Full text of DOI:10.1007/BF03020955

367
History of Anesthesia
In the arms of Morpheus:
the development of mor-
phine for postoperative
pain relief
Gillian R. Hamilton BA,
Thomas F. Baskett MB FRCSC
Purpose: To analyse the historical development of morphine for postoperative analgesia and how this develop-
ment was shaped by the evolution of anesthetic techniques.
Methods: After a systematic review of the literature, information was gathered from primary sources.
Principal Findings: In ancient medicine, some plant derivatives were used to alleviate pain including: alcohol,
cannabis, mandrake, and opium. Over the past two centuries, opium and its derivatives have become the most
widely used analgesics for severe pain. Before the development of general anesthesia, surgery was only per-
formed out of extreme necessity. It is probable that an analgesic such as opium would have been given following
surgery although its use may not have been recorded. The first description of postoperative opium was by James
Moore in 1784. Morphine was isolated from opium by Friedrich Serturner in 1805. However, it was not until the
development of the hypodermic needle and syringe nearly 50 yr later that the use of morphine became wide-
spread. Over the last century, various delivery systems for morphine have been developed including sub-
arachanoid and epidural injection, and more recently patient-controlled intravenous, epidural and intranasal
analgesia. In addition, many new opioids have been synthesized.
Conclusion: Since its isolation from opium almost 200 yr ago, morphine remains the most widely used analgesic
and the standard against which all new opioids for postoperative pain relief are compared.
Objectif : Décrire le développement historique de la morphine comme analgésique postopératoire et montrer
comment il a été façonné par l’évolution des techniques anesthésiques.
Méthode : On a d’abord passé systématiquement en revue la documentation pertinente, puis rassemblé les
informations des principales sources.
Constatations principales : La médecine ancienne utilisait certains dérivés de plantes pour soulager la douleur:
l’alcool, le cannabis, la mandragore et l’opium. Au cours des deux derniers siècles, l’opium et ses dérivés sont
devenus les analgésiques les plus utilisés contre la douleur vive. Avant l’avènement de l’anesthésie générale, l’in-
tervention chirurgicale n’était réalisée qu’en cas d’extrême nécessité. Il est probable qu’un analgésique comme
l’opium ait été administré à la suite d’une opération sans qu’on en consigne l’emploi. La première description de
l’utilisation postopératoire d’opium revient à James Moore en 1784. La morphine a été isolée de l’opium par
Friedrich Serturner en 1805. Cependant, son usage ne s’est répandu qu’avec l’arrivée, 50 ans plus tard, de l’ai-
guille hypodermique et de la seringue. Pendant le siècle dernier, on a mis au point différents systèmes d’adminis-
tration de la morphine, y compris l’injection sous-arachnoïdienne et péridurale et, plus récemment, l’analgésie
intraveineuse, péridurale et intranasale contrôlée par le patient. De plus, nombre de nouveaux opioïdes ont été
synthétisés.
Conclusion : Depuis que la morphine a été isolée de l’opium, il y a près de 200 ans, elle demeure l’analgésique
le plus utilisé et une norme de comparaison pour tout nouvel opioïde utilisé pour soulager la douleur postopéra-
toire.
From the Department of Obstetrics and Gynaecology, Dalhousie University, 5980 University Avenue, Halifax, Nova Scotia B3J 3G9
Canada.
Address correspondence to: T.F. Baskett MB FRCSC. Phone: 902-420-6788; Fax: 902-428-8640.
Accepted for publication December 12, 1999.
CAN J ANESTH 2000 / 47: 4 / pp 367–374

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CANADIAN JOURNAL OF ANESTHESIA
AIN is an integral part of life and, as such,
attempts to relieve pain must be as old as
human-kind. Some of the earliest pharmaco-
logical methods of pain relief included the
1 ounce powder of cinnamon, and 1 ounce powder of
cloves.6 Sydenham’s laudanum was used in Europe
and North America into the early 20th century.
Several other opioid preparations were popular in the
18th and 19th centuries. “Black-drop”, otherwise
known as Lancaster or Quaker’s Black Drop, con-
tained opium, verjuice, nutmeg, saffron and yeast, and
was reputedly three times stronger than laudanum.
