老年骨质疏松女性髋部骨密度、骨转换指标与血脂、血清尿酸相关性研究

目的研究老年骨质疏松女性髋部骨密度(bone mineral density,BMD)与血清总胆固醇(total cholesterol,TC)、血清甘油三酯(triglyceride,TG)、血清高密度脂蛋白胆固醇(high density lipoprotein cholesterol,HDL-C)、血清低密度脂蛋白胆固醇(low density lipoprotein cholesterol,LDL-C)和血清尿酸(uric acid,UA)的相关性。方法收集2014年1月1日至2015年12月31日就诊的老年女性骨质疏松患者108例。记录患者的年龄、身高、体重、股骨颈BMD、股骨大转子BMD、股骨粗隆间BMD、髋部整体BMD、Ward’s区BMD、TC、TG、HDL-C、LDL-C、UA、血清I型胶原交联C末端肽(C-terminal crosslinking telopeptide of type I collagen,CTX)、I型原胶原N-端前肽(procollagen type I N propeptide,PINP)、25羟基维生素D(25-OH-Vit D,Vit D-T)及基础疾病情况等资料。髋部BMD、体质量指数(body mass index,BMI)、β-CTX、PINP、Vit D-T、TC、TG、LDL-C、HDL-C、UA相关性检验采用Pearson相关性检验。结果股骨颈BMD与年龄、β-CTX呈负相关,与BMI、Vit D-T、TG、UA呈正相关(r0,P0.05)。股骨大转子BMD与年龄、β-CTX呈负相关(r0,P0.05),与BMI、Vit D-T、TC、TG、LDL-C、UA呈正相关(r0,P0.05)。股骨粗隆间BMD与年龄、β-CTX、PINP呈负相关(r0,P0.05),与BMI、Vit D-T、TC、TG、UA呈正相关(r0,P0.05)。髋部整体BMD与与年龄、β-CTX呈负相关(r0,P0.05),与BMI、Vit D-T、TC、TG、LDL-C、UA呈正相关(r0,P0.05)。股骨Ward’s区BMD与年龄、β-CTX呈负相关(r0,P0.05),与BMI、Vit D-T、TC、LDL-C、UA呈正相关(r0,P0.05)。TC与β-CTX、PINP呈负相关(r0,P0.05),与Vit D-T、UA呈正相关(r0,P0.05)。TG与UA呈正相关(r0,P0.05)。HDL-C与Vit D-T、UA呈正相关(r0,P0.05)。LDL-C与β-CTX、PINP呈负相关(r0,P0.05),与Vit D-T、UA呈正相关(r0,P0.05)。结论骨质疏松患者髋部不同部位骨密度与血脂的相关性不同,适当水平的血清总胆固醇及尿酸有利于维持骨量,预防低骨量及骨质疏松的发生。     

绝经后骨质疏松症患者 CircRNA0048211的表达及其与骨代谢标志物的相关性

目的探讨血清CircRNA₀048211的表达水平对绝经后骨质疏松症(postmenopausal osteoporosis, PMOP)的诊断价值及其与骨特异性碱性磷酸酶(bone specific alkaline phosphatase, BALP)、骨桥蛋白(osteopontin, OPN)、Ⅰ型原胶原N-端前肽(procollagen type I N-terminal propeptide, PINP)及β-胶原降解产物(β-crosslaps, β-CTX)的相关性。方法收集2019年1月至2021年12月进行体检的绝经后女性资料。所有研究对象采用双能X线吸收法检测骨密度(bone mineral density, BMD), 根据BMD水平分为PMOP组、骨量减少组和骨量正常组。比较各组血清CircRNA₀048211、BALP、OPN、PINP及β-CTX的水平。应用二元logistic回归分析PMOP发生的危险因素, 绘制受试者特征曲线(receiver operating characteristic curve, R...     

