三椎体复位固定行腰椎滑脱翻修手术探讨

目的：分析腰椎滑脱症手术失败原因,探讨三椎体复位固定翻修腰椎滑脱症手术失败病例的疗效。方法：回顾性分析2009年1月至2012年12月收治的19例腰椎滑脱症翻修手术病例的临床资料,男12例,女7例;年龄36-68岁,平均51.5岁。其中滑脱节段复位丢失6例,内固定物松动或断裂5例,滑脱加重8例。临床症状有下腰部疼痛、单侧或双侧下肢疼痛麻木等。翻修手术采用后路三椎体椎弓根钉内固定,后路减压、复位,椎体间加后外侧植骨,对初次手术后发生椎弓根钉松动或断裂的椎体采用取出松动或断裂的螺钉,换用加粗或加长椎弓根螺钉进行再次置入,或者采用骨水泥灌注,置入椎弓根螺钉。应用X线正侧位片和伸屈动力位片评价椎间融合的效果,并采用JOA评分对疗效进行评定。结果：翻修手术后均获随访,时间为10-30个月,平均18个月。X线显示所有翻修手术病例植骨融合良好,植骨融合时间5.5-7个月,滑脱椎体再次复位后矫正度无丢失,椎弓根螺钉无松动及断裂。JOA评分改善率为（78.06±3.90）%,以患者手术前及术后6个月随访时的JOA评分进行统计学分析,Ⅰ度滑脱3例,术前评分13.33±1.53,术后26.33±0.58;Ⅱ度滑脱7例,术前评分12.85±2.19,术后26.29±2.21;Ⅲ度滑脱9例,术前评分12.21±2.73,术后26.44±1.81。手术前后比较差异有统计学意义（P〈0.01）。结论：腰椎滑脱症初次手术失败原因主要与内固定物松动断裂和植骨不融合有关。翻修手术采用三椎体椎弓根钉内固定,可获得坚强内固定、充分减压、植骨融合,结合术后对患者功能锻炼的指导,可以取得满意的治疗效果。     

不同手术方式治疗腰椎滑脱症的比较

目的：比较采用不同内固定及植骨融合方式治疗腰椎滑脱症的手术疗效及适应证。方法：应用后路椎弓根螺钉复位内固定后．分别采用后外侧植骨融合术、后路椎体间植骨融合术及前路椎体间植骨融合术治疗不同类型及合并症的腰椎滑脱症患者67例，比较不同术式的手术时间与出血量、手术疗效与并发症、滑脱椎体复位率与复位丢失率以及椎间隙高度。结果：后路椎弓根钉固定加椎体间植骨融合术手术时间最长、出血量最多。手术总体优良率为88．71％，三种术式间无差异。所有椎体间植骨组植骨融合良好，椎间隙高度维持良好，滑脱椎体复位无丢失；12例后外侧植骨者平均复位丢失率为11．24％，2例椎弓根螺钉松动，2枚椎弓根螺钉断裂。结论：退变性腰椎滑脱者宜选用后路椎弓根钉固定加后外侧植骨融合术；峡部裂性腰椎滑脱者宜选用后路椎弓根钉固定加椎体间植骨融合术；腰椎滑脱翻修者宜选用后路椎弓根钉固定加前路椎体间植骨融合术     

颗粒骨植骨在椎弓根钉翻修术中的应用

椎弓根螺钉内固定系统因其能贯穿脊柱三柱，固定坚强，在脊柱外科得到广泛应用。但有时由于技术失误，椎弓根螺钉握持力不够或术后承载负荷过大，致使椎弓根螺钉松动，拔出或断裂，从而导致内固定失败，需进行翻修手术。如何提高椎弓根钉内固定翻修术的疗效，已引起脊柱外科工作者的重视。我院自2003年8月-2005年3月采用颗粒骨植骨行椎弓根钉内固定失败翻修术7例，取得较好效果，总结报告如下。     

