猕猴预致敏后肾移植加速性排斥反应的免疫学及病理学特点

目的 观察猕猴预致敏后肾移植加速性排斥反应的免疫学及病理学变化特点.方法 建立猕猴皮肤预致敏后肾移植加速性排斥反应模型(供、受者各3只).检测3只受者皮肤移植预致敏前、后及肾移植后血清内供者特异性抗体的变化.并在发生排斥反应时对移植肾进行免疫组织化学(测定补体、抗体的沉积及各类型淋巴细胞浸润情况)及病理学分析.结果 3只受者均发生了加速性排斥反应.其中2只受者在预致敏后血清中供者特异性抗体明显增加,对供者的淋巴毒反应明显升高;肾移植后受者血清中供者特异性抗体及针对供者的淋巴毒进一步升高.苏木精-伊红染色显示排斥反应的移植肾内有明显的动脉坏死、血栓形成、间质出血、中性粒细胞浸润;免疫组织化学及荧光染色显示移植肾内有大量的补体、抗体沉积(主要为IgG),而各种类型的淋巴细胞浸润少见.另1只受者体内的供者特异性抗体及对供者淋巴毒反应的升高程度不如前2只明显,病理学变化以肾小管损伤为主.结论 皮肤移植预致敏可以诱导受者产生程度不等的预存抗体,导致大多数移植肾在术后早期发牛主要南抗体和补体介导的严重的急性体液性排斥反应.     

群体反应性抗体检测在肾移植中的应用

目的 了解肾移植受者的ＨＬＡ体液致敏状态及致敏者受者的ＨＬＡ抗体特异性,筛选合适供者。方法 应用配组淋巴细胞板通过微量补体依赖淋巴细胞毒试验检测６２３例患者的群体反应性抗体（ＰＲＡ）。结果 肾移植受者中ＰＲＡ阳性受者占１１．５％,致敏受者移植后排斥反应发生率明显高于非致敏受者（Ｐ〈０．０１）,而移植物存活率则显著低于非致敏受者（Ｐ〈０．０１）。移植后ＰＲＡ水平升高级的排斥发生率和移植物丢失率殚显著     

多供体脐血输注诱导免疫低反应性的研究

目的：通过多供体脐血输注诱导肾移植术前患者产生同种免疫低反应性。方法：选取终末期尿毒症拟行肾移植的患者39例，20例接受多供体脐血输注（脐血组），19例接受成人外周血洗涤红细胞输注（对照组），分别于输血前（T0），输血后1个月（T1），2个月（T2），3个月（T3）及移植术前后动态监测受者混合淋巴细胞培养（MLC）以及血清HLA同种抗体水平的变化。结果：脐血组输血后1，2，3个月受者淋巴细胞对供脐血淋巴细胞及无关成人淋巴细胞的MLC明显下降，脐血组自身前后对照MLC受抑制率可达70％以上；与对照组比较，差异有显著性（P＜0．05）。脐血组移植术前后受者淋巴细胞对供肾淋巴细胞的MLC亦受到明显抑制，和对照组比较，差异有显著性。脐血组输血后血清同种反应抗体水平亦显著下降。7例输血前同种抗体呈阳性反应者，输血后6例转为阴性，1例为明显下降；而对照组输血前4例抗体阳性者无1例下降或转阴。结论：多供体脐血输注能够诱导受者淋巴细胞对供脐血淋巴细胞的特异性免疫低反应性。这一低反应性还可“非特异”地表现为受者对无关成人淋巴细胞和供肾淋巴细胞的免疫低反应性。     