Paregoric was a weaker preparation, named after the
Greek word for “soothing” or “consoling” and
included opium, honey, licorice root, camphor,
aniseed and wine. Dover’s powder, first developed by
the English physician and buccaneer Thomas Dover
(1660-1742), contained opium, salt peter, tartar,
licorice and ipecacuanha.7 Dover claimed, “In two or
three hours at furthest the patient will be free from
pain”. In addition to producing his opium-containing
“sweating powder”, Thomas Dover was the second
captain aboard the privateer Duke that rescued
Alexander Selkirk (Robinson Crusoe) from one of the
Juan Fernández islands in 1709.
The first record of postoperative analgesia was the
use of opium in 1784 by the Glasgow-born London
surgeon James Moore (1763-1834). He clearly real-
ized the limitations of opium for surgical anesthesia,
but praised its postoperative benefits when he wrote:
“Opium...is highly expedient to abate the smarting of
the wound after the operation is over, and to induce
sleep; but the strongest dose we dare venture to give
has little or no effect in mitigating the suffering of the
patient during the operation”.8 In the same year,
Moore also devised an appliance for compression of
nerves producing numbness in a limb before surgery,
presumably by neuropraxia.8
P
plant derivatives: alcohol, cannabis, mandrake, and
opium.1 These analgesics were used for surgical anal-
gesia as long as 2500 yr ago. For example, in the
ancient Indian work the Sushruta Samhita, written
perhaps as early as 400 BC, it was advised that alcohol
be used before surgery to produce insensibility to
pain.2 Dioscorides (Circa 54-58 AD), a Greek physi-
cian and surgeon, recommended patients should take
mandrake mixed with wine before limb amputation:
“For such as cannot sleep, or are grievously pained,
and upon whom being cut, or cauterized they wish to
make a not-feeling pain”.3 Celsus (AD 14-37) in De
Medicina suggests the use of opium before surgery.4
In the Middle Ages, Theodoric, a 13th century monk
and physician, described the spongia somnifera, a mix-
ture of several narcotic substances including, opium,
mandrake, henbane, mulberry, lettuce and hemlock,
all boiled within a sponge, which was then sniffed to
provide anesthesia for surgery.5
Despite the widespread use of these compounds for
surgery there were no concomitant descriptions of
their application for pain relief after surgery, although
it seems logical they would have been so employed.
Only opium and related compounds are still used as
analgesics. The evolution of opium and its derivative
morphine for postoperative pain relief will be
reviewed.
Opium
Opium has been known for millennia to relieve pain
and its use for surgical analgesia has been recorded for
several centuries as noted above. However, its use as
an agent for postoperative pain relief has only been
described since the late 18th century, although it may
have previously been used for this purpose but not
recorded. Over the past two centuries, opium and its
derivatives have emerged as the most effective anal-
gesics for postoperative pain relief.
Five years later, the Scottish surgeon, Benjamin Bell
(1749-1806) also found opium compounds to be
good postoperative analgesics: “In general they prove
most useful when given immediately after, when they
very commonly alleviate that pungent soreness of
which patients at this time usually complain; and by
continuing to give them in adequate doses from time
to time, we are often enabled to keep the patient easy
and comfortable....9
Oral administration
Analgesia following laparotomy was first described
by Ephraim McDowell (1771-1830) in May of 1816.
McDowell gave “...a wine glass full of cherry bounce,
and thirty drops of laudanum...” to a woman follow-
ing laparotomy and surgical removal of a six pound
ovarian tumour, following which she recovered
uneventfully.1 0 Of the five cases of laparotomy and
ovariotomy in his two reports, this was the only one in
which McDowell recorded using postoperative anal-
gesia.10,11
Laudanum, or tincture of opium, was a mixture of
opium, alcohol, and various other ingredients. It was
often given in whiskey or rum and became a widely
used agent to prepare patients for surgery until the
discovery of effective anesthesia. There were many
recipes for laudanum, the most famous being that of
Thomas Sydenham (1624-89). Sydenham’s recipe,
given in his work on dysentery in 1669, contained 1
pound sherry wine, 2 ounces opium, 1 ounce saffron,

Hamilton & Baskett: HISTORY OF MORPHINE
369
Rectal administration
that “the opium...did within a short time stupify,
though not kill the dog”.1 9
The first reference to postoperative opium using the
rectal route of administration was by Shoemaker in
1891. In his Materia Medica and Therapeutics he rec-
ommended a rectal opium suppository which “...qui-
ets the nervous system after operations upon the
female pelvis...”.12
The first subcutaneous placement of morphine was
described in 1836 by the French physician GV
Lafargue. His “inoculation” method involved intro-
ducing a morphine paste under the epidermis by
means of a vaccination lancet.20 Lafargue intended his
inoculation method to have local effect but he specu-
lated that systemic effect might be possible. To satisfy
his curiosity he inoculated himself 13 times in the
forearm and soon became overwhelmed by a sensation
of extreme somnolence.2 1Unfortunately Lafargue was
so preoccupied with his intention to create a local
effect that he failed to recognize the significance of the
systemic action of morphine even though he experi-
enced it himself.
