外侧入路小切口技术在全髋关节置换术中的应用

[目的] 探讨髋外侧小切口全髋关节置换术的可行性、操作方法及优缺点.[方法] 2008年2月～2008年8月,采用外侧入路小切口进行单侧全髋人工关节置换手术28例.分析术中出血量、术后引流量、下床活动时间及髋关节Harris评分.[结果] 切口长度8～10 cm.术中出血量为280～710 ml,平均410 ml;术后引流量为250～600 ml,平均420 ml.患者平均下床时间6.5 d(3～9 d).Harris评分从术前的41.2分提高到术后6个月的91.5分.[结论] 外侧入路小切口具有创伤小、患者术后恢复快、易接受、术后关节功能好等优点,但应注意其适应证及容易发生的并发症.     

小切口微创技术在全髋关节置换术中的应用

目的阐述目前4种常用的微创全髋关节置换技术的应用体会，初步报道早期临床结果。方法自2003年8月至2005年11月采用4种常用的微创入路对92例116髋进行初次全髋关节置换术，男45髋，女71髋，年龄32-73岁，平均年龄64岁。手术方法采用前外路21例髋，后路73髋，双切口4髋，改良Watson-Jones微创入路（OCM）18髋。在92例中诊断为骨关节炎（OA）40髋；股骨头无菌坏死33髋；股骨颈骨折34髋；类风湿关节炎9髋。采用MIS工具和Versys假体。观察围手术期的出血量、手术时间、切口长度、术后功能康复情况及并发症。结果本组共92例，116髋，手术切口6-10cm，平均7cm；双切口微创全髋关节置换手术时间平均120min。而无论是采用单切口前路、后路或者改良Watson-Jones（OCM）手术入路平均手术时间90min。在92例患者中，其中10例行双侧全髋同时置换术中及术后平均输血400-600ml。而单侧全髋关节置换术的患者术中不输血，围手术期平均输血300ml。本组87髋随访6-24个月，平均随访13个月。术后半年随访87例，Harris评分87-92分，平均90.5分。术后1年随访52例，Harris评分90-96分，平均94分。结论4种微创全髋关节置换术均具有创伤小、出血少、术后功能恢复快的优点。OCM手术入路和双切口入路更符合微创全髋关节置换术的理念。     

两种微创入路全髋关节置换术比较

[目的]比较慕尼黑骨科医院（Orthopadische Chirurgie Munchen, OCM）入路和直接外侧入路（direct lateral approach,DLA）全髋关节置换术中的临床疗效。[方法]回顾性分析本院骨科2018年1月—2022年1月全髋关节置换手术病例53例患者的临床资料，根据术前医患沟通结果，18例采取OCM入路，35例采取DLA入路。比较两组围手术期、随访及影像资料。[结果]两组均顺利完成手术，无神经、血管损伤等严重并发症发生。OCM手术时间显著长于DLA组（P<0.05），但是，OCM组切口长度、术中出血量、输血率、术后下床时间及住院时间均显著优于DLA组（P<0.05）。随访时间平均（15.0±3.2）个月，术后随时间推移，两组患者Harris评分、髋伸屈ROM均显著增加（P<0.05）。术前两组间Harris评分、髋伸屈ROM的差异均无统计学意义（P>0.05），术后1个月，OCM组Harris评分、髋伸屈ROM均显著优于DLA组（P>0.05），但术后3个月及末次随访两组上述指标的差异无统计学意义（P>0.0...     

111例后外侧切口人工全髋关节置换术疗效分析

目的探讨经后外侧切口行人工全髋关节置换术的优势。方法采用后外侧切口行非骨水泥型人工全髋关节置111例117髋,单侧全髋105例,男60例,女45例;年龄36~92岁,平均64岁。双侧全髋患者共6例,男5例,女1例;年龄32~46岁,平均37岁,经随访并Harris评分法评分。结果本组随访率95%,随访时间6~72个月,平均39个月。术后髋关节Harris评分平均88.2分,优89髋,良22髋,可4髋,差2髋,优良率达到94.9%。结论人工髋关节置换是一种安全有效的手术,在适当选择手术适应证的前提下,后外侧切口非骨水泥型全髋关节置换术可以达到优异的临床效果。     

微创前入路全髋关节置换治疗老年股骨颈骨折

[目的]比较直接前入路与后外侧入路人工全髋关节置换术治疗老年股骨颈骨折的短期临床疗效。[方法]2015年1月~2016年12月采用直接前方入路(direct anterior approach,DAA)技术行全髋关节置换术12例,其中女7例,男5例,年龄72~86岁,平均(78.70±3.60)岁。另按纳入标准随机抽取17例后外侧入路全髋关节置换术病例作为对照。[结果]DAA组手术切口(8.61±1.22)cm,比后外侧组(12.51±1.65)cm小;手术时间(95.02±10.14)min,比后外侧组(72.05±11.57)min长;术中出血量(155.01±26.03)ml,比后外侧组(220.03±32.53)ml少;术后引流量(109.11±15.52)ml,比后外侧组(158.97±21.82)ml少;差异均具有统计学意义(P<0.05)。术后6个月髋关节Harris评分DAA组为(92.51±5.83)分,与后外侧组(91.88±6.32)分相比差异无统计学意义(P>0.05)。[结论]DAA全髋关节置换,不仅切口小、术中出血量少,且利于置换术后早期功能锻炼。     

