80岁以上高龄结直肠癌患者接受腹腔镜辅助根治手术的围手术期安全性观察

目的:通过比较高龄结直肠癌患者接受腹腔镜辅助根治性手术与传统开腹根治性手术的围手术期情况,了解腹腔镜辅助结直肠癌根治手术对高龄结直肠癌患者的治疗安全性。方法:2006年1月至2008年6月,69例大于等于80岁的结直肠癌患者接受限期性根治手术,其中26例接受腹腔镜辅助结直肠癌根治术(腹腔镜组),男13例,女13例,平均(83.91±3.02)岁(80～90岁);43例接受传统开腹结直肠癌根治术(开腹组),男29例,女14例,平均(83.70±3.43)岁(80～91岁)。回顾性分析比较两组患者的术前评估(ASA评分)、术前合并症情况、手术病理分级(Dukes分期)、术中及术后血气分析变化、术后胃肠道功能恢复时间、住院天数及并发症等围手术期情况。结果:手术前,两组间的ASA评分无显著差异(Ⅰ级5:8,Ⅱ级19:32,Ⅲ级2:3,P>0.05),伴随的合并症发生率无显著差异(19/26,73.1%vs.26/43,60.5%,P>0.05)。腹腔镜组术中未出现高碳酸血症。术后24h与72h出现血气分析异常,分别为5人及2人,与开腹组的18人和7人相比,有显著性差异(P<0.05);腹腔镜组恢复排气时间显著短于开腹组[(2.27±0.46)dvs.(3.68±0.58)d](P<0.05);术后住院天数显著低于开腹组[(14.55±7.21)dvs.(22.16±18.99)d](P<0.05);术后并发症发生率显著低于开腹组(6/26,23.1%vs.18/43,41.9%,P<0.05);两组手术死亡率方面无显著差异,其中腹腔镜组死亡率3.85%,开腹组手术死亡率4.65%(P>0.05)。结论:80岁以上高龄结直肠癌患者选择腹腔镜辅助根治术比传统开腹手术具有术后康复快、并发症少等优势,同时腹腔镜手术不会增加术后死亡率。因此,腹腔镜辅助结直肠癌根治术对于高龄结直肠癌患者具有良好的手术安全性。     

高龄患者腹腔镜辅助结直肠癌切除术的临床疗效

目的:探讨高龄患者(≥70岁)行腹腔镜辅助结直肠癌切除术的安全性和有效性。方法:根据纳入与排除标准,前瞻性纳入2012年1月―2015年1月收治的高龄结直肠癌患者120例,将患者随机分为腹腔镜组和开腹手术组,每组60例,分别行腹腔镜辅助结直肠癌切除术和开腹结直肠癌切除术。比较两组患者的相关临床指标。结果:与开腹组比较,腹腔镜组手术时间(118.23min vs.120.85min,P=0.458)与淋巴结清扫数目(18.12枚vs.17.37枚,P=0.218)无统计学差异,但术中出血量明显减少(307.28mL vs.354.80mL,P=0.000)、术后排气时间明显缩短(38.27h vs.47.02h,P=0.000)、住院时间明显缩短(16.58d vs.20.07d,P=0.000)。两组患者肠瘘、皮下感染、吻合口瘘、肠梗阻、尿路感染和肺部感染发生率差异均无统计学意义(均P0.05)。两组患者术后24个月时复发率(35.0%vs.41.7%,P=0.453)与病死率(13.3%vs.18.3%,P=0.453)差异均无统计学意义。结论:高龄患者行腹腔镜辅助结直肠癌切除术安全有效,值得进一步推广。     

保留左结肠动脉的腹腔镜直肠癌根治术在高龄患者中的应用研究

目的:探讨高龄患者行保留左结肠动脉的腹腔镜直肠癌根治术的安全性与可行性。方法:回顾分析2011年1月至2019年12月233例70岁以上直肠癌患者的临床资料,其中123例接受保留左结肠动脉的腹腔镜直肠癌前切除术(低位结扎组),110例接受肠系膜下动脉根部结扎的腹腔镜直肠癌前切除术(高位结扎组),比较两组患者术前临床资料、手术相关指标及术后恢复指标。结果:两组患者术前临床资料差异无统计学意义(P0.05)。两组均无手术相关死亡病例。低位结扎组与高位结扎组手术时间[(175.3±47.2)min vs.(165.2±48.1)min]、术中出血量[(87.5±60.9)mL vs.(82.5±65.5)mL]、肛门排气时间[(2.7±1.2)d vs.(3.0±1.3)d]、进食流质时间[(2.8±1.6)d vs.(3.1±1.7)d]、住院时间[(9.6±6.3)d vs.(10.3±4.8)d]、淋巴结获取数量[(15.2±3.8) vs.(16.0±4.2)]、术后并发症发生率(22.0%vs. 29.1%)差异均无统计学意义(P0.05)。两组术后吻合口漏发生率(2.4%vs. 8.2%)差异有统计学意义(P0.05)。结论:高龄患者行保留左结肠动脉的腹腔镜直肠癌根治术是安全、可行的,可降低术后吻合口漏发生率。     

