A double-blind comparison of epidural ketamine and diamorphine for postoperative analgesia

Twenty patients who had abdominal hysterectomy under general anaesthesia were randomly assigned to receive either epidural ketamine (30 mg), or epidural diamorphine (5 mg) peri-operatively and on first request for analgesia. Failure to obtain satisfactory analgesia with one of the agents was treated by epidural administration of the other. Pain was assessed by an independent observer, and by the patient using a visual analogue scale. The mean (SD) pain score on recovery from general anaesthesia, on a scale of 0-4, was 2.9 (1.2) for the ketamine group and 1.0 (1.0) for the diamorphine group (p less than 0.01). The mean (SD) time to first request for analgesia was 272 (206) and 72 (41) minutes in the diamorphine and ketamine groups respectively (p less than 0.01). All patients in the diamorphine group obtained adequate analgesia, but all patients in the ketamine group were changed to epidural diamorphine. Epidural ketamine does not appear to be a sufficiently effective alternative to epidural diamorphine for routine use in postoperative pain.     

海洛因依赖患者出现精神症状的临床分析

目的：探讨海洛因依赖患者出现精神症状的临床特点。方法：选用简明精神病量表筛选出海洛因依赖患者120例，按焦虑抑郁、缺乏活力，激活性、思维障碍和敌对猜疑等5个因子及其等级(A和B级)进行临床分析。结果：①120例患者焦虑抑郁因子达100％，其中疑病妄想和自责自罪妄想占25％；②思维障碍因子占52．5％，其中以幻觉和妄想为主占13．3％；③缺乏活力因子占33．3％，其中情感平淡和交流障碍7．5％；④敌对猜疑因子占17．5％，其中由心境抑郁和敌对情绪影响行为的患者4．2％；⑤激活性因子占2．5％。结论：根据海洛因依赖患者精神症状的特点有必要拟订合理的治疗方案以解除躯体依赖；采用心理等方式治疗顽固妄想，才能更加有效的实施戒断依赖，使其早日康复回归社会。     

初次海洛因依赖患者家庭环境因素分析

目的：评估初次海洛因依赖患者的家庭环境状况，探索阿片类物质依赖患者的心理社会康复新方法。方法：运用家庭环境量表(FES-CV)对40例海洛因依赖患者和38例正常人作对照研究，并调查依赖患者的一般情况。结果：初次海洛因依赖患者的家庭环境表现为低亲密度、低情感表达、低文化性、低控制性和高矛盾性的特点，以年轻、未婚、城市居住、家庭经济状况良好、父母多为个体职业、文化程度低为主。结论：初次海洛因依赖患者脱毒后实施针对性家庭干预治疗，对依赖患者的心理社会康复有极大帮助，并可推广到多次吸食海洛因依赖患者。     

Epidural infusion of diamorphine with bupivacaine in labour

We have compared the analgesic effects of three epidural infusions in a randomised, double-blind study of 61 mothers in labour. An initial dose of bupivacaine 0.5% 8 ml was followed by either bupivacaine 0.125%, bupivacaine 0.125% with diamorphine 0.0025% or bupivacaine 0.125% with fentanyl 0.0002%. All infusions were run at a rate of 7.5 ml/hour. Analgesia was significantly better in both the groups receiving opioids. Diamorphine was shown to be the more effective supplement to bupivacaine. The 5% incidence of pruritis in the opioid groups was less than that reported by earlier authors.     

Intradural morphine and diamorphine

This open study of 81 patients having major orthopaedic surgery reviews the duration of analgesia and side-effects of 0.625, 1.25 or 2.5 mg of morphine or 1.25 or 2.5 mg of diamorphine given intradurally in combination with 7.5 mg of cinchocaine at induction of anaesthesia. A significant dose-response relationship for duration of analgesia measured by time to first requirement of postoperative analgesic was found with morphine; 1.25 and 2.5 mg of morphine produced analgesia of longer duration than 0.625 mg. No such dose-response was found for side-effects. There was no significant difference in duration of analgesia between diamorphine 1.25 and 2.5 mg, and the duration was similar to that seen with the higher doses of morphine. An intradural dose of between 0.625 mg and 1.25 mg of either morphine or diamorphine used with cinchocaine and without additional parenteral opiate, may be appropriate.     

