Safety and hemostatic effect of recombinant activated factor VII in cirrhotic patients undergoing partial hepatectomy: a multicenter, randomized, double-blind, placebo-controlled trial

BACKGROUND: Coagulopathy caused by cirrhosis may contribute to excessive bleeding during hepatectomy. We evaluated the hemostatic effect and safety of recombinant factor VIIa (rFVIIa) in cirrhotic patients undergoing partial hepatectomy. METHODS: Patients were randomized to rFVIIa 50 or 100 mug/kg or placebo, administered intravenously 10 minutes before surgery and every second hour during surgery. The primary efficacy end points were the proportion of patients receiving red blood cell (RBC) transfusions and the amount of RBCs transfused. The RBC transfusion trigger was blood loss of 500 mL. Safety end points included thromboembolic and adverse events. RESULTS: No statistically significant effect of rFVIIa treatment on efficacy end points was observed. Serious and thromboembolic adverse events occurred at similar incidences in the study groups. CONCLUSIONS: Using blood loss as a transfusion trigger, the efficacy of rFVIIa in reducing the requirement for RBC transfusion was not established in this study. No safety concerns were identified.     

Dexmedetomidine as an anaesthetic adjuvant in patients undergoing intracranial tumour surgery: a double-blind, randomized and placebo-controlled study

Background. Dexmedetomidine (DEX) has been shown to providegood perioperative haemodynamic stability with decreased intraoperativeopioid requirements. It may have neural protective effects,and thus may be a suitable anaesthetic adjuvant to neurosurgicalanaesthesia. Methods. Fifty-four patients scheduled for elective surgeryof supratentorial brain tumour were randomized to receive ina double-blind manner a continuous DEX infusion (plasma targetconcentration 0.2 or 0.4 ng ml^–1) or placebo, beginning20 min before anaesthesia and continuing until the start ofskin closure. The DEX groups received fentanyl 2 µg kg^–1at the induction of anaesthesia and before the start of operation,the placebo group 4 µg kg^–1, respectively. Anaesthesiawas maintained with nitrous oxide in oxygen and isoflurane. Results. The median times from the termination of N₂O to extubationwere 6 (3–27), 3 (0–20) and 4 (0–13) min inplacebo, DEX-0.2 and DEX-0.4 groups, respectively (P<0.05ANOVA all-over effect). The median percentage of time pointswhen systolic blood pressure was within more or less than 20%of the intraoperative mean was 72, 77 and 85, respectively (P<0.01),DEX-0.4 group differed significantly from the other groups.DEX blunted the tachycardic response to intubation (P<0.01)and the hypertensive response to extubation (P<0.01). DEX-0.4group differed in the heart rate variability from placebo (93vs 82%, P<0.01). Conclusions. DEX increased perioperative haemodynamic stabilityin patients undergoing brain tumour surgery. Compared with fentanyl,the trachea was intubated faster without respiratory depression.      

N-acetylcysteine prevents reactive oxygen species-mediated myocardial stress in patients undergoing cardiac surgery: results of a randomized, double-blind, placebo-controlled clinical trial

