Side effects during continuous epidural infusion of morphine and fentanyl

Respiratory effects, nausea, somnolence, and pruritus were compared during a 48-hr period of continuous epidural morphine (n = 34) and fentanyl (n = 32) infusion in 66 patients following elective total replacement of the hip or knee joint. Respiratory effects were assessed by PaCO2. Side effects were assessed by visual analogue scale and considered to be present when the score was above 30. Assessment was made at preoperative visits then 3, 6, 12, 24, 36, and 48 hr after the epidural injection. The bolus dose and subsequent infusion rate were 3,900 +/- 1,300 micrograms and 427 +/- 213 micrograms.hr-1 for morphine, and 85 +/- 46 micrograms and 56 +/- 27 micrograms.hr-1 for fentanyl. Pain relief was similar in both groups. In the morphine group, PaCO2 elevation and nausea occurred over a period of more than 12 hr (P less than 0.05). In the fentanyl group, there was no PaCO2 change, and nausea was confined to the first few hours. Nausea was more severe (P less than 0.01 at six hours and more frequent (24 hr cumulative incidence, 53 vs 28%, P less than 0.05) in the morphine group. Somnolence was prominent within several hours in two-thirds of patients in both groups. Somnolence continued to decline thereafter in the morphine group, but it was demonstrable in approximately half of the patients throughout the second day in the fentanyl group. The incidence was higher in the fentanyl group at the 48th hr (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)     

Bupivacaine 0.1% does not improve postoperative epidural fentanyl analgesia after abdominal or thoracic surgery

Epidural infusions of fentanyl, in a 10 micrograms.ml-1 concentration, combined with bupivacaine 0.1% were compared with epidural infusions of fentanyl alone for postoperative analgesia following abdominal or thoracic surgery. There were no detectable differences between the two groups in analgesia (mean visual analogue scale pain scores ranging between 15-35 mm), average infusion rates of 7-9 ml.hr-1, and serum fentanyl concentrations which reached 1-2 ng.ml-1. There was no difference in postoperative pulmonary function (pH, PaCO2, SaO2), or bowel function (time to flatus or po fluids). The incidence of side-effects including somnolence, nausea and vomiting, pruritus and postural hypotension was also similar. Of the patients receiving fentanyl and bupivacaine 0.1%, three developed a transient unilateral sensory loss to pinprick and ice, and two of these patients had unilateral leg weakness equal to a Bromage 1 score. The addition of bupivacaine 0.1% does not improve epidural infusions of fentanyl using a 10 micrograms.ml-1 concentration following abdominal or thoracic surgery.     

Disposition and placental transfer of etidocaine in pregnancy

Summary Following epidural administration of etidocaine hydrochloride to non-pregnant and pregnant patients, a similar rate of absorption was observed and there was no significant difference in total systemic blood clearance (Cl_sb) of etidocaine in the two groups. There were no major differences in the urinary excretion of etidocaine and metabolites in 48 h urine in both groups. The ability of pregnant women to form the N-glucuronide of the metabolite ABX (2-amino-2-butyroxylidide) was similar to that of non-pregnant individuals. In vitro experiments showed that the blood/plasma concentration ratio () of etidocaine was significantly higher in pregnant females than in males, presumably due to the lower haematocrit in females. The fraction unbound in plasma (f_p) of etidocaine was low in control subjects (mean 0.057) and was not significantly different in pregnant women of 35 to 37 weeks gestation. A marked increase in f_p was observed in pregnant women during delivery (mean 0.264). This finding has potentially serious clinical implications because it is the unbound drug in blood which is pharmacologically important. Placental transfer of etidocaine was rapid and the cord/maternal venous blood concentration ratio at delivery (CM_b) was, with one exception, always less than unity (mean 0.342). Following epidural administration of etidocaine to pregnant women in labour, measurable concentrations of mono-dealkylated metabolites of etidocaine, PABX (2-N-propylamino-2-butyroxylidide) and EABX (2-N-ethylamino-2-butyroxylidide) were detectable in maternal blood within 5 min and cord blood within 30 min. The CM_b for PABX and EABX was 0.401 and 0.658 respectively.List of Abbreviations Used ABX 2-Amino-2-butyroxylidide - EABX 2-N-Ethylamino-2-butyroxylidide - PABX 2-N-Propylamino-2-butyroxylidide - Cl_sb Total systemic blood clearance - Cl_sp Total systemic plasma clearance - Blood/plasma concentration ratio - f_p Fraction of unbound drug in plasma - f_pw Fraction of free drug in plasma water in blood - C_mb Cord/maternal venous blood concentration ratio at delivery - C_mp Cord/maternal venous plasma concentration ratio at delivery - t_1/2 Terminal phase half-life - t_p Time of attainment of peak plasma concentration - E Mean hepatic extraction ratio - Q Liver blood flow     

Blockade of the NMDA receptor increases developmental apoptotic elimination of granule neurons and activates caspases in the rat cerebellum

