fatal progression of cobalt lung in a diamond polisher.
Am Rev Respir 23 Sosman AJ, Schlueter DP, Fink JN, Barboriak JJ. Hypersensitivity to
Dis 1990; 141: 1373-78.
15 Cugell DW. The hard metal diseases. Clin Chest Med 1992; 13:
269-79.
16 Jederlinic PJ, Abraham JL, Churg A, Himmelstein JS, Epler GR,
Gaensler EA. Pulmonary fibrosis in aluminium oxide workers:
investigation of nine workers, with pathologic examination and
microanalysis in three of them. Am Rev Respir Dis 1990; 142:
1179-84.
17 Vallyathan V, Bergeron WN, Robichaux PA, Craighead JE. Pulmonary
fibrosis in an aluminium arc welder. Chest 1982; 81: 372-74.
18 De Vuyst P, Domortier P, Rickaert F, Van de Weyer R, Lenclud C,
Yernaukt J. Occupational lung fibrosis in an aluminium polisher.
Eur J Respir Dis 1986; 68: 131-40.
19 Bartter T, Irwin RS, Abraham JL, et al. Zirconium compound-induced
pulmonary fibrosis. Arch Intern Med 1991; 151: 1197-201.
20 Townshend RH. Acute cadmium pneumonitis: a 17-year follow-up.
Br J Indust Med 1982; 39: 411-12.
21 Lilis R, Milles A, Lerman Y. Acute mercury poisoning with severe
chronic pulmonary manifestations. Chest 1985; 88: 306-09.
22 Carosso A, Ruffino C, Bugiani M. Respiratory diseases in wood
workers. Br J Indust Med 1987; 44: 53-56.
Mildhypothermia increases blood loss and transfusion
requirements during total hip arthroplasty
Harald Schmied, Andrea Kurz, Daniel I Sessler, Sybille Kozek, Albert Reiter
Summary
Background In-vitro studies indicate that platelet function
and the coagulation cascade are impaired by hypothermia.
However, the extent to which perioperative hypothermia
influences bleeding during surgery remains unknown.
Accordingly, we tested the hypothesis that mild
hypothermia increases blood loss and allogeneic
transfusion requirements during hip arthroplasty.
Methods Blood loss and transfusion requirements were
evaluated in 60 patients undergoing primary, unilateral
total hip arthroplasties who were randomly assigned to
normothermia (final intraoperative core temperature 36·6
[0·4]°C) or mild hypothermia (35·0 [0·5]°C). Crystalloid,
colloid, scavenged red cells, and allogeneic blood were
administered by strict protocol.
Findings Intra- and postoperative blood loss was
significantly greater in the hypothermic patients: 2·2 (0·5)
L vs 1&middot;7 (0&middot;3) L, p<0&middot;001). Eight units of allogeneic packed
red cells were required in seven of the 30 hypothermic
patients, whereas only one normothermic patient required
a unit of allogeneic blood (p<0&middot;05 for administered
volume). typical A decrease in core temperature in patients
undergoing hip arthroplasty will thus augment blood loss
by approximately 500 mL.
Interpretation The maintenance of intraoperative
normothermia reduces blood loss and allogeneic blood
requirements in patients undergoing total hip arthroplasty.
Department of Anaesthesia and Intensive Care Medicine, Hospital
of Amstetten, Austria (H Schmied MD, A Reiter MD);
Thermoregulation Research Laboratory, Department of Anesthesia,
University of California, San Francisco (A Kurz MD, D I Sessler MD);
and Department of Anaesthesia and Intensive Care Medicine,
University of Vienna, Austria (S Kozek MD)
Correspondence to: Dr Daniel I Sessler, Department of Anesthesia,
374 Parnassus Ave, 3rd Floor, University of California,
San Francisco, CA 94143-0648, USA
wood dust. N Engl J Med 1969; 281: 977-80.
24 Vandenplas O, Malo JL, Dugas M, et al. Hypersensitivity peumonitis-
like reaction among workers exposed to diphenylmethane diisocyanate
(MDI). Am Rev Respir Dis 1993; 147: 338-46.
25 Ramage JE Jr, Roggli VL, Bell DY, Piantadosi CC. Interstitial lung
disease and domestic wood burning. Am Rev Respir Dis 1988; 137:
1229-32.
26 van Assendelft AH, Raitio M, Turkia V. Fuel chip-induced
hypersensitivity pneumonitis caused by penicillium species. Chest 1985;
87: 394-96.