OBJECTIVE: Reactive oxygen species have been shown to contribute to myocardial stress in patients undergoing cardiac surgery, as demonstrated by myocardial 8-iso-prostaglandin-F(2)alpha and nitrotyrosine formation. We hypothesized that the reactive oxygen species scavenger N-acetylcysteine attenuates reactive oxygen species-mediated myocardial stress in patients undergoing cardiac surgery. METHODS: Forty patients undergoing coronary artery surgery (mean age +/- SD, 66 +/- 9 years; 9 women and 31 men) were randomized to receive either N-acetylcysteine (100 mg/kg into cardiopulmonary bypass prime followed by infusion at 20 mg.kg(-1).h(-1), n = 20) or placebo (n = 20). Patients and clinical staff were blinded to group assignment. Transmural left ventricular biopsy specimens collected before and at the end of cardiopulmonary bypass were subjected to immunocytochemical staining against 8-iso-prostaglandin-F(2)alpha (primary measure) as an indicator for reactive oxygen species-mediated lipid peroxidation and nitrotyrosine (coprimary measure) as a marker for peroxynitrite-mediated tissue injury. Cardiomyocyte staining was quantitatively determined by using densitometry (in gray units). Global left ventricular function was measured on the basis of fractional area of contraction by using transesophageal echocardiography. RESULTS: Patient characteristics in both groups were comparable. The change in left ventricular cardiomyocyte staining (end of cardiopulmonary bypass--before cardiopulmonary bypass) differed significantly between groups for both primary measures: 8-iso-prostaglandin-F(2)alpha, -1.8 +/- 7.5 gray units (mean +/- SD, N-acetylcysteine group) versus 5.0 +/- 4.1 gray units (placebo group; 95% confidence interval, 2.6-11.0, P =.003); nitrotyrosine, -6.4 +/- 10.0 gray units (N-acetylcysteine group) versus 9.2 +/- 8.4 gray units (placebo group; 95% confidence interval, 9.4-21.7, P <.001). Hemodynamics and clinical outcomes were comparable in both groups. CONCLUSIONS: Reactive oxygen species scavenging with N-acetylcysteine attenuates myocardial oxidative stress in the hearts of patients subjected to cardiopulmonary bypass and cardioplegic arrest.     

Use of noninvasive positive pressure ventilation in patients with severe obesity undergoing esophagogastroduodenoscopy: a randomized controlled trial

BackgroundPatients with severe obesity being considered for bariatric surgery often undergo preoperative esophagogastroduodenoscopy (EGD). Severe obesity is a risk factor for oxygen desaturation events during EGD. The use of noninvasive positive pressure ventilation (NIPPV) to reduce desaturation events during EGD among patients with severe obesity has not been studied.ObjectiveTo evaluate the use of NIPPV among patients with severe obesity undergoing EGD.SettingCommunity hospital endoscopy suite.MethodsA randomized controlled trial evaluated the use of NIPPV in patients with severe obesity undergoing EGD. Patients were randomized into treatment (NIPPV) and control (nasal cannula, NIPPV for rescue) groups. Primary endpoints were oxygen desaturation events ≤94% and oxygen desaturation events <90% requiring intervention. A secondary endpoint was the use of NIPPV as a rescue maneuver.ResultsFifty-six patients with a body mass index of 40 to 60 were randomized (n = 28 treatment and n = 28 control). A statistically significant difference was noted between the groups for desaturation events ≤94% (14.3% of treatment and 57.1% of control groups, P = .002). There was also a statistically significant difference in the risk of a desaturation event <90% requiring intervention (3.5% of treatment and 28.6% of control groups, P = .025). All patients in the control group who developed desaturation events requiring intervention were rescued with NIPPV.ConclusionsThis study demonstrated the successful use of NIPPV as an adjunct to decrease the incidence of desaturation events in patients with severe obesity undergoing EGD.     

Efficacy of aminocaproic, tranexamic acids in the control of bleeding during total knee replacement: a randomized clinical trial

Background. Risks and costs of allogeneic blood transfusionsmandate strategies to reduce blood loss in surgery. The objectiveof this study was to assess the efficacy of antifibrinolytictreatment in reducing perioperative blood loss during totalknee replacement. Methods. A double-blind, randomized and placebo-controlled clinicaltrial was carried out on 127 patients undergoing total kneereplacement. Patients in the study group received tranexamicacid 10 mg kg^–1 i.v. just before the tourniquet was deflatedand 3 h later, or epsilon-aminocaproic acid 100 mg kg^–1before tourniquet deflation followed by continuous perfusion(1 g h^–1) during 3 h. External perioperative blood losswas measured and total blood loss was calculated. The numberof patients transfused and number of packed red cell (PRC) unitstransfused was recorded and possible postoperative thromboemboliccomplications were investigated. Results. Total blood loss [mean (SD)] was 1099 ml (535) in thegroup that received antifibrinolytic agents and 1784 ml (660)in the control group (P<0.001). Five patients (7.5%) in thestudy group and 23 (38.3%) in the control group (P<0.001)received blood transfusions; the first group received a meanof 0.10 PRC unit per patient and the second, 0.58 (P<0.001).Mean reduction in haemoglobin levels (g dl^–1) betweenpreoperative and fifth day postoperative readings was 2.5 (0.9)in the study group and 3.4 (1.2) in the control group (P<0.001).Clinical assessment did not reveal any thromboembolic complications. Conclusions. Antifibrinolytic agents produce a significant decreasein blood loss in patients undergoing total knee replacement,reflected in a reduction in the number of blood transfusionsrequired.     

