结直肠癌肝转移根治性切除预后因素分析

目的 分析影响结直肠癌肝转移患者根治性手术切除预后的临床病理因素,探讨改善患者预后的方法.方法 收集2005年1月至201 1年12月江苏省苏北人民医院和复旦大学附属肿瘤医院收治的103例结直肠癌肝转移根治性切除患者的临床资料.采用Kaplan-Meier法计算生存率,用Log-rank法分析患者生存情况,对各种影响预后的因素分别进行单变量和多变量Cox回归分析.结果 103例患者均获随访,随访时间10～ 60个月,术后1、3、5年生存率分别为90％、49％、39％.单因素分析结果显示:肝转移灶数目、大小、分布、术前CEA水平、手术并发症、术后化疗是肝转移灶切除术后的影响因素(x2值分别为24.732、9.461、9.568、25.948、25.370、5.701,P＜0.05);多因素分析显示,肝转移灶数目、肝转移灶切除术前CEA水平、手术并发症是影响预后的独立因素(Wald=7.974、12.051、11.547,P＜0.05).结论 肝转移灶数目、肝转移灶切除术前CEA水平和手术并发症是影响结直肠癌肝转移患者预后的独立因素.适当扩大手术切除的适应证,加强对高危患者的随访和术后辅助化疗,可能改善肝转移患者的预后.     

胃癌肝转移外科治疗的临床分析

目的 评价胃癌肝转移的外科治疗效果及病理因素对其预后的影响。方法 本组834例胃癌患者中共有91例诊断为肝转移，其中79例为同时性肝转移，12例术后发现异时转移，共21例行胃癌肝转移灶切除术。结果 胃癌肝转移灶切除后1年、3年生存率分别为69％、30％。单转移灶及异时性转移是其有利的预后因素。13例肝转移灶有假包膜形成。结论 单转移灶及异时转移、肿瘤假包膜形成预示胃癌肝转移切除患者有较好的预后。     

胃癌肝转移31例外科治疗体会

目的 探讨胃癌肝转移的外科治疗效果.方法 对我院1997年10月～2006年10月收治的原发性胃癌338例中伴肝转移的31例的临床资料进行回顾性分析.对其中施行同时性胃癌肝转移灶切除术(切除组)的19例和仅行胃癌根治术而未行肝转移灶切除术(未切除组)的12例的术后生存时间进行对比.结果 全组除1例术后死于肝功能衰竭外,其余30例均获得随访.胃癌肝转移灶切除术后1年、3年和5年生存率分别为83.3%、44.4%和33.3%;未切除组术后1年生存率为50.0%,3年及5年生存率为0.两组术后生存时间有显著性差异(P＜0.05).切除组病例中有68.4%在肿瘤和周围肝组织间形成纤维假膜.结论 假包膜形成是有利的预后因素.对于胃癌肝转移病人,特别是有假包膜形成者采用外科治疗预后更好.     

影响结直肠癌肝转移手术切除患者预后的多因素分析

目的 探讨影响结直肠癌肝转移患者手术切除的预后因素。方法 收集1995-2001年间收治的结直肠癌肝转移手术切除患者103例的资料，用Kaplan-Meier法计算术后生存率，以Cox模型进行多变量分析。结果 患者术后1、3年无瘤生存率分别为73．8％和43．7％，术后1、3年累积生存率分别为7g．6％和49．5％。单因素分析显示：术前血清CEA水平、转移灶与原发灶的治疗间隔时间、术中切缘情况、肝门淋巴结转移、肝内卫星灶的存在与否、肝转移灶的最大直径、数目及有无包膜影响患者的术后肝内复发和术后累积生存率，而术后化疗可以提高患者的累积生存率。多因素分析显示：转移灶与原发灶的治疗间隔时间、切缘情况、肝内卫星灶的存在与否和肝转移灶的最大直径是影响肝内复发和累积生存率的独立因素，而肝门淋巴结转移是影响累积生存率的独立因素，有无包膜是影响肝内复发的独立因素。结论 手术切除是结直肠癌肝转移有效的治疗手段。转移灶与原发灶的治疗间隔时间、切缘情况、肝内卫星灶、肝转移灶的大小和包膜、肝门淋巴结转移等是患者预后的独立影响因素。     

