基于增强CT影像组学鉴别胸腺瘤组织学分型

目的 观察基于增强CT影像组学鉴别胸腺瘤组织学分型的价值。方法 回顾性分析226例经病理证实的胸腺瘤患者,按7∶3比例将其分为训练集(n=159)及测试集(n=67);利用最大相关最小冗余(mRMR)及最小绝对收缩和选择算子(LASSO)算法筛选最佳影像组学特征,构建鉴别胸腺瘤组织学分型的影像组学模型;以单因素及多因素logistic回归分析筛选鉴别胸腺瘤组织学分型相关的临床及CT表现,构建临床模型和联合影像组学特征及临床、CT特征的影像组学列线图。绘制受试者工作特征(ROC)曲线,计算曲线下面积(AUC),评价3种模型鉴别胸腺瘤组织学分型的效能并比较其差异,评价影像组学列线图的临床价值。结果 最终基于增强动脉期及静脉期CT筛选出19个最佳影像组学特征,以建立影像组学模型。临床模型由患者年龄、重症肌无力、病灶CT表现形态、侵犯邻近组织及动脉期CT值构成。训练集中,影像组学列线图及影像组学模型区分低危组胸腺瘤与高危组胸腺瘤的AUC (0.91、0.89)均高于临床模型(0.79,Z=3.62、2.49,P均＜0.05),而影像组学列线图与影像组学模型AUC差异无统计学意义(Z=1.54,P=0.12);3种模型在测试集中的AUC差异均无统计学意义(P均＞0.05)。阈值概率为0.1~1.0时,影像组学列线图的临床获益均大于临床模型及影像组学模型。结论 基于增强CT影像组学模型和基于临床、CT表现及影像组学特征的影像组学列线图均有利于鉴别胸腺瘤组织学分型,后者临床获益更高。     

CT影像组学联合CT特征预测肺亚实性结节侵袭性

目的 观察CT影像组学联合CT特征预测肺亚实性结节侵袭性的价值。方法 回顾性分析170例肺亚实性结节患者资料,包括6例非典型腺瘤样增生(AAH)、12例原位腺癌(AIS)、58例微浸润性腺癌(MIA)及94例浸润性腺癌(IAC),将AAH、AIS和MIA归为非侵袭组、IAC归为侵袭组。按7∶3比例将患者分为训练集(n=119,含5例AAH、9例AIS、36例MIA及69例IAC)和验证集(n=51,含1例AAH、3例AIS、22例MIA及25例IAC)。采用单因素及logistic回归分析训练集患者一般资料及病灶CT表现,筛选预测肺亚实性结节侵袭性的独立危险因素并建立CT模型;基于训练集提取及筛选病灶最佳影像组学特征,以之构建影像组学模型。基于CT模型及影像组学模型构建联合模型,并以列线图将其可视化。绘制受试者工作特征(ROC)曲线,计算曲线下面积(AUC),基于验证集评估各模型诊断效能;以校准曲线评价联合模型的校准程度。结果 CT所示结节长径和最大CT值为预测肺亚实性结节为IAC的CT相关独立危险因素,以之构建CT模型。基于训练集筛选出6个最佳影像组学特征并构建影像组学模型。CT模型、影像组学模型及联合模型预测验证集肺亚实性结节侵袭性的AUC分别为0.772、0.785及0.869;联合模型的AUC高于CT模型(Z=2.336,P=0.019)而与影像组学模型差异无统计学意义(Z=1.925,P=0.054),其预测结果与实际结果的一致性较高。结论 CT影像组学联合CT特征可有效预测肺亚实性结节侵袭性。     

超声影像组学结合机器学习模型鉴别肝泡型包虫病与原发性肝癌

目的 观察超声影像组学结合机器学习（ML）模型鉴别肝泡型包虫病（HAE）与原发性肝癌（PHC）的价值。方法 回顾性分析经手术病理证实的95例HAE（HAE组）及97例PHC（PHC组）患者,按7∶3比例将其分为训练集（n=134）及验证集（n=58）;基于二维超声声像图提取影像组学特征,以逻辑回归、朴素贝叶斯、决策树、支持向量机、极限梯度提升、K邻近及梯度提升机共7种算法构建ML模型;绘制受试者工作特征曲线,计算曲线下面积（AUC）,评估各模型鉴别HAE与PHC的效能。结果 共基于训练集数据提取1 688个影像组学特征,最终筛选出7个非零系数特征为最优特征;据以构建的7种ML模型鉴别HAE与PHC效能均良好,在训练集的AUC为0.963～0.997,在验证集为0.871～0.942。结论 超声影像组学结合ML模型鉴别HAE与PHC效能良好。     

