斜外侧入路腰椎椎间融合术临床应用研究进展

<正>腰椎椎间融合术是治疗腰椎退行性疾病的有效术式,可在保持脊柱稳定性的基础上恢复椎间隙高度^[1],为非手术治疗无效的腰椎退行性疾病的首选治疗方式,经过长期的临床实践,证实疗效满意^[2]。斜外侧入路腰椎椎间融合术(OLIF)由Silvestre等^[3]于2012年在Mayer^[4]报道的微创前路椎间融合术的基础上形成。OLIF是近年常用的椎间融合术式之一,其通过腰大肌与腹部大血管之间的天然间隙建立通道,在直视下置入融合器,进行腰椎的间接减压与融合,不破坏肌肉和椎体小关节,具有手术创伤小、手术时间短、术中出血量少、术后恢复快等优点^[3,5]。     

关节内应用氨甲环酸对全膝关节置换术后失血量的影响

[目的]探讨关节腔内应用抗纤溶药物氨甲环酸对全膝关节置换术后失血量的影响。[方法]2012年6月²012年12月,选取100例行初次单侧全膝关节置换术患者,男28例,女72例;年龄552012年12月,选取100例行初次单侧全膝关节置换术患者,男28例,女72例;年龄55⁷8岁,平均65.5岁;骨性关节炎76例,类风湿性关节炎24例,病程178岁,平均65.5岁;骨性关节炎76例,类风湿性关节炎24例,病程1¹5年,平均6.5年。随机分为A、B两组,每组50例。A组在缝合关节囊后向关节腔内注射氨甲环酸1 g,溶于50 ml生理盐水;B组仅给予等量生理盐水关节腔内注射。记录术后失血量、输血量、输血例数、术后血红蛋白浓度和术后3 h纤维蛋白原、凝血酶原时间、活化部分凝血活酶时间等为评价指标。观察患者是否出现下肢深静脉栓塞的临床症状,并于术后第7、14 d行下肢血管多普勒超声检查。[结果]A、B组术后可见失血量、输血量和输血例数比较差异有统计学意义(P<0.05);术后血红蛋白浓度,A组明显高于B组(P<0.05);两组患者术后3 h纤维蛋白原、凝血酶原时间和活化部分凝血活酶时间的比较差异无统计学意义(P>0.05)。术后未发现下肢深静脉血栓形成。[结论]在全膝关节置换术中关节腔内应用氨甲环酸能明显减少患者术后失血量,降低输血率和输血量,并且避免了静脉内应用可能带来的并发症。     

氨甲环酸在全膝关节置换术中的研究进展

全膝关节置换术仍未找到有效减少术后失血的方法,传统的止血带应用会破坏纤溶-凝血的平衡,不利于手术后伤口止血。氨甲环酸是一种纤溶抑制剂,能可逆地阻断纤溶酶原与纤维蛋白的结合,抑制纤维蛋白溶解,有效减少术后出血。但目前氨甲环酸的最佳治疗方案还未明确,关于血栓形成及栓塞事件的发生仍存在许多疑虑。该文就氨甲环酸作为止血药在全膝关节置换术中的作用、不同给药途径、剂量、剂次及安全性等方面的研究进展作一综述。     