In 1845, the Irish surgeon Francis Rynd (1801-
1861) became the first to introduce a fluid subcuta-
neously. In order to treat a patient with trigeminal
neuralgia, Rynd developed a special instrument which
could inject a morphine solution beneath the skin:
“On the 3rd of June a solution of fifteen grains of
acetate of morphia, dissolved in one drachm of cre-
osote, was introduced to the supra-orbital nerve, and
along the course of the temporal, malar, and buccal
nerves, by four punctures of an instrument made for
the purpose.”2 2 No description of the instrument was
given - the predecessor of the modern hypodermic
syringe - until his 1861 publication which described it
as a retractable trocar and cannula that allowed fluid
to enter the tissues by gravity alone.2 3
In 1853, the subcutaneous route of drug adminis-
tration using a syringe and hollow needle was intro-
duced by Alexander Wood of Edinburgh
(1817-1884). Wood did not invent the syringe and
hollow needle but modified a design already manufac-
tured by a local chemist - a “Mr. Ferguson of Giltspur
Street, London”.2 4 Wood’s intention was to produce a
local effect by injecting morphine directly into the
painful area. However, when he checked on his first
patient the morning following a subcutaneous mor-
phine injection he was “a little annoyed to find she
had never wakened; the breathing also was somewhat
deep, and she was roused with difficulty”.2 4Obviously
Wood noticed the systemic effects of the morphine
injection on his patient, but he maintained that its
local analgesic effects were of primary importance.
The systemic action of a subcutaneous opioid injec-
tion was first fully understood in 1858 by the London
surgeon, Charles Hunter. He published one paper on
October 16, 1858 in the Medical Times Gazette advo-
cating Wood’s technique of morphine injection.2 5
Two weeks later he published another paper in the
Morphine
The isolation of morphine from crude opium was one
of the most important discoveries of nineteenth cen-
tury medicine. In the early 1800s Friedrich Serturner
(1783-1841), a pharmacist’s apprentice in Germany,
was working on isolating the active principle of
opium. Serturner’s first discovery in 1805, was a new
acid, “mekonsaure” or “mohnsaure”, present in
opium.1 3 However, trials on dogs revealed that
mekonsaure was inactive. He then reported finding a
water-insoluble crystalline substance which had an
“almost alkaline-like character”; he called this the
“principium somniferum”.1 4 Animal experiments
proved this was indeed an active principle of opium.
Serturner later named the active ingredient of opium
“morphium” after the Greek god of dreams.1 5 In
1817 Serturner published another paper which, unlike
his previous publications, received widespread atten-
tion.1 6 In a French translation of Serturner’s work,
Gay-Lussac added an editorial in which he suggested
the name morphine rather than morphium.1 7
From the time of its discovery by Serturner, mor-
phine was manufactured and used in an oral form,
morphine acetate, which was a difficult and expensive
salt to prepare. In 1831, William Gregory, an
Edinburgh physician and chemist, discovered a cheap
method of isolating and purifying morphine salts.1 8
However, there was no financial or clinical advantage
in the use of morphine over paregoric and laudanum.
These traditional media for delivering opium alkaloids
orally were of similar cost and efficacy, and already
established in the medical and public eye. It was not
until the development of the hypodermic needle and
syringe in the 1850s that the use of morphine became
widespread.
Parenteral administration
Intravenous injection preceded subcutaneous adminis-
tration by almost two centuries. Sir Christopher Wren
(1632-1723), the English architect who designed St.