术后放化疗在高龄Ⅲ期直肠癌患者中的临床应用价值

目的:研究术后放化疗在高龄(≥75岁)III期直肠癌患者中的临床应用价值。方法:回顾性分析2010年1月—2014年1月收治的128例高龄(≥75岁)III期直肠癌患者资料,根据术后是否进行放化疗将患者分为放化疗组(60例)和对照组(68例),比较两组无进展生存期、2年存活率、健康相关的生存质量和术后主要并发症。结果:与对照组比较,放化疗组患者无进展生存期明显延长[(793.58±295.39)d vs.(736.59±305.38)d,P=0.029];2年存活率有增高趋势,但组间差异无统计学意义(91.7%vs.79.4%,P=0.052);术后12个月时健康相关的生存质量评分明显增高(70.25 vs.63.37,P0.001);局部复发率明显降低(16.7%vs.33.8%,P=0.035);放射相关性肠炎(13.3%vs.0.0%)与骨髓抑制(11.7%vs.0.0%)发生率明显增高(P=0.002,P=0.004)。两组患者肠瘘、肠梗阻和贫血发生率均无统计学差异(均P0.05)。结论:术后放化疗虽然增加了术后并发症的发生率,但是显著改善了高龄III期直肠癌患者长期预后。     

不同年龄直肠癌患者行腹腔镜与行开腹根治术的比较

目的 探讨腹腔镜直肠癌根治术在不同年龄患者中受益程度的差别.方法 从2008年1月至2009年3月期间我院对76例患者行直肠癌根治术,大于70岁的老年组34例,其中行腹腔镜根治术16例,开腹根治术18例;小于70岁的中青年组42例,其中行腹腔镜根治术23例,开腹根治术19例.对这2组患者围手术期的各项数据进行回顾性分析,并分别比较2组行腹腔镜与开腹根治术的差异.结果 2组均无手术死亡病例;在术后通气、进食及住院时间方面,2组中的腹腔镜根治术患者均明显短于开腹根治术患者(P＜0.05,P＜0.01);术中出血量及术后镇痛比例也更少(P＜0.01);在平均手术时间及淋巴结清扫数目方面两种手术之间差异均无统计学意义(P>0.05).在中青年组,除切口感染率LR明显低于OR(P＜0.05)外,在并发症发生率和术后生活自理比例方面,腹腔镜根治术与开腹根治术患者比较差异均无统计学意义(P>0.05);而在老年组,腹腔镜根治术患者的各项并发症发生率均明显低于开腹根治术患者(P＜0.05),而术后生活自理比例则显著增高(P＜0.01).结论 腹腔镜下直肠癌根治术可以安全地用于老年及中青年患者.相比较而言,在术后并发症发生率及术后生活质量方面,老年直肠癌患者接受腹腔镜根治术的获益则显得更加明显,腹腔镜根治术对于老年直肠癌患者可能有更好的应用前景.     

无切口腹腔镜直肠癌根治术的临床效果分析

目的探讨无腹部辅助切口腹腔镜直肠癌根治术治疗直肠癌患者的临床疗效。方法选取2013年1月至2014年8月择期行腹腔镜直肠癌根治术的79例患者进行回顾性分析,其中28例患者采用无腹部辅助切口腹腔镜直肠癌根治术治疗(无切口组)、51例患者采用传统的腹腔镜直肠癌根治术治疗(传统组),两组患者数据分析采用SAS10.0进行处理,术中、术后临床资料、VAS评分等计量指标采用均数±标准差(x珋±s)进行描述,比较采用两独立样本t检验;并发症发生率等计数资料比较采用χ2检验;P值0.05为差异具有统计学意义。结果无切口组的手术时间、手术出血量、术后肛门排气时间、住院时间均显著低于传统组(P0.05),两组患者清扫淋巴结数目相比较无统计学意义(P0.05);术后2 h、6 h、12 h、24 h,无切口组的VAS评分均显著低于传统组(P0.05);无切口组的并发症率10.7%、传统组的并发症率15.7%,两组间比较差异无统计学意义(P0.05);无切口组的排便习惯改变率32.1%、2年复发率25.0%、2年生存率85.7%,传统组分别为41.2%、19.6%、86.3%,两组间比较差异无统计学意义(P0.05)。结论无腹部辅助切口腹腔镜直肠癌根治术治疗直肠癌与传统的腹腔镜手术效果无明显差异,但具有创伤更小、术后恢复更快、疼痛程度更低的优势。     