27 Carrington CB, Gaensler EA, Coutu RE, Fitzgerald MX, Gupta RG.
Natural history and treated course of usual and desquamative
interstitial pneumonia. N Engl J Med 1978; 298: 801-08.
28 Crystal RG, Bitterman PB, Rennard SI, Hance AJ, Keogh BA.
Interstitial lung diseases of unknown cause: disorders characterised by
chronic inflammation of the lower respiratory tract. N Engl J Med
1984; 310: 235-44.
29 Turner-Warwick M, Haslam PL. Antibodies in some chronic fibrosing
lung diseases: non organ-specific antibodies. Clin Allergy 1971; 1: 83-95.
30 Turner-Warwick M, Parkes WR. Circulating rheumatoid and
antinuclear factors in asbestos workers. BMJ 1970; 3: 492-95.
Introduction
Mild perioperative hypothermia (core temperature
34-36&deg;C) results from intraoperative heat loss and
anaesthetic-induced inhibition of normal thermo-
regulatory control. Postoperative restoration of a normal
2
core temperature typically requires several hours
increasing the duration of hypothermia well beyond the
time in surgery. Although intraoperative hypothermia can
easily be prevented,3 it remains common;4 no prospective
randomised study has shown adverse outcomes as a result
of mild hypothermia.
In-vitro studies suggest that perioperative hypothermia
may aggravate surgical bleeding by impairing platelet
function and directly reducing clotting factor enzyme
function.5,6 Hypothermia increases the bleeding time, an
inhibition apparently related to defective thromboxane Az
release, upregulation of platelet surface protein GMP-
140, and downregulation of platelet glycoprotein Ib-IX
complex .5 Furthermore, hypothermia prolongs both the
prothrombin (PT) and partial thromboplastin (PTT)
times-most likely via direct inhibition of clotting factor
enzyme function.6
Despite in-vitro evidence that hypothermia impairs
coagulation, the extent to which mild perioperative
hypothermia increases bleeding during surgery remains
unknown. Accordingly we tested the hypothesis that a
policy of maintaining normothermia reduces blood loss
and allogeneic transfusion requirements during hip
arthroplasty. This is a relatively standardised operation
associated with considerable microvascular blood loss.
Methods
We evaluated blood loss and transfusion requirements in patients
undergoing initial, unilateral total hip arthroplasties at the
Hospital of Amstetten, Austria. The study was approved by
review boards at the Hospital of Amstetten, the University of
Vienna, and the University of California at San Francisco;
written informed consent was obtained from participating
patients. We studied 60 patients because a preliminary study
indicated that this number would provide about an 80% chance
of identifying a significant hypothermia-induced increase in
289
blood loss (two-tailed (xO-05). Under the pilot study, 28
patientsat the University of Vienna had been randomly assigned
to normothermia (Teare 36-6 [04]OC, n=13) or hypothermia
(Teare 34-9 [08]OC, n=15). Blood loss was 2-3 [08] and 1-8
[0-61] L in the respective groups (p=007).
In this study, patients were aged 40 to 80 yr, had American
Society of Anesthesiologists physical status 1-3, and weighed
50-100 kg. None of the arthroplasties was for treatment of
tumour. Patients having a history of excessive bleeding or
bruising were excluded as were those having PTT of more than
35 s, PT less than 70% clot formation, fibrinogen less than 200
mg/dL, a platelet count less than 100 000/,L, or any
contraindication to red-cell scavenging. Patients reporting
ingestion of aspirin or non-steroidal anti-inflammatory drugs
within 2 weeks of surgery also were excluded. Per surgical
protocol, all patients were given low-molecular weight heparin
(5000 IU every 8 h) starting 2 h before surgery (Depot Heparin
Immuno, Immuno Inc, Vienna, Austria).
Protocol
Ambient temperature was maintained near 21&deg;C. The patients
were premedicated with 10 mg oral diazepam 1-2 h before
surgery. General anaesthesia was induced by administration of
thiopental sodium 3-5 mg/kg, fentanyl 250 lig, and vecuronium
0-1-0-15 mg/kg. The trachea was intubated, and the lungs
ventilated Anaesthesia
mechanically. was subsequently
maintained with nitrous oxide 60%, isoflurane 0-4-0-8% end-
tidal concentration, and fentanyl: these drugs were administered
in doses sufficient to keep arterial blood pressure within 20% of
pre-induction values.