活体肾移植前对致敏患者的处理经验及疗效分析

目的 总结活体肾移植前对致敏患者的处理经验,并对移植效果进行分析.方法 回顾性分析609例活体肾移植受者的临床资料.根据移植前群体反应性抗体(PRA)水平将受者分为高致敏组(41例,PRA≥30％),低致敏组(102例,PRA为0～30％)和非致敏组(466例,PRA为0).所有受者经HLA抗体检测和淋巴细胞毒交叉配合试验(CDC)确认没有针对供者的HLA抗体后进行肾移植.高致敏组给予抗胸腺细胞球蛋白诱导治疗,低致敏组给予抗白细胞介素2受体单抗诱导治疗.随访1年以上,观察各组术后移植肾功能、急性排斥反应发生率、受者和移植肾存活率及并发症发生率.结果 高致敏组、低致敏组和非致敏组受者术后移植肾恢复正常的时间和1年时肾小球滤过率均无明显差异;3组均未发生超急性排斥反应,急性排斥反应发生率分别为9.76％(4/41)、8.82％(9/102)和8.15％(38/466),术后1年移植肾存活率分别为97.6％(40/41)、97.1％(99/102)和98.1％(457/466),受者存活率分别为97.6％(40/41)、98.0％(100/102)和98.9％(461/466),3组间上述指标的差异均无统计学意义(P＞0.05).高致敏组的感染发生率为31.7％(13/41),明显高于低致敏组的26.5％(27/102)和非致敏组的21.6％ (101/466) (P＜0.05).结论 致敏受者肾移植前经HLA抗体检测和CDC配型,避开受者体内供者特异性抗体针对的供肾,并给予免疫诱导治疗,可以获得与非致敏受者相似的良好效果.     

灵长类动物预致敏后肾移植加速排斥反应模型的建立

目的 建立灵长类动物预致敏后肾移植加速排斥反应模型.方法 取血型相容的正常猕猴配对,预先将供者腹部全层皮肤移植到受者背部,使受者预致敏.2周后再将同一供者的左侧肾脏移植到受者腹腔内,间时切除受者自体双肾,术后予以环孢素A、霉酚酸酯和泼尼松治疗(致敏用药组),不用免疫抑制剂者为对照(致敏对照组),以未致敏的肾移植作为对照组.术后观察受者血肌酐变化、移植物存活时间及病理特点.结果 对照组的4只移植肾存活时间分别为9、18、8、7 d;致敏对照组的3只移植肾存活时间分别为3、3、4 d;致敏用药组的3只移植肾存活时间分别为2、3、4 d.移植皮肤于术后10 d出现排斥反应,至术后14 d被完全排斥.对照组于肾移植1周以后才发牛排斥反应,而致敏者均在肾移植后3 d左右发生较严重的排斥反应.结论 受者被供者皮肤预致敏后再行肾移植,可以加速移植物的排斥,且不能被环孢素A、霉酚酸酯及泼尼松所组成的三联免疫抑制方案逆转.     

酶联免疫吸附法在供、受者淋巴细胞毒交叉配合试验中的应用价值

目的比较酶联免疫吸附（ELISA）法和补体依赖性淋巴细胞毒（CDC）法在供、受者术前进行淋巴细胞毒交叉配合试验中的差异。方法采用ELISA方法，对72例受者的血清和4（）例供者的淋巴细胞进行交叉配合试验，用非离子活性剂将器官移植供者淋巴细胞裂解，提取人类白细胞抗原（HLA）糖蛋白，并与固化在ELISA板上的特异性HLA—Ⅰ类或Ⅱ类单克隆抗体结合，加入受者血清。同时与CDC法进行比较。结果有1对供、受者用ELISA法检测淋巴细胞毒交叉配合试验为阳性，而CDC法检测为阴性，受者行肝肾联合移植后移植肾功能丧失；有2对供、受者用ELISA和CDC法检测均为阳性，均未接受手术；其余供、受者淋巴细胞毒交叉配合试验均为阴性，均接受移植手术。结论ELISA法与CDC法相比，简单易行，耗时不长，且较为敏感，特异性高。     

