颈椎人工椎间盘置换术与颈椎前路椎间盘切除融合术治疗颈椎病的研究进展

颈椎前路椎间盘切除融合术（ACDF）是治疗颈椎病的经典术式,疗效明确,但因责任节段融合引起相邻节段椎间盘压力及未融合节段活动范围增加,导致术后手术关节活动度（ROM）欠缺、邻近节段退行性变（ASD）加速等。针对融合术式存在的弊端,非融合技术颈椎人工椎间盘置换术（CTDR）应运而生,应用于颈椎病的治疗,疗效可靠,可在完成神经减压后保留手术节段ROM,恢复椎间盘高度,降低邻近节段ASD的发生率,克服了ACDF的固有局限^[1-3]。CTDR有明确的适应证和禁忌证^[4],而ACDF的禁忌证较少,2种术式的优劣目前尚无定论。自2005年开始,多个研究中心围绕CTDR和ACDF的疗效优良率、关节ROM、颈椎功能障碍指数（NDI）等方面展开分析比较,得出2种术式的临床疗效相似的结论^[5-9],甚至有部分研究认为CTDR疗效优于ACDF^[10-12]。但因随访时间短,对于CTDR的疗效和预后仍存在争议^[10,13]。近年来,诸多研究^[14-19]在比较CTDR与ACDF预后的同时,还围绕2种术式的医疗支出、恢复周期、运动功能等展开讨论,为术式的个性化选择提供依据。     

颈椎椎间盘突出致脊髓半切综合征误诊为脑卒中1例报告

脊髓半切综合征(BSS)由Brown-Sequard于1849年首次提出^[1],是由外部压迫和内部病变等原因引起的一种罕见的脊髓不完全性损伤,通常发生在颈部^[2]。可由创伤(如枪伤、刺伤、骨折及椎体脱位)和非创伤(如肿瘤、硬膜外血肿、多发性硬化症、辐射等)引发^[3-5],因椎间盘突出导致的BSS相对较少^[6-7]。BSS表现为病变侧损伤平面以下深感觉障碍及上运动神经元性瘫痪;对侧损伤平面以下疼痛、温觉丧失^[8-9],有轻度到严重的神经功能受损。BSS占创伤性脊髓损伤的1%~4%^[10],国内外相关文献报道较少,主要为个案报道^[2,11]。本院急诊科于2020年10月22日收治1例因存在类卒中症状,初期被误诊为急性脑梗死,在下级医院进行过溶栓治疗的BSS患者,现对诊疗过程进行梳理分析,报告如下。     

生物相容高分子水凝胶在椎间盘修复再生方面作用的研究进展

椎间盘退行性变为慢性疾病,会导致脊柱承重不稳,进而损伤脊髓、马尾神经和神经根,60%的70岁以上老年人群会发病^[1-2]。由于椎间盘退行性变的病理学、病理生理学及生物力学机制并不完全清楚,目前的治疗手段仅能减轻疼痛症状,不能完全消除疾病^[3-4]。椎间盘切除术和椎间融合术是治疗椎间盘退行性变的常用术式,但易造成脊柱生物力学的改变^[5]。人工椎间盘可应用于椎间盘退行性变的治疗,但因椎间盘的结构和功能复杂,很难设计出理想的椎间盘假体来保持天然组织结构和生物力学特征。理想的生物组织替代物应具有高强度、高柔性和高韧性^[6]。     