The patients were assigned to normothermia (core
temperature maintained near 36-5&deg;C) or mild hypothermia (core
temperature allowed to decrease to about 35&deg;C). Randomisation
was based on computer-generated codes sealed in sequentially
numbered, opaque envelopes. Patients assigned to normothermia
were actively warmed with an upper-body forced-air cover and a
warmer set to "high" (Bair-Hugger, Augustine Medical, Eden
Prairie, MN, USA). Additionally, intravenous fluids in these
patients were warmed to 37&deg;C. In contrast, active skin and fluid
warming was avoided in patients assigned to hypothermia.
Target minimum haematocrits were prospectively determined
based on ages and cardiovascular status. The target haematocrit
was 26% in patients aged less than 65 yr having no significant
cardiovascular disease. The haematocrit was allowed to decrease
to 28% in patients aged 65 yr or more or having cardiovascular
disease. Significant cardiovascular disease was defined as
previous myocardial infarction, angina, congestive heart failure,
cardiomyopathy, hypertension (a diastolic blood pressure
exceeding 90 mm Hg or requiring chronic drug treatment), or
peripheral vascular disease. Haematocrit was maintained at 30%
or more in patients having both cardiovascular disease and an age
65 yr or more. Preoperative acute normovolemic haemodilution,
to a haematocrit of about 30%, was used in all patients. Removed
blood was immediately replaced with an equal volume of colloid
plasma expander (Haemaccell, Behring Werke AG, Marburg,
Germany). Nearly all intraoperative blood loss was scavenged
using a Shiley Stat autotransfusion system (Dideco, Mirandola,
Italy). The system was primed with 40 000 IU heparin (Immuno
Inc) in 1000 mL solution, of which patients received 300 mL.
Crystalloid was infused throughout surgery at a rate of 10
mL/kg/h. The first 500 mL estimated blood loss were replaced
with additional crystalloid at a ratio of 3 mL/mL blood loss.
Additional blood loss was replaced with colloid, haemodilution
blood, scavenged red cells, and allogeneic transfusions, if
necessary, to maintain target haematocrit. All blood initially
removed from the patients during haemodilution and all unused
scavenged blood was re-infused by the end of recovery.
Allogeneic packed red-blood cells were administered
postoperatively as necessary to maintain the target haematocrit.
Measurements
Core temperatures (T core) were recorded from the tympanic
membrane (Mallinckrodt Anesthesia Products Inc, St Louis,
290
MO, USA). Intraoperative temperatures, end-tidal PCOz and
isoflurane concentrations, heart rates, and oscillometric blood
pressures recorded at 20-min intervals. Postoperatively,
were
temperatures recorded at 30-min intervals for 2 h.
were
Intraoperative fluid balance was tabulated at 20-min intervals,
using aspirated suction volume, return to the cell scavenger,
irrigation volume, and blood returned to the patients from the
cell scavenger. Surgeons at the Hospital of Amstetten do not
routinely use sponges; thus, most shed blood volume could be
accurately-and objectively-recorded from aspirated volume.
Similar methods have been used in previous studies. Blood loss
from the wound drains was subsequently recorded 3 and 12 h
postoperatively, and the following morning.
Spun haematocrits were determined at 30-min intervals
throughout surgery and used to guide intraoperative fluid and
blood administration, as above. Blood haemoglobin
concentrations were determined preoperatively, after
haemodilution, at the end of surgery, and the next morning.
Prothrombin and plasma thrombin times and blood fibrinogen,
anti-thrombin 3, platelet, and haemoglobin concentrations were
also determined by the clinical laboratory preoperatively,
immediately after surgery, and on the first postoperative day. The
PT and PTT were determined at 37&deg;C, the PTT is reported in
seconds (normal 27-35) and the PT is reported as percent clot
formation (normal 70-140). Bleeding times were not measured
because the correlation between bleeding time and blood loss in
individuals is poor.s
Data analysis
Results were analysed after completion of data collection and an
audit confirming integrity of the randomisation process. An
intention-to-treat analysis was used, ie, patients were considered
to be in the temperature group to which they were assigned (even
when target temperatures were not reached).9
Time-dependent results were evaluated using one-way
ANOVA with Dunnetts test for comparison to preoperative
values. Results in the two treatment groups were compared using
unpaired, two-tailedt tests. The number of patients in each
group requiring allogeneic blood transfusion were compared
using a Fisher exact test. Data are presented as means (SD);
p<0-05 identified statistically significant differences.
