氟比洛芬酯防治丙泊酚注射痛临床探索

目的观察氟比洛芬酯防治丙泊酚注射液注射痛的效果。方法90例ASk Ⅰ～Ⅱ级采用丙泊酚注射液诱导全麻病人，随机分成六组，各15例。A组静推氟比洛芬酯5m1（含量50mg），60min后开始丙泊酚注射液诱导麻醉；B组静推氟比洛芬酯5ml，30min后开始丙泊酚注射液诱导麻醉；C组静推氟比洛芬酯5ml，10min后开始丙泊酚注射液诱导麻醉；D组静推氟比洛芬酯5ml后用压脉带扎于肘部印秒后开始静推丙泊酚注射液麻醉诱导；E组静推氟比洛芬酯60s后开始静推丙泊酚注射液麻醉诱导;F组静推氟比洛芬酯5ml后即刻开始丙泊酚注射液麻醉诱导。结果疼痛发生率及疼痛评分：A组、B组与c组比较差异有显著性（P＜0．05），A组与B组比较差异无显著性（P＞0．05），E组、F组与D组比较差异有显著性（P＜0．05），E组或F组与A组或B组比较差异无显著性（P＞0．05），D组与A、B组比较差异有显著性（P＜0.05）。结论氟比洛芬酯对预防丙泊酚注射液注射痛有效，用药后即刻予丙泊酚注射液时对注射痛预防效果最好。     

氟比洛芬酯预处理用于减轻丙泊酚注射痛的剂量探讨

目的:本试验探讨应用氟比洛芬酯减轻患者丙泊酚注射痛的最佳剂量.方法:200例行气管内插管全身麻醉的患者随机分为A、B、C和D组,每组各50例.注射丙泊酚前2 min,A组在静注氟比洛芬酯75mg;B组静注氟比洛芬酯50 mg;C组静注静注氟比洛芬酯25 mg;D组静注生理盐水7.5 mL.4组均用止血带阻断前臂静脉2 min.接着静脉注射丙泊酚0.5 mg/kg,通过4点口述评定量表(VRS)评估丙泊酚注射痛并记录发生疼痛频数.结果:A组和B组的VRS均比C组和D组的低;A组和B组注射痛的发生率均比C组和D组的低,差异均有统计学意义.结论:注射丙泊酚前2 min静注氟比洛芬酯50 mg或75 mg,同时用止血带阻断前臂静脉2min均能有效地减轻丙泊酚注射痛,且氟比洛芬酯50mg足以有效地减轻丙泊酚注射痛.     

氟比洛芬酯和利多卡因联用缓解异丙酚注射痛的随机对照研究

目的 探讨联合应用氟比洛芬酯和利多卡因做静脉预处理缓解异丙酚注射痛的效果.方法 将160例拟行择期手术的ASI 1～2级全麻患者随机分为对照组、利多卡因组(Lc组)、氟比洛芬酯组(FA组)和氟比洛芬酯和利多卡因联用组(联用组),每组各40例.所有患者在给药前均先以橡胶止血带阻断其局部静脉回流,随后分别给予对照组0.9％ NS7 mL,FA组氟比洛芬酯注射液5mL(50 mg)+0.9％ NS 2 mL,Lc组2％利多卡因2mL(40 mg)+0.9％ NS 5 mL,联用组氟比洛芬酯注射液5mL (50 mg) +2％利多卡因2mL (40 mg);2 min后撤止血带,在5s内给入0.5 mg/kg的异丙酚.给药同时由另一位麻醉师以相同的方式及问题询问患者注射部位情况,采用VRS评分.结果 4组间一般情况比较无明显差异.Lc组、FA组、联用组的异丙酚注射痛发生率明显低于对照组(P＜0.05),联用组疼痛发生率低于其余3组.在注射痛强度评分方面,Lc组和联用组的疼痛强度明显低于对照组.术后24 h随访,患者注射部位无红肿、静脉炎或药疹等不良反应情况,亦无预期的胃肠刺激症状.结论 氟比洛芬酯和利多卡因联用做静脉预处理可有效缓解异丙酚注射痛,且不会增加不良反应.     

