负压封闭引流技术在显微外科中应用的探讨

目的 报道负压封闭引流技术(VSD)在显微外科领域内应用效果. 方法 对不能一期闭合的离断伤创面24例和骨外露或者肌腱外露创面46例,行VSD后再行组织移植修复术;对肌瓣表面游离植皮创面12例,以VSD覆盖植皮表面. 结果 7～10 d去除VSD,24例再植术后创面肉芽组织新鲜,生长良好,肢体血供未受影响;46例骨外露或者肌腱外露创面未见或少见脓性分泌物,二期移植的组织瓣或皮肤均成活;12例肌瓣表面游离植皮者,肌瓣和植皮均成活. 结论 VSD能预防和控制感染,提高组织瓣或植皮的成活率.用于治疗不能一期闭合的离断伤创面,骨外露或者肌腱外露创面以及肌瓣上游离植皮创面具有良好的辅助治疗效果.     

肌瓣及皮瓣修复胫骨骨外露创面的治疗体会

目的报道经骨折复位固定手术及负压封闭引流处理后的外伤性皮肤软组织缺损伴胫骨骨外露创面,采用肌瓣、皮瓣修复的疗效。方法 2013年2月-2016年1月,对51例重度胫腓骨开放粉碎性骨折,采用内或外固定架固定术后,其中24例皮肤软组织缺损或坏死伴胫骨外露,予清创及VSD治疗,采用肌瓣、皮瓣修复骨外露创面。结果肌瓣、皮瓣均成活,其中2例呈慢性骨髓炎,余皮肤软组织缺损伴骨外露创面完全愈合。结论肌瓣、皮瓣修复皮肤软组织缺损伴胫骨骨外露创面,手术成功率高,可为伤区提供良好的血运,可有效控制感染及增加骨愈合率。     

比目鱼肌胫骨骨膜瓣逆行转位术的临床应用

目的 探讨比目鱼肌胫骨骨膜瓣修复胫骨中、下段严重粉碎性骨折、骨不连、骨缺损合并软组织缺损的临床疗效. 方法 从2000年7月至2010年12月,应用比目鱼肌胫骨骨膜瓣逆行转位术修复19例胫骨开放性骨折并胫前软组织缺损骨外露、10例胫骨骨折内固定术后伤口感染组织坏死致胫骨及内固定物外露、5例胫骨创伤性骨髓炎清创后骨缺损并软组织缺损、3例胫骨骨不连合并胫前软组织缺损.结果 本组37例肌骨膜瓣均成活,其中1例术后肌瓣部分坏死,经再次清创、负压封闭吸引、植皮后愈合;1例肌骨膜瓣边缘小窦道,经换药后2个月愈合;其余创面均Ⅰ期愈合,随访0.5～7.0年,无感染复发、窦道形成,骨愈合时间6～ 10个月,所有患者均恢复负重和行走功能. 结论 比目鱼肌胫骨骨膜瓣逆行转位术,修复软组织缺损同时能促进骨的愈合,是修复胫骨中、下段严重粉碎性骨折、骨不连、骨缺损合并软组织缺损的有效方法.     

部分腹直肌肌瓣加皮片移植修复下肢骨折后骨或钢板外露

目的：探讨游离部分腹直肌肌瓣加皮片移植修复下肢骨折后骨或钢板外露的方法及疗效。方法：2009年10月-2010年12月,笔者单位应用游离部分腹直肌肌瓣加皮片移植修复下肢骨折后骨或钢板外露患者共7例,其中胫骨开放性骨折术后骨质外露4例,胫骨骨折术后钢板外露2例,腓骨骨折术后钢板外露1例。结果：术后除1例植皮部分坏死换药后创面愈合外,其余移植肌瓣及植皮全部成活,术后外形及功能良好,患者均较满意。结论：游离部分腹直肌肌瓣加皮片移植修复下肢骨折后骨或钢板外露具有血供丰富、抗感染力强和顺应性好,术后外形美观等优点,且供区损伤小,只取部分腹直肌,保留了腹直肌的大部分功能,是修复下肢骨或钢板外露,尤其是伴骨髓炎或感染创面的理想方法。     

GustiloⅢB和ⅢC型胫骨骨折骨固定及组织瓣修复的临床分析

目的 探讨GustiloⅢB和GustiloⅢC型胫骨骨折骨固定及组织瓣修复的方法和时机的选择. 方法 GustiloⅢB和GustiloⅢC型胫骨骨折患者136例,男102例,女34例；年龄14～ 68岁,平均34岁.损伤程度:GustiloⅢB型98例,GustiloⅢC型38例.骨固定修复方法选择:一期行外固定架固定113例,钢板内固定4例；二期行骨固定19例.软组织修复方法选择:一期行带血管蒂组织瓣转位修复创面67例;一期行吻合血管游离组织瓣修复7例；62例一期行VSD负压封闭一周至数周后,二期行游离植皮9例,胫后动脉肌间隙穿支皮瓣11例,腓动脉穿支皮瓣13例,腓肠肌肌(皮)瓣14例,交腿皮瓣15例. 结果 本组所有患者创面皆完全愈合.术后随访10～24个月,121例患者骨折愈合;12例患者因大段骨缺损,二期行骨移植术后正常愈合;3例患者因感染并发骨髓炎、窦道形成,经再次手术,骨折端延期愈合；骨折愈合时间为5～12个月,平均7个月. 结论 GustiloⅢB、ⅢC型胫骨骨折的一期或二期骨固定及组织瓣修复各有优缺点,如有条件争取一期骨固定及组织瓣修复为最好.     