结直肠癌肝转移的临床病理特征与术后生存关系分析

目的通过分析结直肠癌肝转移临床病理学特征与术后生存因素的相互关系,寻找更多更准确的能够影响预后的指标对预后生存的影响,为结直肠癌肝转移患者的治疗策略提供参考。方法回顾性分析第二军医大学东方肝胆外科医院2006年1月至2009年12月期间收治并经手术治疗的233例结直肠癌肝转移患者的临床资料,采用Kaplan-Meier法计算生存率及生存曲线,并进行单因素分析,采用log-rank法进行统计学检验。将经单因素分析对预后有统计学意义的危险因素带入COX多因素回归模型,计算独立预后因素。结果本组患者术后中位生存期为37.0个月,术后1、3及5年累积生存率分别为93.0%、61.0%、17.0%。接受根治性手术患者的术后中位生存期、3及5年累积生存率优于姑息性手术者:40.53个月比27.20个月、59.0%比29.0%、20.0%比0(P0.05)。对于总体生存期而言,单因素分析结果显示,手术方式、肝转移瘤切除术后首次复发时间、肝内转移灶数目、肝内转移灶最大直径、手术切缘、肝外不可切除转移灶及周围组织或器官侵犯、是否合并慢性肝病(慢性肝炎、脂肪肝、肝硬变)、术前血清CEA水平、CA19-9水平、是否为同时性肝转移、原发灶TNM分期、肝转移瘤生长位置和肝转移瘤包膜是否完整这13项是影响预后的因素(P0.05);COX多因素分析结果显示,姑息性手术方式、同时性肝转移、肝转移瘤生长位置广泛、肝转移瘤无完整包膜、肝内转移灶多发、肝内转移灶最大直径3 cm、存在肝外不可切除转移灶及周围组织或器官侵犯和未合并慢性肝病(慢性肝炎、脂肪肝、肝硬变)这8项因素是对结直肠癌肝转移患者术后生存产生影响的独立危险因素(P0.05)。结论手术治疗可以使结直肠癌肝转移患者获得长期生存,姑息性手术方式、同时性肝转移、肝转移瘤生长位置广泛、肝转移瘤无完整包膜、肝内转移灶多发、肝内转移灶最大直径3 cm,存在肝外不可切除转移灶及周围组织或器官侵犯、未合并慢性肝病(慢性肝炎、脂肪肝、肝硬变)等是影响结直肠癌肝转移患者术后预后的独立危险因素。     

结直肠癌肝转移患者的预后因素分析

目的：分析结直肠癌伴肝转移患者手术切除后影响术后生存率的危险因素。方法：回顾性分析54例手术治疗的结直肠癌肝转移患者的临床及随访资料,对相关因素行单因素和多因素分析。结果：单因素分析显示,原发癌分化程度、淋巴转移、肝转移灶数目、肝转移灶肿瘤大小、手术方式及是否术后进行综合治疗等为影响患者预后的因素（均P<0.05）;多因素分析表明,手术方式、淋巴结转移和原发肿瘤分化程度是主要危险因素（均P<0.05）。结论：及早发现并进行根治切除以及加强术后综合治疗是提高本病远期疗效的关键。

     

结直肠癌肝转移复发再次肝切除术的疗效与预后分析

目的 探讨再次肝切除术在结直肠癌肝转移复发治疗中的应用价值.方法 回顾性分析43例结直肠癌肝转移复发再次肝切除术和67例结直肠癌肝转移复发内科化疗的临床资料.结果 结直肠癌肝转移复发再手术组和化疗组1,3,5年生存率分别为83.7％,51.1％,27.9％和65.7％,20.6％,3.0％(P＜0.05或P＜0.01).再次肝切除组无手术死亡病例,并发症发生率为32.6％.单因素分析显示肝脏复发转移灶个数,切缘情况,CEA,肿瘤大小,肿瘤分化程度与预后有关.多因素回归分析结果表明,仅有肝脏复发转移灶个数和肿瘤大小为影响预后的独立因素.结论 再次肝切除术对于结直肠癌肝转移复发是安全的治疗方案,肿瘤负荷较小(癌直径＜5 cm和转移灶＜3个)的患者预后较好;再次手术可以延长结直肠癌肝转移复发患者的生存时间.     