不同浓度利多卡因复合丙泊酚对注射痛的预防效果观察

探讨分析不同浓度利多卡因复合丙泊酚对注射痛的预防效果。选取160全身麻醉择期手术的患者随机分为A、B、C、D、E组,A组仅给予丙泊酚注射,B组给予的丙泊酚注射液中含有10ml0.5%利多卡因,C组给予的丙泊酚注射液中含有10ml1%利多卡因,D组给予的丙泊酚注射液中含有10ml 2%利多卡因,E组在注射丙泊酚之前给予利多卡因40mg/2ml;用药后五组患者疼痛情况差异具有统计学意义(P<0.05),两两比较,A组患者与B、C、D、E组患者疼痛情况差异具有统计学意义(P<0.05),B组患者与A、C、D、E组患者疼痛情况差异具有统计学意义(P<0.05),C组患者与A、B、D患者疼痛情况差异具有统计学意义(P<0.05),D组患者与A、B、C、E组患者疼痛情况差异具有统计学意义(P<0.05),D组患者用药后疼痛发生率最低,差异具有统计学意义(P<0.05),用药前、用药后五组患者平均动脉压、心率及血氧饱和度差异均无统计学意义(P>0.05);在丙泊酚注射液中加入利多卡因可有效降低患者的注射痛,尤其是注射液中加入2%利多卡因降低疼痛效果最佳,并且不同浓度利多卡因复合丙泊酚注射液对麻醉效果未造成影响,可推广。     

不同剂量利多卡因预处理对罗库溴铵注射痛的影响

目的比较利多卡因不同剂量预处理对罗库溴铵注射痛的影响。方法 120例行全身麻醉择期手术的患者按照完全随机的方法分为利多卡因10mg3mL预处理组（A组）,利多卡因25mg3mL预处理组（B组）,利多卡因50mg3mL预处理组（C组）,生理盐水3mL预处理组（D组）。观察不同剂量的利多卡因预处理对罗库溴铵注射痛的影响。结果 A、B、C和D组注射罗库溴铵的疼痛发生率分别为53%、27%、3%和90%。与生理盐水预处理组相比,利多卡因预处理组能明显减轻罗库溴铵引起的注射痛（P〈0.01）;剂量越大,效果越明显。结论利多卡因10、25、50mg预处理均能显著降低罗库溴铵注射时引起的疼痛,以50mg利多卡因更为有效。     

不同方法注射利多卡因对预防儿童丙泊酚注射痛的效果比较

目的:比较预注和混用利多卡因对于儿童丙泊酚静脉注射痛的预防作用。方法:120例儿外科患儿分为A组(先静脉注射0.5 mg/kg利多卡因30 s后使用注射丙泊酚全麻诱导)和B组(丙泊酚和1%利多卡因按20∶1混合液全麻诱导),每组均为60例,观察患儿从开始注射丙泊酚到意识消失过程中出现的注药手臂运动情况和面部表情的反应,评估疼痛的发生率和强度。结果:A组注射痛的发生率为68.3%,其中中重度痛(中度痛+重度痛)发生率为38.3%。B组注射痛的发生率为36.7%,其中中重度痛发生率为18.3%。两组相比,B组注射痛及中重度痛的发生率均明显降低(均P<0.01)。结论:丙泊酚和1%利多卡因按20∶1混合液较预注射0.5 mg/kg利多卡因30 s后注射丙泊酚更能有效缓解患儿注射痛。     

地佐辛预防丙泊酚注射痛的随机、对照、双盲研究

目的探讨静脉预先注射地佐辛预防丙泊酚注射痛的临床效果。方法 160例拟在全麻下行择期手术患者,随机分为对照组(C组)、利多卡因组(L组)、芬太尼组(F组)和地佐辛组(D组),每组40例。C组经静脉预先注射生理盐水3ml,L组预先注射利多卡因30mg,F组预先注射芬太尼0.1mg,D组预先注射地佐辛10mg。2分钟后推注0.5mg/kg丙泊酚,同时行注射部位疼痛评分。结果 L组、D组丙泊酚注射痛总发生率和严重程度低于C组(P<0.05);D组丙泊酚注射痛总发生率低于F组(P<0.05),D组不良反应发生率低于F组(P<0.05)。结论静脉预先注射地佐辛能有效减轻丙泊酚注射痛的发生率和严重程度,且安全性较高。     

