七氟醚在新生儿全身麻醉中的应用

目的 研究七氟醚在新生儿伞麻中的应用.方法 60例年龄1～27 d新生儿患儿随机均分为两组接受气管插管全麻:Ⅰ组使用8%七氟醚诱导、4%浓度维持;Ⅱ组采用8%七氟醚、芬太尼3 μg/kg、罗库溴铵0.5 mg/kg诱导,3%七氟醚维持.监测术前、切皮时、手术开始后15、30、60min及缝皮时的心率、血压.记录诱导至插管时间、停药至自主呼吸恢复时间和术毕至拔管时间.结果 Ⅰ组诱导至插管时间长于Ⅱ组(P<0.05),停药至自主呼吸恢复时间以及术毕至拔管时间明显短于Ⅱ组(P<0.01).与术前相比,Ⅱ组切皮时、手术开始后15 min的心率减慢、血压降低(P<0.05);与Ⅱ组比较,Ⅰ组切皮时、手术开始15 min的心率明显增快、血压明显升高(P<0.05).结论 七氟醚全凭吸入麻醉较七氟醚静吸复合麻醉安全性高.     

七氟醚和丙泊酚对老年冠心病患者麻醉诱导期心率变异性的影响

目的 观察七氟醚和丙泊酚对老年冠心病患者全麻诱导期心率变异性(HRV)的影响.方法 40例择期行上腹部手术老年冠心病患者,年龄60～80岁,ASAⅡ或Ⅲ级,随机均分为七氟醚(S组)和丙泊酚(P组):分别予4%七氟醚或靶控输注丙泊酚3μg/ml行麻醉诱导.分别记录麻醉前(基础值)、诱导后5、10、15、20 min SBP、DBP、HR及HRV的变化.结果 与麻醉前比较,诱导后5、10 min两组SBP、DBP下降,HR减慢(P＜0.05).诱导后5、15 min P组SBP、DBP显著低于S组,P组HR快于S组(P＜0.05).在麻醉诱导中,S组主要是低频(LF)逐渐降低,P组则是高频(HF)逐渐降低.结论 与靶控输注丙泊酚麻醉比较,七氟醚吸入麻醉对血流动力学影响较轻,诱导相对平稳,更适合老年冠心病患者的麻醉诱导.     

小儿七氟醚和异氟醚快速吸入诱导的比较

目的:比较小儿使用高浓度七氟醚和异氟醚加氧化亚氮快速吸入诱导的区别。方法:38例4～11岁,未使用术前药小儿随机分为二组,七氟醚组(n=20),吸入5％七氟醚,60％氧化亚氮;异氟醚组(n=18)吸入3.5％异氟醚,60％氧化亚氮。观察两组小儿采用快速吸入诱导方法时,睫毛反射和疼痛反应消失时间,以及药物的刺激性和诱导平稳程度的区别;同时观察两种方法对小儿循环功能的影响。结果:七氟醚组的诱导效果较为满意,其睫毛反射时间,疼痛反应消失时间均明显快于异氟醚组,分别为63.45±16.27(秒),189.40±28.70(秒)和75.82±22.60(秒),231.62±77.74(秒)(P<0.01);异氟醚对气道的刺激性较大,小儿吸入时躲闪,咳嗽,喉痉挛,兴奋以及分泌物增加的发生率明显高于七氟醚组;两组吸入诱导对小儿的血压无明显的影响。结论:小儿使用高浓度七氟醚吸入诱导是较为理想的麻醉诱导方法之一,与异氟醚比较,其吸入诱导平稳,对气道的刺激性较小,诱导时间明显缩短。     