Effects of adjunct intrathecal magnesium sulfate to bupivacaine for spinal anesthesia: a randomized, double-blind trial in patients undergoing lower extremity surgery

Purpose  

The aim of this study was to evaluate the effect of additional magnesium sulfate (MgSO₄) 100 mg to intrathecal (IT) isobaric 0.5% bupivacaine 3 ml on spinal anesthesia in patients undergoing lower extremity orthopedic surgery.     

Health-related quality of life and cost-effectiveness analysis of gum chewing in patients undergoing colorectal surgery: results of a randomized controlled trial

Background: Postoperative ileus (POI) and anastomotic leakage (AL) following colorectal surgery severely increase healthcare costs and decrease quality of life. This study evaluates the effects of reducing POI and AL via perioperative gum chewing compared to placebo (control) on in-hospital costs, health-related quality of life (HRQoL), and assesses cost-effectiveness.

Methods: In patients undergoing elective, open colorectal surgery, changes in HRQoL were assessed using EORTC-QLQ-C30 questionnaires and costs were estimated from a hospital perspective. Incremental cost-effectiveness ratios were estimated.

Results: In 112 patients, mean costs for ward stay were significantly lower in the gum chewing group when compared to control (€3522 (95% CI €3034–€4010) versus €4893 (95% CI €3843–€5942), respectively, p?=?.020). No differences were observed in mean overall in-hospital costs, or in mean change in any of the HRQoL scores or utilities. Gum chewing was dominant (less costly and more effective) compared to the control in more than 50% of the simulations for both POI and AL.

Conclusion: Reducing POI and AL via gum chewing reduced costs for ward stay, but did not affect overall in-hospital costs, HRQoL, or mapped utilities. More studies with adequate sample sizes using validated questionnaires at standardized time points are needed.     

Prehospital fast track care for patients with hip fracture: Impact on time to surgery,hospital stay,post-operative complications and mortality a randomised,controlled trial

IntroductionAmbulance organisations in Sweden have introduced prehospital fast track care (PFTC) for patients with suspected hip fracture. This means that the ambulance nurse starts the pre-operative procedure otherwise implemented at the accident & emergency ward (A&E) and transports the patient directly to the radiology department instead of A&E. If the diagnosis is confirmed, the patient is transported directly to the orthopaedic ward. No previous randomised, controlled studies have analysed PFTC to describe its possible advantages.The aim of this study is to examine whether PFTC has any impact on outcomes such as time to surgery, length of stay, post-operative complications and mortality.MethodsThe design of this study is a prehospital randomised, controlled study, powered to include 400 patients. The patients were randomised into PFTC or the traditional care pathway (A&E group).ResultsTime from arrival to start for X-ray was faster for PFTC (mean, 28 vs. 145 min; p < 0.001), but the groups did not differ with regard to time from start of X-ray to start of surgery (mean 18.40 h in both groups). No significant differences between the groups were observed with regard to: time from arrival to start of surgery (p = 0.07); proportion operated within 24 h (79% PFTC, 75% A&E; p = 0.34); length of stay (p = 0.34); post-operative complications (p = 0.75); and 4 month mortality (18% PFTC, 15% A&E p = 0.58).ConclusionPFTC improved time to X-ray and admission to a ward, as expected, but did not significantly affect time to start of surgery, length of stay, post-operative complications or mortality. These outcomes were probably affected by other factors at the hospital. Patients with either possible life-threatening conditions or life-threatening conditions prehospital were excluded.     