氟比洛芬酯、利多卡因复合丙泊酚用于无痛人工流产镇痛

目的观察氟比洛芬酯、利多卡因复合丙泊酚用于无痛人工流产的镇痛效果。方法将拟行人工流产的300例随机分为3组,Ⅰ组手术开始前予丙泊酚2mg/kg静脉注射 Ⅱ组手术开始前予芬太尼50μg、丙泊酚2mg/kg静脉注射 Ⅲ组术前30min予氟比洛芬酯50mg溶于10ml0.9%氯化钠溶液中缓慢静脉推注,手术开始前依次静脉注射利多卡因1mg/kg,丙泊酚2mg/kg。后根据患者抵抗运动强弱追加丙泊酚0.5～1mg/kg,至体动消失。观察记录术中镇痛效果、视觉模拟评分（VAS）及术中各时间段脉搏、平均动脉压（MAP）、脉搏氧分压（SpO2）,并比较麻醉后不良反应及并发症发生率。结果3组脉搏及MAP与术前比较差异有统计学意义（P〈0.05） Ⅲ组镇痛效果、VAS、丙泊酚用量、唤醒时间、术中呼吸暂停发生率、注射部位疼痛及其他并发症发生率与Ⅰ组、Ⅱ组比较差异有统计学意义（P〈0.05）。结论氟比洛芬酯、利多卡因复合丙泊酚用于无痛人工流产麻醉效果满意,可减少药物用量,不良反应小,有利于病人术后恢复。     

艾司洛尔预处理对丙泊酚注射痛的影响

目的：观察小剂量艾司洛尔预处理对丙泊酚静脉注射痛的影响。方法：美国麻醉医师协会（ASA）分级为Ⅰ～Ⅱ级且择期行全麻手术的患者120例,随机分为3组,每组40例。经左前臂桡侧浅静脉置入20G套管留置针。麻醉诱导前左上臂包裹气压止血带,加压至70mmHg后,按分组以3mL/10s速度分别静脉注射：0.9%氯化钠液3mL（C组）,利多卡因0.5mg/kg（L组）,艾司洛尔0.25mg/kg（E组）,60s后松开止血带,将2mg/kg丙泊酚在20s内缓慢注入。随后静脉注射芬太尼、维库溴胺,行气管插管全麻。采用4分制记录3组患者丙泊酚注射痛评分,并记录药物预注前（T0）、气管插管前（T1）、气管插管后1min（T2）、气管插管后3min（T3）的平均动脉压（MAP）和心率（HR）。结果：注射痛的发生率C组为65%（26/40）,而L组为10%（4/40）,E组为25%（10/40）,与C组相比显著降低（P〈0.01）。L组和E组中度和重度疼痛的发生率均显著低于C组（P〈0.05和P〈0.01）。E组与L组比较,差异无统计学意义（P〉0.05）。结论：小剂量艾司洛尔预处理合用止血带可有效缓解丙泊酚注射痛。     

混合预注舒芬太尼及利多卡因在无痛胃镜检查中缓解丙泊酚注射痛的临床观察

【目的】观察预给舒芬太尼和（或）利多卡因预防无痛胃镜检查中丙泊酚注射痛的效果。【方法】采用双盲法,选择行无痛胃镜检查的患者200例,随机分为舒芬太尼组（S组）、利多卡因组（L组）、舒芬太尼联合利多卡因组（SL组）及生理盐水组（C组）,每组50例。给予丙泊酚前1min,四组患者分别静脉注射舒芬太尼（0．2μg／kg,2mL）、利多卡因40mg（2mL）、舒芬太尼＋利多卡因（0．2μg／kg＋40mg）以及生理盐水（2mL）。所有患者以0．5mL／s速度缓慢静脉注射丙泊酚100mg,从预给药开始由另外一名麻醉医生观察是否发生注射痛及严重程度。【结果】与C组比较,L组、S组及SL组注射痛发生率和严重程度均明显降低（P〈0．05）,与S组及L组比较,SL组注射痛发生率及严重程度明显降低（P〈0．05）。【结论】预给舒芬太尼或利多卡因均可有效减少丙泊酚注射痛的发生率以及减轻丙泊酚注射痛的严重程度,且联合舒芬太尼及利多卡因效果更佳。     

Comparison of lidocaine, metoclopramide, and flurbiprofen axetil for reducing pain on injection of propofol in Japanese adult surgical patients: a prospective, randomized, double-blind, parallel-group, placebo-controlled study