氨甲环酸减少同期双侧全髋置换围术期失血有效性及安全性研究

[目的]探讨静脉10 mg/kg氨甲环酸减少同期双侧全髋关节置换术(total hip arthroplasty,THA)围术期失血的有效性及安全性。[方法]回顾四川大学华西医院2011年7月²013年7月所有同期双侧全髋关节置换术,设定纳入排除标准后共纳入57例。其中静脉使用10 mg/kg氨甲环酸31例,未使用26例。氨甲环酸组患者于每侧手术切皮前均完成静脉单次使用10 mg/kg氨甲环酸,对照组不使用。对比术前及术后不同时间点血红蛋白(HB)值及红细胞压积(HCT)值的差异;根据Gross方程计算围术期总失血量;统计两组输血量及输血率;根据术后第5d双下肢静脉彩超结果判断术后深静脉血栓及肌间静脉血栓发生率,统计肺栓塞的发生率及术后住院天数,应用SPSS统计软件得出结论。[结果]氨甲环酸组术后1、3 d HB值及HCT值明显高于对照组,P<0.05,差异有统计学意义,但术后第5 d差异无统计学意义。氨甲环酸组围术期平均失血(1 811.6±490.8)ml,明显低于对照组(2 408.6±511.3)ml,P<0.05,差异有统计学意义。氨甲环酸组患者术后8例(25.8%,8/31),对照组14例(53.8%,14/26)输血,P<0.05,差异有统计学意义。氨甲环酸组人均输血量0.68 U,明显低于对照组1.23 U,P<0.05,差异有统计学意义。两组患者术后深静脉血栓、肌间静脉血栓、肺栓塞发生率及术后平均住院日比较差异无统计学意义。[结论]静脉单次10 mg/kg氨甲环酸于每侧关节置换前单次用药是控制同期双侧THA围术期失血安全、有效的方法。     

氨甲环酸联合术中自体血回输在THA中的应用

目的探讨氨甲环酸联合术中自体血回输在全髋关节置换术中应用的安全性及有效性和两者的治疗效果。方法 2019年1月至2020年12月行初次单侧全髋关节置换术患者60例,分成3组,每组20例。A组:术中未使用氨甲环酸和术中自体血回输。B组:术中使用氨甲环酸。C组:术中使用氨甲环酸和自体血回输。通过对3组患者术前第1天、术后第1天和术后第5天的凝血酶原时间、活化部分凝血激酶时间、纤维蛋白原、D-二聚体、血红蛋白、血小板、红细胞、白细胞、C-反应蛋白、血沉数值的比较,统计术中出血量、回输血量、术后引流量、总失血量、异体输血总量、异体血输血率,记录发生下肢肌间静脉血栓、下肢深静脉血栓、肺动脉栓塞并发症的数据,分析氨甲环酸、氨甲环酸联合术中自体血回输在全髋关节置换术中应用的有效性及安全性和两者的治疗效果。结果氨甲环酸联合术中自体血回输在全髋关节置换中的应用,可以减少围手术期的出血量、术中出血量、术后引流量、异体血的总输入量和异体血输血率。结论围手术期总出血量在1000ml左右的全髋关节置换手术,采用氨甲环酸联合术中自体血回输,可使大约65%的需要异体血输血的患者避免异体血输血,有效节约血液资源,临床上值得推广应用。     

氨甲环酸在人工全膝关节置换术中的应用

一、临床应用历史氨甲环酸（TranexamicAcid,TXA）是一种抗纤溶药物,其结构与赖氨酸类似,能竞争性阻抑纤溶酶原在纤维蛋白上的吸附,防止其激活,保护纤维蛋白不被纤溶酶所降解和溶解,从而达到止血的效果。自上世纪60年代以来,氨甲环酸在临床多个领域中的应用,均取得了良好的效果。Ker等对多学科手术后使用氨甲环酸的随机对照研究进行了荟萃分析,筛选出自1972年到2011年发表的共129篇文献,     

氨甲环酸在初次全髋关节置换术中的应用

全髋关节置换术(total hip arthroplasty,THA)是骨科常见的大手术之一。近年来随着我国老年化进程的不断加快,THA术在全国范围内的不断推广,围手术期如何减少出血、降低输血量已成为众多关节骨科医生关注的焦点。氨甲环酸(tranexamic acid,TXA)属纤溶蛋白溶解药,与纤溶酶原的赖氨酸结合位点(LBS)具有高亲和性,可竞争性结合LBS位点,阻断纤溶酶重链与纤维蛋白间的结合,抑制纤维蛋白降解从而达到止血的目的,被广泛应用于心脏外科、儿童外科、妇产科等手术中。但就TXA在初次THA术中的使用方式、临床效果以及可能存在的潜在风险等方面则缺乏足够的研究且充满争议。本文拟就TXA的药理机制、临床功效及安全性、经济社会效益等加以综述。     