下肢手术患者罗哌卡因与布比卡因蛛网膜下腔阻滞效果的比较前瞻性、多中心、随机、双盲研究

目的 比较单侧下肢手术患者罗哌卡因和布比卡因蛛网膜下腔阻滞的效果.方法 本试验为前瞻性、多中心、随机、双盲的临床研究.拟行单侧下肢手术患者218例,ASA Ⅰ或Ⅱ级,年龄18～64岁,体重指数18～24 kg/m2,性别不限.随机分为2组,R组(n=110)蛛网膜下腔注射5 ms/ml罗哌卡因3.5 ml;B组(n=108)蛛网膜下腔注射5 mg/ml布比卡因2.5 ml.采用改良的Bromage评分法评估非术侧下肢的运动阻滞效果,记录起效时间和维持时间;采用针刺法评估感觉阻滞效果,记录起效时间和维持时间;评估术中麻醉质量与肌松效果;记录不良反应的发生情况.结果 与B组比较,R组运动阻滞起效时间延长,运动阻滞和感觉阻滞维持时间缩短(P＜0.05或0.01),感觉阻滞起效时间差异无统计学意义(P＞0.05);两组运动阻滞和感觉阻滞有效率差异无统计学意义(P＞0.05);两组麻醉质量和肌松效果均较好,麻醉质量比较差异无统计学意义(P＞0.05),R组肌松效果优于B组(P＜0.05);两组不良事件发生率均较低,且差异无统计学意义(P＞0.05).结论 下肢手术患者采用罗哌卡因蛛网膜下腔阻滞时,术中麻醉质量及肌松效果良好,且其运动阻滞维持时间较布比卡因短,有利于术后的恢复,其临床效果更具优越性.     

Transurethral prostate resection and bleeding: a randomized,placebo controlled trial of role of finasteride for decreasing operative blood loss

PURPOSE: Bleeding associated with transurethral prostate resection can often be significant and lead to increased morbidity and occasionally mortality. It has been shown that finasteride decreases bleeding in patients with hematuria of prostatic origin. We hypothesized that bleeding in patients undergoing transurethral prostate resection could be decreased by giving finasteride for 2 weeks before surgery. MATERIALS AND METHODS: A total 70 patients scheduled to undergo elective transurethral prostate resection were randomized to receive 5 mg. finasteride daily or placebo for 2 weeks before surgery. Serum hemoglobin was measured before and after surgery, and the following day. The volume of irrigation fluid used and its hemoglobin concentration as well as resected prostate weight were recorded. RESULTS: Of the 68 patients who underwent transurethral prostate resection 2 were withdrawn before surgery, and so 32 received finasteride and 36 received placebo. There was significantly less mean blood loss in irrigation fluid in the finasteride group than in the control group (43.6 versus 69.3 gm. hemoglobin, p = 0.011). The mean difference was more significant when blood loss per gm. resected prostate was calculated (2.65 versus 4.65 gm. hemoglobin per gm. prostate, p < 0.01). CONCLUSIONS: This study shows that finasteride given for 2 weeks preoperatively decreases bleeding in patients undergoing transurethral prostate resection. Further study is required to determine the optimal timing and dose duration to minimize blood loss and identify how relevant such a decrease in bleeding is in clinical practice.     

A comparison of incidences of vertebral fracture in Japanese patients with involutional osteoporosis treated with risedronate and etidronate: a randomized, double-masked trial

To demonstrate the clinical benefit of risedronate at 2.5mg daily in the treatment of involutional osteoporosis, the effect of risedronate on incidence of vertebral fracture was compared with that of etidronate. A total of 547 patients with one to four vertebral fractures were randomized to receive either treatment with 2.5mg/day of risedronate or intermittent treatment (treatment of 2 weeks and off period of 10 weeks) with 200mg/day of etidronate for 96 weeks in a double-masked fashion. All patients received 200mg calcium supplement daily. Lateral and anteroposterior thoracic and lumbar spine radiographs were obtained at baseline and at 24, 48, 72, and 96 weeks. Cumulative incidence rates of patients who had at least one new or worsening vertebral fracture during the 96-week period were 12.3% for risedronate and 14.2% for etidronate, and it was verified that the fracture prevention effect of risedronate was not inferior to that of etidronate. The incidence rates of fracture during the initial 24-week period were 8.8% for risedronate and 6.0% for etidronate, but the cumulative incidence rate of fracture from 24 to 96 weeks was lower in the risedronate group (3.9%) as compared to the etidronate group (8.7%). Height loss was significantly less in the risedronate group (–0.28cm) than in the etidronate group (–0.70cm) after 96 weeks. Decreases in bone resorption markers including urinary total deoxypyridinoline and NTX were significantly greater in the risedronate group than in the etidronate group throughout the treatment period. An improvement of patient QOL was observed in both groups. No significant difference in the incidence of adverse events was observed between the two treatments. Daily oral risedronate (2.5mg) was shown to provide an effective therapy for involutional osteoporosis in Japanese patients with good tolerability.     

