结肠黏膜重建尿道治疗复杂性超长段尿道狭窄

目的:探讨结肠黏膜重建尿道治疗复杂性超长段尿道狭窄的应用价值与疗效.方法:对既往已有平均2.5次不成功的尿道修复史的35例患者,采用结肠黏膜一期尿道成形术,治疗其复杂性超长段尿道狭窄.所用结肠黏膜重建的尿道长10～20cm,平均14.6cm.术后分别行尿道造影,检测尿流率,部分患者行尿道镜检查.结果:患者术后随访3～60个月,平均28.5个月.31例术后排尿通畅,最大尿流率大于15 ml/s.1例因结肠黏膜新尿道与前列腺部尿道吻合区血供较差,术后继发尿道狭窄;1例在术后3个月并发尿道外口狭窄,经手术矫正后排尿通畅;2例分别在术后46,20个月时发生与重建尿道无关的球膜部尿道狭窄,采用口腔黏膜尿道成形术后排尿通畅.结论:利用结肠黏膜重建尿道治疗复杂性超长段尿道狭窄或闭锁,是一种可行而有效的方法,尤其是适合在较多常规方法治疗失败者.     

游离黏膜组织重建尿道治疗复杂性尿道狭窄的临床研究

目的 探讨利用游离黏膜一期尿道成形治疗复杂性尿道狭窄或闭锁的疗效。方法 2000年8月至2004年7月采用2种游离黏膜一期尿道成形术治疗73例复杂性尿道狭窄。术前42例已行耻骨上膀胱造瘘，余31例最大尿流率1．2～6．5ml／s。用游离结肠黏膜(n=22)重建尿道长10～18cm，平均13cm；用口腔黏膜(n=51)重建尿道长3～11cm，平均5cm。术后随访分别行逆行尿道造影及尿流率，部分患者行尿道镜检查。结果随访2～48个月，平均19个月。术后排尿通畅67例(91．8％)。发生再次狭窄4例，其中结肠黏膜重建者1例，口腔黏膜重建者3例；排尿欠畅2例，定期行尿道扩张；尿道皮肤瘘2例；结肠腹壁瘘1例。1例结肠黏膜重建尿道者术后47个月移植物活检示结肠黏膜的组织形态学基本无变化。结论口腔与结肠黏膜均可作为较理想的尿道替代物，口腔黏膜较适合狭窄段不长的尿道修复，结肠黏膜较适合复杂性超长段尿道狭窄或缺损的治疗。     

结肠粘膜重建尿道的动物实验与临床应用

目的　探讨结肠粘膜代尿道治疗复杂性前尿道长段狭窄或闭锁的可行性。　方法　 6条雌性杂种成年狗在全麻下切开尿道 ,剥离全段尿道粘膜 ,取相等长度的结肠粘膜替代尿道粘膜 ,12周后将狗处死 ,取尿道组织作病理检查。采用结肠粘膜替代尿道一期尿道成形术治疗 1例复杂性前尿道长段狭窄患者 ,术后 3个月分别行逆行尿道造影 ,尿道镜和尿流率检查。　结果　 6条狗移植于尿道的结肠粘膜全部成活 ,部分腺上皮转变为移行上皮细胞。采用结肠粘膜替代尿道的患者术后排尿通畅 ,移植段尿道无狭窄 ,最大尿流率 30ml/s。　结论　结肠粘膜代尿道是治疗复杂性前尿道长段狭窄或闭锁的一种有效方法 ,可用于不适合应用包皮或膀胱粘膜及颊粘膜时的尿道重建     

