恶性骨肿瘤保肢术应用的可行性

目的为了探讨保肢手术在治疗恶性骨肿瘤中的可行性。方法我们回顾了自1994年6月以来在我科诊治的12个恶性骨肿瘤病例。手术方法有瘤段切除人工关节置换2例，瘤段骨切除灭活再植4例，瘤段切除带血管蒂髂骨移植1例，瘤段切除关节融合2例，瘤段切除同种异体半关节移植1例，瘤段切除2例。并阐述常见术后并发症及处理原则。关节肢体功能评价参照Enneking标准。结果平均随访3年4个月(10个月至5年)。9例无复发。肢体功能优良率达66．7％。结论结果提示保肢手术在治疗恶性骨肿瘤中是切实可行的，并可达到较高的成功率。     

人工关节在恶性骨肿瘤保肢治疗中的应用

目的：探讨人工关节在恶性骨肿瘤保肢治疗中的应用疗效。方法：对21例恶性骨肿瘤患者进行人工关节置换保肢治疗，其中铰链式膝关节10例，股骨近端假体5例，人工肱骨头4例，人工肩胛骨1例，人工肘关节1例。结果：随访1～7年，平均4年，局部复发率9．5％，最终保肢率90．5％；所有患者人工关节置入均超过6个月，参照Enneking(MSTS)评定标准，平均得分21．2分，优良率76．2％。结论：人工关节置换术应用于恶性骨肿瘤的保肢治疗可以取得满意的疗效，正确掌握手术适应证、肿瘤的完整切除和软组织重建是手术成功的关键。     

膝关节周围恶性骨肿瘤的保肢治疗

目的 探讨对膝关节周同恶性骨肿瘤切除后，采用不同方法行保肢治疗的效果，比较其优缺点：方法 自1995年1月至2004年10月收治了膝关节周围恶性骨肿瘤39例。39例39肢均行肿瘤节段截除、肢体重建手术：其中人工假体置换16例、复合骨移植16例、旋转成形7例。肿瘤按照Enneking分期：IB期13例，ⅡA期3例，ⅡB期23例。比较三种保肢手术后局部复发率、并发症和膝关节功能MSTS评分：结果 局部复发率：人工假体置换12．5％，复合骨移植12．5％，旋转成形无局部复发；术后平均膝关节功能MSTS评分：人工假体置换88％，复合骨移植88．7％，旋转成形68％，差异有统计学意义：结论 人工假体置换术和复合骨移植术应用于相对局限、无转移的膝周围恶性肿瘤术后重建，具有并发症少、恢复快、功能好等优点，但仍有一定的转移率和局部复发率。旋转成形术局部复发率低，但功能较差.     

肿瘤型假体置换术后再手术的原因与策略

目的探讨分析肿瘤型假体置换术后再手术的原因和策略。方法回顾1994年1月～2004年12月完成的85例肿瘤型假体置换术，其中21例因各种原因再次手术。男13例，女8例。再手术时年龄18～58岁。分别为骨肉瘤10例，软骨肉瘤4例，骨巨细胞瘤5例，骨纤维肉瘤2例，均由病理组织学证实。股骨远端9例，胫骨近端8例，股骨近端2例，肱骨近端及髋臼处各1例。Enneking分期IB期5例，ⅡB期16例。再手术距首次手术时间2周～20年。再手术的原因：肿瘤复发8例，假体松动5例，切口不愈合4例，关节脱位3例，假体断裂1例。行截肢术和肿瘤假体翻修术各6例，肿瘤扩大切除术3例，病灶清除腓肠肌内侧头肌瓣移位术4例，切开复位术和关节旷置术各1例。结果18例获随访1～5年，平均3年4个月。其中4例骨肉瘤患者因肺转移而死亡，余14例均无瘤生存，假体无松动，切口愈合良好。关节功能在可评价的13例患者中，参照保肢术后肢体功能评价标准，优2例，良5例，可4例，差2例。再手术后保留肢体功能满意率为84．6％，优良率为53．8％。结论肿瘤复发是肿瘤假体置换术后再手术的最常见原因，假体松动是导致肿瘤假体翻修术的另一主要因素；再手术时应根据不同原因行相应的治疗策略，在不违反保肢手术原则下，仍可行保留肢体的手术，并可获得满意的治疗效果。     