Hormonal and metabolic stress responses after major surgery in children aged 0-3 years: a double-blind, randomized trial comparing the effects of continuous versus intermittent morphine

Children aged 0–3 yr were stratified for age and randomizedto receive either continuous morphine (CM, 10 µg kg^–1 h^–1)with three-hourly placebo boluses or intermittent morphine (IM,30 µg kg^–1 every 3 h) with a placeboinfusion for postoperative analgesia. Plasma concentrationsof epinephrine, norepinephrine, insulin, glucose and lactatewere measured before and at the end of surgery and 6, 12 and24 h after surgery. Pain was assessed with validated painscales [the COMFORT scale and a visual analogue scale (VAS)]with the availability of additional morphine doses. Minor differencesoccurred between the randomized treatment groups, the oldestIM group (aged 1–3 yr) having a higher blood glucoseconcentration (P=0.003), mean arterial pressure (P=0.02) andCOMFORT score (P=0.02) than the CM group. In the neonates, preoperativeplasma concentrations of norepinephrine (P=0.01) and lactate(P<0.001) were significantly higher, while the postoperativeplasma concentrations of epinephrine were significantly lower(P<0.001) and plasma concentrations of insulin significantlyhigher (P<0.005) than in the older age groups. Postoperativepain scores (P<0.003) and morphine consumption (P<0.001)were significantly lower in the neonates than in the older agegroups. Our results show that continuous infusion of morphinedoes not provide any major advantages over intermittent morphineboluses for postoperative analgesia in neonates and infants. Br J Anaesth 2001; 87: 390–9     

Single-dose aprepitant vs ondansetron for the prevention of postoperative nausea and vomiting: a randomized, double-blind phase III trial in patients undergoing open abdominal surgery

Background: The neurokinin₁ antagonist aprepitant is effective for preventionof chemotherapy-induced nausea and vomiting. We compared aprepitantwith ondansetron for prevention of postoperative nausea andvomiting. Methods: Nine hundred and twenty-two patients receiving general anaesthesiafor major abdominal surgery were assigned to receive a singlepreoperative dose of oral aprepitant 40 mg, oral aprepitant125 mg, or i.v. ondansetron 4 mg in a randomized, double-blindtrial. Vomiting episodes, use of rescue therapy, and nauseaseverity (verbal rating scale) were documented for 48 h aftersurgery. Primary efficacy endpoints were complete response (novomiting and no use of rescue therapy) 0–24 h after surgeryand no vomiting 0–24 h after surgery. The secondary endpointwas no vomiting 0–48 h after surgery. Results: Aprepitant at both doses was non-inferior to ondansetron forcomplete response 0–24 h after surgery (64% for aprepitant40 mg, 63% for aprepitant 125 mg, and 55% for ondansetron, lowerbound of 1-sided 95% CI > 0.65), superior to ondansetronfor no vomiting 0–24 h after surgery (84% for aprepitant40 mg, 86% for aprepitant 125 mg, and 71% for ondansetron; P< 0.001), and superior for no vomiting 0–48 h aftersurgery (82% for aprepitant, 40 mg, 85% for aprepitant, 125mg, and 66% for ondansetron; P < 0.001). The distributionof peak nausea scores was lower in both aprepitant groups vsondansetron (P < 0.05). Conclusions: Aprepitant was non-inferior to ondansetron in achieving completeresponse for 24 h after surgery. Aprepitant was significantlymore effective than ondansetron for preventing vomiting at 24and 48 h after surgery, and in reducing nausea severity in thefirst 48 h after surgery. Aprepitant was generally well tolerated.