基于肺部CT生境模型预测表皮生长因子受体突变型肺腺癌脑转移

目的 观察基于肺部CT生境模型预测表皮生长因子受体（EGFR）突变型肺腺癌脑转移（BM）的价值。方法 回顾性分析198例EGFR突变型肺腺癌患者肺部平扫CT资料,按7∶3比例将其分为训练集（n=138）与测试集（n=60）并进一步划分BM亚组与非BM亚组。筛选训练集亚组间差异有统计学意义的变量构建逻辑回归（LR）临床模型;分别于瘤体及瘤体亚区提取特征,基于随机森林、高斯过程（GP）及支持向量机（SVM）算法构建影像组学及生境模型并筛选其中泛化能力最佳者,基于泛化能力最佳影像组学、生境模型及临床模型预测值构建LR联合模型;绘制受试者工作特征曲线,计算曲线下面积（AUC）,评估各模型预测EGFR突变型肺腺癌BM的效能,以Spearman相关分析观察EGFR突变型肺腺癌Ki-67水平与生境特征的相关性。结果 LR临床模型、GP影像组学模型、SVM生境模型及LR联合模型预测训练集EGFR突变型肺腺癌BM的AUC分别为0.700、0.726、0.801及0.834,在测试集分别为0.754、0.600、0.715及0.848。LR联合模型在训练集的AUC高于LR临床模型（P＜0.001）、在测试集的AUC高于GP影像组学模型（P=0.010）;其在训练集的效能相比GP影像组学模型及SVM生境模型均有显著正向提高[综合判别改善指数（IDI）=8.60%、8.55%,P均＜0.001]。EGFR突变型肺腺癌Ki-67水平与生境图谱中的habitatmap_original_glszm_lalgle呈低度正相关（│r_s│=0.201,P=0.004）。结论 基于肺部CT生境模型可有效预测EGFR突变型肺腺癌BM。     

建立临床-影像学联合列线图模型早期识别TACE抵抗肝细胞癌

目的 建立预测TACE抵抗肝细胞癌(HCC)的临床-影像学联合列线图模型,评价其早期识别TACE抵抗HCC的价值。方法 回顾性分析218例接受TACE的HCC患者临床资料,以其中137例作为训练集,81例作为验证集。采用Cox风险回归模型,基于训练集临床及影像学资料筛选预测TACE抵抗HCC的独立因素;建立列线图模型,评价其判断训练集与验证集中TACE抵抗低、高危HCC患者中位总生存期(OS)的差异;并以校准曲线及决策曲线验证列线图模型的校准度及临床价值。结果 回归分析显示巴塞罗那临床肝癌(BCLC)分期、肿瘤最大径、边界及病灶数目是影响HCC患者中位OS的独立因素。列线图模型判断的训练集及验证集TACE抵抗低、高危HCC患者中位OS差异均有统计学意义(P均＜0.05)。校准曲线及决策曲线显示临床-影像学联合列线图模型校准度良好,可使患者净获益。结论 临床-影像学联合列线图预测模型可用于早期判别TACE抵抗HCC。     