结肠黏膜尿道成形术治疗复杂性超长段尿道狭窄三例报告

目的 探讨结肠黏膜尿道成形术治疗复杂性超长段尿道狭窄的应用价值与疗效.方法 回顾性分析3例复杂性超长段尿道狭窄患者资料.年龄分别为71、64、48岁,病程分别为3个月、6个月、6年;尿道狭窄段长度分别为13、18、12 cm.采用狭窄段尿道切除,截取12～18 cm乙状结肠,利用结肠黏膜重建尿道.术后行尿道造影、尿流率及尿道镜随访检查.结果 3例手术均获成功,切U愈合良好,无尿漏;拔除尿道支架管后患者排尿通畅.术后6周复查最大尿流率分别为16.7、19.6、26.4 ml/s;术后3个月尿道造影见移植段尿道管径均粗大;术后6个月尿道镜检查2例见结肠黏膜色泽良好,表面光滑,无糜烂,无瘢痕,吻合口愈合好;活检黏膜腺上皮细胞形态未改变,腺体稍萎缩.3例术后分别随访28、16、3个月,排尿通畅.结论 结肠黏膜尿道成形术是治疗复杂性超长段尿道狭窄或闭锁的一种行之有效的方法.     

前尿道代后尿道成形术治疗男性复杂性后尿道狭窄

目的探讨长段复杂性后尿道狭窄治疗新方法。方法采用分期前尿道代后尿道成形术治疗3例复杂性后尿道长段狭窄（6．5—10．0cm）患者。第一期行阴茎转位尿道端端吻合术，术后3—6个月行二期阴茎伸直、尿道会阴造口术，6个月后行第三期前尿道成形术（Johanson Ⅱ期尿道成形术）。结果例1术后排尿通畅，膀胱尿道造影检查示尿道通畅，双侧输尿管返流近消失，最大尿流率18．8ml／s，随访2年，最大尿流率18ml／s，无剩余尿。例2术后排尿通畅，最大尿流率19．5ml／s，无剩余尿，尿道扩张可顺利通过22F尿道探子。例3经会阴一耻骨联合径路行第一期阴茎转位尿道端端吻合术、尿道直肠瘘、尿道会阴瘘切除、修补术，术后尿道直肠瘘及尿道会阴瘘治愈，但因耻骨联合切口感染致吻合口狭窄，有待进一步治疗。结论分期前尿道代后尿道加前尿道重建方法是治疗男性长段复杂性尿道狭窄的有效方法。     

带蒂皮瓣在复杂性长段尿道闭锁中的应用

目的 探讨带蒂皮瓣在复杂性长段尿道闭锁中的应用. 方法 复杂性长段尿道闭锁患者18例,其中阴茎悬垂部尿道闭锁4例、前尿道完全闭锁7例、前后尿道均闭锁7例.尿道闭锁长度平均15.1(8.7～23.0)cm.伴尿道会阴瘘8例,后尿道直肠瘘7例,假道形成8例.病因:骨盆骨折伴后尿道狭窄术后7例,尿道膀胱内灌注化疗所致4例,球部尿道狭窄术后3例,淋病性尿道狭窄行尿道扩张术后2例,长期留置导尿管所致2例.经会阴切除闭锁尿道,修补直肠瘘;根据尿道缺损长度,应用带蒂皮瓣行一期尿道成形术. 结果 平均随访14(12～18)个月.术后3个月,15例排尿通畅,最大尿流率平均16.9(16.5～21.7)ml/s.1例皮管过长迂曲,排尿困难,切除多余皮管后排尿正常;1例尿道吻合口感染导致再狭窄,切除狭窄段,行尿道端端吻合术后排尿通畅;I例因血肿感染后尿瘘,行尿瘘修补术治愈.术后6个月,17例最大尿流率平均17.0(15.0～22.0)ml/s,1例真性尿失禁无法测定.术后9～18个月,17例最大尿流率平均17.5(15.8～22.5)ml/s. 结论 带蒂皮瓣一期尿道成形术可作为修复复杂性长段尿道闭锁的方法之一.     

