开腹和腹腔镜手术治疗小儿肠旋转不良的临床对比研究

【摘要】〓目的〓比较开腹手术和腹腔镜手术治疗小儿肠旋转不良的治疗效果。方法〓收集2012年至2014年的肠旋转不良患儿资料,传统开腹手术68例,腹腔镜手术30例,分别比较两组间的手术时间、术后进食时间和术后并发症等的差别。结果〓开腹手术时间较腹腔镜手术时间短,但术后开始进食时间及全量进食时间较腹腔镜手术组的时间长,两组之间比较有统计学意义;开腹手术术后并发症8例,腹腔镜手术术后并发症4例,两组间比较无统计学意义。结论〓腹腔镜Ladd?蒺s手术术后肠功能恢复快,可早期恢复进食,术后并发症无增加,用于治疗小儿肠旋转不良是安全而有效的。     

腹腔镜与开腹D2远端胃切除术治疗胃癌的Meta分析

目的：评价腹腔镜辅助D2远端胃切除术治疗胃癌的价值。 方法：收集1995—2010年公开发表的实施D2淋巴清扫的腹腔镜辅助远端胃切除术和开腹远端胃切除术治疗胃癌的中文和英文文献,对两种术式的手术时间、出血量、清扫淋巴结数目、排气及进食时间、住院时间、并发症发生率、病死率和复发率共9个效应量进行Meta分析。 结果：筛选出符合纳入标准的8项研究（1 065例）。与开腹组比较,腹腔镜辅助组的出血量和并发症减少,胃肠功能恢复时间、进食时间和住院时间缩短,但手术时间延长（均P<0.05）。两组清扫淋巴结数目、病死率和复发率的差异无统计学意义（均P>0.05）。 结论：腹腔镜辅助远端胃D2根治术具有侵袭性小、并发症少、恢复快的优点,能够获得与开腹手术相当的根治效果和短期疗效。     

腹腔镜与传统开腹手术治疗国人远端胃癌的Meta分析

目的：系统评价腹腔镜与传统开腹手术治疗国人远端胃癌的有效性和安全性。 方法：计算机检索国内外文献数据库（时限均从建库开始至2013年5月）,收集腹腔镜与开腹手术治疗国人远端胃癌的随机对照试验,使用RevMan 5.2软件进行Meta分析。 结果：最终纳入6个研究,555例患者,其中腹腔镜组278例,开腹组277例。Meta分析结果显示,与开腹组比较,腹腔镜组在术中出血量、术后排气时间、首次进食时间、术后住院时间、切口长度、术后镇痛剂的使用例数、并发症发生率均明显减少（均P<0.05）;但手术时间延长、术中淋巴结清扫数目减少（均P<0.05）。 结论：腹腔镜远端胃癌根治术围手术期并发症少,患者恢复快,安全可行,但手术时间长,术中淋巴结清扫数目少。     

腹腔镜与开放手术治疗胆总管囊肿临床效果的Meta分析

目的：通过Meta分析的方法比较腹腔镜与开腹手术治疗先天性胆总管囊肿的有效性和安全性。 方法：检索国内外数据库中有关腹腔镜与开腹手术治疗小儿胆总管囊肿效果的回顾性分析或病例对照研究,再根据制定的标准筛选文献行Meta分析。 结果：最终纳入10篇文献,共1?394例患者,其中589例行腹腔镜手术（腹腔镜组）,805例行开腹手术（开腹组）。与开腹组比较,腹腔镜组手术时间延长（WMD=54.51,95% CI=24.37~84.64,P<0.05）;术中失血量减少（WMD=-16.27,95% CI=-21.16~-11.39,P<0.05）;术后首次排气时间、进食时间缩短（WMD=-1.2,95% CI=-1.22~-1.18;WMD=-1.31,95% CI=-1.62~-1.00,均P<0.05）;术后住院时间与并发症发生率减少（WMD=-3.04,95% CI=-4.08~-2.36;OR=0.37,95% CI=0.15~0.90,均P<0.05）。 结论：腹腔镜手术相对于开腹手术治疗胆总管囊肿具有明显的优势;随着腹腔镜技术与术者水平的不断提高,腹腔镜手术将成为治疗胆总管囊肿首选术式。     

腹腔镜全胃切除术治疗进展期胃癌安全性与有效性的Meta分析

目的：系统评价腹腔镜全胃切除术治疗进展期胃癌的手术安全性和淋巴结清扫程度。 方法：计算机检索多个国内外文献数据库,收集腹腔镜全胃切除术对比开腹全胃切除术治疗进展期胃癌所有随机对照试验和回顾性研究,检索时间截止2014年3月。根据纳入和排除标准筛选文献、提取资料和进行质量评价,用RevMan 5.2软件进行Meta分析。 结果：最终纳入6篇文献,共1 115例,其中腹腔镜手术547例,开腹手术568例。Meta分析显示,与开腹全胃切除术相比,腹腔镜全胃切除术治疗进展期胃癌术后并发症少、术中出血量少、术后住院时间短,但手术时间较长（均P<0.05）;淋巴结清扫数目差异无统计学意义（P>0.05）。 结论：腹腔镜全胃切除术治疗进展期胃癌与开腹全胃切除术相比有一定的微创优势,手术安全性好,且淋巴结清扫程度相似。     

