不同手术方式行全胸腹主动脉替换的临床研究

目的 比较手术治疗的效果,探讨不同手术方式行全胸腹主动脉替换术的适应证和具体手术方法,明确常温非体外循环下全胸腹主动脉替换的可行性和安全性.方法 2009年2月到2011年5月,46例CrawfordⅡ型胸腹主动脉瘤(thoracoabdominal aortic aneurysm,TAAA)患者行全胸腹主动脉替换术(total thoracoabdominal aortic aneurysm repair,tTAAAR).根据术式不同,分为深低温停循环tTAAAR(A)组15例和常温非体外循环tTAAAR(B)组31例.计数资料采用精确概率的x2检验和计数资料经正态性检验后采用t检验等统计学方法,比较了患者的术前、术中和术后ICU治疗情况以及围术期病死率、并发症发生率等.结果 A组和B组术后早期死亡(26.67％对3.20％,P=0.033)和一过性脑功能障碍发生率(33.30％对3.30％,P=0.018)差异有统计学意义.两组手术时间(P＜0.0001)、降主动脉阻断时间(P ＜0.0001),输注红细胞(P=0.013)差异亦有统计学意义.术前情况、内脏缺血时间、脊髓缺血时间、ICU治疗时间、带气管插管时间、脊髓损伤、肾功能不全等差异无统计学意义,P＞0.05.结论 常温非体外循环全胸腹主动脉替换术安全、可靠.适应证为可在常温下建立降主动脉到髂动脉旁路循环的胸腹主动脉动脉瘤.肋间动脉重建是重要的脊髓保护手段.     

主动脉瘤腔内修复术后早期炎性反应研究进展

<正>主动脉瘤系主动脉的病理性扩张,包括胸主动脉瘤(thoracic aortic aneurysm,TAA)、胸腹主动脉瘤(thoracoabdominal aortic aneurysm,TAAA)、腹主动脉瘤(abdominal aortic aneurysm,AAA)和主动脉夹层(aortic dissection,AD)[1]。目前,腔内修复术(endovascular aortic repair,EVAR)已成为     

腔内技术治疗胸腹主动脉瘤的进展

胸腹主动脉瘤(thoracoabdominal aortic aneurysm,TAAA)是指动脉瘤同时累及胸降主动脉及腹主动脉段,发生率为(5.9~10.4)/10万人[1]。通常情况下,TAAA的预后很差,未经治疗时有80%会发生破裂[2]。由于其病变范围广、内脏区多根分支动脉受累、术后高死亡率及高并发症发生率等问题,一直是治疗的难点。传统的开放手术采用多分支人工血管重建主动脉及内脏动脉血供,但是术后并发症如呼吸衰竭、脊髓缺血、肾功能衰竭等仍然不能忽视。     

非体外循环下全主动脉弓替换术治疗主动脉弓降部动脉瘤的早、中期结果

目的 评价采用常温、非体外循环下全主动脉弓替换手术治疗主动脉弓、降部动脉瘤的术后早、中期结果.方法 2004年4月至11月,对连续7例主动脉弓降部动脉瘤病人实施常温、非体外循环下全主动脉弓替换手术.术后对所有病人进行长期随访,随访截止日期为2011年3月.7例均为男性,年龄23～75岁,中位年龄57岁.真性动脉瘤3例,假性动脉瘤4例,其中1例为弓降部巨大假性动脉瘤覆膜支架置入术失败者.采用胸部正中与左胸前外侧联合切口,全身肝素化后,依次在升主动脉前外侧壁安放主动脉侧壁钳,降主动脉与头臂动脉分别放置主动脉阻断钳,将带四分支人工血管依次与升主动脉行端-侧吻合、与降主动脉及3支头臂动脉行端-端吻合,最后闭合升主动脉残端,切除弓降部主动脉瘤壁.结果 平均胸降主动脉阻断(13.6±5.6)min,左颈总动脉阻断(5.7±0.8)min,无名动脉阻断(7.8±2.5)min,左锁骨下动脉阻断(11.2±1.5)min.术后使用呼吸机平均(12.3±4.1)h.病人全部生存.与同期常温体外循环下主动脉弓替换手术组相比,本组机械通气时间显著减少.无神经系统并发症.术后CT扫描结果显示,主动脉弓降部人工血管形态佳,吻合口周围无渗漏或假性动脉瘤形成.全组平均随访(79.7±2.1)个月,病人生活质量良好,复查CT结果均未见异常.无远期死亡.结论 在常温、非体外循环状态下实施全主动脉弓替换手术,是一种治疗主动脉弓、降部真性或假性动脉瘤的安全、有效的方法,严格把握手术适应证是手术成功的关键.

