肺移植急性排斥反应的诊治(附三例报告)

目的观察和探讨肺移植急性排斥反应的临床表现、诊断方法、经支气管活检排斥反应的病理分类和治疗。方法2002年9月至2003年6月，分别为3例肺气肿、肺功能重度减损的患者进行了单肺移植。其中后2例为同一供者的左、右肺，第2例受者HLA无1个位点匹配。结果第1例左肺移植术后第9d发生1次急性排斥(A2b级)，经大剂量甲泼尼龙冲击治疗后症状消退；第2例右肺移植第7d持续发生急性排斥(A4c级)，经甲泼尼龙冲击并用OKT3治疗无效，术后第15d死亡；第3例左肺移植第9d、第15d发生2次急性排斥(A3a级)，经甲泼尼龙冲击并用OKT3治疗8d后缓解。结论选择组织相容性好的供、受者进行肺移植，是成功的保证。肺组织活检成为诊断急性排斥的金标准，对肺移植急性排斥反应的及时诊治是减少术后死亡率的关键。     

心肺联合移植11例单中心经验

目的总结心肺联合移植经验。 方法回顾性分析2015年9月至2018年11月广州医科大学附属第一医院完成的11例心肺联合移植受者临床资料。男性7例,女性4例,平均年龄(32±11)岁。原发病为艾森曼格综合征3例,特发性肺动脉高压4例,复杂先天性心脏合并肺血管病变、肺动脉栓塞、双肺移植术后心肺功能衰竭及扩张型心肌病合并慢性阻塞性肺疾病各1例。供者选择参照肺移植及心脏移植标准。11例受者均采用胸骨正中切口,经主动脉和上、下腔静脉远端插管建立体外循环,切除受者心肺后,植入供肺和供心,依次吻合气管、主动脉、上腔静脉及下腔静脉。 结果11例受者中,4例术后30 d内死亡,其中2例死于胸腔及纵隔出血,2例死于脑血管并发症;术后30 d至1年死亡3例,死因为排斥反应引起的移植物功能障碍及感染、移植物功能障碍导致的多器官功能衰竭。术后1年有4例受者存活。 结论严格选择供、受者以及术中后纵隔彻底止血可显著降低心肺联合移植手术死亡率,提高受者术后生存率及生存时间。     

不同受者同期分别接受同一供者的心、肺移植六例

目的为提高供者器官的利用率，探讨将同一供者的心、肺同期移植给不同受者的可行性及手术方法。方法采用原位灌洗、整块切取的方法获得3例供者的心脏和双肺，分别同期移植给3例终末期心脏疾病患者和3例终末期肺脏疾病患者。供者先行机械通气，然后开胸，主动脉及肺动脉分别插入灌注管，经主动脉插管灌注HTK液，经肺动脉插管灌注改良棉子糖低钾右旋糖酐液，对心、肺进行灌洗，然后整块切取心、肺。受者手术前进行供心、肺的分离，然后再次进行心、肺的逆行灌洗（通过上、下肺静脉插管和主动脉根部或者经腔静脉冠状窦逆行插管）。施行单侧肺移植者，再将左、右供肺分离。3例肺移植受者中，1例行左单肺移植，其他2例为非体外循环下序贯式双肺移植；3例心脏移植者均采用双腔静脉吻合法施行原位心脏移植。结果1例左单肺移植受者术后恢复良好；1例双肺移植受者术后出现右肺上叶静脉栓塞，于术后第9天再次手术，切除右肺上叶，后痊愈出院；另1例双肺移植受者，术后出现支气管吻合口狭窄，并发肺部感染，经对症治疗后好转出院，术后7个月死于重症感染。1例心脏移植受者术后早期出现肾功能衰竭，经血液透析治疗后痊愈出院，3例心脏移植受者术后生活质量良好，心功能恢复到0-I级。结论将同一供者的心、肺分别移植给不同受者，能充分利用供者器官，方法可行，效果良好。     