腹腔镜与开腹Ladd手术治疗新生儿肠旋转不良的比较

目的比较腹腔镜与开腹Ladd手术治疗新生儿肠旋转不良(排除肠坏死)的效果。方法我院2013年1月~2017年5月对74例新生儿肠旋转不良但不伴肠坏死行开腹(49例)或腹腔镜镜Ladd手术(25例),比较2组患儿手术时间、住院时间、术后并发症等情况。结果腹腔镜组手术时间中位数118、0(86. 5,137. 5) min,明显长于开腹组63. 0(55. 0,70. 5) min(Z=-5. 328,P=0. 001);住院时间中位数13. 0(11. 6,16. 0) d,与开腹组14. 0 (10. 5,21. 0) d无统计学差异(Z=-0. 791,P=0. 729)。2组术后粘连性肠梗阻(χ~2=0. 034,P=0. 853)、再扭转(Fisher精确检验,P=1. 000)、切口感染(Fisher精确检验,P=1. 000)、漏诊(Fisher精确检验,P=0. 338)发生率无统计学差异。结论腹腔镜下Ladd手术治疗于新生儿肠旋转不良,不增加术后并发症,同时具有恢复快,美观等优点,可以在腹腔镜下将肠管顺利复位,使手术顺利完成。     

腹腔镜对比传统开放手术治疗直肠癌临床效果的Meta分析

目的：对比腹腔镜直肠癌手术和传统开腹手术的临床效果。 方法：检索近20年来发表的关于比较腹腔镜与传统开腹手术治疗直肠癌临床效果的随机对照试验。按纳入标准筛选文献,用Review Manager 5.1软件行Meta分析。 结果：最终纳入14个随机对照试验,共2 114例患者,其中腹腔镜组1 111例,开腹组1 003例。腔镜组与传统开腹组比较,术中出血量少、胃肠功能恢复时间及下床活动时间早、住院时间缩短、伤口感染减少,差异均有统计学意义（均P<0.05）;手术并发症发生率包括输尿管损伤、尿潴留、肠梗阻、吻合口瘘,切口疝,两组组间差异均无统计学意义（均P>0.05）;两组在淋巴结清扫数量、标本长度、环周切缘阳性率、局部复发、切口或穿刺口种植转移、远处转移、3,5年总体生存率、3,5年无病生存率等指标上均无统计学差异（均P>0.05）。 结论：腹腔镜直肠癌手术术中出血少、术后恢复快、住院时间短,肿瘤根治效果与传统开腹手术相仿,可作为治疗直肠癌的标准术式。     

腹腔镜与开腹脾切除贲门周围血管离断术治疗门脉高压症的Meta分析

目的：系统评价腹腔镜与开腹行脾切除贲门周围血管离断术治疗门静脉高压症的疗效及安全性。方法：计算机检索国内外文献数据库,收集腹腔镜与开腹行脾切除贲门周围血管离断术比较研究的相关论文,根据纳入、排除标准筛选文献、提取资料并评价质量后,采用RevMan5.2软件进行Meta分析。结果：未获得随机临床对照试验,最终仅纳入11个临床对照试验,共494例患者,腹腔镜组227例,开腹组267例。Meta分析结果显示,腹腔镜组手术时间长于开腹组,腹腔镜组术中出血量、手术并发症发生率少于开腹组,腹腔镜组术后住院时间短于开腹组,腹腔镜组住院费用高于开腹组;差异均有统计学意义（均P<0.05）。结论：腹腔镜脾切除贲门周围血管离断术与开腹手术比较,具有术中出血量少、并发症发生率低等优点,但手术时间长,住院总费用高。因受纳入研究的数量和质量的影响,结果尚需谨慎对待。

     

腹腔镜手术与开腹手术治疗克罗恩病疗效的Meta分析

目的：比较腹腔镜手术与开腹手术在治疗克罗恩病（CD）围手术期并发症发生率与长期疗效。 方法：检索中英文数据库,收集相关的非随机对照研究,根据Cochrane Reviewers手册5.0筛选文献、提取资料、评价文献质量,使用RevMan 5.2软件进行Meta分析。 结果：最终纳入23篇非随机对照研究,共2?101例患者,其中1?006例行腹腔镜手术（腹腔镜组）,1?095例行开腹手术（开腹组）。Meta分析结果显示,腹腔镜组低围手术期总并发症明显低于开腹组（RR=0.74,95% CI=0.6~0.91,P=0.004）;长期随访中,腹腔镜组术后切口疝的发生率明显降低（RR=0.21,95% CI=0.07~0.68,P=0.009）,但术后疾病的复发率及肠梗阻发生率的差异无统计学意义（均P>0.05）。 结论：腹腔镜手术治疗CD病在降低围手术期总并发症与术后切口疝的发生率方面优于开腹手术。     

腹腔镜和开腹结直肠癌手术对机体免疫功能影响的Meta分析

目的：比较腹腔镜和开腹结直肠癌手术对机体免疫功能影响。 方法：收集1995年1月—2012年12月有关比较腹腔镜和开腹结直肠癌手术对机体免疫功能影响的随机对照研究（RCT）的中英文文献,对相关指标行Meta分析。 结果：共纳入13篇RCT文献,共959例患者,其中腹腔镜组465例,开腹组494例。Meta分析结果显示,术后第1~14天,腹腔镜组CD3+与CD4+T淋巴细胞活性、CD4+/CD8+比值均高于开腹组（均P<0.05）;腹腔镜组自然杀伤细胞活性在术后第7天明显高于开腹组（对比时间点为术后第1、3、7天）（P<0.05）;两组术后第3天的免疫球蛋白（IgA、IgG、IgM）水平比较无统计学差异（均P>0.05）;腹腔镜组白细胞介素6水平在术后第1天明显低于开腹组（对比时间点为术后第4小时及第1、3、7天）（P<0.05）;腹腔镜组C反应蛋白水平在术后第1~7天明显低于开腹组（对比时间点为术后第1、3、7、14天）。 结论：腹腔镜结直肠癌手术较开腹手术对机体免疫系统影响较小,且能够较好地保留机体免疫系统抵御病原入侵和杀伤肿瘤细胞的功能。     

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.