血清骨膜素水平与老年髋部骨折患者骨密度相关性研究

目的探索老年髋部骨折患者骨膜素(sP ostn)水平与骨密度的相关性。方法纳入108例患有骨质疏松性髋部骨折的老年女性和106名年龄不匹配的无骨折女性作为对照。在2 d内骨折后测量其临床特征、骨密度(bone mineral density,BMD)和骨转换标志物(包括sP ostn水平)。对于108例患者,检测1年内的随访sP ostn水平。结果骨折后sP ostn的初始水平显著高于对照组。在整个队列中,sP ostn与股骨颈BMD,骨Ⅰ型胶原N-端前肽(PINP)和Ⅰ型胶原交联C-末端肽(β-CTX)相关(P均0. 05)。多变量分析后,sP ostn仍然是股骨颈BMD的独立危险因素。骨折后7 d内采样的sP ostn从第2天开始急剧增加,然后减少并在360 d保持在略高的水平。sP ostn的变化与骨折后第7天β-CTX(P0. 05)和PINP(P0. 05)的变化呈正相关。结论高sP ostn水平是老年女性急性髋部骨折患者股骨颈低BMD的独立预测因素。     

金天格胶囊的短期疗效及其对骨转化标志物的影响：基于44名志愿者的研究报告

目的 评判金天格胶囊(JTG)的短期疗效及观察其对骨转化标志物的影响。方法 志愿加人金天格胶囊疗效评估的44名本院职工,按双能X线(DEXA)的检测结果分为骨密度（Bone Mineral Density,BMD)异常组与正常对照组,均连续服用金天格胶囊1个月。用药前后检测骨转化生化指标:总I型胶原氨基端延长肽(PINP)、β胶联降解产物（β-CTX)。疗程结束后,用数字模拟评分法（VAS)评定短期疗效;组内及组间比较采用t检验,比较PINP、β-CTX的变化情况。结果 金天格胶囊治疗后,BMD异常组的酸痛不适症状显著缓解;BMD正常组的PINP、β-CTX与治疗前无明显差异;BMD异常组PINP增加,β-CTX稍减低。结论 金天格胶囊具有双向调节作用,可以在短时间内促进成骨细胞活性,抑制破骨细胞,有助于维持骨形成与骨吸收的动态平衡。     

维生素K2结合钙剂在甲状腺功能亢进症继发骨质疏松症中的临床应用

目的探讨维生素K_2对甲状腺功能亢进性骨质疏松症患者骨密度、骨代谢指标及细胞因子水平变化的影响。方法选取2014年7月至2015年7月来我院治疗的57例甲状腺功能亢进性骨质疏松症患者作为研究对象,随机分为治疗组(n=29)和对照组(n=28)。对照组给予钙剂治疗,治疗组给予维生素K2联合钙剂治疗,为期12个月。检测所有对象治疗前后髋部及腰椎的骨密度(bone mineral density,BMD)、骨代谢指标[骨钙素(osteocalcin,BGP)和总I型前胶原氨基端延长肽(total Nterminal propeptide of type I procollagen,PINP)]以及细胞因子[胰岛素样生长因子-1(insulin-like growth factor,IGF-1)、白细胞介素(interleukin,IL)-2、6(IL-2、IL-6)],并进行比较。结果治疗前,两组患者的BMD、BGP、PINP及IL-2、IL-6和IGF-1比较差异无统计学意义(P0.05);治疗12个月后,治疗组髋部及腰椎的BMD水平显著高于对照组(P0.05);治疗组BGP、PINP水平显著低于对照组(P0.05);治疗组IL-2水平显著高于对照组(P0.05);治疗组IL-6和IGF-1水平显著低于对照组(P0.05)。结论维生素K2可以明显提高甲状腺功能亢进性骨质疏松患者的骨密度、降低骨转换,提高IL-2表达且降低IL-6和IGF-1水平,对骨质疏松有保护作用。     

骨肽对老年股骨粗隆间骨折内固定骨代谢的影响

[目的]探讨骨肽注射对老年股骨粗隆间骨折内固定患者骨代谢的影响。[方法]老年股骨粗隆间骨折患者120例,随机分为两组。PFNA内固定术后,骨肽组60例给予骨肽注射液静脉滴注1个月,非骨肽组60例未给予骨肽静脉滴注。比较两组血清骨代谢指标、骨密度(BMD)、Harris评分和骨折愈合时间。[结果]治疗后1、6个月,两组患者血清PINP与CTX水平均较治疗前显著下降(P0.05),骨肽组患者PINP与CTX水平显著低于非骨肽组(P0.05);治疗后1、6个月,骨肽组BGP、25 (OH) D3与BMD均较治疗前显著升高(P0.05),骨肽组血清25(OH) D3高于非骨肽组(P0.05)。患者血清PINP、CTX与BMD呈显著负相关(P0.05);骨肽组Harris评分和骨折愈合时间均优于非骨肽组(P0.05)。[结论]应用骨肽可改善老年股骨粗隆间骨折内固定患者骨代谢,增加骨密度,从而促进骨折愈合与髋骨功能恢复。     