Background: Pain on injection is a recognized adverse event (AE) of propofol administration for the induction of general anesthesia. Pretreatment with lidocaine, metoclopramide, or flurbiprofen axetil has been reported to be effective in reducing propofol-induced pain. However, no studies comparing the efficacy of these 3 drugs for preventing pain on injection of propofol have been identified. Objective: The aim of this study was to compare the efficacy of lidocaine, metoclopramide, and flurbiprofen axetil for reducing pain on injection of propofol in Japanese adult surgical patients. Methods: This prospective, randomized, double-blind, parallel-group, placebo-controlled study was conducted at the Department of Anesthesiology, Ushiku Aiwa General Hospital, Ibaraki, Japan. Japanese patients scheduled to undergo elective surgery were eligible for inclusion in the study. Patients were randomized into 4 groups to receive IV lidocaine 40 mg, metoclopramide 10 mg, flurbiprofen axetil 50 mg, or placebo (saline), preceded by venous occlusion with a rubber tourniquet for 2 minutes, and followed by the administration of propofol 0.5 mg/kg into the largest vein of the hand through a 20-gauge IV cannula. Immediately after the administration of propofol, an investigator blinded to treatment interviewed each patient on injection-site pain. Responses were scored on a 4-point verbal rating scale (0 = none, 1 = mild pain, 2 = moderate pain, and 3 = severe pain). Incidence and intensity of pain (as assessed by mean pain scores) were determined in each of the 4 study groups. AEs at the injection site (eg, pain, edema, wheal, inflammation), extrapyramidal disturbance, and symptoms or signs associated with gastrointestinal (GI) ulceration were assessed by the study investigator for 24 hours following surgery using spontaneous reporting and patient interview. Results: A total of 100 patients (54 women, 46 men) aged 22 to 65 years were enrolled in the study. The patients' mean (SD) age was 42 (12) years. Their mean (SD) height was 161 (8) cm and their mean (SD) weight was 59 (9) kg. Each treatment group comprised 25 patients. There were no significant differences in demographic characteristics between treatment groups. The overall incidence of propofol-induced pain was 24% (6/25 patients) with lidocaine (P = 0.001), 28% (7/25 patients) with metoclopramide (P = 0.001), and 36% (9/25 patients) with flurbiprofen axetil (P = 0.001), compared with placebo (92%, [23/25 patients]). The median pain score was less in patients who had received lidocaine (0), metoclopramide (0), or flurbiprofen axetil (0) than in those who received placebo (2) (all, P = 0.001). The incidence and severity of such pain were not significantly different between the lidocaine-, metoclopramide-, and flurbiprofen axetil-treated groups. There were no reported injection-site AEs, extrapyramidal disturbance, or symptoms or signs associated with GI ulceration observed. Conclusions: In this study of Japanese adult surgical patients, lidocaine 40 mg, metoclopramide 10 mg, and flurbiprofen axetil 50 mg, preceded by venous occlusion for 2 minutes, were effective in reducing pain during the injection of propofol. The analgesic efficacy of these 3 drugs was comparable for minimizing such pain.     

Reducing the Pain of Microemulsion Propofol Injections: A Double-Blind,Randomized Study of Three Methods of Tourniquet and Lidocaine

Background

Although the new formulation of lipid-free microemulsion propofol (MP) has some advantages over the lipid emulsion, it reportedly produces more injection pain than lipid-based propofol. Intravenous lidocaine with application of a rubber tourniquet before administration of propofol is considered to be the best method for reducing injection pain; however, this technique is not perfect.

Objective

The goal of this study was to evaluate the effect of different methods of tourniquet application and lidocaine administration on MP injection pain.

Methods

This single-center, randomized controlled clinical trial was conducted in 140 patients aged 18 to 65 years. Patients were randomly divided into 4 groups (n = 35 each). Group A received MP (2 mg/kg) after lidocaine (0.6 mg/kg) with a tourniquet with arm down (venous engorgement); group B received MP after lidocaine with a tourniquet with arm up (venous gravity drainage); group C received MP with a tourniquet with arm down; and group D (control group) received MP only (with no tourniquet). In groups A and C, the tourniquet was released after MP; in group B, the tourniquet was released before MP. Injection pain was evaluated by using a verbal pain score (VPS). The bispectral index, the time from the beginning of drug injection to the loss of eyelash reflex, and time to the lowest bispectral index value were recorded.