四例慢性阻塞性肺病行单肺移植的体会

目的 总结同种异体肺移植治疗慢性阻塞性肺病的体会。方法 4例慢性阻塞性肺病患者，1例为双肺弥漫性肺气肿，另3例为双肺重度弥漫性肺气肿并部分相互融合成肺大疱，但肺大疱占据胸腔不足1／3。4例均接受尸体供肺移植，为双肺弥漫性肺气肿的1例接受右肺移植，弥漫性肺气肿并部分相互融合成肺大疱的3例接受左肺移植，此3例分别于术中（1例）和术后（2例）接受右肺减容术。术后采用他克莫司、霉酚酸酯及泼尼松预防排斥反应，同时给予达利珠单抗或抗胸腺细胞球蛋白进行诱导治疗。结果4例手术经过顺利，1例术后第5d发生急性排斥反应，经甲泼尼龙冲击治疗逆转。2例受者顺利出院，并存活至今，最长1例存活已超过2年。2例分别于肺移植术后第74d、77d死亡。结论 终末期双肺弥漫性肺气肿可行单侧肺移植治疗，如果对侧肺有重度弥漫性肺气肿，特别是部分融合成大疱易破裂者，可同期期行对侧肺减容。     

心、肺联合移植治疗艾森曼格综合征一例

我院于2003年9月20日为1例艾森曼格综合征患者施行心、肺联合移植手术,获得成功,患者现已存活10月余,生活质量较术前明显提高。现报道如下。资料与方法一、一般资料患者,男,20岁。活动后心悸、气促8年,近5年加重,并出现唇、甲发绀。入院检查后,确诊为艾森曼格综合征,决定行心、肺联合移植术。二、供者手术取胸部正中切口,切开心包后广泛游离,两侧至肺静脉,上自无名静脉、奇静脉、无名动脉。肺动脉注射前列地尔1000μg,结扎上腔静脉,切断下腔静脉,并切开左心耳,阻断主动脉及肺动脉,经主动脉根部插管灌注冷晶体停跳液1500ml,肺动脉内灌注LPD液3000ml,切断主动脉,肺充氧后退出气管插管,夹住气管,将双肺及心脏整块取出,放在装有4℃LPD液的无菌塑料袋内,冰桶保存。至手术室后,供心及供肺进行必要修整,并再次行冷灌注,供心的灌注量为1000ml,供肺的灌注量为3500ml,肺灌注压15~25mm Hg。心、肺冷缺血时间为178min。三、受者手术受者取胸骨正中切口。因右侧胸腔广泛粘连,先进行游离。肝素化后,上、下腔静脉及升主动脉分别插管,建立体外循环,机器转流后,切除心脏及全肺,保留两侧膈神经及部分心包,于隆突上...     

亲属活体肾移植101例分析

目的 总结16年亲属活体肾移植的经验。方法 101例亲属活体肾移植，除3例为夫妻间供肾外，其余为血缘亲属供肾。供、受者为同卵孪生2例，HLA全配24例，HLA单倍体相同69例，HLA有5个抗原错配者4例，HLA完全错配者2例。73例取供者右肾，28例取左肾；100例经开放手术取肾，1例经腹腔镜取肾。术后采用环孢素A（或他克莫司）、硫唑嘌呤（或霉酚酸酯）及泼尼松预防排斥反应。结果 所有供者术后1周内出院，随访6个月，血肌酐正常。术后96例受者存活，存活时间最长者达15年，其中4例移植肾功能丧失，其原因分别为超急性排斥反应（1例，术中切除肾脏）、慢性移植肾肾病与肾病复发（3例）；5例死亡，除1例术后发生移植肾功能恢复延迟，透析期间因肺出血死亡外，另4例死亡与移植肾无关。术后5例发生急性排斥反应，4例Banff分级为Ⅰ级，经甲泼尼龙冲击治疗，4例逆转，1例无效，恢复透析治疗。术后2例发生尿瘘，5例发生移植肾输尿管慢性梗阻，经手术治疗痊愈。结论 术前对供、受者进行全面综合评估是亲属活体肾移植成功的保证；亲属活体肾移植的组织配型好，供肾缺血时间短，排斥反应发生少，免疫抑制剂用量小，移植肾长期存活率高。     