An in Vitro Study of Diamorphine Permeation Through Premature Human Neonatal Skin

The permeation kinetics of diamorphine through human premature neonatal cadaver skin over a range of gestational ages between 24 and 36 weeks was investigated using small diffusion cells. A strong inverse correlation was noted between the apparent permeability coefficient and the gestational age of the skin (P < 0.01; n = 26). The calculated apparent permeability coefficients decreased with gestational age from 6.0 × 10 ^–2 cm · hr^–1 at 24 weeks' gestation to 5.2 × 10^–6 cm · hr^–1 at 36 weeks' gestation. The amount of diamorphine remaining bound within the skin at the end of the in vitro experiments did not change significantly with gestational age of the skin. Diamorphine was subject to degradation over the course of the in vitro experiments to produce significant amounts of 6-mono-acetylmorphine and evidence is presented to suggest that this was due to residual skin esterase activity. It is calculated that the steady-state flux rate of diamorphine through neonatal skin observed in these experiments would be sufficient to obtain a therapeutic plasma concentration of morphine assuming a 2-cm² area for application and a delivery rate of 15 µg hr ^–1 kg^–1. However, the prolonged half-life of morphine in the premature neonate would result in a delay of some hours before the attainment of this level.     

Morphine, morphine-6-glucuronide and morphine-3-glucuronide pharmacokinetics in newborn infants receiving diamorphine infusions

1The pharmacokinetics of morphine, morphine-6-glucuronide (M6G) and morphine-3-glucuronide (M3G) were studied in 19 ventilated newborn infants(24–41 weeks gestation) who were given a loading dose of 50 μg kg⁻¹ or 200 μg kg⁻¹ of diamorphine followed by an intravenous infusion of 15 μg kg⁻¹ h⁻¹ of diamorphine. Plasma concentrations of morphine, M3G and M6G were measured during the accrual to steady-state and at steady state of the diamorphine infusion. 2Following both the 50 μg kg⁻¹ or 200 μg kg⁻¹ loading doses the mean steady-state plasma concentration (±s.d.) of morphine, M3G and M6G were 86±52 ng ml⁻¹, 703±400 ng ml⁻¹ and 48±28 ng ml⁻¹ respectively and morphine clearance was found to be 4.6±3.2 ml min⁻¹ kg⁻¹. 3M3G formation clearance was estimated to be 2.5±1.8 ml min⁻¹ kg⁻¹, and the formation clearance of M6G was estimated to be 0.46±0.32 ml min⁻¹ kg⁻¹. 4M3G metabolite clearance was 0.46±0.60 ml min⁻¹ kg⁻¹, the elimination half-life was 11.1±11.3 h and the volume of distribution was 0.55±1.13 l kg⁻¹. M6G metabolite clearance was 0.71±0.36 ml min⁻¹ kg⁻¹, the elimination half-life was 18.2±13.6 h and the volume of distribution was 1.03±0.88 l kg⁻¹. 5No significant effect of the loading dose (50 μg kg⁻¹ or 200 μg kg⁻¹) on the plasma morphine or metabolite concentrations or their derived pharmacokinetic parameters was found. 6We were unable to identify correlations between gestational age of the infants and any of the determined pharmacokinetic parameters. 7M3G:morphine and M6G:morphine steady-state plasma concentration ratios were 11.0±10.8 and 0.8±0.8, respectively. 8The metabolism of morphine in neonates, in terms of the respective contributions of each glucuronide pathway, was similar to that in adults.     

Postoperative analgesia in major orthopaedic surgery. Epidural and intrathecal opiates

Sixty-two patients were given morphine 2 mg and 69 patients were given diamorphine 0.5 mg by either the epidural or intrathecal route. All had undergone either total hip replacement or spinal disc surgery. Forty-nine out of 131 patients required no further analgesia. Diamorphine was superior to morphine and the intrathecal route more effective than the epidural. Headache, pruritus, urinary retention and nausea and vomiting were recorded, the incidence of the latter being unacceptably high, particularly when the drugs were administered by the intrathecal route: one patient required resuscitation. It is suggested that previously reported respiratory depression using these techniques is associated with the administration of other analgesics contemporaneously; that dosage should be limited to one-fifth of the estimation intramuscular dose; and that patients should be observed in a recovery ward for 24 hours.     

Intrathecal diamorphine for analgesia after Caesarean sectionA dose finding study and assessment of side-effects

Eighty women undergoing elective Caesarean section under spinal anaesthesia using hyperbaric bupivacaine 0.5% were randomly allocated to receive, in addition, intrathecal diamorphine 0.125, 0.25 or 0.375 mg or saline. Postoperative morphine requirements, measured using a patient-controlled analgesia system, were reduced in a dose-dependent manner by diamorphine. Pain scores were significantly lower at 2 and 6 h following the two larger doses of diamorphine. Less supplemental analgesia was required intra-operatively if intrathecal diamorphine had been given. The incidences of vomiting and pruritus were also dose-related. No respiratory rates of less than 14 breath.min⁻¹ were recorded and the incidence of oxygen saturation readings less than 95% and 90% did not differ between groups. There were no adverse neonatal effects. Intrathecal diamorphine in the present study was found to be safe in doses of up to 0.375 mg following Caesarean section. However, minor side-effects were frequently observed.