Abstract：

Objective Study the early and midterm results of a technique-total aortic arch replacement without using extracorporeal circulation or aortic bypass for the treatment of aortic aneurismal disease involving the transverse aortic arch and proximal descending aorta. Methods Between April and November 2004, 7 consecutive patients with true (n = 3) or false (n =4) aortic aneurysm underwent this procedure. The mean follow-up was 6. 6 years. The median age at operation was 57years ( range 23 to 75 years). Normothermia general anesthesia and median sternotomy combined with left anterior thoracotomy were administered. A partially occluding clamp was placed on ascending aorta and a longitude aortic incision was made. Anastomosis of a branched graft to ascending aorta in an end-to-side fashion was commenced. The descending aorta distal to the aneurysm was occluded and transected, and anastomosed to the distal end of the branched graft in an end-to-end fashion. Finally,the arch vessels were divided and anastomosed to the branches of the graft and the aneurysm excised. Results The average cross-clamp time of descending aorta, left common carotid artery, and innominate artery was (13.6 ±5.6)min, (5.7 ±0.8)min, and (7.8±2.5) min respectively. The mean intubation time was (12.3 ±4.1) hours. There were no adverse outcomes or neurologic complications in this series. All patients survived and recovered completely. The mean follow-up time was (79.7 ±2.1) months. All patients lead a normal life. There was no late death. CT follow-up study 6 years after surgery reveals no abnormal image. Conclusion Total aortic arch replacement without cardiopulmonary and aortic bypass is a feasible and effective method for the aortic aneurismal disease involving the transverse aortic arch and proximal descending aorta in selected patients.     

复杂主动脉瘤血管腔内治疗的现状及展望

复杂主动脉瘤主要是指近肾腹主动脉瘤(juxtarenal abdominal aortic aneurysms,JRAAA)和胸腹主动脉瘤(thoracoabdominal aortic aneurysms,TAAA).开放性手术治疗复杂性主动脉瘤常常需要胸腹联合切口、腹腔干或肾上腹主动脉阻断和内脏动脉的显露,因此它不管是对于血管外科医师还是患者本人都是一个考验.胸腹主动脉瘤开放性手术30 d和1年的病死率为19%和31%[1].自从1991年Parodi等[2]实行第1例肾下腹主动脉瘤腔内修复术后,这种微创修复动脉瘤的方法显示出了比开放手术更低的并发症和病死率,对于老年和全身情况不能耐受手术的患者则更具优势[3-4].     

胸腹主动脉瘤的手术方法及治疗要点

胸腹主动脉瘤(thoracoabdominal aortic aneurysm,TAA)是指动脉瘤同时累及胸腔段和腹腔段主动脉或侵犯到内脏动脉的腹主动脉瘤,临床上多采用Crawford分型,按动脉瘤的波及范围分为4型,由于病变范围广,病情进展快,加上病理部位特殊,给外科治疗带来许多困难.术中大出血、休克、心搏骤停和多脏器功能衰竭是常见的致死原因;截瘫和肾功能衰竭又是灾难性手术并发症,迄今仍然是一种挑战性手术.目前报道胸腹主动脉瘤的致死率为20%～34%.     