Results

Group A showed significantly less incidence of pain than the control group when MP was injected. The mean VPS was significantly lower in groups A, B, and C than in group D (the control group). The VPS of group A was significantly lower than that in group B. Other observed values were not significantly different.

Conclusions

We concluded that intravenous retention of lidocaine with the application of a rubber tourniquet under venous engorgement of the arm reduces the incidence and intensity of MP injection pain. Clinical trial registry: UMIN000010725.     

托烷司琼复合利多卡因预防丙泊酚注射痛的疗效观察

目的观察托烷司琼复合利多卡因预防丙泊酚注射痛的效果。方法采取随机双盲法将符合标准择期拟行手术的200例患者分为4组,I组（n=50）：生理盐水2mL;II组（n=50）：2％利多卡因40mg;Ⅲ组（n=50）：托烷司琼5mg;IV组（n=50）：托烷司琼5mg与2％利多卡因40mg。四组从静脉注射上述药物lmin后,以0．5mL／s的速度按2mg／kg脉注射丙泊酚进行诱导。根据Ambesh四分法观察每组疼痛的发生率及程度。结果Ⅱ、Ⅲ、Ⅳ实验组与对照组I组比较均可以明显降低丙泊酚静脉注射疼痛的发生率及严重程度（P〈0．05）,而Ⅱ、Ⅲ实验组间差异无统计学意义（P〉0．05）,Ⅱ组与Ⅳ组间（P〈0．05）及组与Ⅳ组间（P〈0．05）差异有统计学意义。结论在丙泊酚静脉注射前缓慢预注托烷司琼复合利多卡因能有效预防丙泊酚注射痛的发生率及严重程度。     

Flurbiprofen axetil preceded by venous occlusion in the prevention of pain on propofol injection in the hand: a prospective, randomized, double-blind, vehicle-controlled, dose-finding study in Japanese adult surgical patients

BACKGROUND: Pain on injection is still a major problem with propofol used for general anesthesia. A number of techniques for reducing propofol-induced pain on injection have been tried, with variable results. Flurbiprofen axetil, a prodrug of the nonsteroidal anti-inflammatory drug flurbiprofen, has been used for postoperative pain management but has not been studied for managing pain on injection of propofol when preceded with venous occlusion. OBJECTIVE: The present study was undertaken to examine the efficacy of flurbiprofen axetil for reducing pain on propofol injection in Japanese adult surgical patients. METHODS: This prospective, randomized, double-blind, vehicle-controlled, dose-finding study was conducted at the Department of Anesthesiology, University of Tsukuba Institute of Clinical Medicine, Tsukuba, Japan. Japanese patients aged 18 to 65 years scheduled to undergo elective surgery were eligible. Patients were randomized to receive flurbiprofen axetil IV at 1 of 3 doses (25, 50, or 75 mg), or vehicle (control group), preceded by manual venous occlusion with a rubber tourniquet for 2 minutes and followed by administration of 25% of the total calculated dose of propofol (2 mg/kg), injected into the largest vein of the hand through a 20-gauge IV cannula. During propofol injection, a researcher who was blinded to treatment assignment asked each patient about his or her pain at the injection site. Responses were scored on a 4-point scale (0 = none, 1 = mild, 2 = moderate, 3 = severe). Median pain intensity scores in each group were determined. Adverse effects (AEs) at the injection site (pain, edema, wheal, or inflammation) were monitored for up to 24 hours after surgery. RESULTS: A total of 120 patients (62 men, 58 women; mean [SD] age, 41 [12] years, mean [SD] height, 162 [8] cm; mean [SD] body weight, 58 [10] kg) were enrolled. Each treatment group comprised 30 patients. No significant between-group differences in demographic characteristics were found. A significantly higher proportion of patients in the control group (77%) experienced pain compared with the flurbiprofen axetil 50- and 75-mg groups (47% and 43%, respectively; both, P < 0.01). The median pain intensity scores were significantly lower in the flurbiprofen axetil 50- and 75-mg groups (both, 0 [no pain]) compared with controls (2 [moderate]; both, P < 0.01). The incidence and intensity of propofol-induced pain were statistically similar between the flurbiprofen axetil 25-mg and control groups. The incidence and intensity of pain associated with the injection of propofol were significantly lower in the flurbiprofen axetil 50- and 75-mg groups compared with the 25-mg group (incidence, 70% [both, P < 0.05]; median pain intensity score, 1 [mild] [both, P < 0.01]). No AEs were observed. CONCLUSION: In this study of Japanese adult surgical patients, flurbiprofen axetil at doses of 50 and 75 mg, preceded by venous occlusion for 2 minutes, was found to be effective in reducing propofol-induced pain on injection.     