Foley管牵引固定尿道拖入术治疗外伤性后尿道狭窄

目的　探讨Foley管作为牵引固定装置行尿道拖入术治疗外伤性后尿道狭窄或闭锁的方法。　方法　采用此方法治疗外伤性后尿道狭窄或闭锁患者 2 3例 ,对其临床资料进行总结。　结果　随访 6～ 12个月 ,14例排尿通畅 ,无需尿道扩张 ;7例术后近期需行尿道扩张 ;2例失败 ,其中 1例为狭窄段较长、术后尿道张力大所致 ,1例由伤口感染引起。 18例术后尿流率检查 :最大尿流率 15～2 3ml/s,平均 19ml/s;平均尿流率 10～ 13ml/s,平均 12ml/s。　结论　该手术方法操作简单、损伤小、并发症少、效果满意 ,临床应用价值较高     

结肠黏膜尿道成形治疗复杂性超长段尿道狭窄的长期疗效

目的 观察结肠黏膜尿道成形术治疗复杂性超长段尿道狭窄的长期效果和影响因素. 方法 2000年10月至2009年9月采用结肠黏膜尿道成形治疗复杂性超长段尿道狭窄46例.年龄17 ～70岁,平均39岁.尿道狭窄段长10.0～20.0 cm,平均15.2 cm.术前有平均2.7次不成功的尿道修复史.通过定期门诊或电话随访进行术后疗效评估,包括排尿情况和尿流率检查,部分患者行尿道造影和尿道镜检查等.以不需要任何处理包括尿道扩张,能正常排尿,尿流率在正常范围内者视为手术成功. 结果 结肠黏膜重建尿道的长度为11.0～21.0 cm,平均15.4 cm.1例失访,余45例随访20～120个月,平均62个月.发生与手术相关的并发症4例(8.9％),其中3例于术后3、8和24个月发生尿道外口狭窄,1例术后29个月发生结肠黏膜新尿道与尿道近端吻合口狭窄.另2例发生与结肠黏膜尿道成形术无关的尿道狭窄. 结论 结肠黏膜尿道成形术治疗复杂性超长段尿道狭窄术后长期效果理想;影响术后效果的因素是尿道口狭窄和吻合口狭窄.     

阴囊纵隔皮瓣尿道成形术治疗长段前尿道狭窄

目的 总结阴囊纵隔皮瓣尿道成形术治疗长段前尿道狭窄的手术经验.方法 本组41例患者,年龄17～76岁,平均42.7岁,病程4～38个月,平均15个月.术前经逆行尿道造影、排泄性膀胱尿道造影均证实前尿道狭窄.狭窄段长度3cm～7cm,平均4.1 cm.术前27例尿流率测定均为低平曲线,最大尿流率3.5～6.9 ml/s,平均5.7 ml/s.运用阴囊纵隔皮瓣尿道成形术治疗长段前尿道狭窄.结果 41例患者随访12～36个月,平均23.1个月.术后排尿通畅39例,测定最大尿流率16～36ml/s,平均17.2 ml/s.出现并发症4例,其中尿道狭窄2例,尿道毛石形成2例,本组无尿瘘发生.结论 运用阴囊纵隔皮瓣尿道成形术治疗长段前尿道狭窄,手术成功率高,并发症少,是治疗长段前尿道狭窄的良好术式.     

舌黏膜尿道成形治疗尿道狭窄的初步报告

目的:探讨舌黏膜补片法尿道成形治疗尿道狭窄的疗效。方法:采用舌黏膜尿道成形治疗尿道狭窄14例。尿道狭窄段3.5~14cm,平均6.2cm;术前耻骨上膀胱造瘘8例,余6例排尿均较为困难,最大尿流率2.5~5.5ml/s,平均3.8ml/s。结果:术后随访2~8个月,1例因伤口感染致尿道皮肤瘘,余患者均排尿通畅,最大尿流率增至22~51ml/s,平均29.6ml/s。结论:舌黏膜具有取材方便、对患者创伤小、抗感染力强等特点,是一种较好的尿道替代物,尤其适合尿道狭窄段<6cm的患者。     

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.