腹腔镜辅助及开腹手术在结直肠癌中的近期临床疗效比较

目的探讨腹腔镜辅助手术及开腹手术在结直肠癌患者中的近期临床疗效。方法本研究采用回顾性病例对照研究,将2015年6月至2017年2月本院收治的80例结直肠癌患者分为腹腔镜辅助组和开腹组,每组40例,分别实施腹腔镜辅助结直肠癌根治术和开腹结直肠癌根治术。比较两组手术相关指标,术后并发症发生情况及标本肿瘤学指标。结果腹腔镜辅助组手术时间长于开腹组,住院总费用明显多于开腹组,切口长度明显短于开腹组,术中出血量明显少于开腹组,术后首次排气及排便时间、开始进流食时间、下床活动时间均明显早于开腹组,术后住院时间明显短于开腹组,术后并发症总发生率明显低于开腹组,经比较差异有统计学意义(P<0.01)。两组标本肿瘤学指标比较均无明显统计学差异(P>0.05)。结论腹腔镜辅助结直肠癌根治术可降低术后并发症发生率、缩短住院时间、促进患者术后胃肠功能的恢复。     

腹腔镜下结直肠癌根治术中联合腹腔热灌注化疗的临床研究

目的:探讨腹腔镜下结直肠癌根治术中联合腹腔热灌注化疗(IHPC)的安全性及可行性。方法:将120例进展期结直肠癌患者随机分成治疗组和对照组,每组各60例。两组患者均接受腹腔镜下结直肠癌根治术,治疗组术中行IHPC联合术后m FOLFOX6方案静脉化疗;对照组单纯行术后m FOLFOX6方案静脉化疗。比较两组患者手术相关指标、术后恢复情况、术后并发症、不良反应、局部复发率及远处转移率。结果:两组患者在手术相关指标、术后恢复情况、术后并发症方面差异均无统计学意义(均P>0.05);治疗组术后低蛋白血症和低钠血症的发生率明显高于对照组(20.0%vs.6.7%;15.0%vs.3.3%,均P<0.05);腹腔局部复发率和远处转移率明显低于对照组(6.7%vs.18.3%;8.3%vs.23.3%,均P<0.05);两组短期总生存率相当(P>0.05)。结论:腹腔镜下结直肠癌根治术中IHPC联合术后静脉化疗安全可靠,对局部复发及远处转移疗效较好。     

腹腔镜与开腹手术治疗结直肠癌术中及术后并发症发生率的比较

目的:比较腹腔镜与开腹结直肠癌根治术围手术期并发症发生率的差异。方法:将我院近4年间122例结直肠癌患者随机分为两组,其中腹腔镜组62例,开腹组60例。观察比较两组术中及术后并发症的发生情况。结果:术中并发症发生率两组差异无统计学意义(P>0.05)。术后并发症比较,腹腔镜组优于开腹组,差异具有统计学意义(P<0.05);其5年生存率两组差异无统计学意义(P>0.05)。结论:应用腹腔镜行结直肠癌根治术可以达到开腹根治术的效果,且可减少术后并发症。     

老年患者经腹腔镜与开腹直肠癌根治术的比较

目的:探讨腹腔镜手术治疗70岁以上老年人直肠肿瘤的可行性与有效性。方法:回顾总结腹腔镜辅助与开放直肠癌根治术治疗70岁以上老年患者直肠肿瘤的经验。比较同期21例腹腔镜手术(腹腔镜组)与26例开放手术(开腹组)的安全性、并发症以及术后恢复情况。结果:两组均无手术死亡。开腹组术后并发症发生率(42.3%)显著高于腹腔镜组(14.3%)(P<0.05)。腹腔镜组患者术后肠道通气时间与进食时间分别为(2.9±0.5)d、(3.5±0.3)d,与开腹组(4.2±0.7)d、(5.1±0.6)d相比差异有显著性(P<0.05)。两组手术时间、术中出血与住院天数差异无统计学意义(P>0.05)。结论:腹腔镜结直肠手术治疗70岁以上老年人直肠肿瘤安全有效,对于老年直肠癌患者有良好的应用前景。     