负压封闭引流技术结合肌瓣转移游离植皮治疗小腿及足踝部软组织缺损伴骨外露

目的 探讨负压封闭引流(VSD)技术结合肌瓣转移游离植皮治疗小腿及足踝部大面积软组织缺损伴骨外露的疗效. 方法 2006年3月至2011年12月共收治52例小腿及足踝部大面积软组织缺损伴骨外露患者,男37例,女15例;年龄24 ～ 66岁,平均38.9岁;软组织缺损面积:20 cm×15cm～35 cm×30cm,骨外露面积:6 cm×4 cm～lO cm×5 cm.开放性骨折按Gustilo分型:Ⅲ A型17例,Ⅲ B型35例.急诊清创后利用邻近肌瓣转移最大限度覆盖骨外露,缩小骨外露范围,裸露骨质钻数个小孔后使用VSD技术治疗待创面肉芽组织生长良好后,采用游离植皮术联合持续VSD技术修复创面.小腿及足踝部功能按Lowa踝关节评分标准评定. 结果 52例患者应用VSD技术治疗1～4次,骨外露被完全覆盖时间为6 ～ 29d,平均18.2d.所有患者术后获6个月至5年(平均为2年8个月)随访,所有患者软组织缺损区的创面肉芽组织生长快、质地好,骨外露被快速生长的肉芽组织所覆盖,创面游离植皮全部成活.骨折愈合时间为3～6个月(平均4个月).5例发生跟腱挛缩致马蹄足畸形,后期行矫正术.无合并感染、骨坏死和慢性骨髓炎等并发症发生.小腿及足踝部功能按Lowa踝关节评分标准评定:优9例,良33例,可8例,差2例,优良率为80.8％. 结论 VSD技术结合肌瓣转移游离植皮治疗小腿及足踝部大面积软组织缺损伴骨外露,可避免截肢和复杂手术,是一种简单、快捷、有效的治疗方法.     

吻合血管的游离肌肉瓣加网状皮片移植修复胫骨骨折合并骨外露及感染创面

目的介绍应用吻合血管的游离肌肉瓣加网状皮片移植修复胫骨骨折合并骨外露及感染创面的新方法。方法26例胫骨骨折合并骨外露及感染创面患者依伤情选择手术时机,5例采用一期吻合血管的游离肌肉瓣加网状皮片移植覆盖骨外露创面；6例急诊清创术后2周行二期修复；其余15例入院前胫骨远端感染严重,均采用二期肌肉瓣加网状皮片移植覆盖骨外露创面。结果26例中22例术后肌肉瓣及皮片全部成活；2例皮片部分坏死,2例创口延迟愈合,经换药均二期愈合。随访10～24个月(平均18个月),皮片色泽、质地、弹性均良好,无瘢痕挛缩。骨折均已愈合。结论肌肉瓣血运丰富,是修复胫骨远端感染及骨外露创面的理想方法,比较适合覆盖大面积软组织损伤合并骨外露创面和小腿远端慢性窦道及慢性骨髓炎骨外露创面。     

VSD联合腓肠肌肌瓣治疗小腿复杂软组织缺损

目的探讨小腿复杂多发软组织缺损的修复方法。方法对地震伤后小腿多发软组织缺损造成骨外露,钢板外露的病患5例,经清创,腓肠肌肌瓣转移,封闭负压引流术（vacuum sealing drainage,VSD）覆盖创面7～10 d后行中厚皮片植皮治疗。结果移植肌瓣全部成活,创面一期愈合3～6个月,骨折愈合,伤口无感染。本组均获随访,随访时间5～10个月,平均7.5个月。膝踝关节功能无明显障碍,负重行走肢体无变形,无并发症。创面平均愈合时间为20d。结论 VSD技术联合腓肠肌肌瓣是治疗小腿复杂软组织缺损的有效方法。     

负压封闭引流技术在Gustilo-Anderson Ⅱ~Ⅲ型开放骨折中的应用

目的探讨负压封闭引流技术(VSD)在Gustilo-AndersonⅡ~Ⅲ型开放骨折治疗中的作用。方法对25例Gustilo-AndersonⅡ~Ⅲ型开放骨折患者的断端软组织缺损一期无法缝合的骨外露创面行VSD治疗,术后冲洗引流,二期植皮或皮瓣、复合组织瓣修复。结果 13例一期清创用VSD治疗,二期植皮或皮瓣修复;10例经再次或多次行VSD治疗,创面新鲜后植皮或皮瓣、复合组织瓣修复。2例感染,经换药、引流,抗感染治疗,延期行复合骨瓣修复创面痊愈。创面愈合时间18~56(35±11)d。25例均获随访,时间10~24(18±6)个月,骨折均达临床愈合。无创伤性骨髓炎发生。结论对于Gustilo-AndersonⅡ~Ⅲ型开放骨折皮肤软组织缺损较重患者行VSD治疗,可为二期修复创造了良好的条件。     

局部筋膜瓣联合植皮在头面部骨外露创面修复中的应用

目的:探讨运用局部筋膜瓣加植皮修复头面部骨外露创面的临床疗效。方法:选择2016年6月-2018年12月笔者科室应用局部筋膜瓣加植皮修复有骨外露的头面部创面13例患者,其中外伤6例,皮肤恶性肿瘤7例。根据创面面积大小及形状,在创面旁切取获得适当大小筋膜瓣,范围3cm×6cm^6cm×9cm,经折叠后覆盖骨外露创面,将中厚皮片植于筋膜瓣上,术后观察植皮成活情况,评估临床疗效。结果:13例患者筋膜瓣及植皮均成活良好,术后随访1~6个月,外形良好。结论:局部筋膜瓣加植皮修复骨外露创面效果肯定,外形好,值得在临床推广使用。     

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.