后外侧入路微创全髋关节置换术的临床初步探讨

[目的]探讨后外侧入路微创全髋关节置换术的可行性和初步疗效。[方法]自2002年3月~2005年8月,采用后外侧入路微创技术完成27例全髋置换术。[结果]手术切口7.5~12cm,平均8cm;手术时间50~95min,平均66min;术中出血量200~550ml,平均280ml;术后均放负压引流,24h平均引流量100~370ml,平均160ml。平均随访时间2.6年(1~4年),未发生全身及局部并发症。[结论]后外侧入路单切口微创行全髋关节置换具有创伤小、出血少、恢复快的优点,是值得推荐的微创全髋关节置换技术。     

微创与常规全髋关节置换术的临床疗效比较

[目的]比较微创全髋关节置换术与传统全髋关节置换术的临床疗效.[方法] 2008年1月～2010年1月在本院行单侧全髋关节置换术的156例患者随机分为观察组和对照组,两组患者均接受全麻或硬膜外麻醉后,对照组患者接受传统标准后外侧入路全髋关节置换术,观察组患者接受前外侧入路微创全髋关节置换术.比较两组患者手术情况、住院时间、Harris评分和术后并发症.[结果]观察组患者的切口长度、术中失血量、术后引流量和住院时间较对照组显著减少(P＜0.叭),但是手术时间较对照组延长(P＜0.05);观察组患者在术后3、6个月、1年时Harris评分较对照组显著升高(P＜0.01),但是术后2年时两组患者Harris评分差异无统计学意义(P＞0.05);两组患者术后并发症差异无统计学意义(P＞0.05).[结论]前外侧入路微创全髋关节置换术具有减少术后损伤、缩短住院时间、加快术后髋关节功能恢复的优势,值得临床推荐.     

微创小切口人工全髋关节置换术在晚期股骨头坏死治疗中的应用

目的探讨微创小切口人工全髋关节置换术在晚期股骨头坏死治疗中的应用价值。方法2003年3月始，采用微创技术治疗18例22髋国际骨循环学会（Association Research Circulation Osseous，ARCO）分期Ⅲ、Ⅳ期股骨头坏死患者，其中男13例，女5例，年龄24～57岁；体重指数（body mass index，BMI）24．6（17．1～30．1），术前髋关节Harris评分平均46分。均采用改良的后外侧切口、非骨水泥假体行人工全髋关节置换术（微创组）。与同期常规人工全髋置换术的18例22髋（对照组，术前髋关节Harris评分平均43分）进行比较，包括：围手术期出血量、切口长度及术后早期功能恢复情况等。结果术后两组均获随访6～20个月，平均11个月。对照组1髋术后2d脱位，微创组中无并发症发生；微创组手术切口长9．3cm（8．7～10．5cm），较对照组16．8cm（14．0～20．0cm）短，差异有统计学意义（P〈0.01）；两组术后随访6个月时Harris评分分别为92、90分，差异无统计学意义（P〉0.05）；手术时间相近，但围手术期出血量及引流量微创组较少，两组差异有统计学意义（P〈0．05）；微创组术后恢复较快。结论微创小切口全髋关节置换术，手术创伤小、出血少，术后恢复较快，但开展此手术的初期，应由有经验的医师及有相应设备的医院、有选择地用于晚期股骨头坏死患者的治疗。     

小切口全髋关节置换的手术体会

[目的]探讨小切口人工全髋关节置换手术的优缺点。[方法]比较32例37髋小切口人工全髋关节置换术与普通切口人工全髋关节置换术在切口长度、手术时间、术中出血量、术后引流量、住院时间及并发症等方面的异同。[结果]小切口组平均切口长度为7．7cm，普通切口组为11．5cm（P〈0．05）；小切口组平均手术时间为95min，普通切口组为51min（P〈0．05）；小切口组术中平均出血量为380ml，普通切口组为299ml（P〈0．05）；小切口组及普通切口组在术后引流量及住院时间方面无显著性差异（P〉0．05）；小切口组1例术中出现大转子尖骨折、股骨颈截骨过多、髋臼内凸，1例因髋臼安放角度异常于术后第3d出现髋关节脱位，行扩大切口调整髋臼假体角度后恢复正常；普通切口组术中、术后无1例出现并发症。[结论]与普通长度切口全髋关节置换手术相比，小切口手术在出血量、组织损伤程度、手术时间方面并无明显优势；由于切口小，术野受限，手术操作比较困难，易出现假体安装位置异常等问题。在熟练做好普通切口全髋置换手术、不增加手术损伤的前提下，可尽量减小手术切口长度，没有必要刻意追求小切口全髋置换手术。     

微创髋关节置换手术的临床研究

目的评价微创髋关节置换手术的优越性、可行性及临床效果。方法对52例53个髋关节进行微创髋关节置换手术,采用后外侧切口,长6~10 cm。同时,比较了微创髋关节置换术与传统髋关节置换术在切口长度、术中出血、术后引流、术前术后红细胞变化、输血情况、手术时间、术后疼痛、早期活动情况、近期和远期疗效、并发症、Harris评分等方面的不同。结果手术切口平均长8 cm,切口长短与肥胖正相关,在相同条件下,微创髋关节置换手术明显减少了术中出血、术后引流、手术时间、术后疼痛,无并发症,可早期活动、近期疗效良好,远期疗效待随访,Harris评分平均87分。结论微创技术在人工髋关节置换手术中是行之有效的,值得推广。     

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.