椎弓根钉固定在10岁以下小儿胸腰椎疾患治疗中的应用

目的：探讨10岁以下小儿胸腰椎椎弓根钉固定的可行性及安全性。方法：对19例平均年龄6．5岁的胸腰椎疾患患儿，2例骨折脱位患者采用后路短节段椎弓根钉复位固定；3例肿瘤患者采用后路切除肿瘤、短节段椎弓根钉固定；10例先天性半椎体患者采用后路半椎体切除、椎弓根钉矫形固定或前后联合手术；4例脊柱侧凸患者采用后路椎弓根钉矫形固定。椎弓根钉置入点及方向与成人相似，螺钉直径为拟固定椎弓根横径的80％～90％，长度达椎体的70％～80％。手术后观察各螺钉位置，随访观察内固定稳定性及神经功能情况。结果：共置入83枚椎弓根钉，术中3个椎弓根破裂造成矫形时螺钉松动，均上移或下移一个节段完成固定；术后检查3枚螺钉位置不良，因未造成神经损害，对固定的稳定性无影响，未做处理。无脊髓神经和血管损伤及感染。18例获得平均24个月随访，1例术后1年螺钉断裂进行了翻修，其余患者无内固定松动。3例术前有神经功能障碍的患者均有明显恢复。结论：在详细的术前计划，选择恰当直径的椎弓根钉、精湛的外科技术下行小儿胸腰椎椎弓根螺钉固定是安全可行的。     

生物活性玻璃结合椎弓根钉翻修术治疗腰椎内固定失败

目的探讨生物活性玻璃(商品名固骼生,NovaBone)结合椎弓根钉翻修术治疗腰椎内固定失败的临床疗效。方法自2004年1月~2006年1月共行腰椎经椎弓根内固定391例,发生内固定失败11例,其中椎弓根螺钉断裂3例,松动或退出8例。失败病例的初次诊断:L4椎体滑脱症6例,L5椎体滑脱症2例,L1椎体爆裂性骨折2例,L2椎体压缩性骨折1例,术前均有不同程度的腰腿痛症状。手术采用经椎弓根植入生物活性玻璃、重新椎弓根钉固定加腰椎后外侧植骨融合术,术后定期摄X线片,观察内固定位置、融合情况和腰腿痛症状改善情况。结果经10~25个月(平均12.3个月)随访,手术均获成功,所有切口一期愈合,无再次内固定失败,所有后外侧植骨均达到骨性融合,腰部功能恢复满意。结论生物活性玻璃结合椎弓根钉翻修术治疗腰椎内固定失败是一种安全可靠、简单有效的手术方法。     

短节段椎弓根内固定系统术后断裂临床分析

目的分析胸腰段短节段椎弓根螺钉固定系统在临床应用中出现的断裂问题及原因，以提高手术成功率及手术效果。方法1995年3月～2003年10月应用短节段椎弓根螺钉固定治疗胸腰椎脊柱疾患592例，其中13例断裂加上外院来我院治疗的椎弓根内固定系统断裂11例，共24例。研究脊柱各节段断裂情况、其系统断裂部位及断裂因素。结果骨折16例，腰椎滑脱6例，腰椎不稳2例。螺钉断裂14例，共19颗(断钉部位：螺钉根部断裂18颗，螺钉中部断裂1颗，)；连接棒断裂10例，共14根(均为棒的根部)。T114例，L18例，L25例，L54例，S13例。不锈钢系统22例，镍钛合金系统2例。断钉时间：术后发现断钉10～32个月，平均18．85个月。结论短节段椎弓根螺钉系统断裂是一个复杂的问题，内固定系统的材料、设计、类型以及手术、术后处理等因素均可以导致其断裂。因此，术前详细的计划、内固定系统的选择、完善的手术操作及合理的术后处理对预防其断裂是十分重要的。     

