Monograph: |
Dextran 70
Dextran 70 consists of dextrans (glucose polymers) of weight
average molecular weight about 70 000 that are derived from
the dextrans produced by the fermentation of sucrose by
means of a certain strain or substrains of lauconosroc me-
senteroides.
A white or almost white powder. Very soluble in water-, very
slightly soluble in alcohol; slightly soluble in ether.
Incompatibilities may arise from the slightly acid pH of dex-
tran 70 preparations.
Crystals may form in solutions of dextran if they are stored at
low temperatures. These may be redissolved by warming for
a short time.
Adverse Effects and Treatment
Infusions of dextrans may occasionally produce hy-
persensitivity reactions such as fever, nasal conges-
tion, joint pains, urticaria, hypotension, and
bronchospasm. Severe anaphylactic reactions occur
rarely and may be fatal. Dextran-reactive antibodies
may arise in response to dietary or bacterial polysac-
charides in patients who have not previously re-
ceived dextran. Nausea and vomiting have also been
reported. These reactions are treated symptomati-
cally after withdrawal of the dextran. Dextran 40 can
cause renal impairment as a result of increased
urinary viscosity, capillary oozing has also been
associated with its use.
Dextran I may be used to block the forma-
tion of dextran-reactive antibodies and hence the hy-
persensitivity reactions.
Effects on the blood. Disseminated intravascular coagula-
tion and acute respiratory distress syndrome developed fol-
lowing hysteroscopy during which 1200 mL of dextran 70
was used to dilate the uterus.' The large volume used was
considered to have contributed to the reaction by increasing
the systemic absorption of the dextran solution.
Hypersensitivity. In a retrospective study of allergic reac-
tions to dexiran 40 and dexiran 70 reported in Sweden from
1970 lo 1979,' there were 478 reports of reactions. 458 of
which were considered to be due to dextran, out of 1 365 266
infusions given. There was a male to female ratio of 1.5 to I
for all reactions and a ratio of 3 to I for the most severe reac-
tions. The mean age of the patients was higher in those with
severe reactions. Of the 28 fatal reactions. 27 occurred within
5 minutes of the start of the infusion and 25 when less than
25 mL had been infused. Three of the fatal reactions occurred
after a test dose of only 0.5 to 1.0 mL and it was strongly
recommended that such test doses should not be used.
An anaphylactic reaction has also been reported' more than
75 minutes after intraperitoneal instillation. After successful
symptomatic treatment symptoms recurred 20 minutes later,
due to slow absorption of dextran from the peritoneal cavity.
No further reaction occurred after removal of 200 mL of in-
traperitoneal fluid by culdocentesis.
Anaphylactoid reactions following BCG vaccination have
been attributed to hypersensitivily to dextran included in the
formulation.
Precautions
Dextran infusions produce a progressive dilution of
oxygen-carrying capacity, coagulation factors, and
plasma proteins and may overload the circulation.
They are therefore contra-indicated in patients with
severe heart failure, bleeding disorders such as hy-
pofibrinogenaemia or thrombocytopenia or renal
failure anil should be administered with caution to
patients with impaired renal function, haemorrhage.
chronic liver disease, or those at risk of developing
pulmonary oedema or heart failure. Central venous
pressure should be monitored during the initial peri-
od of infusion to detect fluid overload. Also patients
should be watched closely during the early part of
the infusion period, and the infusion stopped imme-
diately if signs of anaphylactic reactions appear. In-
fusions should also be stopped if there are signs of
oliguria or renal failure. The haematocril should not
he allowed to fall below 30% and all patients should
be observed for early signs of bleeding complica-
tions. The bleeding time may be increased especial-
ly in patients receiving large volumes of dextrans.
Deficiency of coagulation factors should be correct-
ed and fluid and electrolyte balance maintained. De-
hydration should be corrected before or at least
during dextran infusions, in order to maintain an ad-
equate urine flow.
The anticoagulant effect of heparin may be en-
hanced by dextran.
The higher molecular weight dextrans may interfere
with blood grouping and cross matching of blood,
while the lower molecular weight dextrans may in-
terfere with some methods. Therefore, whenever
possible, a sample of blood should be collected be-
fore giving the dextran infusion and kept frozen in
case such tests become necessary.
The presence of dextran may interfere with the de
termination of glucose, bilirubin, or protein in blood
or urine.
Pharmacokinetics
After intravenous infusion dextrans with a molecu-
lar weight of less than 50 000 are excreted un-
changed by the kidney. Dextrans with a molecular
weight greater than 50 000 are slowly metabolised
to glucose. Small amounts of dextrans are excreted
into the gastro-intestinal tract and eliminated in the
faeces.
About 50% of dextran 70 is excreted unchanged in
the urine within 24 hours.
Uses and Administration
Dextran 70 is a plasma volume expander used in the
management of hypovolaemic shock. As a
6% solution dextran 70 exerts a colloidal osmotic-
pressure similar to that of plasma proteins and thus
produces less expansion of plasma volume than dex-
trans of a lower molecular weight, although the ex-
pansion may have a longer duration because of less
rapid renal excretion. Dextran 70 also reduces blood
viscosity and inhibits sludging or aggregation of red
blood cells. It is used in the prophylaxis of postop-
erative thrombo-embolic disorders.
Dextran 70 is given by intravenous infusion as a 6%
solution in sodium chloride 0.9% or glucose 5%.
Doses depend on the severity of the plasma loss and
on the degree of haemoconcentration.
In shock, the usual initial dose for rapid expansion
of plasma volume is 500 to 1000 mL infused at a
rate of 20 to 40 mL per minute. A suggested maxi-
mum dose is 20 mL per kg body-weight during the
first 24-hour period and 10 mL per kg per day there-
after; treatment should not continue for longer than
3 days. Patients may also require administration of
blood, coagulation factors, and electrolytes.
For the prophylaxis of pulmonary embolism or ve-
nous thrombosis in moderate- to high-risk patients
undergoing surgery a dose of 500 to 1000 mL may
be given over 4 to 6 hours either during or immedi-
ately following surgery. A dose of 500 mL should be
given on the next day and in high-risk patients on
subsequent alternate days for up to two weeks after
the operation.
A 32% solution of dextran 70 has been instilled into
the uterus in a dose of 50 lo 100 mL as a rinsing and
dilatation fluid to aid hysteroscopy.
Dextran 70 is also an ingredient of artificial tears.
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