Results
The morphometric characteristics, duration of surgery,
anaesthetic management, and haemodynamic responses
were comparable in the two groups. By design, final
intraoperative core temperatureapproximately 1 5&deg;C
was
warmer in thepatients assigned warming. Among
to extra
those assigned to extra warming, final intraoperative core
temperature exceeded 36&deg;C in all but one; among the
unwarmed patients, all but two had final core temperature
less than 36&deg;C. 2 h postoperatively, Teare remained
significantly cooler in the unwarmed patients (table 1).
Only final intraoperative and 2-h postoperative core temperatures differed significantly
in the two groups (two-tailed, unpaired t-tests; *lndlcates p<005). Results are
presented as mean (SD).
Table 1: Morphometric characteristics, duration of surgery,
anaesthetic management, and haemodynamic responses

Total blood loss was significantly greater m the hypothermic patients at each
measured time (two-tailed, unpaired t-tests). The hypothermic patients required more
intraoperative crystalloid and heta-starch. Seven of the 30 hypothermic patients
required transfusion of 8 units of allogeneic blood within 24 h of surgery, whereas only
1 unit of allogeneic blood was required in 1 of the 30 normothermic patients. The
section labelled "postoperative fluid administration" refers to the first 3 h after
surgery. Results are presented as means (SD). NS mdicates ps005. P values for the
volume of intraoperative colloid administration and allogeneic blood requirement were
virtually identical when calculated using a non-parametric (Wilcoxon) statistic.
Table 2: Haemoglobin, blood loss, administered fluid, and
allogeneic transfusion requirements
Partial thromboplastin times and blood fibrinogen and
anti-thrombin 3 concentrations were normal and similar
preoperatively in both groups, and did not change
significantly during the study. The prothrombin time
decreased significantly from 94 (17)% clot formation
preoperatively, to 65 (10)% immediately after surgery,
and remained 67 (9)% the following morning. Blood
platelet number decreased significantly from 244 000
(59 000)/RL preoperatively to 195 000 (44 000)/IiL
immediately after surgery and then to 162 000 (48 000)/
ILL the following morning. However, values in the two
groups never differed significantly.
Blood loss was significantly greater in the hypothermic
patients at the end of surgery, and 3, 12, and 24 h after
surgery. Eight units of allogeneic packed red cells were
required in seven of the 30 hypothermic patients, whereas
only a single normothermic patient required a unit of
allogeneic blood (p<0-05 for administered volume). Most
blood loss occurred after surgery, and all allogeneic blood
was given postoperatively. Initial haemoglobin
concentrations were comparable in the two groups, but
were somewhat (although not significantly) less in the
hypothermic patients on the first postoperative day
(table 2).
Discussion
Consistent with in-vitro data,5,6 our results indicate that
mild hypothermia significantly increased bleeding. Less
than 2&deg;C perioperative core hypothermia increased blood
loss about 500 mL (1 unit). Because we used
haemodilution and returned scavenged red cells to our
patients, relatively few required allogeneic transfusions.
Nonetheless, many more hypothermic patients required
allogeneic transfusions and the overall volume transfused
was significantly greater in the unwarmed patients.
In addition to its direct cost (excess cost of blood in our
hypothermic patients was about$US1050), the
administration of allogeneic blood carries risks of
infection, transfusion reaction, immune suppression, and
may violate religious dictates of some patients. 10
There are three major pathways by which hypothermia
might augment surgical blood loss: impaired platelet
function, reduced intrinsic and extrinsic clotting, and
increased fibrinolysis. Hypothermia significantly impairs
platelet function, an inhibition apparently related to
defective thromboxane Az release, upregulation of platelet
surface protein GMP-140, and downregulation of platelet
glycoprotein Ib-IX complex. The platelet function defect
(as assessed by bleeding time) is related to local
temperature, rather than core temperature." Wound
temperature, however, is largely determined by core
temperature and will be distinctly higher in normothermic
patients.
The prothrombin and partial thromboplastin times
remain nearly normal in hypothermic patients when
tested in the usual manner.23 The difficulty with these
studies, however, is that the tests were performed at 37&deg;C.