MRI影像组学及临床特征联合模型预测高强度聚焦超声治疗子宫肌瘤效果

目的 观察基于MRI影像组学及临床特征建立的联合模型预测高强度聚焦超声(HIFU)治疗子宫肌瘤效果的效能。方法 回顾性分析257例接受HIFU治疗的单发子宫肌瘤患者,基于治疗前盆腔轴位T2WI、T1WI、T1对比增强(T1C)及表观弥散系数(ADC)图提取病灶影像组学特征。分别以XGBoost特征选择算法及XGBoost分类器建立预测HIFU即刻消融率和随访肌瘤体积缩小率的影像组学联合临床特征模型A和B。按8∶2比例将数据集分为训练集(n=202)和测试集(n=52),采用受试者工作特征(ROC)曲线和混淆矩阵评估模型的预测效能。结果 经XGBoost算法选择后纳入10个影像组学特征,包括4个T1WI、2个T2WI、1个T1C及3个ADC图影像组学特征,结合肌瘤背侧距骶骨距离和T2WI信号强度构建模型A;纳入10个影像组学特征,含4个T1WI、3个TIC及3个ADC图影像组学特征,结合肌瘤T2WI信号强度构建模型B。ROC曲线结果显示,模型A预测训练集和测试集HIFU治疗肌瘤即刻消融率的曲线下面积(AUC)分别为0.94[95%CI(0.90,0.96)]和0.90[95%CI(0.81,0.97)],模型B预测训练集和测试集肌瘤体积缩小率的AUC分别为0.98[95%CI(0.97,0.99)]、0.91[95%CI(0.81,0.98)]。结论 MRI影像组学联合临床特征模型可有效预测HIFU治疗子宫肌瘤近期及远期效果。     

临床-超声列线图预测急性缺血性脑卒中短期预后

目的 观察临床-超声列线图预测急性缺血性脑卒中（AIS）短期预后的价值。方法 回顾性分析168例接受血管内介入治疗的AIS患者,根据治疗后3个月改良Rankin量表评分将其分为预后良好组（n=134）及预后不良组（n=34）。比较组间临床及超声资料,采用最小绝对收缩和选择算子（LASSO）算法及Cox回归方程分析AIS短期预后的独立影响因素,以之分别构建临床、超声及临床-超声列线图模型;绘制受试者工作特征曲线,计算曲线下面积（AUC）,评估各模型预测AIS短期预后的效能。结果 发病至入院时间、美国国立卫生院卒中量表（NIHSS）评分、Alberta卒中项目早期CT评分（ASPECTS）、斑块时间-强度曲线强度均值（TIC-M）及峰值强度（TIC-P）和伽马拟合曲线的AUC均为AIS短期预后的独立影响因素（P均＜0.05）。临床、超声及临床-超声列线图模型预测AIS短期预后的AUC分别为0.888、0.758及0.921,以临床-超声列线图模型的预测效能最高（P均＜0.05）。结论 临床-超声列线图可有效预测AIS短期预后。     

CT影像组学联合临床及CT特征预测胸腺上皮肿瘤TNM分期

目的 观察CT影像组学联合临床及CT特征预测胸腺上皮肿瘤（TET）TNM分期的价值。方法 回顾性分析216例经手术病理证实的单发TET患者,以其中151例TNM Ⅰ期为早期组,将27例TNM Ⅲ期及38例Ⅳ期归为晚期组（n=65）。采用单因素分析组间临床资料及胸部CT表现。分别基于平扫（NECT）及增强CT（CECT）提取并筛选最佳影像组学特征,建立预测TET TNM分期的影像组学模型RM_NECT、RM_CECT,联合组间差异有统计学意义的临床及CT特征构建RM_NECT-临床、RM_CECT-临床及RM_{NECT-临床-CT、}RM_{CECT-临床-CT}。按7∶3比例将患者分为训练集（n=151）及 验证集（n=65）,采用重复5折交叉验证法于训练集训练模型,并于验证集验证其效能。结果 组间临床症状及CT所示病灶周围脂肪浸润、纵隔淋巴结肿大、胸腔积液差异均有统计学意义（P均＜0.05）。分别基于NECT及CECT筛选出2个及9个最佳影像组学特征,以之构建相应模型。验证集中,RM_{NECT-临床-CT}预测TET TNM分期的AUC（0.864）高于RM_NECT及RM_NECT-临床（AUC=0.634、0.721,Z=3.081、2.937,P=0.002、0.003）,RM_{CECT-临床-CT}的AUC（0.920）高于RM_CECT及RM_CECT-临床（AUC=0.689、0.751,Z=2.698、2.390,P=0.007、0.017）。结论 CT影像组学联合临床及CT特征能有效预测TET TNM分期。     