Paul’s Cathedral, was the first to inject liquid into a
vein. Working with the celebrated chemist Robert
Boyle in 1659, Wren injected an infusion of opium into
a vein on the hind leg of a dog using a goose quill as the
needle and an animal bladder as the syringe. He noticed

370
CANADIAN JOURNAL OF ANESTHESIA
same journal, reporting that the injection of morphine
at a site remote from the painful area produced equal
pain relief. Hunter concluded “The idea that the relief
results from localisation of the remedy in the painful
part is erroneous—equal relief being afforded in either
case”.2 6 This was the beginning of a heated debate
between Hunter and Wood, which was carried out
through correspondence in the British Medical
Journal and Lancet. Wood claimed the local effects of
morphine injected subcutaneously were of primary
importance, whereas Hunter claimed the systemic
effects were paramount. Part of their debate also
included an argument over the name for the tech-
nique. Hunter coined the term “hypodermical” in
1863, but Wood insisted that Hunter’s “hypodermi-
cal” was identical to his own “subcutaneous” injec-
tion.27,28 Although both words refer to the same
technique, the difference apparently lay in the purpose
of the injection - local vs systemic. In the end, the
Medical and Chirurgical Society of London appointed
a special committee to settle the question of whether
systemic or local effects of morphine injection were of
primary importance. After two years the results were
published and unanimously favoured Hunter.29 To
some extent Wood has been vindicated by the discov-
ery of peripheral opioid receptors.30,31
The first recorded use of subcutaneous morphine
for postoperative pain-relief was in 1863 by James
Paget (1814-1899). Paget gave 1/3 grain (20 mg)
morphine by subcutaneous injection after a leg ampu-
tation under chloroform anesthesia, “...with the view
of inducing freedom from pain, and some refreshing
sleep after a return to consciousness.”3 2 According to
the report, this practice “... had been in use for some
time at the Middlesex Hospital, and has afforded
much comfort and ease, especially after many of the
more important and painful operations”. Paget rec-
ommended 1/4 to ½ grain (15-30 mg), “...according
to circumstances.”3 2
Corning unintentionally produced epidural rather than
spinal anesthesia since no cerebrospinal fluid was
reported to have been recovered in his syringes.3 4
Corning speculated his method might be used as an
alternative to general anesthesia. His idea came to
fruition 14 yr later in the hands of the German surgeon
August Bier (1861-1949) who described six cases in
which “cocainization of the spinal cord” was performed
for surgery on the lower extremities.35 All of his patients
experienced post-anesthetic headache, nausea and vom-
iting. In the time-honored manner of the day, Bier and
his assistant also attempted spinal injections of cocaine
on each other, as recorded in this paper. They both
developed severe headaches, and a number of cuts,
bruises and burns were acquired while testing the effi-
cacy of analgesia.3 5
One year later, Rudolph Matas (1860-1957), a vas-
cular surgeon from New Orleans, was probably the
first to inject an opioid by the spinal route. Matas
often used a saline solution, containing both cocaine
and morphine, for his spinal injections. The addition
of morphine was intended to prolong the effect of
cocaine as well as to provide sedation.3 6Another early
record of spinal injection of morphine comes from the
annual report of the Dundee Royal Infirmary for
1909-10. In a list of 35 spinal anesthetics given that
year, nine contained morphine combined with
hyoscine and atropine. Although not specified in the
report, the injections were probably given for pain
relief and this may be the first deliberate use of spinal
morphine for postoperative analgesia.3 7
Spinal opioid injections seemed to fall out of favour
after these few anecdotal reports in the early 1900s.
However, interest resumed after the biochemical
demonstration, in 1973, of opioid receptors in the
brain38,39 and then in 1977 in the spinal cord.40,41 In
1976, before the discovery of spinal cord opioid
receptors, Yaksh and Rudy administered various opi-
oids including morphine into the spinal subarachnoid
space in rats.4 2 They noted that the opioids produced
an action (blocked spinal reflexes and decreased
response to painful stimuli) limited to the spinal cord
and speculated these opioids caused a direct action on
pain transmission in the substantia gelatinosa.42 The
following year Snyder discovered that opioids exert
their action through selective opioid receptors located
in both the brain (especially in the limbic system and
periaqueductal gray area of the brainstem) and spinal
cord (particularly localized in the substantia gelati-
nosa), thus implying that opioid analgesia can be
mediated in both regions.40,41
Although intravenous, subcutaneous and intramus-
cular routes of administration remain important meth-
ods of postoperative pain relief, great advances have
been made with the introduction of regional tech-
niques such as spinal and epidural injection.
