曲拉通X-100对制备猪胸主动脉脱细胞血管基质影响的实验研究

目的为将内皮细胞和平滑肌细胞种植于脱细胞血管基质(Acellular Tissue Matrix,ACTM)上形成组织工程化血管提供实验依据.方法用曲拉通(Triton)X-100等试剂制备猪胸主动脉ACTM,并寻找曲拉通X-100的最佳浓度.取家猪的新鲜去除外膜胸主动脉56根,随机分成7组,每组分别浸入不同浓度的曲拉通 X-100中作用144 h～240 h.标本作HE弹力纤维染色,大体、光镜及透射电镜观察.结果经上述试剂处理后,光镜及透射电镜检查显示,制备出的猪胸主动脉脱细胞血管基质由胶原纤维、弹力纤维和某些不可溶的、变性细胞器构成.曲拉通 X-100最佳浓度为1%.时间为176.25 h±5.5 h.结论本方法可成功制备猪胸主动脉ACTM,1%曲拉通 X-100是制备血管ACTM的良好试剂.     

不同浓度曲拉通X-100对制备颌下腺脱细胞基质的影响

目的探讨制备颌下腺脱细胞基质生物衍生支架材料过程中曲拉通X-100的最佳浓度。方法用3组不同浓度的曲拉通X-100试剂对30个颌下腺腺体进行脱细胞处理，并通过光镜、透射电镜及扫描电镜观察。结果0．5％和1％曲拉通X-100组脱细胞后，光镜下见大部分细胞轮廓存在，呈拥挤状态。透射电镜下见细胞膜破损，细胞器破碎，形成多个散在的碎块。扫描电镜下见细胞膜被破坏，表面呈丰窝状改变。而3．0％曲拉通X-100组脱细胞后，光镜下见颌下腺细胞成分完全消失，胶原纤维呈网状排列。透射电镜下见细胞器及细胞核消失，只见残留的细胞轮廓。扫描电镜下见细胞完全消失，只残留空虚的陷窝，基质胶原纤维粗细不等，相互交错呈网状结构。结论在制备颌下腺脱细胞基质时曲拉通X-100试剂的最佳浓度是3．0％。     

骨髓间充质干细胞复合脱细胞血管基质构建组织工程血管的初步研究

目的：探讨骨髓间充质干细胞复合脱细胞血管基质构建组织工程血管的可行性。方法：采用胰蛋白酶、乙二胺四乙酸和曲拉通X-100对兔主动脉进行脱细胞处理，制备成脱细胞血管基质；体外分离和扩增人骨髓间充质千细胞，并将其作为种子细胞种植于脱细胞血管基质上，复合构建组织工程化人工血管。结果：制备的脱细胞血管基质由胶原、弹力纤维等组成，未见细胞成分残留；体外扩增的人骨髓间充质干细胞种植于脱细胞血管基质上可生长增殖。结论：骨髓间充质干细胞与脱细胞血管基质支架材料复合可成功构建组织工程血管，有望为血管缺损的修复提供一种全新的技术方法和手段。     

脱细胞基质与血管内皮细胞体外相容性的研究

目的 将猪血管内皮细胞和异体猪血管脱细胞基质相结合，探讨开发一种制备血管移植物的新方法。方法 分别利用0．1％胰蛋白酶、0．02％乙二胺四乙酸钠(EDTA)和1．0％Triton X—100对猪主动脉作用24小时和176小时进行脱细胞。异体猪血管内皮细胞分离出来并进行体外细胞扩增，再将脱细胞的血管内表面种植上血管内皮细胞。通过光镜和扫描电镜检测脱细胞血管基质是否存在细胞成分和内皮细胞是否生长其上。结果 酶—化学除垢剂的脱细胞方法几乎使细胞完全脱落，且基质纤维的三维结构变得疏松。体外扩增的异体猪血管内皮细胞可以种植在脱细胞基质上并且具有伸展和增殖功能。结论 Triton X—100和胰蛋白酶制备的脱细胞基质与异体猪血管内皮细胞具有良好的生物相容性，能结合到一起并在体外生成血管移植物。     

