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British Journal of Anaesthesia 1996;
76: 484–486
CLINICAL INVESTIGATIONS
Dose requirements, efficacy and side effects of morphine and
pethidine delivered by patient-controlled analgesia after
gynaecological surgery
G. STANLEY, B. APPADU, M. MEAD AND D. J. ROWBOTHAM
patients gave written informed consent to the study
which was approved by the local Ethics Committee.
We have compared the dose requirements and side
Patients were instructed in the use of the PCA
effects of morphine with those of pethidine when
machine (Graseby) on the day before surgery. A
administered by patient-controlled analgesia in 40
visual analogue scale (VAS) for assessment of nausea,
patients (ASA I–II, 20–65
yr) after elective total
pain and satisfaction was also explained. Each VAS
abdominal hysterectomy. Patients were allocated
comprised a 100-mm unmarked line, the ends of
randomly, in a double-blind manner, to receive
which denoted extremes of the variables in question,
either morphine (bolus dose 2
mg, lockout time
that is no nausea—extreme nausea; no pain—worst
10 min) or pethidine (bolus dose 20 mg, lockout
pain imaginable; very unhappy—delighted with
time 10 min) for postoperative pain relief. Mean
24-h morphine and pethidine consumption was 70
All patients were premedicated with temazepam
10–20 mg orally, 1 h before surgery. Anaesthesia was
SEM 6.2) mg and 660 (67.8)
mg, respectively
(ratio 1 : 9.4). There were no significant differences
induced with propofol 2 mg kg1 and tracheal in-
in postoperative sedation, nausea, pain relief and
tubation and positive pressure ventilation were
patient satisfaction (VAS 0–100
facilitated by the use of vecuronium 0.1 mg kg1.
quirements for antiemetics. Four patients receiving
Anaesthesia was maintained with 1 % isoflurane and
pethidine were withdrawn because of postoperative
66 % nitrous oxide in oxygen, and fentanyl
confusion and one receiving morphine because of
2–4 g kg1.
intractable nausea and vomiting. The 95 % con-
Patients were allocated randomly (sealed en-
fidence interval for this difference between the
velopes) to receive morphine or pethidine by PCA
groups for VAS scores of sedation, nausea and pain
(morphine 2 mg bolus, lockout 10 min; pethidine
were approximately 30 mm. (
Br. J. Anaesth. 1996;
20 mg bolus, lockout 10 min). The drug solution was
76: 484–486)
prepared such that 1 ml contained either morphine 2 mg or pethidine 20 mg. The anaesthetist and nurse
Key words
investigators were blinded to the contents of the
Analgesia, postoperative. Analgesia, patient-controlled. Analge-
PCA syringe. Operation of the PCA device was
sics opioid, morphine. Analgesics opioid, pethidine.
recorded by a printer (Hewlett–Packard Thermal Printer).
Morphine and pethidine are used commonly for
During the immediate recovery period, opioid was
patient-controlled analgesia (PCA). There are some
administered i.v. in a double-blind fashion in either
clinical situations where pethidine may be preferred
1-mg (morphine) or 10-mg (pethidine) increments in
to morphine, for example in asthmatics (anticholin-
the recovery room. Increments were given every
ergic action of pethidine) and after bowel anasto-
2–4 min by the anaesthetist conducting the study,
moses (dehiscence with morphine [1]) but the choice
until pain control was judged to be comfortable and
is often based on other perceived differences in
satisfactory by the patient. PCA was then com-
efficacy and side effects such as quality of analgesia
and tendency to nausea and vomiting. However,
VAS scores for pain, nausea and satisfaction were
there are few data in the literature to enable proper
made at 4, 8 and 24 h after commencing PCA.
Sedation (wide awake—unable to stay awake) was
PCA enables comparison of the potency, efficacy
also assessed at 4, 8 and 24 h by the blinded observers
and side effects of opioids in the treatment of pain
using a VAS scoring system. At the end of the 24-h
after surgery [2, 3]. Therefore, we have examined, in
study period, patients were asked to describe their
a prospective, randomized, double-blind study, the
appreciation of overall pain, nausea and vomiting
relative efficacy and side effects of morphine and
which was assessed on a three-point verbal scale
G. STANLEY, FRCA, B. APPADU, MD, FRCA, M. MEAD, FRCA,
Patients and methods
D. J. ROWBOTHAM, MD, MRCP, FRCA, FFARCSI, University De- partment of Anaesthesia, Leicester Royal Infirmary, Leicester
We studied 40 patients, ASA I–II, aged 20–65 yr,
LE1 5WW. Accepted for publication: December 1, 1995.
undergoing total abdominal hysterectomy. All
Correspondence to B.A.
Patient-controlled analgesia after gynaecological surgery
(none/slight, moderate, severe). Patient satisfaction
Table 4 Three-point verbal scoring at 24 h. No significant
was assessed in a similar manner. All measurements
were made by a blinded investigator. Prochlorper-
azine 12.5 mg i.m. was given for nausea on patient
request by the nursing staff who were also blinded to the opioid used.
Data were analysed by Student's
t-test, Mann–
Whitney
U test and chi-square test with Yates'
correction, as appropriate. MANOVA for repeated
measures was used for visual analogue scores.