Neuraxial administration
The New York neurologist, Leonard Corning (1855-
1923) described the first use of spinal anesthesia in
1885.33 He injected a cocaine solution into the space
between the eleventh and twelfth thoracic vertebre in a
man with “spinal weakness and seminal incontinence”
and achieved decreased sensation and impaired reflexes
in the lower extremities.3 3 It has been argued that
This demonstration of opioid receptors in the spinal
cord led to the reintroduction of spinal opioid injection

Hamilton & Baskett: HISTORY OF MORPHINE
371
for clinical use. The next recorded use of spinal opioid
injection in humans appears in the literature in 1978
when Wang used spinal morphine injections for relief of
cancer pain. He also speculated that the technique
might be useful for postoperative analgesia.4 3
effects by acting at peripheral sites, particularly where
there is inflammation. In 1991, Stein and colleagues
were the first to describe that morphine injected intra-
articularly in the knee joint following arthroscopy
considerably reduced postoperative pain.3 0 The anal-
gesic effect of the morphine was shown to be mediat-
ed by a local action and not by CNS redistribution.
Since this study, numerous randomized controlled tri-
als have been done to assess reduction of postoperative
pain following injection of opioid into the knee. A sys-
tematic review of 36 of these randomized controlled
trials concluded that intra-articular morphine may be
effective in reducing postoperative pain following
knee surgery.54
A similar reintroduction of the use of epidural mor-
phine occurred following the discovery of the opioid
receptors in the spinal cord. In 1901, a new method of
regional anesthesia was described in France by Jean
Sicard (1872-1929)44 and one week later in the same
journal by Fernard Cathelin (1873-1945).4 5 Both
investigators described injection into the epidural fat
surrounding the spinal cord dura. Sicard named the
technique “extradural injection by the sacrococcygeal
route” whereas Cathelin named the method “epidural
injection by the sacral canal”. Cathelin was the first to
use the technique for surgery in four patients undergo-
ing inguinal hernia repair. Unfortunately, a reduced but
not complete loss of sensation was achieved in these
operations. He also speculated that epidural injection
might be a useful technique for pain relief in: rectal can-
cer, hemorrhoidal fissures and, an obstetrical indication,
“accouchement douloureux”. Almost 80 yr were to
pass before opioids were injected into the epidural space
for pain relief by Behar and colleagues in 1979.4 6
Following this report, the use of epidural opioids for
postoperative pain relief quickly gained acceptance and
several publications in the early 1980s confirmed its
efficacy.47–49 Ultimately, it was the discovery of opioid
receptors in the spinal cord that led to the effective
treatment of postoperative pain by neuraxial adminis-
tration without profound sedative effects.
Other opioid delivery systems currently under
investigation and with the potential for postoperative
pain control include the pulmonary route of adminis-
tration using a powder form of morphine or fentanyl.
Patient controlled analgesia
One currently popular method of pain control, patient
controlled analgesia (PCA), was first proposed by the
Boston dentist William Morton (1819-1868) for use
in labour.5 5 Morton first suggested “self-serve” anes-
thesia in 1847 by allowing the woman in labour to
hold an ether sponge to her face when she felt pain.
He wrote: “...it is best, in most cases in this stage of
labour, to allow her to hold the sponge herself, and
apply it to her mouth when she feels a pain coming
on.” This was the forerunner of patient-controlled
inhalation analgesia with nitrous oxide and oxygen
mixtures, popular in the 1940s-70s.
The first use of intravenous opioids with patient con-
trolled analgesia was also in obstetrics. In a 1969 lec-
ture, James S. Scott, from the University of Leeds in
England, reported the use of “self-service” intravenous
analgesic administration in his obstetric practice over
the preceding five years.5 6 This was offered to any
woman who had experienced inadequate analgesia in
her first labour. She could be given control of her own
pain relief through a specially designed apparatus with a
spring, which the woman compressed when she needed
pain relief, allowing meperidine to be delivered through
the intravenous infusion. The first postoperative use of
PCA with an opioid was described by Sechzer in
1967.57 Postoperative patients pressed an analgesic-
demand button which alerted the nurse to give a small
amount of intravenous morphine or meperidine until
the pain was controlled. Sechzer concluded that this
“analgesic-demand method was ...an excellent system
for treatment for postoperative pain”.57
Submucosal administration
Submucosal routes of administration have also been
used with success in the delivery of opioids postopera-
tively. These include transnasal, transmucosal, and sub-
lingual administration. For example, transnasal and
transmucosal opioids have been used for pre-induction
of anesthesia in children50,51 and have the potential for
postoperative use. Sublingual buprenorphine has been
used postoperatively with good analgesic success on
both a scheduled and patient-demand basis.5 2
Transdermal administration
The transdermal delivery of opioids has also gained
recent popularity for both palliative care and postop-
erative pain control. In particular, the transdermal fen-
tanyl patch has been used since the late 1980s for
postoperative analgesia.5 3
Intra-articular administration
Recently, opioids have been found to exert analgesic
Since intravenous PCA was introduced by Scott,
new delivery systems have been developed using the

372
CANADIAN JOURNAL OF ANESTHESIA
6 Sigerist HE. Laudanum in the works of Paracelsus. Bull
Hist Med 1941; 9: 530–44.