人工假体在膝关节周围骨肿瘤保肢治疗中的应用

目的：探讨对膝关节周围骨肿瘤切除后，采用人工全膝关节置换达到保肢的疗效。方法：1996—2000年共收治骨肿瘤患者11例，年龄18～55岁，其中恶性骨巨细胞瘤6例，骨肉瘤2例，软骨肉瘤2例，纤维肉瘤1例。股骨下端病变7例，胫骨上端病变4例。肢体功能重建方法为特制的人工全膝关节置换术。结果：本组11例经3～6年随访，8例无瘤存活，3例带瘤存活。术后肢体功能按Enneking评分系统评分，平均为21．5分，总优良率72．7％，其中股骨远端肿瘤术后平均为22．3分，胫骨近端肿瘤术后平均为20．0分。结论：采用特制的人工全膝关节置换术，能有效治疗膝关节周围低度恶性或恶性骨肿瘤，达到良好保肢效果。     

膝关节周围恶性肿瘤保肢术后感染的治疗及影响因素分析

目的总结膝关节周围恶性肿瘤保肢术后感染的治疗经验以及对影响感染的因素进行分析。方法以2008年1月—2017年12月因膝关节周围恶性肿瘤行保肢术的212例患者作为研究对象,其中术后发生关节感染14例。2例急性感染给予敏感抗生素治疗;12例慢性感染一期清创并植入抗生素骨水泥占位器,待感染控制后二期行假体翻修(8例)、膝关节融合(2例)、截肢术(2例)。对患者年龄、性别、保肢术前化疗周期、骨髓抑制情况、血清白蛋白、血红蛋白、保肢手术时间,以及保肢术后引流时间、输血量进行分析,筛选保肢术后感染的危险因素;观察感染、肿瘤复发情况,采用Enneking评分系统评价肢体功能。结果单因素分析显示,保肢术前化疗周期、骨髓抑制情况、保肢手术时间以及术后引流时间是保肢术后感染的影响因素(P0.05);多因素分析显示,保肢手术时间、保肢术前化疗周期以及保肢术后引流时间是保肢术后感染的危险因素(P0.05)。14例患者中1例于二期术后6个月因交通事故死亡,13例获随访12.2～48.0个月,平均19.9个月。2例急性感染者均治愈。11例慢性感染者中,2例一期术后占位器半脱位;9例感染治愈,2例感染复发。术后12个月,13例患者肢体功能Enneking评分为12～26分,平均20分。1例发生肺转移,余未发现肿瘤转移、复发。结论保肢手术时间、保肢术前化疗周期以及保肢术后引流时间是膝关节周围恶性肿瘤保肢术后感染的危险因素。尽早进行病原学检查及药物敏感性试验是治疗此类术后感染的关键,一期行清创联合抗生素骨水泥占位器可有效治愈感染,挽救患者肢体。     

骨肿瘤人工关节保肢术后继发截肢的回顾性研究

背景：人工关节置换术是骨肿瘤切除术后骨缺损的主要重建方法,目前有关骨肿瘤患者接受人工关节保肢术后继发截肢的报导较少。目的：分析骨肿瘤患者接受人工关节保肢术后继发截肢的风险因素。方法：随访1995年10月至2011年10月接受人工关节保肢治疗的骨肿瘤患者1459例。收集包括病史、诊断、治疗过程、术后并发症情况、转归等临床资料,并对上述资料进行相关的统计学分析。结果：1459例中70例保肢失败而接受二期截肢手术,继发截肢率为4.80%。截肢手术的原因包括肿瘤局部复发54例;人工关节周围深部感染14例;保肢术后肢体远端急性缺血坏死2例。人工关节保肢术距离截肢手术的时间为6d至122个月,平均18.1个月。结论：人工关节保肢术可有效重建骨肿瘤患者的骨缺损,其远期并发症较少,但仍有保肢失败继发截肢的风险。肿瘤局部复发和深部感染是继发截肢的主要因素。病理性骨折是肢体肿瘤患者接受人工关节保肢术后继发截肢的重要危险因素。降低人工关节保肢术后局部复发和深部感染的发生率可有效降低继发截肢的风险。继发截肢的风险随保肢术距离截肢手术的时间间隔延长而逐渐降低。     