斜外侧入路腰椎椎间融合术的应用进展

腰椎椎间融合术（LIF）被广泛应用于腰椎椎间盘退行性疾病^[1-2]。LIF包括前/后路椎间融合术（ALIF/PLIF）、经椎间孔腰椎椎间融合术（TLIF）、极外侧/直接外侧腰椎椎间融合术（XLIF/DLIF）等,这些术式具有一定的临床疗效,亦各有优缺点^[3-4]。Mayer^[5]于1997年首先提出一种微创手术入路,Silvestre等^[6]于2012年将其正式命名为斜外侧腰椎椎间融合术（OLIF）,该术式提供了一条通过腹膜后血管鞘和腰大肌前缘间隙到达腰椎的入路,通过避开固有结构,降低了血管及神经丛的损伤风险,同时有较大的操作空间可更好地清除椎间盘及置入更大的椎间融合器,避免暴露引起术后并发症。近年来,OLIF广泛应用于治疗腰椎退行性疾病,相比传统椎间融合术,OLIF具有创伤小、出血少、恢复快及融合率高等优点^[6]。本文从OLIF的手术技术,适应证及禁忌证,临床应用及并发症等方面进行分析,综述如下。     

全可视脊柱内窥镜下靶向侧隐窝入路治疗腰椎椎体后缘离断症

椎体后缘离断症（PRAS）又称腰椎后缘椎骨内软骨结节、腰椎软骨板破裂症等,常见合并腰椎椎间盘突出并继发腰椎椎管狭窄,引起下肢神经根性疼痛、麻木或间歇性跛行,严重时伴有马尾神经症状^[1-3]。根据离断物的大小和位置,分为小中央型、小外侧型、大单侧型、大中央型、大双侧型^[4]。虽然传统后路开放手术是治疗PRAS的有效方法^[2,5-6],但随着脊柱内窥镜技术、微创理念及手术工具的不断改进,近年来,有学者^[7-11]采用脊柱内窥镜技术治疗PRAS,并取得了满意疗效。但对于下位椎体后上缘大中央型PRAS,内窥镜技术处理具有一定的挑战性^[12],如经椎间孔内窥镜脊柱系统（TESSYS）盲视处理上关节突时血管及神经损伤风险较高;Yeung脊柱内窥镜系统（YESS）操作区域不精准,无法到达侧隐窝^[13]。近年来的全可视内窥镜技术在可视下操作,提高了手术的安全性,但若充分显露神经根及硬膜囊,需要去除较多的关节突,影响脊柱长期稳定^[14-15]。2018年6月-2020年7月,河南省直第三人民医院采用全可视脊柱内窥镜下靶向侧隐窝入路技术治疗PRAS患者32例,该技术可在保留小关节完整性的前提下,切除上关节突下半部腹侧以及部分椎体后上缘,彻底切除致压物,疗效良好,现报告如下。     

单侧椎弓根螺钉联合对侧椎板关节突螺钉内固定椎间融合术的研究进展

椎弓根螺钉(PS)内固定技术由Roy-Camille等^[1]于1970年首次报道,特别是其联合椎间融合器植骨的应用,具有固定节段短、稳定性好、融合率高、疗效确切等优点,成为腰椎固定融合的标准术式^[2-3]。但双侧PS内固定增加了邻近节段的应力^[4],特别是采用正中切口显露的操作,存在切口大、软组织剥离范围广、出血量大等缺点^[5-6]。虽然经皮和经肌间隙入路明显减小了手术切口、减少了创伤和出血量,但固定方式和力学特性并没有改变^[7-9]。椎板关节突螺钉(TLFS)内固定技术由Magerl^[10]于1984年首次完整地描述,并报道了与PS联合应用的初步实践。TLFS可较好地控制腰椎三维6个方向的运动^[11-12],具有切口小、创伤小、操作简单等优点^[13-14]。单侧PS联合对侧TLFS内固定(联合固定)于2005年由Jang等^[15]首次报道,在临床上获得快速推广应用,成为一种独立、有效的腰椎固定融合方法^[6,16-17]。本文从生物力学、临床应用及适应证等方面对联合固定椎间融合术的进展作如下综述。     