There is considerable evidence that both the prothrombin
and partial thromboplastin times are highly sensitive to
the temperature at which the tests are performed.6,14These
tests may, therefore, fail to accurately assess individual
clotting potential unless conducted at the patients
temperature. Most likely, both intrinsic and extrinsic
clotting is substantially impaired by hypothermia in vivo.
The fibrinolytic system normally regulates the balance
between formation of haemostatic plugs and restoration of
blood flow after clot formation. The conversion of
plasminogen to plasmin is the core of this mechanism,
and is largely enhanced by tissue-type plasminogen
activator. In contrast to platelet function and the
coagulation cascade, fibrinolysis remains normal during
mild hypothermia;15 these data suggest that hypothermia-
induced coagulopathy does not result from excessive clot
lysis.
We used two methods to reduce blood loss in our
patients: haemodilution and red-cell scavenging. Surgical
bleeding and allogeneic transfusion requirements might
have been further reduced had our management included
other methods such as regional anaesthesia, deliberate
hypotension, or use of autologous blood donated before
surgery.
Excessive bleeding is only one reason to maintain
intraoperative normothermia. It is well established that
mild hypothermia causes postoperative shivering and
decreases comfort. Recent evidence suggests that mild
intraoperative hypothermia may also predispose toward
myocardial ischaemia,16 aggravate surgical wound
infections,17,18 and prolong drug action.19,zo Taken together,
these factors indicate that surgical patients should be kept
normothermic (core temperature =36&deg;C) unless
hypothermia is specifically indicated. We suspect that a
policy of maintaining normothermia will also decrease
blood loss during other surgical procedures.
This study was supported by Augustine Medical Inc, the Joseph Drown
and Max Kade Foundations, and National Institutes of Health grant RO1
GM49670. Mallinckrodt Anesthesia Products Inc, donated thermocouples
and thermometers. The authors do not consult for, accept honoraria from,
or own shares or share options in any anaesthesia- or surgery-related
company.
291
References
1 Matsukawa T, Sessler DI, Sessler AM, et al. Heat flow and distribution
during induction of general anesthesia. Anesthesiology 1995; 82:
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2 Kurz A, Sessler DI, Narzt E, et al. Postoperative hemodynamic and
thermoregulatory consequences of intraoperative core hypothermia.
J Clin Anesth 1995; 7: 359-66.
3 Kurz A, Kurz M, Poeschl G, et al. Forced-air warming maintains
intraoperative normothermia better than circulating-water mattresses.
Anesth Analg 1993; 77: 89-95.
4 Frank SM, Beattie C, Christopherson R, et al. Epidural versus general
anesthesia, ambient operating room temperature, and patient age as
predictors of inadvertent hypothermia. Anesthesiology 1992; 77:
252-57.
5 Michelson AD, MacGregor H, Barnard MR, et al. Reversible
inhibition of human platelet activation by hypothermia in vivo and in
vitro. Thrombosis and Haemostasis 1994; 71: 633-40.
6 Rohrer M, Natale A. Effect of hypothermia on the coagulation cascade.
Crit Care Med 1992; 20: 1402-05.
7 Khuri S, Wolfe JA, Josa M, et al. Hematologic changes during and after
cardiopulmonary bypass and their relationship to the bleeding time and
nonsurgical blood loss. J Thorac Cardiovasc Surg 1992; 104: 94-107.
8 Rodgers RPC, Levin J. A critical appraisal of the bleeding time.
Seminars in Thrombosis and Hemostatsis 1990; 16: 1-20.
9 Meinert CL, ed. Clinical trials: design, conduct, and analysis. New
York: Oxford Univeristy Press, 1986.
10 Lubarsky DA, Hahn C, Bennett DH, et al. The hospital cost (fiscal
year 1991/1992) of a simple perioperative allogeneic red blood cell
transfusion during elective surgery at Duke University. Anesth Analg
1994; 79: 629-37.
Comparison of leg compression stocking and oral horse-chestnut
seed extract therapy in patients with chronic venous insufficiency
C Diehm (representing the steering committee and investigators) *,
Summary
Background Diseases of the venous system are widespread
disorders sometimes associated with modern civilisation
and are among the major concerns of social and
occupational medicine. This study was carried out to
compare the efficacy (oedema reduction) and safety of
compression stockings class II and dried horse chestnut
seed extract (HCSE, 50 mg aescin, twice daily).