原位心脏移植治疗终末期心脏病141例

目的分析总结原位心脏移植治疗终末期心脏病的临床疗效及经验。方法为141例终末期心脏病患者施行原位心脏移植术,原发病包括扩张性性心肌病118例,肥厚性心肌病2例,限制性心肌病2例,缺血性心肌病9例,原发性心脏恶性肿瘤4例,瓣膜性心肌病3例,其它病因3例。供心冷缺血时间为(191.0±28.5)m in,供心卵圆孔未闭者9例,大室间隔缺损者1例,冠状动脉开口异常者1例。9例卵圆孔未闭的供心,先行卵圆孔缝闭术,然后再行移植;1例大室间隔缺损的供心,先行室间隔缺损修补术,然后再行移植;1例冠状动脉开口异常的供心,复跳后心肌收缩乏力,遂施行右冠状动脉松解术,其后复跳良好。120例行双腔静脉吻合法原位心脏移植术,19例行标准Stanford原位心脏移植术,2例行全心脏移植术。主动脉阻断时间为(53.0±4.5)m in,吻合时间为(41.5±5.5)m in。术后应用环孢素A(或他克莫司)、激素及霉酚酸酯预防排斥反应,28例患者同时应用达利珠单抗1~5剂。结果手术成功率为97.9%,术后随访1~65个月,1年、3年、5年存活率分别为90.8%、84.6%、81.4%,术后1年内的主要死因是急性排斥反应、感染、移植物功能衰竭及心脏肿瘤转移,术后中远期的主要死因是急性排斥反应、感染、肾功能衰竭及移植心脏冠状动脉硬化。术后并发症以急性排斥反应、感染、肾功能异常、移植心脏功能衰竭多见。结论终末期心脏病行原位心脏移植的临床疗效良好;远期需注意对急性排斥反应、感染及移植心脏冠状动脉硬化的监测及治疗。     

肾移植术后西罗莫司联合减量或停用环孢素A的应用体会

,患者存活率为86.7%.至4年随访终点,存活26例患者中25例移植肾功能良好.2例发生急性排斥反应,经甲泼尼龙冲击治疗后逆转.17例次发生感染,经抗感染处理后全部康复.2例术后发生移植肾功能恢复延迟,免疫抑制方案未做调整,分别在术后32 d和58 d恢复泌尿.结论 肾移植术后采用SRL联合CsA和糖皮质激素作为初始治疗,术后3个月开始减少直至停用CsA是有效、安全和可行的.     

原位心脏移植30例临床分析

目的对30例心脏移植进行分析总结。方法30例患者中,24例的原发病为扩张型心肌病,4例为终末期瓣膜性心肌病,1例为终末期缺血性心肌病,1例为病毒性心肌炎行双心室辅助术后1个月。均在体外循环下行原位心脏移植术,3例采用标准心脏移植术式,27例采用双腔静脉吻合心脏移植术式,体外循环时间(75±24)min,主动脉阻断时间(72±8)min。术后采用环孢素A、霉酚酸酯和泼尼松预防排斥反应,根据血环孢素A的浓度调整CsA的用量。术后早期,每天行心肌内心电图及超声心动多普勒监测,以便早期发现急性排斥反应,必要时行心内膜心肌活检。结果30例患者中,术后死亡5例,3例死于低心排,1例死于感染所致的多器官功能衰竭,1例死于出血。术后并发症有低心排、心律失常、三尖瓣返流、右心衰竭、细菌和真菌感染、肾功能异常及血糖升高,上述并发症除导致死亡者外,其余经治疗好转;4例发生急性排斥反应,给予甲泼尼龙冲击治疗,并调整免疫抑制剂的用量后排斥反应逆转。结论术后并发症的预防和及时正确的处理,是心脏移植成功的关键,尤其是对感染、急性排斥反应、右心功能不全及肾功能异常的预防和处理。     

改良的大鼠左肺原位移植模型

目的在建立大鼠左肺原位移植模型中采用一种新的缝合方法。方法左肺原位移植模型的供、受者均为SD大鼠。为了使肺静脉张开便于吻合,左肺移植期间持续进行供肺肺动脉低压灌注4℃的低钾右旋糖苷(LPD)液;采用连续外翻褥式缝合法吻合支气管膜部、肺静脉、肺动脉,快速进行左肺原位移植。术后采用环孢素A 霉酚酸酯 甲泼尼龙三联免疫抑制方案。术后4周,开胸阻断11例存活大鼠的右侧肺门,检测阻断前及阻断后的动脉血氧分压和动脉血二氧化碳分压。结果55例SD大鼠左肺移植成功,平均吻合时间为(36.2±9.6)min,手术成功率为91.7%。1周存活率为70.9%;2周存活率为50.9%;4周存活率为21.8%。术后发生肺动脉栓塞1例,于术后第3 d死亡,其余受者均未发现吻合口狭窄及栓塞。阻断右侧肺门前与阻断后15 min动脉血气比较,差异有统计学意义(P<0.01)。结论大鼠左肺原位移植模型中采用新的缝合方法,具有简单有效、实用可靠的优点。     

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 Teaspoon Pump for Pumping Blood with High Hydraulic Efficiency and Low Hemolysis Potential