补体依赖-流式细胞术-淋巴细胞毒交叉配型实验方法的研究

目的提高识别介导肾移植术后严重排斥反应的抗供者HLA抗原IgG类抗体的准确性,建立补体依赖-流式细胞术-淋巴细胞毒交叉配型(Flow-CDC)实验方法。方法62例等待肾移植受者的血清,分别与33份供者淋巴细胞进行100次经典补体依赖微量淋巴细胞毒交叉配型(NIH-CDC)及Flow-CDC实验,依照受者移植前PRA分为PRA阴性组(25例)和PRA阳性组(75例),比较方法学差异;并观察5例PRA阳性受者的NIH-CDC、Flow-CDC及临床肾移植效果。结果PRA阴性组NIH-CDC与Flow-CDC均为阴性;PRA阳性组中,NIH-CDC阳性24例(32.0%),Flow-CDC阳性31例(41.3%),2种CDC方法阳性率比较差异有统计学意义(χ2=5.14,P=0.016)。100例CDC中,NIH-CDC与Flow-CDC结果吻合率93%,相关系数0.80。4例接受NIH-CDC和Flow-CDC均阴性的供肾PRA阳性患者,术后未发生排斥,近期效果良好;另1例PRA阳性患者接受了NIH-CDC阴性Flow-CDC阳性肾移植,术后发生加速排斥反应而丧失移植肾。结论Flow-CDC能特异性识别针对供者H...     

HLA配型对群体反应性抗体阳性的肾移植受者人/肾存活率的影响

目的探讨HLA交叉反应组（CREGs）配型对群体反应性抗体（PRA）阳性肾移植受者人／肾存活率的影响。方法应用美国莱姆德公司LAT1240、LM720R、SSP2LB试剂，准确检测112例PRA阳性肾移植受者体内PRA的水平及其抗体的特异性，评估其致敏状态，应用CREGs配型标准选择最匹配的供者。结果112例受者中，HLA-Ⅰ类抗体阳性43例，Ⅱ类抗体阳性39例，Ⅰ、Ⅱ类抗体均为阳性30例；HLA配型0～5个位点错配数分别为6、39、38、21、7、1例，术后移植肾发生加速性排斥反应2例、急性排斥反应18例、慢性排斥反应5例、移植肾功能延迟恢复（DGF）4例，因排斥反应导致移植肾切除1例，死亡13例（其中移植肾带功能死亡5例）。目前人存活99例，肾存活96例，5年、3年和1年肾存活率分别为86．21％、86．96％和91．96％。结论运用CREGs配型原则，能使供、受者间的HLA相配率显著提高，可减少PRA对肾移植的不良影响，提高PRA阳性受者的人／肾存活率。     

肾移植病人群体反应性抗体的检测

肾移植是治疗晚期肾功能衰竭的最佳方法,而影响移植肾存活主要原因排斥反应,尤其是超急性排斥反应及早期急性排斥反应造成移植肾不可逆损伤导致手术失败。组织配型是肾移植病人寻找合适供者,减少术后排斥反应发生,提高移植成功率和移植肾存活率的重要措施。本文对389例肾移植受者术前进行群体反应抗体(PRA)检测,探讨其与淋巴细胞交叉配合试验(CDC)和术后排斥发生的关系及该技术在临床肾移植工作中的实用价值。     

肾移植术后供者特异性抗体对移植肾近期效果的影响

目的 评价肾移植术后供者特异性抗体(Ds-Ab)对移植肾近期效果的影响。方法 对2001年1月至2002年7月间进行尸肾移植的92例受者，使用酶联免疫吸附(ELISA)法，检测受者血清中HLA抗体水平，随访1年。结果 16例(17．4％)受者术后出现供者特异性抗体。抗体阳性组急性排斥发生率(56．3％)高于抗体阴性组(11．9％)，P=0．000；移植肾功能延迟恢复的发生率(12．5％)与抗体阴性组(9．2％)比较，差异无显著性，P=0．102；供者特异性抗体阳性组受者发生急性排斥后，移植肾肌酐水平高于抗体阴性组或无急性排斥组。结论 供者特异性抗体与肾移植术后急性排斥有关，可能影响近期移植肾功能。     

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.