静吸复合麻醉下七氟醚与异氟醚对颅内压的影响

目的:在颅内顺应性正常神经外科病人,观察1.0 MAC七氟醚与异氟醚对颅内压的影响。方法:垂体瘤或颅咽管瘤手术病人16例,随机分为两组:A组为咪唑安定 芬太尼 1.0 MAC异氟醚;B组为咪唑安定 芬太尼 1.0 MAC七氟醚。选择L_(3～4)行蛛网膜下腔穿刺。麻醉诱导采用芬太尼-咪唑安定-阿曲库铵。插管后维持稳定30分开始吸入七氟醚(或异氟醚)。分别于麻醉前、吸入麻醉药前、达预定呼气末浓度30分内观察监测指标。结果:1.0 MAC七氟醚和异氟醚均可显著降低脑灌注压,异氟醚作用较强。吸入1.0 MAC七氟醚后颅内压首先呈显著性下降,15分后回复至基础水平。吸入1.0 MAC异氟醚后颅内压无显著性变化。结论:在颅内顺应性正常患者,1.0 MAC七氟醚和异氟醚均可安全用于神经外科麻醉。     

地氟醚与七氟醚麻醉对老年病人术后认知功能的影响

目的 探讨地氟醚及七氟醚复合麻醉对老年病人术后认知功能恢复的影响。方法 70例择期行全膝或全髋关节置换术的病人,年龄均在65岁以上。静注芬太尼、异丙酚、琥珀胆碱快速诱导插管后随机分为地氟醚和异氟醚组。麻醉诱导前及手术后1、3、6及24h应用Mini-Mental State（MMS）测试方法评定其认知功能。结果 与术前相比,两组病人术后1h MMS值均明显降低。地氟醚组由29.5±0.5降至27.8±1.7;七氟醚组由29.2±1.0降至27.4±1.7。其中85％以上病人术后3h MMS恢复至术前水平。两组病人术前及术后1、3、6及24h MMS比较均无显著差异。结论 老年病人应用地氟醚或七氟醚麻醉,其术后认知功能恢复相似,仅有一过性认知障碍。     

小儿全麻诱导吸入七氟醚和异氟醚的临床观察

七氟醚是近年来用于临床的新型吸入麻醉药,具有血气分配系数低、吸收和恢复快及刺激性小等优点。本研究对小儿使用七氟醚吸入诱导并与异氟醚吸入诱导进行比较。资料与方法一般资料择期行扁桃体切除术患儿76例,年龄1～13岁,ASAⅠ级,随机分为七氟醚组和异氟醚组。七氟醚组40例,男14例,女26例,年龄(6.3±2.2)岁,体重(20.8±7.4)kg。异氟醚组36例,男12例,女24例,年龄(7.0±2.6)岁,体重(23.6±8.7)kg。麻醉方法所有患儿均不使用术前药,常规禁食6～8h。使用德国Drager公司Fabius Aeomed Vaporizer Vp300定量挥发器提供的七氟醚(凯特力,江苏恒…     

七氟醚和异氟醚吸入麻醉对压力反射敏感性比较的观察

临床观察发现七氟醚对病人血液动力学的影响与异氟醚相似 ,但七氟醚麻醉组病人的心率慢于异氟醚麻醉组。我们试验用升高和降低血压来干涉压力感受器 ,比较七氟醚 氧化亚氮和异氟醚 氧化亚氮全麻中手术患者压力感受器的功能 ,推测自主神经在两者心率变化差异中的作用。资料和方法选择 32例全麻手术病人 ,年龄 30～ 46岁 ,体重 45～ 6 7ｋｇ ,ＡＳＡⅠ～Ⅱ级 ,无高血压及其它心血管系统并发症。征得病人同意随机分为七氟醚组 (Ｓ组 16例 )和异氟醚组 (Ⅰ组 16例 )。全麻诱导用芬太尼 0 1ｍｇ、硫喷妥钠 5ｍｇ/ｋｇ、琥珀酰胆碱 1 5ｍｇ/ｋｇ …     