Abstract: Virtually all blood pumps contain some kind of rubbing, sliding, closely moving machinery surfaces that are exposed to the blood being pumped. These valves, internal bearings, magnetic bearing position sensors, and shaft seals cause most of the problems with blood pumps. The original teaspoon pump design prevented the rubbing, sliding machinery surfaces from contacting the blood. However, the hydraulic efficiency was low because the blood was able to "slip around" the rotating impeller so that the blood itself never rotated fast enough to develop adequate pressure. An improved teaspoon blood pump has been designed and tested and has shown acceptable hydraulic performance and low hemolysis potential. The new pump uses a nonrotating "swinging" hose as the pump impeller. The fluid enters the pump through the center of the swinging hose; therefore, there can be no fluid slip between the revolving blood and the revolving impeller. The new pump uses an impeller that is comparable to a flexible garden hose. If the free end of the hose were swung around in a circle like half of a jump rope, the fluid inside the hose would rotate and develop pressure even though the hose impeller itself did not "rotate"; therefore, no rotating shaft seal or internal bearings are required.     

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.     

Tissue perfusion in relation to cardiac output during continuous positive-pressure ventilation and administration of propranolol or verapamil

Background : Our objective was to determine whether administration of propranolol or verapamil modifies the hemodynamic adaptation to continuous positive-pressure ventilation (CPPV), in particular the regional distribution of cardiac output (CO).
Methods : General hemodynamics and regional blood flows assessed by microsphere technique (15 (μm) were recorded in 16 anesthetized pigs during spontaneous breathing (SB) and CPPV with 8 cm H₂O end-expiratory pressure (CPPV8) before and after intravenous administration of propranolol (0.3 mg · kg⁻¹ followed by 0.15 mg · kg⁻¹ · h⁻¹, n=8) or verapamil (0.1 mg · kg⁻¹ followed by 0.3 mg · kg⁻¹ · h⁻¹, n=8).
Results : CPPV8 depressed CO by 25% without shifts in its relative distribution with the exception of a noteworthy increase in adrenal perfusion. Propranolol increased arterial blood pressure, and due to a fall in heart rate, CO dropped by 25%. The kidneys and, to a lesser extent, the splanchic region and central nervous system received increased fractions of the remaining CO at the expense of skeletal muscle flow. Similar patterns were seen during SB and CPPV8 such that the combination of propranolol and CPPV8 depressed CO by 50%. The circulatory effects of verapamil were less evident but myocardial perfusion tended to increase.
Conclusions : The combination of propranolol or verapamil with CPPV does not result in any specific hemodynamic interaction in anesthetized pigs, except that the combined effect of propranolol and CPPV may severely reduce CO.     

Volatile anaesthetics reduce adhesion of blood platelets under low-flow conditions in the coronary system of isolated guinea pig hearts

Background : Inhibitory effects of volatile anaesthetics on platelet aggregation have been demonstrated in several studies. However, the influence of volatile anaesthetics on intracoronary platelet adhesion has not been elucidated so far.
Methods : Isolated hearts of guinea pigs were perfused with buffer in the absence or presence of volatile anaesthetics (0.5 and 1 MAC) at constant coronary flow rates of 5 ml/min for 25 min, then 1 ml/min for 30 min and again 5 ml/min for 10 min. Before, during and after low-flow perfusion, a bolus of human platelets was applied into the coronary system. To simulate thrombogenic conditions, 0.3 U/ml human thrombin was infused during low-flow perfusion and reperfusion. The number of platelets sequestered to the endothelium was calculated from the difference between coronary in- and output of platelets. The myocardial production of lactate and consumption of pyruvate and coronary perfusion pressure were also determined.
Results : At a flow rate of 5 ml/min only about 3% of the applied platelets did not emerge from the coronary system, in any group. In contrast, 13.1±1.2% (mean±SEM) of infused platelets became adherent in low-flow perfusion in the control group without anaesthetic. The adherence was reduced with each 1 MAC isoflurane (to 6.2±1.2%), sevoflurane (to 4.4±0.9%) or halothane (to 3.2±1.5%) (each P <0.05 vs. control). Volatile anaesthetic, 0.5 MAC, did not inhibit platelet adhesion to a statistically significant extent in any case. Perfusion pressure and metabolic parameters were not statistically different between the control and the hearts exposed to anaesthetics.
Conclusion : Volatile anaesthetics in a concentration of 1 MAC can reduce the adhesion of platelets in the coronary system under reduced flow conditions. This action does not arise from vasodilation or inhibition of ischaemic stress.     

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.     

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.