猪胸主动脉脱细胞血管基质的制备

目的 完全去除猪胸主动脉的细胞,制备成血管脱细胞基质。方法 采用胰酶和TritonX-100制备猪胸主动脉脱细胞基质。根据TritonX-100的浓度将实验分为0.1％、0.2％、0.5％、1.0％、2.0％、5.0％等6组。标本进行大体、光镜、电镜观察,并进行DNA含量的测定。结果0.1％、0.2％、0.5％、1.0％、2.0％、5.0％浓度的TritonX-100能分别在(104.0±3.8)h、(89.6±3.4)h、(74.4±3.9)h、(72.8±2.5)h、(72.0±0.0)h、(72.0±0.0)h内完全脱除猪胸主动脉的细胞,同时较好地保持了胶原纤维和弹性纤维的原有排列和分布。TritonX-100的脱细胞作用呈浓度依赖性,最佳脱细胞浓度为0.5％。结论 本方法可以成功制备大血管脱细胞基质,可以进一步用于组织工程带瓣管道或瓣膜的研究。     

可吸收脱细胞猪主动脉基质构建人工食管的实验研究

目的探讨应用可吸收脱细胞猪主动脉基质制备人工食管进行食管替代的可行性.方法应用胰酶、Triton X-100制备脱细胞猪主动脉基质.切除实验犬5 cm颈段食管,用两片脱细胞猪主动脉基质缝制的人工食管进行重建,观察存活情况和愈合过程.结果6只实验犬无死亡,发生吻合口瘘1只,1只在行内镜下扩张治疗时新生食管破裂死亡.病理结果显示术后2周时有疏松结缔组织及大量新生血管形成,4周时大部分人工食管被食管黏膜上皮覆盖,镜下见黏膜上皮细胞约5～8层,12周时上皮细胞分化至8～10层,有黏膜下腺体结构及肌肉组织.原人工食管大部分已吸收,无法用肉眼分辨人工和正常食管.结论可吸收猪胸主动脉脱细胞血管基质可作为理想的代食管材料,能较好诱导组织的再生,有较好的应用前景.     

脱细胞猪主动脉基质替代犬食管缺损的实验研究

目的 探讨应用脱细胞猪主动脉基质制备人工食管进行食管替代的可行性。方法应用胰酶、Triton X-100制备脱细胞猪主动脉基质。切除5cm实验犬食管，用两片脱细胞猪主动脉基质缝制成人工食管进行重建，观察存活情况和愈合过程。结果6只实验犬无围手术期死亡，发生吻合口瘘1只，1只在行内镜下扩张治疗时导致新生食管破裂死亡。组织学结果显示术后2周时有疏松结缔组织及大量新生血管形成，4周时大部分人工食管被上皮细胞覆盖。12周时上皮细胞分化至8．10层，有黏膜下腺体结构及肌肉组织。原人工食管已完全吸收，无法用肉眼分辨人工和正常食管。结论猪胸主动脉脱细胞血管基质可作为理想的代食管材料，能较好诱导组织的再生，有较好的应用前景。实验为人工食管的临床应用研究提供了依据。     

超声波联合曲拉通X-100制备猪去细胞的主动脉支架

目的 探讨超声波联合曲拉通X-100制备猪升主动脉去细胞支架的方法及效果.方法 从体质量相近的中华实验猪制备新鲜主动脉标本280份,随机分为4组:空白对照组、曲拉通X-100(Triton X-100)和SDS(十二烷基磺酸钠)组、曲拉通X-100组、超声波联合曲拉通X-100组,通过组织学及电镜观察、生物力学性能测定、免疫组织化学检测Ln和Fn的蛋白表达变化等分析比较各组去细胞的效果.结果 超声波联合曲拉通X-100组可完全去除动脉内膜细胞,组织形态、生物力学等保持良好.层粘连蛋白(Ln)和纤维连接蛋白(Fn)的阳性面积×平均吸光度值分别是0.01470±0.001 60、0.01340±0.000 29,明显优于传统的化学去细胞方法.结论 超声波联合曲拉通X-100组去细胞效果优于传统化学去污剂,是较理想的制备猪动脉去细胞支架的方法.     