白藜芦醇对绝经后骨质疏松女性骨代谢和氧化代谢产物水平的影响

目的 探讨白藜芦醇对绝经后骨质疏松症妇女骨代谢和氧化代谢产物水平的影响。方法 选取 2015年11月至 2017年11月在成都市第二人民医院就诊的84例绝经后骨质疏松症患者作为研究对象,随机分为治疗组和对照组。治疗组的患者每天服用白藜芦醇,对照组的患者给予安慰剂片。3个月后,测量各组患者的血清骨代谢标志物[I型前胶原氨基端前肽(PINP)、骨钙素(BGP)、骨碱性磷酸酶(BALP)、I 型胶原 C 末端肽特殊序列(β-CTX)]和氧化代谢产物[蛋白羰基(PCO)、高级氧化蛋白产物(AOPP)、总抗氧化能力(TAC)、Akatsu(MDA)]水平的改变。结果 服用白藜芦醇治疗后,治疗组血清PINP 、BGP 、BALP 、β-CTX 、PCO、AOPP和MDA水平较治疗前显著降低(P＜0.05),治疗后两组之间的差异具有统计学意义(P＜0.05);治疗组血清TAC水平较治疗前显著升高(P＜0.05),治疗后两组之间的差异具有统计学意义(P＜0.05)。然而,对照组治疗前后的PINP 、BGP 、BALP 、β-CTX 、PCO、TAC、AOPP和MDA指标,其差异并没有统计学意义(P＞0.05)。结论 白藜芦醇可以降低绝经后骨质疏松症女性体内氧化应激和高骨转化速度。     

绝经后2型糖尿病患者血清25(OH)D、Leptin与骨代谢的相关性

目的探讨绝经后2型糖尿病(type 2 diabetes mellitus,T2DM)女性患者血清25-羟维生素D(25-hydroxyvitamin D,25(OH)D)、瘦素(leptin,LEP)水平与骨代谢之间的关系。方法选取遵义医学院附属医院内分泌科住院的绝经后T2DM女性患者130例,根据骨密度分为骨量正常组(A组,n=40)、骨量减少组(B组,n=45)和骨质疏松组(C组,n=45),同期选取50名健康绝经后女性作为空白对照组(NC组,n=50)。收集所有受试者临床资料及生化指标,测定血清25(OH)D、LEP、β-胶原降解产物(β-Crosslaps,β-CTX)、I型胶原N-端前肽(N-aminoterminal propeptide of type I collagen,PINP)及骨钙素(bone gla protein,BGP)水平。Spearmen相关分析绝经后T2DM合并骨质疏松症(osteoporosis,OP)患者血清骨代谢指标的相关因素分析;Logistic回归分析绝经后T2DM患者合并OP的影响因素。结果①与NC组比较,A、B、C三组中25(OH)D、PINP、BGP水平均明显降低,而LEP、β-CTX水平明显升高(P0.05);②与A组比较,B组、C组中25(OH)D、PINP水平均明显降低,而LEP、β-CTX、BGP水平明显升高(P0.05);③与B组比较,C组中25(OH)D、PINP水平均明显降低,而LEP、β-CTX、BGP水平明显升高(P0.05);Spearmen相关分析显示,血清25(OH)D与PINP呈正相关,与β-CTX呈负相关,与BGP无明显相关性;血清LEP与PINP呈负相关,与β-CTX、BGP无关;Logistic回归分析显示BMI、HbA1c、25(OH)D、LEP、PINP与β-CTX均是绝经后T2DM患者合并骨质疏松的独立危险因素。结论血清25(OH)D水平的降低及LEP水平的升高,可能共同参与了绝经后T2DM女性患者OP的发生发展。     