结直肠癌肝转移的外科治疗

目的探讨结直肠癌肝转移的手术疗效。方法1996年8月～2000年8月手术治疗结直肠癌肝转移患者31例,行原发癌与转移癌同时切除者9例,结直肠癌根治术后6月再切除肝转移灶者18例;切除肝转移灶后2月再切除原发病灶者4例。原发灶行右半结肠切除5例,横结肠切除4例,左半结肠切除7例,Dixon术12例,Miles术3例。肝转移灶行左外叶切除5例,左半肝切除2例,右后叶切除4例,右前叶切除2例,左或右肝不规则切除18例。结果全组无手术死亡。术后粘连性肠梗阻1例,切口感染3例,经对症治疗后均痊愈出院。平均随访6.4(0.5～8)年,1、2、5年生存率分别为100%、80.6%、29.0%。同期手术者与分期手术者5年生存率分别为33.3%和27.3%,无统计学差异(P>0.05)。结论对结直肠癌肝转移患者应积极争取手术切除,术后可配合其他综合治疗;对原发灶早期诊断、早期手术治疗及辅助化疗有利于防止结直肠癌肝转移。     

结直肠癌伴同时性肝转移的治疗

目的 探讨结直肠癌伴同时性肝转移患者的临床相关病理因素以及手术治疗.方法 回顾性分析1994年8月至2006年12月收治患者的临床资料及随访结果,比较结直肠癌无肝转移和有同时性肝转移患者的病理特点及不同程度肝转移患者和不同手术处理的预后.结果 2019例原发性结直肠癌患者中发生同时性肝转移者166例(8.10%).多因素分析显示:术前CEA水平、Ducks分期、肿瘤分化程度与浆膜浸润是同时性肝转移发生的高危因素;同时性肝转移术后1、3、5年生存率分别为69%、21%、9%;不同程度肝转移(H1、H2、H3)组间预后差异有统计学意义(X2=23.35,P<0.01).根治性手术切除组总体生存率明显高于姑息切除和未能切除组生存率(X2=21.18,P<0.01);姑息切除组和未切除组近期生存率差异有统计学意义(P<0.01),远期生存率差异无统计学意义(P=0.13).结论 结直肠癌伴同时性肝转移患者肝转移程度不同预后也不同.能够根治性切除的结直肠癌伴同时性肝转移预后较好,姑息切除原发病灶可提高近期预后和生活质量.     

结肠癌肝转移外科治疗的临床与病理分析(附25例报告)

目的　探讨结肠癌肝转移的外科治疗方法及其病理因素对预后的影响。方法　本组79例结肠癌肝转移患者中共有 2 5例接受原发灶根治术以及肝转移灶切除术或射频消融术。其中 14例进行了原发灶根治术及肝脏转移灶切除术 ,11例进行了肝脏转移灶射频消融术。结果　本组结肠癌肝转移患者术后 1年、3年生存率分别为 84 %、4 8%。分化程度高以及单个转移灶的患者预后较好。肝脏肿瘤切除与肝脏肿瘤射频消融术后患者生存时间无明显差异。结论　结肠癌肝转移患者原发肿瘤的分化程度、肝脏转移灶的数量对预测患者的预后有一定的作用。手术切除及射频消融术对治疗结肠癌肝转移能够达到较为接近的治疗效果。     

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 comparison of the inhibitory effects of four volatile anaesthetics on the metabolism of chlorzoxazone, a substrate for CYP2E1, in rabbits

Background: Halothane inhibits in vitro and in vivo activity of cytochrome P-450 (CYP) 2E1. There are several fluorinated volatile anaesthetics besides halothane, and most of them are defluorinated by CYP2E1. It is unclear whether other fluorinated anaesthetics inhibit the in vivo activity of CYP2E1.
Methods: We compared the inhibitory effects of therapeutic concentrations of four inhalational anaesthetics, halothane, enflurane, isoflurane, and sevoflurane, on chlorzoxazone metabolism in rabbits receiving artificial ventilation.
Results: All four inhalational anaesthetics decreased arterial blood pressure and increased plasma chlorzoxazone concentration. However, no significant differences in the plasma chlorzoxazone concentration were found between the four anaesthetics. The estimated chlorzoxazone clearance increased after beginning inhalation with all four agents, but no significant difference in clearance was noted between agents.
Conclusions: At therapeutic concentrations, the in vivo inhibitory effect on chlorzoxazone metabolism was similar for all four inhalational anaesthetics examined, even though their chemical characteristics and extent of hepatic metabolism differ considerably.     

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.     

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.