Elimination of neurons produced in excess naturally occurs during brain development through programmed cell death. Among the many survival factors affecting this process, a role for neurotransmitters acting on specific receptors has been suggested. We have performed an in vivo pharmacological blockade of the N-methyl-D-aspartate (NMDA) subtype of glutamate receptors, using the competitive NMDA receptor antagonist CGP 39551 at developmental stages corresponding to those at which a survival dependence on the stimulation of this receptor has been demonstrated for cerebellar granule neurons explanted in culture (typically from postnatal day 7 to postnatal day 11 or 13). We were able to demonstrate an increased level of DNA fragmentation in the cerebellum of the treated rats. At the P11 stage, in particular, the fragmented DNA extracted from the cerebellum of CGP 39551-treated pups showed a clear laddering of nucleosomal fragments after agarose-gel electrophoresis. Accordingly, in situ TUNEL technique showed a remarkable increase of cells positive for nucleosomal DNA fragmentation, particularly in the inner granular layer of the cerebellum of treated rats at P11 stage. Therefore, the natural rate of apoptotic elimination of cerebellar granule neurons is considerably enhanced under conditions of pharmacological blockade of the NMDA receptor, thus demonstrating, for the first time in vivo, a clear survival dependence of these neurons upon the stimulation of the NMDA receptor. Concomitantly with the increased rate of apoptotic elimination of granule neurons, the activity of two death proteases of the caspase family, in particular of caspase 3 and caspase 1 at a lower extent, was remarkably increased in the cerebellum of the treated rats. On the contrary, a marker related to the normal differentiation process of granule neurons, the enzyme ornithine decarboxylase, was strongly decreased in its activity in the cerebellum of treated rat pups.     

胃癌术后镇痛对肠功能恢复的观察与护理

目的　探讨胃癌手术后硬膜外持续镇痛对患者肠功能的影响。方法　对 6 0例胃癌术后病人进行随机分组 ,PCEA(pa tientcontrolledEpiduralanalgesia)组 :采用硬膜外持续镇痛 (30例 ) ;对照组 :采用间断注射镇痛剂 (30例 ) ,观察肠蠕动、肛门排气时间及不良反应。结果　肠蠕动恢复时间PCEA组 (5 2 1± 4 3)h ,对照组 (5 1 5± 4 4 )h。肛门排气时间PCEA组 (6 5 4±7 5 )h ,对照组 (5 6 1± 9 3)h。PCEA组不良反应明显少于对照组。结论　术后镇痛不影响胃癌术后肠蠕动恢复 ,但应加强术后早期活动的指导     

三种补肾方对老年大鼠下丘神经递质的影响

目的：观察三种补肾方对24个月龄老年大鼠下丘氨基酸类神经递质的影响.方法：采用反相高效液相色谱(HPLC)荧光法、受体放射分析法、RT PCR法测定大鼠下丘的氨基酸递质含量、受体特异性结合量及受体亚单位的mRNA表达.结果：24个月龄大鼠下丘存在兴奋/抑制失衡,表现为下丘γ 氨基丁酸(GABA)能抑制作用减弱,可能与耳鸣发病率随年龄增长而增加有关.补肾息鸣经验方使24个月龄大鼠下丘氨基酸类神经递质介导的抑制作用上调和兴奋作用下调；左归丸及右归丸使24个月龄大鼠下丘兴奋性与抑制性氨基酸类神经递质(Asp、Tau、GABA)含量均有明显上升.结论：对肾虚耳鸣的治疗应在补肾的基础上结合开窍活血等药物.     

The effect of combined spinal‐epidural (CSE) anaesthesia and size of spinal needle on postoperative hearing loss after elective caesarean section

The effect of combined spinal epidural (CSE) anaesthesia and size of spinal needle on postoperative hearing loss after elective caesarean section The exact aetiology of vestibulocochlear dysfunction after spinal anaesthesia is unknown. Low‐frequency hearing loss occurs after spinal anaesthesia. The aim of this study was to investigate the effects of combined spinal–epidural (CSE) anaesthesia and size of spinal needle on vestibulocochlear dysfunction, using pure tone audiometry performed pre‐ and on the first and the second day postoperatively. Forty‐five patients who were to undergo elective caesarean section were evaluated. In group I, CSE anaesthesia (18 G Tuohy, 25 G Whitacre pencil‐point‐design spinal needles) was performed in 15 patients. In group II, spinal anaesthesia was performed in 15 patients with 25 G Whitacre pencil‐point‐design spinal needles and, in group III, spinal anaesthesia was performed in 15 patients with 22 G Whitacre pencil‐point‐design spinal needles. In the pre‐ and on the first and the second day postoperatively, the pure tone audiogram was performed in the audiology laboratory of our hospital, using a calibrated Kamplex Diagnostic Audiometer AC 40 in a noise‐free room. When the CSE anaesthesia group and 22 G spinal group were compared for change in hearing between the pre‐ and postoperative periods, a statistically significant difference was observed at R‐right ear 125 Hz (P < 0.025) and at L‐left ear 125 Hz (P < 0.023), and at L‐left ear 1000 Hz (P < 0.036) and at R‐right ear 1500 Hz (P < 0.006), and at L‐left ear 1500 Hz (P < 0.022). At other frequencies, the difference was insignificant. When the CSE anaesthesia group and 25 G spinal group were compared for change in hearing between the pre‐ and postoperative periods, no statistically significant difference was detected at any frequency tested. When 22 G spinal group and 25 G spinal group were compared for change in hearing between the pre‐ and postoperative periods, there was some hearing loss at low frequency, although this difference did not reach statistical significance. The positive correlation of low‐frequency hearing loss and increased pressure in the epidural space (which decrease the risk of cerebrospinal fluid leakage through the dura) suggests that cerebrospinal fluid leakage via the spinal puncture hole is not the only factor involved. Perioperative fluid replacement alone may not prevent hearing loss but CSF loss through the dural puncture site should also be prevented.     

