CT引导下适形冷冻消融治疗溶骨性转移瘤

目的评估CT引导下适形冷冻消融治疗溶骨性转移瘤的安全性及局部疗效。方法收集在我院就诊的溶骨性骨转移瘤患者36例(共51处病灶),所有患者均有明确的病理诊断且经双膦酸盐类药物治疗2个月后疼痛无缓解。患者均接受CT引导下适形冷冻消融治疗,并于治疗后即刻、2个月后分别行增强CT检查以评估治疗效果及观察有无并发症。分析患者在术前、术后1周及术后2个月的视觉模拟评分系统(VAS)疼痛评分结果。结果所有患者顺利完成手术,未出现严重并发症。治疗后2个月均未见局部复发、增强CT均未见强化;2例患者出现新发转移灶。患者术后1周[(4.18±0.82)分]及2个月[(2.36±1.01)分]VAS疼痛评分均较术前[(7.13±1.55)分]下降(P均0.05)。结论 CT引导下适形冷冻治疗溶骨性转移瘤局部疗效显著、安全性较高。     

CT引导下经皮穿刺乙醇消融治疗无功能性肾上腺肿瘤

目的探讨CT引导下经皮无水乙醇消融术(PEI)对无功能性肾上腺偶发瘤的治疗价值。方法21例肾上腺偶发瘤,均为单发病灶。病灶直径均小于5 cm,其中7例病灶直径小于3 cm。采用CT引导下无水乙醇瘤内注射进行治疗,每个病灶治疗次数不少于2次,治疗后1~2个月,行CT平扫和增强扫描,观察肿瘤大小、坏死情况。结果PEI治疗后CT增强扫描复查,13个病灶(包括直径小于3 cm的7个病灶)完全坏死;8个病灶大部分坏死,经过重复治疗,病灶彻底坏死。已随访1~3年,未见肿瘤复发。结论无功能性肾上腺偶发瘤采用CT引导下经皮穿刺乙醇消融疗法治疗疗效确切,创伤小。     

PET/CT显像中SUVmax对骨转移瘤与骨髓瘤鉴别诊断的价值

目的 回顾性分析未知原发灶的多发性骨破坏患者PET/CT显像中骨髓瘤与骨转移瘤病变SUVmax的特征,为临床鉴别诊断提供依据.方法 CT或MRI发现的多发骨破坏患者119例,其中71例PET/CT检查后行病理检查,男40例,女31例;年龄37～87岁,平均61-3岁.病理确诊骨髓瘤21例,骨转移瘤41例.测量骨髓瘤和骨转移瘤每个骨病变的SUVmax并进行比较,采用ROC曲线获得鉴别诊断的分界点.采用单因素方差分析比较不同形态学特征(溶骨性和成骨性)骨转移瘤与骨髓瘤SUVmax的差异.结果 PET/CT在骨髓瘤病例中共检出315个病灶,在骨转移瘤病例中共检出684个病灶.骨髓瘤病灶SUVmax(3.42±1.96)值明显低于转移瘤病灶(7.03±4.15).SUVmax值为4.45时,鉴别骨髓瘤和骨转移瘤的敏感性和特异性分别为80.4%和72.4%.溶骨性骨转移瘤病灶SUVmax值(8.02±4.85)明显高于成骨性骨转移瘤(4.79±2.61)和骨髓瘤(3.37±1.92),而成骨性骨转移瘤与骨髓瘤病灶的SUVmax值差异无统计学意义(P>0.05).结论 PET/CT对未知原发灶的多发性骨破坏患者骨髓瘤与骨转移瘤的鉴别诊断具有潜在的价值,多发性骨破坏病灶SUVmax值较低和溶骨性破坏可提示骨髓瘤.     

CT引导125I粒子植入术治疗非小细胞肺癌

目的探讨CT引导下125I粒子植入术治疗非小细胞肺癌（NSCLC）的临床应用价值。方法对24例NSCLC患者,采用治疗计划系统计算布源,在CT引导下将125I粒子植入瘤灶内。术后1个月复查胸部CT、血常规及血清肿瘤标记物,此后每3个月复查脑部和肺部CT,每6个月行全身骨扫描复查,随访12个月观察局部病灶控制情况及并发症。结果肺部目标病灶完全缓解6例（6/24,25.00%）,部分缓解18例（18/24,75.00%）。术后发生少量气胸4例,痰中带血4例,发热5例,给予对症治疗后1～3天症状消失。术后1个月1例患者出现白细胞轻度下降,所有患者血清肺癌相关肿瘤标记物水平均不同程度好转。随访期内1例患者发生对侧肺转移,2例出现骨转移,1例脑转移,无死亡患者。结论 CT引导下125I粒子植入术治疗NSCLC创伤小、疗效显著、并发症少,是肺癌综合治疗的重要手段。     

肝动脉化疗栓塞联合CT导向经皮瘤内注射无水乙醇治疗肝转移瘤

目的探讨肝动脉化疗栓塞联合CT导向经皮瘤内注射无水乙醇治疗肝转移瘤的临床疗效。方法将48例(132个瘤灶)不能手术切除的肝转移瘤患者随机分为两组,对25例(68个瘤灶,治疗组)施行肝动脉栓塞化疗术(TACE)和CT导向经皮瘤内注射无水乙醇(PEI)治疗,对23例(64个瘤灶,对照组)施行单纯TACE。全部病例随访10~43个月并比较两组的疗效。结果治疗组和对照组的肿瘤缩小率分别为66.2%和48.4%;1、2、3年的生存率分别为92.0%,80.0%,64.0%和78.3%,65.2%,47.8%;局部复发率分别为16.0%和39.1%。两者比较均有明显差异(P<0.05)。结论TACE联合CT导向PEI在肝转移瘤治疗中可相互协同,疗效优于单纯TACE。     