胸腹主动脉瘤的治疗

<正>胸腹主动脉瘤(thoracoabdominal aortic aneurysm,TAAA)是一种累及降主动脉及腹主动脉的动脉瘤样变,因其死亡率高及手术难度大而成为血管外科治疗难点之一,其与降主动脉瘤和腹主动脉瘤主要区别为TAAA累及内脏动脉,手术治疗需要胸腹联合切口,介入手术也不能简单使用直型覆膜支架治疗,因而,治疗的手术方式及技巧与降主动脉瘤和腹主动脉瘤截然不同。TAAA自然病程死亡率高,传统的治疗方式为开放手术。而杂交手术,开窗支架、分支型支架及多层裸支架等介入治疗方法的应用使更微创的方式治疗TAAA成为可能。     

一期次全或全主动脉替换术的中期随访结果

目的 总结一期全主动脉替换术治疗全程主动脉瘤的中期随访结果.方法 2004年2月至2008年7月22例全程主动脉瘤的患者接受一期次全(7例)或全主动脉替换术(15例).男性17例,女性5例,年龄19～47岁.慢性A型夹层动脉瘤15例,主动脉根部瘤合并慢性B型夹层动脉瘤5例,主动脉根部瘤合并弓部和胸腹主动脉瘤1例,慢性B型合并急性A型夹层动脉瘤1例.手术均在全身麻醉深低温停循环顺行性脑灌注下进行.采用胸骨正中切口+左后外胸腹联合切口.采用分段阻断法用人工血管置换全部病变主动脉.结果 无手术死亡病例.术后早期死亡1例,死于多器官功能衰竭.术后发生脑梗死2例,二次开胸止血7例.存活21例,随访3～56个月,平均(35.0±16.9)个月,情况良好,无晚期死亡.1例David+全主动脉替换术患者术后1年因主动脉瓣反流行主动脉瓣置换术.此外无再手术病例.结论 一期次全或全主动脉替换术是治疗全程主动脉瘤的有效方法.手术结果满意,术后中期随访效果良好.     

胸腹主动脉瘤手术治疗中的截瘫并发症

胸腹主动脉瘤（thoracoabdominal aortic aneurysm，TAAA）是指胸主动脉和腹主动脉联合动脉瘤，按照性质可分为真性动脉瘤、假性动脉瘤和夹层动脉瘤。治疗方式主要包括传统外科手术、腔内修复术（endovascular aneurysm repair，EVAR）以及近来新兴的“杂交手术”（hybrid treatment），即联合利用传统外科手术重建脏器血管和腔内技术修复动脉瘤。传统外科手术治疗TAAA已有半个多世纪，术式历经不断改进；EVAR技术应用十余年来发展迅猛，已经历几代产品的变革。但迄今为止无论何种术式，因脊髓缺血而造成截瘫这一灾难性的并发症仍无法完全解决。     

累及内脏动脉分支的主动脉疾病治疗对策探讨

内脏动脉分支主要指肾动脉、腹腔动脉和肠系膜上动脉的范围.累及内脏动脉分支的主动脉疾病主要有胸腹主动脉瘤(thoraco-abdominal aortic aneurysm,TAAA)、主动脉夹层(aortic dissection,AD)和腹主动脉瘤(abdominal aortic aneurysms,AAA)等疾病.经典的胸腹主动脉瘤,Crawford-Safi五型分型:Ⅰ型,病变从左锁骨下动脉始,延伸至腹主动脉上段,正好位于肾动脉水平以上,没累及肾动脉.Ⅱ型,病变最广泛,从左锁骨下动脉始,延伸至腹主动脉分叉处.Ⅲ型,病变从降主动脉下部,约第6肋间隙处,延伸至腹主动脉分叉处.Ⅳ型,病变累及全部腹主动脉,从膈肌处主动脉至腹主动脉分叉处.Ⅴ型,病变从第6肋间隙处的降主动脉,延伸至肾动脉水平以上的部位.     

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.