猪主动脉脱细胞基质的简化制备及生物学评价

目的应用酶法制备猪主动脉脱细胞基质，并评价其生物学性能。方法取新鲜屠宰的16根肉猪降主动脉，长10～12cm，应用0．1％胰蛋白酶和0．01％EDTA于37℃震荡条件下脱除细胞成分，HE和Masson染色行脱细胞基质的组织学观察，扫描电镜和透射电镜观察超微结构改变。应用单轴拉伸方法比较脱细胞前和脱细胞后48、96和120h时材料两断端厚度、极限抗张强度（ultimate tension stress，UTS）和断裂伸长率（strain of failure，SOF），绘制应力-应变曲线。取成年杂种犬3只，体重20～30kg，雌雄不限。将脱细胞前后片状主动脉基质埋植于犬脊柱两侧皮下，分别于埋植后1、3和6周取材，行HE染色观察，参照半定量的Wakitani评分法，对取材时的大体形态、浸润细胞种类和数量、新生血管等指标进行比较，观察宿主炎性细胞反应和脱细胞基质变化。将犬内皮细胞种植于猪脱细胞基质，HE染色和扫描电镜观察细胞相容性。结果HE染色和电镜检查显示在96h可将新鲜猪主动脉细胞成分脱除，Masson染色显示细胞外纤维成分保留完整。脱细胞前后的动脉基质厚度、UTS和SOF差异均无统计学意义（P〉0．05），但UTS显示降低趋势，SOF则呈现增加趋势，应力-应变曲线呈现力学强度降低和延展性增加的变化趋势。犬皮下埋植，各组脱细胞标本炎性细胞浸润明显减轻，6周时以成纤维细胞浸润为主，且基质中见新生毛细血管。半定量组织学评分，在大体观察、浸润细胞种类和数量方面与脱细胞前比较有统计学意义（P〈0．05）；新生血管数量比较，差异无统计学意义（P〉0．05）。HE染色和扫描电镜显示种植的内皮细胞可在基质表面形成单细胞层。结论应用0．1％胰蛋白酶和0．01％EDTA持续振荡96h制备的猪主动脉脱细胞基质，在生物力学、免疫原性和细胞相容性方面可满足血管组织工程的需要。     

全生物化组织工程血管的体外构建

目的 探讨组织工程血管的体外构建:脱细胞血管基质的制备.血管平滑肌细胞和血管内皮祖细胞的体外诱导培养和种植方法.方法 处理猪胸主动脉来获得脱细胞血管基质,采用二步种植法先后种植体外培养的平滑肌细胞和内皮细胞.结果 动脉管壁细胞全部脱除,脱细胞基质胶原蛋白含量与新鲜动脉相似,胶原纤维、弹性纤维呈网状排列,无断裂,基质保持完好.脱细胞血管基质的极限应力比新鲜动脉绀织减小20%[新鲜动脉:(1.1510±1.2870)×10-2,脱细胞血管基质:(0.9215±1.7000)×10-2,t=34.137,P<0.01].种植的平滑肌细胞和内皮细胞生长良好.结论 平滑肌细胞和内皮细胞种植于脱细胞血管基质后生长良好,可体外构建组织工程血管.     

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.     

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.     

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.     

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.     

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.     

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.     

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.     

Systemic analgesia adapted to the children's condition

A concept of balanced analgesia using nonsteroidal anti-inflammatory drugs (NSAIDs), paracetamol (acetaminophen), opioids, and corticosteroids can also be used in patients with pre-existing illnesses. NSAIDs are the most effective treatment for acute pain of moderate intensity in children; however, these drugs should be avoided in patients at increased risk for serious side effects, e.g. patients with renal impairment, bleeding tendency, or extreme prematurity. NSAIDs can be given with minimal risks to the younger child with mild to moderate asthma, and, in these patients, the use of steroids can be encouraged; in addition to their antiemetic and analgesic action, a beneficial effect on asthma symptoms can be expected. In the non-intubated child with cerebral trauma, exaggerated sedation caused by opioids and increased bleeding tendency caused by NSAIDs must be avoided. In neonates and small infants, the oral administration of sucrose or glucose is helpful to minimize pain reaction during short uncomfortable interventions.