CORRESPONDENCE
among whom coagulopathy is
common. Any reduction in short-term
morbidity produced by epidural
analgesia would be outweighed by even
a low rate of paraplegia. However, the
risk of haematoma should be minimal
in patients undergoing off-pump
CABG surgery, since they receive only
small amounts of heparin and are
unlikely to develop a coagulopathy.
The combination of epidural analgesia
with off-pump surgery might,
therefore, show even greater reductions
in short-term morbidity.
Another reason for caution when
interpreting studies comparing off-
pump with on-pump CABG surgery is
the concept that cardiopulmonary
bypass is one uniformly malevolent
entity. In reality, equipment and
techniques differ vastly. One pertinent
part is the salvage of blood from the
pericardial cavity to limit the need for
transfusion through activation of the
coagulation and inflammatory systems.
Moreover, the blood contains
microparticles and lipid emboli that are
returned to the patient and could cause
adverse outcomes such as cognitive
decrements.4 Therefore, cardiopulmo-
nary bypass in itself may not be a cause
of adverse outcome after on-pump
CABG surgery, but rather a peripheral
technique such as pericardial salvage,
and excluding or washing blood from
this source might reduce them.5
Clearly, Angelini and colleagues
show off-pump CABG surgery to be a
practical technique. However, its
advocacy, especially for sick elderly
people, should be tempered until the
long-term cardiac outcome is known to
be similar to that for on-pump CABG
surgery—97% graft patency at 15 years
after surgery.
R Peter Alston
Department of Anaesthesia, Critical Care and
Pain Medicine, Royal Infirmary of Edinburgh,
Edinburgh EH3 9YW, UK
(e-mail: p.alston@ed.ac.uk)
1 Angelini GD, Taylor FC, Reeeves BC,
Ascione R. Early and midterm outcome
after off-pump and on-pump surgery in
Beating Heart Against Cardioplegic Arrest
Studies (BHACAS 1 and 2): a pooled
analysis of two randomised controlled trials.
Lancet 2002; 359: 1194–99.
2 Alston RP. Off-pump coronary artery
surgery and the brain. Br J Anaesth 2000;
84: 549–52.
3 Scott NB, Turfrey DJ, Ray DAA, et al. A
prospective randomized study of the
potential benefits of thoracic epidural
anesthesia and analgesia in patients
undergoing coronary artery bypass grafting.
Anesth Analg 2001; 93: 528–35.
4 Brooker RF, Brown WR, Moody DM, et al.
Cardiotomy suction: a major source of brain
lipid emboli during cardiopulmonary
bypass. Ann Thorac Surg 1998; 65: 1651–55.
5 Amand T, Pincemail J, Blaffart F,
Larbuisson R, Limet R, Defraigne JO.
1254
For personal use. Only reproduce with permission from The Lancet Publishing Group.
Levels of inflammatory markers in the blood
processed by autotransfusion devices during
cardic surgery associated with
cardiopulmonary bypass circuit. Perfusion
2002; 17: 117–23.
Avoid hormones in
gastrointestinal
angiodysplasia
Sir—Humphrey Hodgson (May 11,
p 1630)1 asks whether there is any
reason for exposing patients with
gastrointestinal angiodysplasia to the
potential morbidities of oestrogen
therapy. There are good reasons for not
prescribing hormones.
In a randomised controlled trial and
a cohort study, no benefit was reported
from oestradiol and norethisterone use,
in contrast to a very small short trial in
which patients had lower transfusion
requirements.
It is unsurprising that giving
hormones to patients with bleeding
results in confusion. In studies of the
vascular changes in endometrial blood
vessels caused by a large range of
progestagens and oestrogens, I found
that commonly used combinations
of these two hormones caused
abnormalities in arterioles, sinusoids,
or both. At the same time, lowered zinc
and raised copper concentrations
interfere with immune system
regulation that can raise the risk of
gastrointestinal infections.2
The large Royal College of General
Practitioners’ Oral Contraceptive
Study3 shows increases in a wide range
of infections and vascular diseases after
hormone treatment. The increased
relative risk of death from vascular
disease among ever users was 4·2,
which rose with age and smoking to
7·4. Current users also had a significant
60% increase in diseases of the arteries,
arterioles, and capillaries.4 Abnormal
abdominal, hepatic, pulmonary, and
leg blood vessels have been noted in
women taking hormones for less than
5 years.5
The taking of female sex hormones
can increase the risk of vascular
diseases, thrombosis with possible
secondary haemorrhages, and
infections, which can also increase the
risk of bleeding. Use of such hormones
for bleeding disorders, including
hereditary haemorrhagic telangiectasia,
therefore, does not seem sensible.
Ellen C G Grant
20 Coombe Ridings, Kingston-upon-Thames,
Surrey KT2 7JU, UK
(e-mail: ellencggrant@onetel.net.uk)
1 Hodgson H. Hormonal therapy for
gastrointestinal angiodysphasia. Lancet
2002; 359: 1630–31.
THE LANCET • Vol 360 • October 19, 2002 • www.thelancet.com
2 Grant ECG. The pill, hormone replacement
therapy, vascular and mood over-reactivity
and mineral imbalance. J Nutr Environ Med
1998; 8: 105–16.
3 Anon. Further analyses of mortality in oral
contraceptive users: Royal College of
General Practitioners’ Oral Contraception
Study. Lancet 1981; 1: 541–46.
4 Incidence of arterial disease among oral
contraceptive users: Royal College of
General Practitioners’ Oral Contraception
Study. J R Coll Gen Pract 1983; 33:
75–82.
5 Irey NS, Manion WC, Taylor HB. Vascular
lesions in women taking oral contraceptives.
Arch Pathol 1970; 89: 1–9.
Opioid prescription in
Italy: new law, no effect
Sir—It is estimated that millions of
patients with cancer worldwide
experience moderate to severe cancer
pain. Unrelieved cancer pain
continues to be a major public-health
concern, despite available treatment.
The use of opioids is the cornerstone
of cancer-pain management. Mis-
guided national health policies, non-
availability of drugs, and inadequate
education of physicians and the public
are the main barriers to the
prescription of opioids. The trend of
increasing medical use of opioids to
treat pain does not seem to be
contributing to increases in
the health consequences of opioid
analgesic abuse.1
In many European countries,
governments and legislators have been
restrictive about the use of opioids.2 In
Italy, restrictive prescribing regulations
emerged as the most important barrier
to adequate pain management by
family physicians.3 In February, 2001,
the Italian government approved a law
aimed at facilitating opioid
prescription for cancer pain. It seems
less restrictive and would potentially
have improved the prescription.
We calculated, for the existing
opioids commercially available in Italy
used mostly for cancer pain, the
amount sold 6 months before approval
of the new law and 6 months after, to
assess changes in the attitudes of
Italian physicians in prescribing
opioids. Data are presented in the
table. Morphine has been marketed as
a slow-release preparation by two
Before After
Opioids 0·22 0·22
Transdermal fentanyl 0·0005 0·0054
Morphine 1* 0·1904 0·0074
Morphine 2* 0·0240 0·1785
*From two different anonymised companies.
Opioid use in mg per person in general
population sold before and after change
in opioid prescription law