七氟醚静吸复合麻醉与全凭静脉麻醉用于小儿手术的比较

目的 比较七氟醚静吸复合麻醉与丙泊酚、芬太尼全凭静脉麻醉用于小儿手术的临床效果.方法 60例4～14岁ASA Ⅰ级择期行外科手术的小儿,随机均分为丙泊酚、芬太尼全凭静脉麻醉组(丙泊酚组)和七氟醚静吸复合麻醉组(七氟醚组).丙泊酚组静脉麻醉诱导,静脉麻醉药物维持.七氟醚组七氟醚麻醉诱导,七氟醚麻醉维持.记录术中血流动力学变化,术后麻醉恢复情况.结果 两组诱导方法都能实现快速诱导,且丙泊酚组麻醉诱导起效更快,意识消失时间、插管时间较七氟醚组缩短(P＜0.01).而七氟醚组麻醉诱导对心率的影响更小,诱导更平稳.七氟醚组苏醒时间、拔管时间、定向力恢复时间和PACU滞留时间均短于丙泊酚组(P＜0.01).结论 七氟醚静吸复合麻醉后术中循环稳定,术后清醒迅速、平稳,可安全有效地应用于小儿手术.     

小儿七氟醚麻醉苏醒期间躁动的研究

目的 观察小儿七氟醚麻醉苏醒期在不同年龄和不同麻醉时的躁动情况.方法 选择学龄前儿童(3～5岁)及学龄儿童(6～9岁)各60例拟进行双侧扁桃体摘除术和腹股沟斜疝修补术患儿,分别均分为学龄前儿童静-吸复合组(A1组)及七氟醚吸入组(A2组),学龄儿童静-吸复合组(B1组)及七氟醚吸入组(B2组).A1、B1纽静-吸复合麻醉诱导采用静注咪唑安定0.1 mg/kg、丙泊酚2 mg/kg、芬太尼2 μg/kg;A2、B2组吸入麻醉诱导采用8%七氟醚吸入.维持吸人3%～5%七氟醚,调节氧浓度1～2 L/min,将肺泡最低有效浓度值控制在1.3～1.5 MAC.术毕记录手术时间、拔管时间(停药至拔除气管导管的时间)和苏醒时间(停药至呼之睁眼的时间),并记录躁动发生情况.结果 同一年龄不同麻醉方式组患儿:术后轻、中、重度躁动发生率A2组明显高于A1组、B2组明显高于B1组(P<0.05).不同年龄同一麻醉方式组的患儿:术后轻、中度躁动发生率A1组明显高于B1组、A2组明显高于B2组(P<0.05);而重度躁动发生率A2组明显高于B2组(P<0.05)(表1).结论 学龄前儿童及吸入麻醉苏醒期躁动发生率高.     

Beagle犬异氟醚注射液MAC测定及其对循环的影响

目的测定Beagle犬异氟醚注射液(8%,容积比)最低肺泡有效浓度(MAC静脉),观察其诱导对循环的影响,并与异氟醚吸入最低肺泡有效浓度(MAC吸入)进行比较。方法将Beagle犬12只随机分为异氟醚注射液静脉组(静脉组)和异氟醚吸入组(吸入组)。采用上下法和夹尾刺激测定两组的MAC。监测并记录诱导前及诱导期间的MAP、HR和SpO2变化。结果MAC静脉(1.08±0.16)%明显小于MAC吸入(1.35±0.10)%(P<0.05)。静脉组诱导开始至插管所需时间短于吸入组(P<0.01),且静脉组异氟醚平均诱导用量明显少于吸入组(P<0.01);静脉组停药至拔管时间和停药至站立时间均短于吸入组(P<0.01)。吸入组插管后即刻的MAP和HR均高于插管前(P<0.05),而静脉组插管后即刻的MAP和HR与插管前相比差异无统计学意义。结论MAC静脉明显小于MAC吸入。与吸入异氟醚相比,异氟醚注射液静脉诱导速度快、用药量少、苏醒快、气管插管反应轻。     

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.