弥散加权成像瘤内及瘤周影像组学预测乳腺癌组织学分级

目的 观察弥散加权成像（DWI）瘤内及瘤周影像组学预测乳腺癌组织学分级的价值。方法 回顾性分析700例经病理诊断单发乳腺癌患者术前DWI,按8∶2比例分为训练集（n=560,含381例Ⅰ+Ⅱ级和179例Ⅲ级）和测试集（n=140,含95例Ⅰ+Ⅱ级和45例Ⅲ级）。手动勾画瘤内ROI（ROI_瘤内）,将其自动外扩3、5 mm,获得瘤周ROI（ROI_{+3 mm}和ROI_{+5 mm}）,以及瘤内-瘤周ROI（ROI_{瘤内+3 mm}、ROI_{瘤内+5 mm}）。提取并筛选最佳影像组学特征,构建影像组学模型（RM）用于预测乳腺癌组织学分级_;绘制受试者工作特征曲线,计算曲线下面积（AUC）,评估各模型预测效能。以校准曲线评估模型校准度,以决策曲线分析（DCA）评估其临床实用性。结果RM_瘤内、RM_{+3 mm}、RM_{+5 mm}、RM_{瘤内+3 mm}及RM_{瘤内+5 mm}在训练集的AUC分别为0.750、0.724、0.749、0.833及0.807,在测试集分别为0.723、0.718、0.736、0.759及0.782。各模型AUC差异在训练集中均有（P均＜0.01）而在测试集均无统计学意义（P均＞0.05）,且校准度均较高。DCA显示阈值为0.02～0.88时RM_{瘤内+瘤周}在训练集、阈值为0.40～0.72时其在测试集的临床净收益更大。结论 DWI瘤内及瘤周影像组学均可有效预测乳腺癌组织学分级,瘤内-瘤周影像组学诊断效能更高。     

甲状腺髓样癌术后生存影响因素分析及列线图的构建

背景与目的 目前用于评估甲状腺髓样癌（MTC）预后的主要方式采用TNM分期系统，但该系统不能个体化预测患者的预后。因此，需要建立专门针对MTC的精准预后指标体系。本研究分析影响MTC患者术后生存的因素，并构建MTC术后生存列线图。方法 选取2004—2015年SEER数据库MTC数据，共筛选出符合条件的1 884例患者纳入研究。将患者按3∶1随机分为训练集（1 413例）和验证集（471例），比较两组临床数据基线特征差异。采用单因素和多因素Cox回归模型筛选影响MTC生存的独立因素，Kaplan-Meier生存曲线分析其对预后的影响。基于Cox回归分析筛选出的结果建立MTC术后患者生存列线图。通过一致性指数（C-index）、ROC曲线、曲线下面积（AUC）、校准曲线和决策曲线分析（DCA）对列线图进行验证和评估。结果 单因素分析结果显示，性别、年龄、原发肿瘤分期、淋巴结转移、远处转移、是否甲状腺全切除、肿瘤是否侵犯甲状腺被膜、是否行放射治疗均影响患者预后（均P<0.05）；Cox回归分析结果显示，性别、年龄、远处转移、侵犯甲状腺被膜、是否行甲状腺全切除术、是否放疗为MTC患者的独立预后因素（均P<0.05）。Kaplan-Meier生存曲线显示，男性患者、年龄≥49岁、伴远处转移、肿瘤侵犯甲状腺被膜、未行甲状腺全切除术、接收放疗患者预后更差。用患者性别、年龄、远处转移、甲状腺被膜受侵、手术方式构建了MTC患者2、5、10年的生存列线图。该列线图训练集的C-index为0.755（95% CI=0.741~0.769），验证集为0.725（95% CI=0.699~0.769）。ROC曲线用于评估列线图的区分度，在训练集2、5、10年的AUC值分别为0.79、0.779、0.766；在验证集分别为0.78、0.725、0.733。校准曲线结果显示该列线图预测的生存率和实际生存率具有一致性。DCA将列线图与AJCC第6版TNM分期的临床相比，该列线图的在5年和10年生存评估中均显示出更大的净收益。结论 性别、年龄、远处转移、甲状腺被膜侵犯、手术方式是影响MTC患者生存的独立因素；MTC术后生存列线图模型在一定程度上能够更准确地进行患者个体生存预测，帮助临床医师做出适当的个体化临床决策。     

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.     

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.     

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.     

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.