地仲强骨胶囊治疗骨质疏松症的安全性和疗效研究

目的探索地仲强骨胶囊治疗骨质疏松症的安全性和疗效。方法选取132例绝经后骨质疏松症患者随机分为治疗组(n=66)和对照组(n=66)。对照组给予阿仑膦酸钠治疗,治疗组给予地仲强骨胶囊治疗,为期治疗12个月。检测治疗前后两组患者股骨颈及腰椎的骨密度及VAS评分改变,同时测定血清骨代谢指标:I型胶原羧基端肽β特殊序列(β-CTX)和I型胶原氨基端延长肽(PINP)的水平,记录两组治疗总有效率和药物不良反应。结果治疗组的治疗总有效率为84.85%,而对照组为77.27%,两组比较差异有统计学意义(P0.05)。治疗12个月,两组股骨颈及腰椎密度都有不同程度的升高,VAS评分都有不同程度降低,其中治疗组骨密度和VAS评分变化更明显,和对照组比较有明显的统计学意义(P0.05)。同时,治疗组血清β-CTX水平均降低,PINP水平均升高,而对照组β-CTX和PINP水平均降低,两组比较有明显的统计学意义(P0.05)。两组患者治疗均未发现明显药物不良反应。结论地仲强骨胶囊治疗骨质疏松症安全有效。     

益肾密骨方对肾虚型骨质疏松症患者骨形成的影响

目的研究益肾密骨方对骨质疏松症(肾虚型)患者骨形成的影响。方法将我院60例肾虚型骨质疏松症患者,分为试验组(30例,应用益肾密骨方加减法治疗)与对照组(30例,应用钙尔奇D片),观察时间为1年。观察两组及组间用药前后腰椎骨密度(bone mineral density,BMD)、骨形成指标骨钙素(BGP)、Ⅰ型前胶原氨基端前肽(PINP)变化。结果用药后试验组腰椎BMD、血清BGP与PINP水平明显升高,与用药前比较差异有统计学意义(P 0. 01);与对照组相比,试验组血清BGP与PINP水平明显高于对照组(P0. 01)。结论益肾密骨方具有明显的补肾强骨作用,其机制可能是促进骨形成。     

Reduction of Plasma Fibrinogen, Immunoglobulin G, and Immunoglobulin M Concentrations by Immunoadsorption Therapy with Tryptophan and Phenylalanine Adsorbents

Abstract Immunoadsorption (1A) therapy with tryptophan (TR-350) or phenylalanine (PH-350) adsorbents has been used to reduce the concentration of serum antibodies in human lymphocyte antigen (HLA)-immunized patients. Other forms of plasma purification have been reported to reduce the level of fibrinogen, which affects the blood properties. In this study we investigated the effects of IA therapy using both adsorbents on plasma fibrinogen and immunoglobulins G and M in 13 patients (8 patients were treated with TR-350, and 5 patients were treated with PH-350). During each session 1 plasma volume (2.8 ± 0.4 L of plasma) was processed through the immunocolumn and then returned to the patient together with the blood cells. Compared with the pretreatment values, the plasma fibrinogen, IgG, and IgM concentrations were significantly reduced after IA therapy (p < 0.01 for TR-350; p < 0.04 for PH-350). There was a positive correlation between the degree of reduction of plasma proteins and the number of IA treatments given. A nonpara-metric test (Wilcoxon's signed-rank test or the Mann-Whitney test) was used for statistical analysis. We conclude from our study that IA therapy effectively lowers the plasma levels of fibrinogen, IgG, and IgM and thus can be considered a valuable alternative to other blood purification methods.     

Is the recovery profile of mivacurium independent of the rate of decay of its plasma concentration in patients with normal plasma cholinesterase activity?