人工膝关节置换术中静脉注射氨甲环酸对减少术后失血的临床观察

[目的]评价术中静脉注射氨甲环酸减少人工膝关节置换术术后出血量、降低围手术期输血率的临床效果,证实静脉途径应用氨甲环酸不增加血栓的风险性。[方法]分析2014年1月~2015年10月由同一组外科医生完成的连续120例单侧人工膝关节置换术患者的临床资料,其中60例术中静脉滴注15 mg/kg的氨甲环酸,另一组60例患者为未使用氨甲环酸组。通过测定患者手术前后血红蛋白(Hgb)的变化估算出术后失血量,并记录所有患者的输血情况。[结果]使用氨甲环酸组患者的总失血量、显性失血量、输血率显著低于未使用氨甲环酸组,差异有统计学意义;两组患者隐性失血量比较未见明显差异;两组下肢深静脉血栓的发生率无显著性差异。[结论]术中静脉使用氨甲环酸可以减少人工膝关节置换术后的总失血量、显性失血量,降低输血率。不增加下肢深静脉血栓的发生率。     

氨甲环酸不同给药方法对失血量和凝血功能的影响

目的探讨氨甲环酸静脉给药和手术切口内局部给药对腰椎后路椎间融合术患者围手术期失血量和凝血功能的影响。方法择期行腰椎单节段或双节段腰椎后路椎间融合术的90例患者随机分为3组,每组30例。静脉给药组于手术开始后静脉滴注20mg/kg氨甲环酸注射液;局部给药组于缝合切口前向切口内注入20mg/kg氨甲环酸注射液;对照组不给予氨甲环酸。比较3组患者的术中失血量、术后引流量、术后血红蛋白浓度、术后输血例数及发生下肢深静脉血栓、肺栓塞的例数。比较凝血功能指标凝血酶原时间(PT)、活化部分凝血活酶时间(APTT)和血栓弹力图(TEG)参数。结果与对照组比较,静脉给药组和局部给药组术后引流管的出血量减少(P0.01),且局部给药组的输血比例更低,术后血红蛋白浓度更高(P0.05)。3组的PT和APTT比较差异无统计学意义。静脉给药组的TEG参数α角和MA值大于对照组(P0.01)。结论氨甲环酸静脉给药和局部给药均可减少腰椎后路椎间融合术患者围手术期失血量,且局部使用对凝血功能的影响更小。     

氨甲环酸对减少单侧全膝关节置换术后出血的疗效观察

[目的]探讨不同剂量氨甲环酸对减少单侧全膝关节置换术后出血的疗效及安全性。[方法]选取2012年7月²013年7月因骨性关节炎行单侧全膝关节置换的142例患者进行研究。采用随机数表法将患者分为三组,A组48例,松止血带前30 min给予100 ml 5%葡萄糖注射液静脉点滴;B组48例,松止血带前30 min将氨甲环酸0.75 g稀释于100 ml 5%葡萄糖注射液后静脉点滴;C组46例,松止血带前30 min将氨甲环酸1.5 g稀释于100 ml 5%葡萄糖注射液后静脉点滴。比较患者术后总出血量、显性出血、隐性出血及部分凝血活酶时间(APTT)、凝血酶原时间(PT)、凝血酶原国际标准化比值(PT-INR)、D二聚体等方面。同时三组患者术后第5 d行下肢血管彩超,均随访3个月,观察是否出现下肢深静脉血栓。[结果]三组患者术后总出血量、显性出血量、术后引流量、术后3 d输血人数及术后D-二聚体两两比较,差异有统计学意义(P<0.01)。三组患者术中出血量、术后隐性出血量、术后3 h PT、APTT、PT-INR比较差异无统计学意义(P>0.05),三组患者血栓栓塞事件差别无统计学意义。[结论]单侧全膝关节置换术松止血带前30 min应用氨甲环酸不能明显减少患者术后的隐性出血,但能够显著减少术后总出血量、显性出血量及术后异体血输血人数,剂量为1.5 g时更为有效,并且不会增加患者术后血栓形成风险。     

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.