Methods Equivalence of both therapies was examined in a
novel hierarchical statistical design in 240 patients with
chronic venous insufficiency. Patients were treated over a
period of 12 weeks in a randomised, partially blinded,
placebo-controlled, parallel study design.
Findings Lower leg volume of the more severely affected
limb decreased on average by 43&middot;8 mL (n=95) with HCSE
and 46&middot;7 mL (n=99) with compression therapy, while it
*Listed on p 294
Department of Internal Medicine/Vascular Medicine, Affiliated
Teaching Hospital, University of Heidelberg, Guttmannstrasse 1,
76307 Karlsbad-Langensteinbach, Germany (C Diehm MD);
Department of Medical Data Processing and Biomathematics,
University of Bochum, Germany (H J Trampisch PhD, S Lange MD);
Department of Clinical Research/Klinge Pharma GmbH, Germany
(C Schmidt PhD)
Correspondence to: Prof C Diehm, Rehabilitations Krankenhaus,
Karlstad-Langensteinbach Postfash 10327, 7516, Karlsbad,
Germany
292
11 Valeri CR, Khabbaz K, Khuri SF, et al. Effect of skin temperature on
platelet function in patients undergoing extracorporeal bypass. J Thorac
Cardiovasc Surg 1992; 104: 108-16.
12 Bunker JP, Goldstein R. Coagulation during hypothermia in man. Proc
Soc Exp Biol Med 1958; 97: 199-202.
13 Goto H, Nonami R, Hamasaki Y, et al. Effect of hypothermia on
coagulation (abstract). Anesthesiology 1985; 63: 107.
14 Reed L, Johnston TD, Hudson JD, et al. The disparity between
hypothermic coagulopathy and clotting studies. J Trauma 1992; 33:
465-70.
15 Csete M, Washington DE, Sessler DI, et al. Core hyperthermia
increases fibrinolytic activity. Crit Care Med (in press).
16 Frank SM, Beattie C, Christopherson R, et al. Unintentional
hypothermia is associated with postoperative myocardial ischemia.
Anesthesiology 1993; 78: 468-76.
17 Sheffield CW, Sessler DI, Hunt TK. Mild hypothermia during
isoflurane anesthesia decreases resistance to E coli dermal infection in
guinea pigs. Acta Anaesthesiol Scand 1994; 38: 201-05.
18 Kurz A, Sessler DI, Lenhardt R, et al, and the Study of Wound
Infection and Temperature (SWIFT) group. Perioperative
hypothermia increases the incidence of surgical wound infections and
prolongs duration of hospitalization (abstract). Anesthesiology 1955; 83:
A227.
19 Heier T, Caldwell JE, Sessler DI, et al. Mild intraoperative
hypothermia increases duration of action and spontaneous recovery of
vecuronium blockade during nitrous oxide-isoflurane anesthesia in
humans. Anesthesiology 1991; 74: 815-19.
20 Leslie K, Sessler DI, Bjorksten AR, et al. Mild hypothermia alters
propofol pharmacokinetics and increases the duration of action of
atracurium. Anesth Analg 1995; 80: 1007-14.
HJ Trampisch, S Lange, C Schmidt
increased by 9&middot;8 mL with placebo (n=46) after 12 weeks
therapy for the intention-to-treat group (95% Cl: HCSE:
21&middot;1-66&middot;4; compression: 30&middot;4-63&middot;0; placebo: 40&middot;0-20&middot;4).
Significant oedema reductions were achieved by HCSE
(p=0&middot;005) and compression (p=0&middot;002) compared to
placebo, and the two therapies were shown to be
equivalent (p=0&middot;001); in this design, however, compression
could not be proven as standard with regard to oedema
reduction in the statistical test procedure. Both HCSE and
compression therapy were well tolerated and no serious
treatment-related events were reported.
Interpretation These results indicate that compression
stocking therapy and HCSE therapy are alternative
therapies for the effective treatment of patients with
oedema resulting from chronic venous insufficiency.
Lancet 1996; 347: 292-94
Introduction
Chronic venous insufficiency cannot be deemed a minor
health impairment; patients with venous system disease
require hospital or sanatorium treatment, including
surgical intervention, and often are propelled into early
retirement. The therapeutic objective in managing venous
insufficiency is intervention at an early and therapeutically
favourable stage of the disease process in order to prevent
time-consuming and expensive complications. Reducing
the increased capillary permeability and associated
oedema may improve microcirculation in the terminal
vessels and-possibly-prevent or delay ulceration. Two