Background: The duration of action of muscle relaxants is poorly correlated to the rate of decay of their plasma concentration. The plasma concentration of mivacurium may rapidly decrease below its active concentration because of the extensive hydrolysis of mivacurium. By inflating a tourniquet on one upper limb for 3 min after the administration of atracurium, mivacurium or vecuronium, we studied the influence of the initial decline of their plasma concentration on their effect. Methods: In 50 patients anaesthetised with thiopental, isoflurane and fentanyl, the effect of bolus doses of 0.15 or 0.25 mg . kg^?1 mivacurium (MIV 15, MIV 25), 0.3 or 0.5 mg . kg^?1 atracurium (ATR 30, ATR 50) and 0.06 or 0.1 mg . kg^?1 vecuronium (VEC 06, VEC 10) were measured on both arms (evoked response of the adductor pollicis to train-of-four stimulation every 12 s), a tourniquet being applied on one arm just before and during 3 min after the muscle relaxant bolus. Results: Tourniquet inflation of 3 min almost abolished the neuromuscular effect of mivacurium. In the vecuronium groups and in the ATR 50 group, tourniquet inflation did not modify the maximum degree of depression of the twitch response. Also, the duration of action of vecuronium was unaffected by the tourniquet. In the ATR 30 group, times to return of the twitch response to 25% (duration 25%) and 75% (duration 75%) of control response were significantly shorter in the cuffed arm, 23 min vs 27 min, and 41 min vs 45 min, respectively. In the ATR 50 group, only duration 25% was significantly shorter in the cuffed arm (41 min vs 45 min). Conclusion: The results suggest that the rate of decline of the plasma concentration of mivacurium is so rapid, that a very low and almost clinically ineffective concentration is present as soon as 3 min after its administration. The results also indicate that the recovery from a mivacurium-induced neuromuscular blockade is not influenced by the rate of decay of its plasma concentration in patients with genotypically normal plasma cholinesterase.     

Membranes in Artificial Organs

Abstract: Membrane processes play a pivotal and enabling role in modern replacement therapy for acute and chronic organ failure and in the management of immunologic diseases. In fact, virtually all contemporary extracorporeal blood purification methods employ membrane devices, and the next generation of artificial organs and tissue engineering therapies are almost certain to be similarly grounded in membrane technology. In this short essay, we comment on the similarities and differences among synthetic membranes and their natural counterparts and also provide a critical overview of the demographics and technology of hemodialysis, hemofiltration, apheresis, oxygenation, and emerging membrane technologies and applications.     

The multiply injured child

Blunt trauma is the principal cause of childhood death in many developed countries. This review outlines the differences between adults and children with respect to resuscitation and treatment of orthopaedic injuries in a child with polytrauma. Recent advances in techniques of fracture stabilization are reported.     

Dilemma of Membrane Biocompatibility and Reuse

Abstract: Numerous articles have been published on the multiple use of dialyzers and on the effect of different reprocessing chemicals and techniques on the dialyzer biocompatibility and performance. The results often appear contradictory, especially those comparing standard biocompatibility parameters. Despite this confusion, a discerning review of the published works allows certain limited conclusions to be drawn. Reprocessing of used hemodialyzers changes the biocompatibility profile of a dialyzer as defined by the parameters complement activation. leukopenia, and cytokine release. The effect of reprocessing depends on the chemicals and reprocessing technique applied and also on the type of membrane polymer being subjected to the reprocessing procedure. Reports of pyrogenic reactions indicate that the flux of the membrane also influences how suitable it is for safe reuse. An increased risk of allergic and pyrogenic reactions appears to be associated with dialyzer reuse. Furthermore, there has been a lack of investigations into the immunologic effect of the layer of adsorbed and chemically altered proteins that remains on the inner surface of reprocessed dialyzers. We conclude that the clinical benefit of dialyzer reuse cannot be generally accepted from a biocompatibility point of view.     

The analgesic effect of racemic ketamine in patients with chronic ischemic pain due to lower extremity arteriosclerosis obliterans

Background : Ketamine in sub-dissociative doses has been shown to have analgesic and phantom-Limb pain, where conventional treatment has often failed. Chronic ischemic pain due to lower extremity arteriosclerosis obliterans often responds poorly to analgesics, and the pain-generating mechanisms are not well understood.
Methods : Eight patients with rest pain in the lower extremity due to arteriosclerosis obliterans were given sub-dissociative doses of 0.15, 0.30, or 0.45 mg/kg racemic ketamine and morphine 10 mg as a 5-min infusion on four separate days in a cross-over, double-blind, randomised protocol. Plasma levels of (S)- and (R)-ketamine and their nor-metabolites were analysed with an enantioselective high-performance liquid chromatography (HPLC) method. Pain levels were evaluated with a visual analogue scale (VAS).
Results : Individual pain levels were highly variable during and after all the infusions but the pooled pain levels showed a dose-dependent analgesic effect of ketamine with a transient but complete pain relief in all patients at the highest dose (0.45 mg/ kg). Side-effects, mainly disturbed cognition and perception, were pronounced and dose-dependent. Morphine 10 mg had an analgesic peak at 20 min and 5/8 patients had complete pain relief. The remaining 3 patients also had high baseline pain scores, indicating a higher analgesic potency for the 0.30 and 0.45 mg/ kg ketamine doses than for morphine 10 mg.
Conclusion : We have demonstrated a potent dose-dependent analgesic effect of racemic ketamine in clinical ischemic pain. Due to a narrow therapeutic window, this analgesic effect is probably best utilised in combination with other analgesics.     