Unbearable/severe
Unhappy/miserable
There were no significant differences in age, weight,
Moderately happy
temazepam premedication, duration of surgery and
Happy/delighted
dose of fentanyl administered during surgery (table 1).
Mean 24-hour postoperative opioid consumption
with 95 % confidence intervals (CI) for the dif-
by PCA was morp hine 70 (SEM 6.2) and pethidine
ferences, are shown in table 2. There was no
660 (67.8) mg (ratio 1 : 9.4). There were no significant
difference also in the number of doses of prochlor-
differences between the groups in the VAS scores for
perazine administered (table 3).
pain, nausea, sedation or satisfaction, and these data,
Overall pain, nausea and vomiting, and satisfaction
scores obtained at the end of the study are shown in
Table 1 Patient characteristics (mean (SD or range)). No
table 4. These data include those patients (see below)
significant differences
who were withdrawn from the study. There were no significant differences between the two groups.
Four patients in the pethidine group became
disorientated and confused, 2–3 h after commencing
PCA. They were withdrawn from the study and
symptoms disappeared 2–3 h after removing PCA.
There were no signs of respiratory depression, the
Duration of surgery (min) 65.79 (24.51)
maximum total amount of incremental pethidine received by these patients in the recovery room was 30 mg and overall no patient received more than 50 mg of pethidine in total.
Table 2 Mean (SEM) and 95 % confidence intervals for the
One patient in the morphine group was withdrawn
differences in visual analogue scores for pain, nausea, sedation and satisfaction at 4, 8, 24 h
because of intractable nausea and vomiting. This patient became severely nauseated after receiving
morp hine 3 mg i.v. in the recovery room and was
withdrawn from the study 3 h later. Her symp toms
remained for several hours despite the use of
prochlorperazine and ondansetron.
Discussion
We found no significant differences between mor-
phine and pethidine PCA over a 24-h period in pain,
nausea and vomiting, sedation and patient satis-
faction. The 95 % CI for the differences between the
groups for VAS scores of pain, nausea and sedation
were approximately 30 mm. The clinical importance
of this difference is uncertain but we believe that it is
unlikely to be significant. However, one patient was
severely nauseated after a small dose of morp hine
and was withdrawn from study.
Our data are similar to those obtained in patients
receiving morphine, pethidine or oxymorphone via
Table 3 Number (%) of patients requiring prochlorperazine. No significant differences
PCA after elective Caesarean section during extra- dural anaesthesia [4]. Also, there were no differences
Prochlorperazine Morphine
between morphine and pethidine after open chole-
doses (
n)
cystectomy [5]. The comp arison in this study was
less clear as its primary purpose was to investigate
the efficacy and side effects of nalbuphine. However,
there may be significant differences between mor-
phine and pethidine when delivered via PCA in
British Journal of Anaesthesia
children [6]. Morphine was associated with better
undergoing elective hysterectomy. However, our
analgesia and greater sedation, with no other dif-
work gives further evidence to the view that
ferences in side effects.
pethidine may be associated with an increased
Morphine : pethidine potency ratios of between
incidence of postoperative confusion.
1 : 10 and 1 : 12 have been described in the post- operative period [5 7, 8]. Our ratio of 1 : 9.4 is
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Source: http://www.icupsychosis.org.uk/documentation/059.pdf
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The Hendra Virus Report Chapter 4: Hendra virus in humans This chapter discusses the nature of Hendra virus in humans. 4.1 Description of Hendra virus in humans There have been seven recorded cases of Hendra virus in humans.56 In all cases infection resulted from close contact with the bodily fluids of infected horses. Of the seven cases, five people are believed to have been exposed to the virus while performing autopsies, nasal lavages or endoscopies, while the other two had close contact with a dying horse. Hendra virus was not a confirmed or suspected diagnosis in any of these cases at the time of contact with the horse. Of the seven recorded human infections, there have been four deaths. One of those deaths occurred 13 months after the initial infection. The remaining three persons did not survive their initial infections. The first known human case of the virus occurred in the Brisbane suburb of Hendra in 1994, where two people were infected. A horse trainer died from the virus, while a stable worker survived an influenza-like illness that was later identified as Hendra virus. The second death occurred in Mackay in 1995, when a male person developed severe encephalitis. It was later found that he had been exposed to Hendra virus during the autopsy of two horses 13 months earlier. At the time, the cause of death of the horses was unknown.57 The male person had been hospitalised with aseptic meningitis shortly after the autopsies but his illness was not identified as Hendra virus at that time. The next human case of Hendra virus occurred in North Queensland in 2004, where a private veterinarian performed an autopsy on a horse. She developed a mild influenza-like illness approximately seven days later, and recovered. This illness was subsequently diagnosed as Hendra virus, and the deceased horse was assumed to be a Hendra virus case. The most recent human cases of Hendra virus infection occurred during the 2008 Redlands incident (two people) and the 2009 Cawarral incident (one person). In the Redlands incident, a private veterinarian and a veterinary nurse employed at the same veterinary clinic developed acute influenza-like illnesses followed by encephalitis. They had both performed a nasal cavity lavage on a seemingly well horse in the days before it developed clinical signs of Hendra virus. The veterinarian, Dr Cunneen, had also performed an autopsy on another horse that was later found to have died of Hendra virus.58 Dr Cunneen passed away five weeks later. The veterinary nurse survived the infection but continues to experience significant ill-effects.
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