Vasopressor hormone response following mesenteric traction during major abdominal surgery

Background : We investigated the vasopressor hormone response following mesenteric traction (MT) with hypotension due to prostacyclin (PGI₂) release in patients undergoing abdominal surgery with a combined general and epidural anesthesia. Methods : In a prospective, randomized, placebo-controlled study we administered 400 mg ibuprofen (i.v.) in 42 patients scheduled for abdominal surgery. General anesthesia was combined with epidural anesthesia (T4-L1). Before as well as 5, 15, 30, 45, and 90 min after MT we recorded plasma osmolality, hemodynamics and measured 6-keto-PGFlα (stabile metabolite of PGI₂), TXB₂ (stabile metabolite of thromboxane A₂) active renin, and arginine vasopressin (AVP) plasma concentrations by radioimmunoassay. Catecholamine levels were assessed by high-pressure liquid chromatography (HPLC) with electrochemical detection. Results : Following MT, arterial hypotension occurred along with a substantial PGI₂ release. This was completely abolished by ibuprofen administration. Although plasma levels of 6-keto-PGF_1α (1133 (708) vs. 60 (3) ng/L, median (median absolute deviation), P=0.0001, placebo vs. ibuprofen) remained significantly elevated, blood pressure was restored within 30 min after MT in the placebo group. At the same point in time plasma concentrations of TXB² (164 (87) vs. 58 (1) ng/L, P=0.0001), epinephrine (46 (33) vs. 14 (6) ng/L, P=0.001), AVP (41 ± (18) vs. 12 (7) ng/L, P=0.0004), and active renin (27 (12) vs. 12 (4) ng/L, P = 0.001) were significantly higher in placebo-treated patients. Conclusion : Under combined general and epidural anesthesia arterial hypotension following MT due to endogenous PGI₂ release is associated with enhanced release of AVP, active renin, epinephrine and thromboxane A₂, presumably contributing to hemodynamic stability within 30 min after MT.     

A comparison of the inhibitory effects of four volatile anaesthetics on the metabolism of chlorzoxazone, a substrate for CYP2E1, in rabbits

Background: Halothane inhibits in vitro and in vivo activity of cytochrome P-450 (CYP) 2E1. There are several fluorinated volatile anaesthetics besides halothane, and most of them are defluorinated by CYP2E1. It is unclear whether other fluorinated anaesthetics inhibit the in vivo activity of CYP2E1.
Methods: We compared the inhibitory effects of therapeutic concentrations of four inhalational anaesthetics, halothane, enflurane, isoflurane, and sevoflurane, on chlorzoxazone metabolism in rabbits receiving artificial ventilation.
Results: All four inhalational anaesthetics decreased arterial blood pressure and increased plasma chlorzoxazone concentration. However, no significant differences in the plasma chlorzoxazone concentration were found between the four anaesthetics. The estimated chlorzoxazone clearance increased after beginning inhalation with all four agents, but no significant difference in clearance was noted between agents.
Conclusions: At therapeutic concentrations, the in vivo inhibitory effect on chlorzoxazone metabolism was similar for all four inhalational anaesthetics examined, even though their chemical characteristics and extent of hepatic metabolism differ considerably.     

Microspheres Based Detoxification System: A New Method in Convective Blood Purification

Abstract: A variety of protein-bound or hydrophobic substances, accumulating as a result of pathologic conditions such as exogenous or endogenous intoxications, are removed poorly by conventional detoxification methods because of low accessibility (hemodialysis), insufficient adsorption capabilities (hemosorption), low efficiency (peritoneal dialysis), or economic limitations (high-volume plasmapheresis). Combining advantages of existing methods with microspheric technology, a module-based system was designed. Major operating parameters of the latter can be modified to allow for adjustment to individual clinical situations. An extracorporeal blood circuit including a plasmafilter is combined with a secondary high-velocity plasma circuit driven by a centrifugal pump. Different microspheric adsorbers can be combined in one circuit or applied in sequence. Thus, a prolonged treatment can be tailored using specially designed selective adsorber materials. Comparing this system with existing methods (high-flux hemodialysis, molecular adsorbent recycling system), results from our in vitro studies and animal experiments demonstrate the superior efficiency of substance removal.     

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.     