胸腰椎短节段椎弓根螺钉内固定翻修的原因和预防

目的　探讨胸腰椎短节段椎弓根内固定翻修的原因 ,寻找避免内固定失败或失败翻修的方法。方法　 2 1例胸腰椎短节段椎弓根螺钉内固定术后螺钉松动 5例、位置不佳 8例、断裂 6例和选择不当 2例。临床症状有腰背部及下肢疼痛、麻木等。应用调整、更换、取出和聚甲基丙烯酸甲酯 (PMMA)灌注修复椎弓根螺钉等翻修方式。结果　 2 1例患者中 8例调整、 2例PMMA灌注椎弓根、 5例更换内固定、 6例取出内固定。术后随访 6～ 13个月 ,平均 8 4个月。 17例翻修术后患者术前的局部及下肢痛症状消失 ,X线检查显示椎弓根螺钉位置良好 ,原有的畸形消失。结论　技术性原因 (椎弓根螺钉位置不佳、松动、选择不当 )共 15例 ,占 71 4 % ,是造成翻修手术的主要原因。严格掌握脊柱椎弓根螺钉的适应证 ,提高椎弓根螺钉植入的准确率 ,是减少翻修术有效方法     

胸腰椎短节段椎弓根螺钉内固定翻修的原因和预防

目的 探讨胸腰椎短节段椎弓根内固定翻修的原因，寻找避免内固定失败或失败翻修的方法。方法 21例胸腰椎短节段椎弓根螺钉内固定术后螺钉松动5例、位置不佳8例、断裂6例和选择不当2例。临床症状有腰背部及下肢疼痛、麻木等。应用调整、更换、取出和聚甲基丙烯酸甲酯(PMMA)灌注修复椎弓根螺钉等翻修方式。结果 21例患者中8例调整、2例PMMA灌注椎弓根、5例更换内固定、6例取出内固定。术后随访6～13个月，平均8．4个月。17例翻修术后患者术前的局部及下肢痛症状消失，X线检查显示椎弓根螺钉位置良好，原有的畸形消失。结论 技术性原因(椎弓根螺钉位置不佳、松动、选择不当)共15例，占71．4％，是造成翻修手术的主要原因。严格掌握脊柱椎弓根螺钉的适应证，提高椎弓根螺钉植入的准确率，是减少翻修术有效方法。     

三维CT导航在腰椎再次手术及翻修术中椎弓根螺钉置入的应用研究(附13例报告)

目的探讨三维CT导航在腰椎再次手术及翻修手术椎弓根螺钉置入中的准确性及安全性。方法回顾性研究自2008年9月~2009年9月,收治因腰椎再次手术及翻修需进行椎弓根螺钉系统内固定13例,其中腰椎间盘术后继发椎管狭窄4例,腰椎置钉失败2例,全椎板或半椎板切除术后腰椎不稳4例、椎体滑脱3例。在减压解除神经根压迫同时在三维CT导航引导下行椎弓根螺钉固定矫形。采用术中G型臂X线机正侧位摄片与导航路径进行比较测量以及术后三维影像系统(CT、MRI)评估螺钉位置的准确性,螺钉完全位于椎弓根内为置钉位置准确,记录螺钉平均置入时间。结果共置入62枚螺钉,术中及术后X线片评估椎弓根螺钉置钉准确度为100%,术后三维影像评估螺钉位置准确率为91.8%,螺钉平均置入时间(4.7±0.7)min/枚,未出现螺钉置入相关的近期并发症。结论腰椎再次手术及翻修手术患者术中应用CT三维影像导航辅助行椎弓根螺钉置入,可以有效的提高置钉的精确性以及保证了安全性,降低了脊柱再次手术及翻修手术的风险性,减少放射线的暴露强度。     

腰椎滑脱术后失效翻修初步探讨

目的：探讨腰椎滑脱术后失效的原因、翻修对策及疗效。方法：8例腰椎滑脱术后失效翻修患者,男3例,女5例;年龄42～71岁,平均54岁。其中椎弓根螺钉断裂6例,椎间融合器塌陷、椎弓根螺钉断裂1例,骨质疏松、内植物松动1例。临床症状有畸形、局部疼痛、下肢疼痛麻木等。翻修行后路减压、复位,椎体间、后外侧植骨,经椎弓根加粗和（或）加长螺钉内固定。结果：所有患者术后获6～24个月随访,平均16个月。翻修术后患者原有症状基本缓解,手术总优良率87.5%。无术后感染并发症,均获得骨性融合。结论：技术性原因是造成腰椎滑脱术后失效的主要原因。后路椎弓根螺钉复位内固定加椎体间、后外侧植骨融合术不失为有效翻修方法之一,手术操作规范是翻修疗效满意的关键。     

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.     

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.