剖宫产术后硬膜外镇痛产妇血及初乳中吗啡含量的监测

目的　监测剖宫产术后硬膜外镇痛产妇血及初乳中的吗啡含量 ,探讨微量吗啡对新生儿的影响。　方法　选择剖宫产术的产妇 10 0例 ,分为实验组和对照组各 5 0例 ,两组均为连续硬膜外麻醉 ,穿刺点选择 L1 ～ L3,麻醉药为 2 %利多卡因 15～ 2 0 m l,在手术结束时 ,实验组将吗啡缓慢注入硬膜外管 2 mg然后拔管。于术后 1h取产妇的静脉血 3m l,采集产妇术后 3、6 h尿样及术毕 6～ 12 h采集新生儿尿样 3m l;在产后 4 8h内收集产妇的初乳 3～ 5 m l。　结果　观察组 96 % (48/ 5 0 )的镇痛效果较对照 16 % (8/ 5 0 )明显 ,差异有显著性 (P<0 .0 5 ) ,观察组血吗啡浓度 <5～ 118μg/ m l,初乳吗啡浓度 <5～ 30 .4μg/ L ,产妇尿 92 %呈阳性 ,新生儿尿 13.3%呈阳性。两组产妇和新生儿的生命体征比较差异无显著性。　结论　剖宫产术后硬膜外腔应用吗啡镇痛 ,产妇哺乳对新生儿没有影响 ,是安全可行的。     

曲马多与哌替啶用于硬膜外麻醉病人术中及术后寒颤治疗的比较

目的 评价曲马多与哌替啶在治疗硬膜外麻醉中出现的寒颤效果。方法 将60例在硬膜外阻滞下行下腹手术且发生了寒颤的病人(ASAI～Ⅱ级)随机分为三组：A组，静脉注入生理盐水5ml；B组：经静脉注入哌替啶0．5mg／kg；C组，经静脉注入曲马多1mg／kg，分别记录用药前及用药后l、3、5min寒颤评分及各组出现的不良反应。结果 A组治疗前后寒颤评分无显著差别，B组和C组均于治疗5min后寒颤停止；A组和C组均未出现恶心，呕吐等副作用，而B组中恶心，呕吐，呼吸抑制，嗜睡等副作用均有数例。结论 曲马多lmg／kg经静脉注射与哌替啶0．5mg／kg经静脉注射相比更适于用来处理硬膜外阻滞下出现的寒颤。     

Effects of intermittent exposure to aflatoxin B1 on DNA and RNA adduct formation in rat liver: dose-response and temporal patterns.

We studied the effects of intermittent exposure to aflatoxin B1 (AFB1) on hepatic DNA and RNA adduct formation. Fisher-344 male rats were fed 0.01, 0.04, 0.4, or 1.6 ppm of AFB1 intermittently for 8, 12, 16, and 20 weeks, alternating with 4 weeks of dosing and 4 weeks of rest. Other groups of rats were fed 1.6 ppm of AFB1 continuously for 4, 8, 12, and 16 weeks. Control rats received AFB1-free NIH-31 meal diet. AFB1-DNA and -RNA adducts were measured by HPLC with fluorescence detection. The data are presented as total DNA or RNA adducts. The DNA and RNA adduct levels increased or decreased depending on the cycles of dosing and rest. Rats removed from treatment 1 month after 1 or 2 dosing cycles (8 and 16 weeks of intermittent exposure) showed approximately a twofold decrease in DNA adduct levels and a two- to elevenfold decrease in RNA adduct levels compared with rats euthanized immediately after the last dosing cycle (12 and 20 weeks of intermittent exposure). Our data indicate that DNA and RNA adducts increased linearly, from 0.01 ppm to 1.6 ppm of AFB1 after 12 and 20 weeks of intermittent treatment. A linear dose response was also apparent for DNA but not for RNA adducts after 8 and 16 weeks of treatment. As biomarkers of exposure, AFB1-RNA adducts were three to nine times more sensitive than AFB1-DNA adducts but showed greater variability. These results suggest that binding of AFB1 to hepatic DNA is a linear function of the dose, regardless of the way this is administered. The dose-response relationship for RNA adducts depends on the length of the no-dosing cycles and on the turnover rate of RNA.