椎间盘源性腰痛合并下位椎间隙塌陷2例报告

腰痛为骨科临床常见症状，其可能源于腰椎椎间盘，而椎间盘源性腰痛（DLBP）最常见节段为L₄/L₅和L₅/S₁^[1-3]。DLBP是椎间盘内各种病变（如退行性变等）刺激椎间盘内疼痛感受器引起的功能丧失的下腰痛，不伴根性症状，无神经受压或节段过度活动的影像学证据^[4]。目前DLBP的诊断、治疗仍存在诸多疑问，特别是椎间隙塌陷且MRI显示塌陷节段为“黑间盘”时容易将塌陷节段臆断为责任节段，造成误诊。海军军医大学附属长征医院收治DLBP合并下位椎间隙塌陷患者2例，联合应用椎间盘造影和椎间盘阻滞确诊后行椎间融合术，术后患者腰痛均缓解。现将诊疗过程报告如下，并对诊断存在的争议进行讨论。     

动态稳定系统的生物力学和临床应用进展

动态稳定系统（Dynesys）由Stoll等^[1]在Graf韧带系统的基础上改进设计而成,现已广泛应用于治疗腰椎退行性疾病（LDD）。LDD主要包括腰椎椎间盘突出、继发性腰椎椎管狭窄、退行性椎体滑脱及退行性脊柱侧凸等,当引发严重腰腿部疼痛、神经根压迫等临床症状时往往需要手术治疗。与传统后路腰椎椎间融合术（PLIF）及经椎间孔腰椎椎间融合术（TLIF）相比,Dynesys通过椎弓根螺钉连接产生的动态推拉关系在固定节段对抗异常折弯力和剪切力、改善固定节段应力传导的同时保留固定节段活动度（ROM）,进而减少术后邻近节段退行性变（ASD）的发生^[2]。然而,目前关于Dynesys的临床疗效尚存在争议。本文对近年来国内外关于Dynesys的相关研究进行分析,从生物力学、临床应用等方面作如下综述。     

混合现实技术引导的经皮内窥镜下腰椎椎间盘切除术的初步探索与应用

经皮内窥镜下腰椎椎间盘切除术（PELD）已经成为治疗腰椎椎间盘突出症（LDH）的首选方法^［1-3］。腰椎椎间盘突出类型多样化,术前须精确定位突出椎间盘的“靶点”位置,确定进针点、深度和角度等相关参数,以便术中可按照术前设计快速准确地穿刺和置入工作通道,这是靶向穿刺技术的核心,也是尽可能减少不必要创伤并发症的基础^［4］。常规手术通道的建立,需要根据椎间盘突出的不同病理类型并结合临床实践确定,且术中需要C形臂X线机透视辅助,存在学习曲线陡峭、辐射量大、手术风险高等问题^［5-6］。混合现实（MR）技术是近年发展起来的一门新兴技术,其将虚拟现实（VR）技术与增强现实（AR）技术相结合,操作者可从MR技术呈现的全息影像中获取相关信息,从而实现虚拟和真实的交互^［7-8］。目前,MR技术在复杂的脑外科手术、髋关节手术中已有应用,并获得良好的临床疗效^［9-11］,但尚无其应用于PELD的报道。本研究组在MR技术引导下,对1例LDH患者行PELD,取得了良好的临床疗效,现报告如下。     

Quadrant系统下单侧内固定治疗老年腰椎退行性疾病

腰椎退行性疾病是引起腰腿痛的常见原因,在老年人群中发生率超过50%^[1]。腰椎融合术是治疗腰椎退行性疾病的有效方法,可稳定椎体、恢复椎间高度,临床疗效良好^[2-3]。目前椎间融合术的金标准是双侧椎弓根内固定术,可为椎体间接提供坚固内固定,但坚固内固定会导致邻近节段退行性变及骨量丢失^[4]。有研究报道,单侧和双侧内固定治疗腰椎退行性疾病的临床疗效无显著差异^[5]。本院2016年6月—2018年1月采用Quadrant系统下单侧内固定治疗老年腰椎退行性疾病患者33例,疗效满意,现报告如下。     

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.