骨转移瘤的误诊分析

目的 提高对骨转移瘤的认识，降低骨转移瘤的误诊率。方法 通过对骨转移瘤的发生机制、发病率、好发部位、骨转移瘤来自非骨原发肿瘤的顺序、监床表现与诊断方法等的认识，并对临床工作中5例被误诊为骨转移瘤病例长期随访结果进行分析。结果 5例均获得远期随访，24～96个月（平均57.6个月），患者生活良好。例1、2为肺癌与前列腺癌，未见肿瘤复发与骨转移。例4、5为脊柱结核，病情稳定，病灶修复。例3为L3S1椎间盘炎。分析误诊的原因为读片未能很好地结合临床全面考虑；对先进影像检查所见缺乏经验，认识不足。结论 大多数骨转移瘤通过详细分析病史、临床表现及影像学检查可以明确诊断。X线检查、核素全身骨扫描、CT、MR等先进诊断技术对诊断骨转移瘤有重要作用。先进的影像检查技术敏感性强，特异性较差，但仍可从中找出诊断的规律，相互补充，提高诊断正确率。此外，新的核素鹰眼系统及MR弥散加权像可提高对老年良性（如骨质疏松）与恶性（如骨转移瘤）椎体压缩性骨折的鉴别诊断。     

经导管动脉化疗栓塞在肝细胞癌骨转移治疗中的应用初探

目的初步探讨经动脉化疗栓塞术（TACE）治疗原发性肝细胞癌（HCC）骨转移瘤的应用价值。方法收集中山大学附属第一医院伴有骨转移瘤的HCC患者15例,3例（20．0％）为多发性骨转移,12例（80．0％）为单发转移。TACE治疗骨转移瘤前后行影像学检查,以目测模拟法（VAS法）对局部疼痛程度进行分级,治疗后随访3个月以上。结果所有患者成功行局部骨转移灶TACE治疗,术中无并发症。15例患者术前VAS评分均在7分以上,术后局部疼痛均有不同程度缓解。按VAS评分标准,1个月后随访完全缓解3例,明显缓解7例,轻度缓解5例。治疗后3个月疼痛缓解的有效率为80．0％,至6个月时总体有效率仍达58．3％。影像学评价的治疗有效率达86．7％。TACE后1个月5例患者AFP下降〉50％,8例下降〉30％,2例下降〉20％。术后3个月生存率为100％,6个月生存率为80％。结论TACE可有效控制肝细胞癌骨转移灶的局部生长、缓解疼痛,有助于患者生存质量的提高。     

对比脉冲序列造影成像技术评估肝癌无水酒精治疗疗效的应用

目的探讨应用对比脉冲序列（CPS）超声造影成像技术评价PEI治疗疗效的价值。方法在47例原发性肝癌（HCC）病人PEI治疗后，采用超声造影剂声诺维（Sono Vue）、Acuson Sequior512超声仪和CPS实时造影成像技术进行超声造影显像，观察病灶的血流灌注，并与常规彩超及增强CT进行对照，超声检查后随访半年以上。结果应用CPS实时造影成像技术，本组的64个病灶PEI治疗后肝肿瘤灭活诊断正确率96．8％，与增强CT检查结果相同，明显高于常规彩超的64．1％。结论超声造影能于PEI治疗后判断肿瘤坏死情况，可望成为评价肝癌PEI治疗疗效的可靠方法。     

药物去势治疗后前列腺癌骨转移灶的组织病理变化

目的 了解药物去势治疗后前列腺癌骨转移灶的组织变化。方法 对7例前列腺及骨转移灶穿刺结果阳性的前列腺癌骨转移患者采用药物去势治疗，对比观察原发肿瘤和骨转移灶组织去势前后变化。结果 7例治疗后2个月前列腺肿物消失。5例PSA在2个月内恢复至正常水平，其中2例因脊髓压迫症状行骨科手术，骨病灶病理检查发现腺泡型癌细胞消失，肿瘤骨小梁数量减少，免疫组化PSA染色阴性。2例局部骨灶进行性发展者行骨病灶切除，病灶处组织学检查发现腺泡型癌细胞，其中夹杂大量的肿瘤样骨组织，免疫组化PSA染色阳性。PSA及影像学检查见有与骨灶局部改变相对应的表现。结论 去势治疗可使前列腺及骨转移灶的肿瘤细胞部分或全部消失，PSA及影像学检查可表现出骨转移灶的相应变化，并为治疗提供确切依据。     

螺旋CT透视引导下经皮穿刺乙酸消融治疗第二肝门区原发性肝癌

目的评价螺旋CT透视(CTF)引导下经皮穿刺乙酸注射治疗(PAI)第二肝门区原发性肝癌的安全性和治疗效果。方法搜集我院2000年10月～2004年8月在实时螺旋CT透视导向下经皮穿刺乙酸注射治疗第二肝门区原发性肝癌23例，共30个病灶。病灶直径3～8cm。根据病灶大小每次注入50％～60％乙酸2～12ml不等．乙酸内加入1～2ml对比剂混匀。注射后1周影像检查，根据情况重复注射1～2次。结果在实时螺旋CT透视下均能准确穿刺到靶点，除15例轻中度疼痛外无其它并发症。全部病例均经B超或螺旋cT随访，3个月时，其中瘤灶缩小12个(40％)，肿瘤大小无变化16个(53％)、肿瘤增大2个(7％)。23例随访3月．全部生存；17例随访1年，10例生存，7例失访；10例随访2年，7例生存，3例失访。结论CTF引导下经皮乙酸消融治疗第二肝门部原发性肝癌是安全有效的。     

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.     

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.     

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.