hand, there was
strong contraction of the vein resulting in a
very slow flow, increase in the pressure failed
to induce a rapid flow and often caused pain
near the site of the infusion.
7. In shocked patients with cold extremities,
the small peNipheral veins commonly used in
giving infusions, may be strongly contracted.
ON COAGULABILITY 11
Since such patients are in urgent need of rapid
replacement of a depleted blood volume,
a large vein should be selected for the infusion.
This is more important if the replacement fluid
is serum or stored plasma. If the infusion must
be given into a small vein and application of
pressure fails to induce a rapid flow, warming
the fluid will lead to dilatation of the vein and
a marked increase in rate.
The authors wish to express their indebtedness to Dr.
Albert Fisher of the Connaught Laboratories, Toronto,
for the measurement of the .pH of infusion fluids, the
preparation of citric acid solution and other assistance.
REFERENCES
1. National Research Council, Washington: Burns, Shock,
Wound Healing and Vascular Injuries, Saunders,
Phila., 1943, P. 159.
2. RAVEN, R. W.: The Treatment of Shock, Oxford War
Manuals, Oxford University Press, 1942, p. 68.
3. WILLCUTT, M. D.: An improved method for the ad-
ministration of human plasma and whole blood,
U.S. Naval Medical Bulletisn, 1943, 41: 213.
4. LUNDY, J. S. AND ROGERS, D. A.: A hand roller for
the rapid intravenous administration of urgently
needed blood or solutions, Proc. Staff Meet., Mayo
Clinic, 1938, 13: 726.
5. MCMICHAEL, J.: Clinical aspects of shock, J. Am. M.
Ass., 1944, 124: 281.
6. SOUTTER, L.: Management of the Cocoanut Grove
burns at the Massachusetts General Hospital, Anin.
Surg., 1943. 117: 930.
7. LANG, K. AND SCHWEIGH, H.: Observations upon the
value of serum and plasma as blood substitutes,
Deut. Militararzt., 1942, 7: 379. .(Abstract in Bull.
of War Med., 1943, 3: 392.
8. JANEWAY, J. C., RICHARDSON, H. B. AND PARK, E. A.:
Experiments on the vasoconstrictor action of blood
serum, Arch. Int. Med., 1918, 21: 565.
9. LANDIs, E. M., WOOD, J. E. AND GUERRANT, J. L.:
Effect of heparin on the vasoconstrictor action of
shed blood tested by perfusion of the rabbit's ear,
Am. J. Physiol., 1943, 139: 26.
10. CHUTE, A. L.: Personal communication.
STUDIES ON INCREASED
COAGULABILITY OF THE BLOOD`
By Theo. R. Waugh, M.D. and
Capt. D. W. Ruddick, R.C.A.M.C.
Montreal
SINCE the discovery of a physiological anti-
coagulant by Howell and Holtl in 1916,
interest has developed in the subject of throm-
bosis from a therapeutic standpoint and has
been increased greatly by the purification2' 3 of
the substance in the form of heparin. Murray,
Jacques, Perrett and Best4 demonstrated in
1937 the effect of heparin as a preventive in
experimental thrombosis, and a year later5
Murray and Best described the clinical use of
this substance and in a subsequent report6 pre-
* From the Departments of Pathology of the Royal
Victoria Hospital and of McGill University, Montreal,
Quebec. Aided by grant from the Associate Committee
on Army Medical Research, National Research Council
of Canada.