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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 Four patients receiving Anaesthesia was maintained with 1 % isoflurane and pethidine were withdrawn because of postoperative 66 % nitrous oxide in oxygen, and fentanyl confusion and one receiving morphine because of 2–4 ␮g kg1.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 References
consistent with these data. 1. Aitkenhead AR, Robinson S. Influence of morphine and While we did not intend to study p ostop erative pethidine on the incidence of anastomotic dehiscence after confusion, it was interesting to note that four colonic surgery. British Journal of Anaesthesia 1989; 63:
230P.
relatively young, healthy patients in our study 2. Owen H, Mather LE, Rowley K. The develop ment and became confused and disorientated in the early clinical use of patient-controlled analgesia. Anaesthesia and postoperative period after small doses of pethidine. Intensive Care 1988; 16: 437–446.
This was not relieved by administration of oxygen, 3. Robinson SL, Rowbotham DJ, Smith G. Morp hine com- although there were no signs of resp iratory de- pared with diamorphine. A comparison of dose requirements
and side-effects after hip surgery. Anaesthesia 1991; 46:
p ression, but imp roved rap idly after cessation of pethidine administration. Postoperative confusion 4. Sinatra RS, Lodge K, Sibert K, Chung KS, Chung JH, with pethidine has been described previously. For Parker A, Harrison DM. A comp arison of morp hine, example, in a recent well designed study of 245 meperidine and oxymorphone as utilized in patient controlled analgesia following Cesarean section. Anesthesiology 1989; postoperative patients, pethidine was associated 70: 585–590.
significantly with postoperative delirium (odds ratio 5. Bahar M, Rosen M, Vickers MD. Self administered nal- 2.7) [9]. However, these patients tended to be older buphine, morphine and pethidine. Comparison, by intra- than those in our study (9 50 yr) and psychological venous route, following cholecystectomy. Anaesthesia 1985; measurements were obtained from day 2 to day 5 40: 529–532.
6. Vetter TR. Pediatric patient-controlled analgesia with mor- after operation. phine versus meperidine. Journal of Pain Symptom Man- Confusion may be caused by norpethidine, a agement 1992; 7: 204–208.
metabolite of pethidine [10]. However, in our study, 7. Tyler DC, Krane EJ. Postoperative pain management in significant plasma concentrations of this metabolite children. Anesthesiology Clinics of North America 1989; 7:
155–170.
were unlikely as relatively small doses of pethidine 8. Tamsen A, Hartvig P, Fagerlund C, Dahlström B, Bondesson were administered before symptoms commenced U. Patient controlled analgesia therapy: Clinical experience. (maximum 50 mg). Many drugs with a central Acta Anaesthesiologica Scandinavica 1982; (Suppl. 74):
anticholinergic action are associated with deranged function of the central nervous system [11] and it 9. Marcantonio ER, Juarez G, Goldmann L, Mangione CM, Ludwig LE, Lind L, Katz N, Cook EF, Orav EJ, Lee TH. may be that the anticholinergic action of pethidine The relationship of postoperative delirium with psycho- was significant in our patients. active medications. Journal of the American Medical As- In conclusion, we have shown little difference in sociation 1994; 272: 1518–1522.
the pharmacodynamics of pethidine and morphine 10. Armstrong PJ, Berston A. Normeperidine toxicity. Anesthesia and Analgesia 1983; 65: 58–63.
with respect to analgesia, nausea and vomiting, 11. Tune L, Holland A, Folstein M, Damlouji N, Garner T, sedation and patient satisfaction using PCA with the Coyle JT. Association of postoperative delirium with raised regimen described in relatively healthy patients anticholinergic drug levels. Lancet 1981; 328: 651–652.

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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.