Bariatric Surgery in Some "Central and East-European (former Eastern bloc)"Countries - Current Status and Prediction for the Next Millennium

Background: Obesity is increasing globallly, including in the formerly "Eastern Bloc" countries. Methods: A survey was made of obesity and bariatric surgery. Results: In the 8 East and Central European countries studied, with total population 300 million, roughly 43% of the population was overweight (BMI 25-30), 23% obese (BMI > 30), with about 15 million people morbidly obese (BMI > 40). From 0-10 morbidly obese individuals/100,000/year undergo bariatric surgery. Conclusion: Most countries were found to provide inadequate treatment for obesity.The majority of the morbidly obese are not treated effectively. However, health-care awareness of obesity and bariatric surgeons are slowly increasing.     

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.     

Influence of dopexamine hydrochloride on haemodynamics and regulators of circulation in patients undergoing major abdominal surgery

Background: Catecholaminergic support is often used to improve haemodynamics in patients undergoing major abdominal surgery. Dopexamine is a synthetic vasoactive catecholamine with beneficial microcirculatory properties. Methods: The influence of perioperative administration of dopexamine on cardiorespiratory data and important regulators of macro- and microcirculation were studied in 30 patients undergoing Whipple pancreaticduodenectomy. The patients received randomized and blinded either 2 μg · kg^?1 · min^?1 of dopexamine (n=15) or placebo (n=15, control group). The infusion was started after induction of anaesthesia and continued until the morning of the first postoperative day. Endothelin-1 (ET-1), vasopressin, atrial natriuretic peptide (ANP), and catecholamine plasma levels were measured from arterial blood samples. Measurements were carried out after induction of anaesthesia, 2 h after onset of surgery, at the end of surgery, 2 h after surgery, and on the morning of the first postoperative day. Results: Cardiac index (CI) increased significantly in the dopexamine group (from 2.61±0.41 to 4.57±0.78 1 · min^?1 · m^?2) and remained elevated until the morning of the first postoperative day. Oxygen delivery index (DO₂I) and oxygen consumption index (VO₂I) were also significantly increased in the dopexamine group (DO₂I: from 416±91 to 717±110 ml/m² · m²; VO₂I: from 98±25 to 157±22 ml/m² · m²), being significantly higher than in the control group. pHi remained stable only in the dopexamine patients, indicating adequate splanchnic perfusion. Vasopressive regulators of circulation increased significantly only in the untreated control patients (vasopressin: from 4.37±1.1 to 35.9±12.1 pg/ml; ET-1: from 2.88±0.91 to 6.91±1.20 pg/ml). Conclusion: Patients undergoing major abdominal surgery may profit from prophylactic perioperative administration of dopexamine hydrochloride in the form of improved haemodynamics and oxygenation as well as beneficial influence on important regulators of organ blood flow.     

Synergistic interaction between the effects of propofol and midazolam with fentanyl on phrenic nerve activity in rabbits

Background: It has been shown that the depressive effects of both propofol and midazolam on consciousness are synergistic with opioids, but the nature of their interactions on other physiological systems, e. g. respiration, has not been fully investigated. The present study examined the effect of propofol and midazolam alone and in combination with fentanyl on phrenic nerve activity (PNA) and whether such interactions are additive or synergistic. Methods: PNA was recorded in 27 anaesthetised and artificially ventilated rabbits. In three groups, propofol, fentanyl and midazolam were administered intravenously in incremental doses to construct dose-response curves for the depressant effects of each one on PNA. In another two groups, the effect of pretreatment with either fentanyl 1 μg · kg^?1 i. v. or midazolam 0.05 mg · kg^?1 i. v. on the effects of propofol and fentanyl respectively on PNA were studied. Results: Propofol and fentanyl caused a dose-dependent depression of PNA with complete abolition at the highest total doses of 16 mg · kg^?1 i. v. and 32 μg · kg^?1 i. v., respectively. In contrast, midazolam in incremental doses to a total of 0.8 mg · kg^?1 reduced mean PNA by 63%, but approximately 12% of PNA remained at a total dose as high as 6.4 mg · kg^?1. The mean ED₅₀s, calculated from dose-response curves, were 5.4 mg · kg^?1, 3.9 μg · kg^?1 and 0.4 mg · kg^?1 for propofol, fentanyl and midazolam, respectively. Initial doses of either fentanyl 1 μg · kg^?1 i. v. or midazolam 0.05 mg · kg^?1 i. v. acted synergistically with subsequent doses of either propofol or fentanyl to abolish PNA at total doses of 8 mg · kg^?1 and 8 μg · kg^?1, respectively. Conclusion: Fentanyl has a synergistic interaction with both propofol and midazolam on PNA and hence potentially on respiration.     

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.