same concept of patient control over dosing. Patient-
controlled epidural analgesia (PCEA) with either an
opioid or a combination of opioid and local anesthet-
ic is used both in obstetrics, and for postoperative
analgesia.58–60 Preferred opioids for PCEA include
synthetic compounds such as fentanyl, sufentanil, and
alfentanil because, as opposed to morphine, they have
high lipophilicity and thus a rapid onset of action.
Subcutaneous PCA using morphine has also been
reported in the literature as an effective method for
postoperative pain control.6 1 Patient-controlled
intranasal analgesia (PCINA) using meperidine or fen-
tanyl, but not morphine, is a recent development
which has been used in palliative care62 as well as for
postoperative pain management.62,63
7 Macht DI. The history of opium and some of its prepa-
rations and alkaloids. JAMA 1915; 64: 477–81.
8 Moore J. A method of preventing or diminishing pain
in several operations. London: J Cadell, 1784. Cited by
Bergman NA. The Genesis of Surgical Anesthesia. Park
Ridge: Wood Library-Museum of Anesthesiology,
1998: 349.
9 Bell B. A System of Surgery, 6th ed., Vol. 2.
Edinburgh: Bell and Bradfute, 1796: 393–7.
10 McDowell E. Three cases of extirpation of diseased
ovaria. Eclect Rep Analyt Rev (Philadelphia) 1817; 7:
242–4.
11 McDowell E. Observations on diseased ovaria. Eclect
Rep Analyt Rev (Philadelphia) 1819; 9: 546–53.
12 Shoemaker JV. Materia Medica and Therapeutics, Vol 2.
Philadelphia, 1891: 785.
13 Serturner FW. Trommsdorff’s Journal der Pharmazie
fur Aerzte, Apotheker und Chemisten 1805; 13:
229–35.
14 Serturner FW. Trommsdorff’s Journal der Pharmazie
fur Aerzte, Apotheker und Chemisten 1806; 14:
47–93.
15 Lockemann J. On Serturner. J Chem Educ 1951; 28:
277.
16 Serturner FW. Ueber das Morphium, eine neue salz-
fahige Grundlage, und die Mekonsaure, als
Hauptbestandtheile des Opiums. Gilbert’s Annalen der
Physik 1817; 55: 56–89.
17 Serturner FW. De la morphine et de l’acide meconique,
consideres comme parties essentielles de l’opium.
Annales de Chimie et de Physique 1817; 5: 21–42.
18 Gregory W. On a process of preparing economically the
muriate of morphia. Edin Med Surg J 1831; 35:
331–8.
Conclusion
Nearly 5000 yr after opium was first cultivated and iso-
lated by the Sumerians, opium and its derivatives
remain the best analgesics. Since the isolation of mor-
phine from opium almost 200 yr ago many different
delivery systems have been used for its administration.
Basic research demonstrated the existence of opioid
receptors in 1973, opening new avenues for the use of
morphine in pain relief. Although many new pain-
relieving compounds have been developed in the twen-
tieth century, morphine remains the standard by which
all new analgesic preparations are judged. For those
who practise surgery and are responsible for postopera-
tive pain relief the sentiments of Thomas Sydenham,
extolling the virtues of opium more than three centuries
ago, remain relevant: “None of us would be calloused
enough to practise our profession without it”.
Acknowledgment
The authors wish to acknowledge the assistance of
Dr. Orlando Hung.
19 Wren C. An account of the rise and attempts, of a way
to conveigh liquors immediately into the mass of
blood. Phil Trans 1665; 1: 128–30.
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