人工假体置换在膝关节周围侵袭性骨肿瘤中的应用

目的: 探讨人工假体在膝关节周围原发侵袭性骨肿瘤保肢术中的临床应用效果。方法: 膝关节周围原发侵袭性骨肿瘤患者 42例。其中股骨远端 24例, 胫骨近端 16例, 腓骨上端 2例。病理类型: 骨肉瘤 21例, 骨巨细胞瘤 (Ⅱ~Ⅲ级) 16例, 软骨肉瘤 4例, 滑膜肉瘤 1例。行骨肿瘤的广泛切除或根治性切除后, 采用人工膝关节假体置换重建, 对骨肉瘤患者同时采用新辅助化疗治疗。结果: 42例患者术后随访 12~72个月, 其中 30例患者无局部复发或远处转移, 12例出现复发。膝关节活动范围: 伸 0°, 屈 85 ~120°。按Enneking法评定功能, ≥23分 22例, 15~22分 17例, <15分 3例, 优良率达到 86%。结论: 人工假体是一种治疗膝关节周围恶性骨肿瘤较好的保肢方法, 能降低局部并发症及提高临床疗效。     

人工全股骨关节置换术治疗股骨恶性原发性骨肿瘤

目的探讨人工全股骨关节置换术治疗股骨恶性肿瘤的适应证和并发症及随访的功能结果。方法回顾1996年10月至2007年10月，人工全股骨关节置换术治疗股骨恶性肿瘤患者共25例，其中男16例，女9例，平均年龄15岁。发病部位于股骨上段的患者有1例，股骨下段的11例，股骨干的13例。肿瘤破坏范围22～28cm，有跳跃灶6例，病理性骨折2例。术前均行组织病理活检，确诊为骨肉瘤的23例，软骨肉瘤的1例，小细胞肿瘤1例。24例行术前化疗，20例术后化疗。手术经患肢外侧入路切除瘤骨，人工全股骨假体置换。结果25例均有随访，平均46个月（3～132个月）。ⅡB期患者20例，其中6例患者出现肺转移（占30％），6例患者死亡，14例患者无瘤存活3～132个月（平均61月）。ⅢB期患者5例，存活9～20个月（平均12．5月），最终死亡。本组3例患者术后6～14个月局部复发（占12％）；23例患者术后恢复行走，占92％，依Enneking骨骼肌肉系统肿瘤术后功能评估系统，肢体功能恢复率41％～90％（平均70％）。3例术后并发神经麻痹；2例术后髋关节脱位，无1例出现术后感染。结论人工全股骨关节置换术适于股骨广泛受侵犯的恶性骨肿瘤患者，能有效地恢复肢体功能；对于Ⅲ期患者，姑息性保肢能有效地改善生活质量。     

骨肿瘤保肢手术中以人工关节重建股骨上端

目的探讨在股骨上端肿瘤患者的保肢手术中以肿瘤型人工髋关节假体重建骨缺损的疗效及并发症。方法回顾分析浙江大学医学院附属第二医院骨科自1999年3月至2006年12月间45例骨肿瘤保肢手术中以肿瘤型人工髋关节重建股骨上端的临床资料，其中转移性肿瘤26例，恶性淋巴瘤2例，骨肉瘤4例，软骨肉瘤3例，恶性纤维组织细胞瘤2例，尤文肉瘤1例，平滑肌肉瘤1例，侵袭性骨母细胞瘤1例，骨巨细胞瘤5例。结果本组患者均获得随访，随访时间8-61个月，平均26个月。所有患者的5年生存率为41％。其中3例发生术后感染，4例患者发生术后髋关节脱位，脱位患者均为全髋重建，3例患者术后局部复发，2例患者发生深静脉血栓形成，1例发生假体周围骨折，假体的5年生存率为82％。43例患者的MSTS评分为（21．0&#177;4．3）分。结论在股骨上端肿瘤的保肢手术中以人工髋关节来重建骨缺损是一种安全、有效的方法，术后关节功能良好。     

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.     

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.     

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.     

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.     

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.