Intravenous endotoxin does not increase tissue extravasation of albumin in rats

Background : It is unclear whether activation of the inducible nitric oxide synthase (iNOS) increases or decreases the extravasation of plasma.
Methods : Chloralose anaesthetised male Wistar rats received E. coli lipopolysacharide (LPS), 3 mg kg^-1 i.v., or the corresponding volume of saline, 3 or 5 h before the end of the experiment. Mean arterial pressure (MAP) and heart rate (HR) were recorded. Tissue clearance of radio-labelled albumin, during the last 2 h of each experiment, was determined by a double-isotope method. In separate animals, the serum concentration of nitrite and nitrate was determined, 5 h after LPS or the solvent.
Main Results : LPS initially decreased MAP and lastingly increased HR. In the 3-h LPS animals (n=8), tissue plasma clearance was lower in the heart and calf muscle and increased only in diaphragm, compared to corresponding control animals (n=8). In the 5-h LPS rats, clearance was lowered (n=8) in the entire gastrointestinal tract and in testes, compared to controls (n=8). The serum nitrite/nitrate concentration was higher in animals given LPS (n=6) than in controls (n=6).
Conclusion : After LPS, tissue clearance of albumin was not increased in any major tissue, in spite of increased serum levels of NO end products. Apparently, after activation of iNOS, the augmented release of NO is not necessarily associated with increased albumin extravasation.     

Adrenaline markedly improves thoracic epidural analgesia produced by a low-dose infusion of bupivacaine, fentanyl and adrenaline after major surgery: A randomised, double-blind, cross-over study with and without adrenaline

Background: Basic pharmacological research indicates that there are synergistic antinociceptive effects at the spinal cord level between adrenaline, fentanyl and bupivacaine. Our clinical experience with such a mixture in a thoracic epidural infusion after major surgery confirms this. The objectives of the present study were to evaluate the effects on postoperative pain intensity, pain relief and side effects when removing adrenaline from this triple epidural mixture. Methods: A prospective, randomised, double-blind, cross-over study was carried out in 24 patients after major thoracic or abdominal surgery. Patients with only mild pain when coughing during a titrated thoracic epidural infusion of about 10 ml · h^?1 of bupivacaine 1 mg · ml^?1, fentanyl 2 μg · ml^?1, and adrenaline 2 μg · ml^?1 were included. On the 1^st and 2^nd postoperative days each patient was given a double-blind epidural infusion, at the same rate, with or without adrenaline. The effect was observed for 4 h or until pain when coughing became unacceptable in spite of a rescue analgesic procedure. Rescue analgesia consisted of up to two epidural bolus injections per hour and i.v. morphine if necessary. All patients received rectal paracetamol 1 g, every 8 h. Fentanyl serum concentrations were measured with a radioimmunoassay technique at the start and end of each study period. Main outcome measures were extent of sensory blockade and pain intensity at rest and when coughing, evaluated by a visual analogue scale, a verbal categorical rating scale, the Prince Henry Hospital pain score, and an overall quality of pain relief score. Results: The number of hypaesthetic dermatomal segments decreased (P <0.001) and pain intensity at rest and when coughing increased (P <0.001) when adrenaline was omitted from the triple epidural mixture. This change started within the first hour after removing adrenaline. After 3 h pain intensity when coughing had increased to unacceptable levels in spite of rescue analgesia (epidural bolus injections and i.v. morphine). Within 15–20 min after restarting the triple epidural mixture with adrenaline, pain intensity was again reduced to mild pain when coughing. Serum concentration of fentanyl doubled from 0.22 to 0.45 ng · ml^?1 (P <0.01), and there was more sedation during the period without adrenaline. Conclusions: Adrenaline increases sensory block and improves the pain-relieving effect of a mixture of bupivacaine and fentanyl infused epidurally at a thoracic level after major thoracic or abdominal surgery. Serum fentanyl concentrations doubled and sedation increased when adrenaline was removed from the epidural infusion, indicating more rapid vascular absorption and systemic effects of fentanyl.