Influence of age on flurbiprofen axetil requirements for preventing pain on injection of propofol in Japanese adult surgical patients: a prospective, randomized, double-blind, vehicle-controlled, parallel-group, dose-ranging study

BACKGROUND: Pain on injection is a recognized adverse event (AE) of propofol administration for the induction of general anesthesia. Preceded by venous occlusion, flurbiprofen axetil, a prodrug of the NSAID flurbiprofen, has been associated with a reduction in pain induced by propofol injection. A review of the literature determined that no published data were available on the influence of age on the requirements for flurbiprofen axetil dose. OBJECTIVE: This study was undertaken to examine the influence of age on flurbiprofen axetil requirements for the treatment of propofol-induced pain on injection in Japanese adult surgical patients. METHODS: This prospective, randomized, double-blind, vehicle-controlled, parallel-group, dose-ranging study was conducted at the Department of Anesthesiology, Institute of Clinical Medicine, University of Tsukuba, Tsukuba, Japan. Young (age 20-40 years) and older (age 60-80 years) Japanese patients scheduled for various types of surgery (eg, cholecystectomy) were eligible. Patients were randomized to receive flurbiprofen axetil at 1 of 2 doses (25 or 50 mg, regardless of body weight) or inactive vehicle (saline), preceded by manual venous occlusion with a rubber tourniquet for 2 minutes and followed by the infusion of the first 25% of calculated propofol dose (0.5 mg/kg at room temperature, 23 degrees C) into the largest dorsal vein of the hand through a 20-G IV cannula (without local anesthesia), followed by the release of the occlusion and delivery of propofol 2 mg/kg. An investigator blinded to treatment questioned each patient about pain intensity during propofol injection which was assessed using a verbal rating scale: 0 = none; 1 = mild; 2 = moderate; and 3 = severe. The overall prevalence of pain was calculated in each group. AEs at the injection site (pain, edema, wheal, inflammation) were assessed by the study investigator for 24 hours after surgery using spontaneous reporting and patient interview. RESULTS: A total of 150 patients, 75 young adults (38 men, 37 women; mean [SD] age, 31 [5] years; mean [SD] height, 163 [7] cm; mean [SD] body weight, 58 [9] kg) and 75 older adults (38 men, 37 women; mean [SD] age, 70 [6] years; mean [SD] height, 154 [8] cm; mean [SD] body weight, 53 [10] kg), were enrolled. Each treatment group comprised 25 patients. No differences in demographic characteristics were observed among the 3 study groups. In young patients, the overall prevalence of propofol-induced pain was significantly lower in patients who received flurbiprofen axetil 50 mg (12 [48%]) compared with that in patients who received flurbiprofen axetil 25 mg (20 [80%]) or vehicle (22 [88%]) (P < 0.05 and P < 0.01, respectively). The median pain intensity score was significantly lower in patients who received flurbiprofen axetil 50 mg (0) compared with that in patients who received flurbiprofen axetil 25 mg (1) or vehicle (2) (P < 0.05 and P < 0.01, respectively). In older patients, the overall prevalences of pain on propofol injection were 9 (36%) in the flurbiprofen axetil 50-mg group and 11 (44%) in the flurbiprofen axetil 25-mg group compared with 21 (84%) in the vehicle group (both, P < 0.01). The median pain score was significantly lower in patients who received flurbiprofen 50 mg (0) or 25 mg (0) than in those who received vehicle (1) (both, P < 0.01). All treatments were well tolerated. CONCLUSIONS: In this small clinical trial in Japanese surgical patients undergoing general anesthesia, flurbiprofen axetil requirements for the reduction of pain during injection of propofol were found to be 50 mg in young adults (age 20-40 years) and 25 or 50 mg in older adults (age 60-80 years), regardless of weight, preceded by venous occlusion for 2 minutes.