Low Frequency Ventilation During Cardiopulmonary Bypass to Protect Postoperative Lung Function in Cardiac Valvular Surgery: The PROTECTION Phase II Randomized Trial.

BACKGROUND: Cardiac surgery with cardiopulmonary bypass (CPB) triggers pulmonary injury. In this trial we assessed the feasibility, safety, and efficacy of low frequency ventilation (LFV) during CPB in patients undergoing valvular surgery. METHODS AND RESULTS: Patients with severe mitral or aortic valve disease were randomized to either LFV or usual care. Primary outcomes included release of generic inflammatory and vascular biomarkers and the lung-specific biomarker sRAGE (soluble receptor for advance glycation end products) up to 24 hours postsurgery. Secondary outcomes included pulmonary function tests and 6-minute walking test up to 8 weeks postdischarge. Sixty-three patients were randomized (33 LFV versus 30 usual care). Mean age was 66.8 years and 30% were female. LFV was associated with changes of sRAGE (soluble receptor for advance glycation end products) levels (geometric mean ratio, 3.05; [95% CI, 1.13-8.24] 10 minutes post CPB, and 1.07 [95% CI, 0.64-1.79], 0.84 [95% CI, 0.55-1.27], 0.67 [95% CI, 0.42-1.07], and 0.62 [95% CI, 0.45-0.85] at 2, 6, 12, and 24 hours post CPB respectively). No changes were observed for any of the generic biomarkers. Respiratory index soon after surgery (mean difference, -0.61 [95% CI, -1.24 to 0.015] 10 minutes post end of CPB), forced expiratory volume after 1 second/forced vital capacity ratio (0.050 [95% CI, 0.007-0.093] at 6 to 8 weeks pos-surgery), Forced vital capacity alone (95% CI, -0.191 L [-0.394 to 0.012]) and 6-minute walking test score at discharge (63.2 m [95% CI, 12.9-113.6]) were better preserved in the LFV group. No other differences were noted. CONCLUSIONS: The use of LFV during CPB in patients undergoing valvular surgery was feasible and safe and was associated with changes in sRAGE levels along with better preserved lung function and walking performance. These observations warrant further investigation in larger future studies. REGISTRATION: URL: https://www.isrctn.com; Unique Identifier: ISRCTN75795633.

Thoracic epidural anesthesia improves early outcomes in patients undergoing off-pump coronary artery bypass surgery: a prospective, randomized, controlled trial.

BACKGROUND: The aim of this two-center, open, randomized, controlled trial was to evaluate the impact of thoracic epidural anesthesia on early clinical outcomes in patients undergoing off-pump coronary artery bypass surgery. METHODS: Two hundred and twenty-six patients were randomized to either general anesthesia plus epidural (GAE) (n = 109) or general anesthesia only (GA) (n = 117). The primary outcome was length of postoperative hospital stay. Secondary outcomes were: arrhythmia, inotropic support, intubation time, perioperative myocardial infarction, neurologic events, intensive care stay, pain scores, and analgesia requirement. RESULTS: Baseline characteristics were similar in the two groups. One patient died in the GAE group. Median postoperative stay was significantly reduced in the GAE, compared with the GA, group (5 days, interquartile range [5-6] vs. 6 days, interquartile range [5-7], hazard ratio = 1.39, 95% CI [1.06-1.82]; P = 0.017). The incidence of arrhythmias and the median intubation time were both significantly lower in the GAE, compared with the GA, group (odds ratio = 0.41, 95% CI [0.22-0.78], P = 0.006 and hazard ratio = 1.73, 95% CI [1.31-2.27], P < 0.001, respectively). Patients in the GAE group were more likely to need vasoconstrictors intraoperatively than in the GA group (odds ratio = 2.50, 95% CI [1.22-5.12]; P = 0.012). The GAE, compared with GA, group reported significantly lower levels of impairment for all pain domains and reduced morphine usage (odds ratio = 0.07, 95% CI [0.03-0.17]; P < 0.001). CONCLUSION: In patients undergoing off-pump coronary artery bypass surgery, the addition of thoracic epidural to general anesthesia significantly reduces the incidence of postoperative arrhythmias and improves pain control and overall quality of recovery, allowing earlier extubation and hospital discharge.

Superior haemodynamic stability during off-pump coronary surgery with thoracic epidural anaesthesia: results from a prospective randomized controlled trial.

OBJECTIVES: Off-pump coronary artery bypass (OPCAB) surgery is a technically more demanding strategy of myocardial revascularization compared with the standard on-pump technique. Thoracic epidural anaesthesia, by reducing sympathetic stress, may ameliorate the haemodynamic changes occurring during OPCAB surgery. The aim of this randomized controlled trial was to evaluate the impact of thoracic epidural anaesthesia on intraoperative haemodynamics in patients undergoing OPCAB surgery. METHODS: Two hundred and twenty-six patients were randomized to either general anaesthesia plus epidural (GAE) (n = 109) or general anaesthesia (GA) only (n = 117). Mean arterial blood pressure (MAP), heart rate (HR) and central venous pressure (CVP) were measured before sternotomy and subsequently after positioning the heart for each distal anastomosis. RESULTS: Both groups were well balanced with respect to baseline characteristics and received a standardized anaesthesia. The MAP decreased in both groups with no significant difference (mean difference (GAE minus GA) -1.11, 95% CI -3.06 to 0.84, P = 0.26). The HR increased in both groups after sternotomy but was significantly less in the GAE group (mean difference (GAE minus GA) -4.29, 95% CI -7.10 to -1.48, P = 0.003). The CVP also increased in both groups after sternotomy, but the difference between the groups varied over time (P = 0.05). A difference was observed at the third anastomosis when the heart was in position for the revascularization of the circumflex artery (mean difference (GAE minus GA) +2.09, 95% CI 0.21-3.96, P = 0.03), but not at other time points. The incidence of new arrhythmias was also significantly lower in the GAE compared with the GA group (OR = 0.41, 95% CI 0.22-0.78, P = 0.01). CONCLUSION: Thoracic epidural with general anaesthesia minimizes the intraoperative haemodynamic changes that occur during heart positioning and stabilization for distal coronary anastomosis in OPCAB surgery.

Myocardial, inflammatory, and stress responses in off-pump coronary artery bypass graft surgery with thoracic epidural anesthesia.

OBJECTIVES: Epidural anesthesia has been suggested to exert a protective effect against the inflammatory and stress responses associated with surgery. The aim of this study was to evaluate the impact of thoracic epidural anesthesia on myocardial cell damage, inflammatory, and stress responses in patients undergoing off-pump coronary artery bypass graft (OPCABG) surgery. METHODS: Seventy-four patients (66 male [89%], mean age 65.2 years [SD 9.6]) undergoing OPCABG surgery were randomly assigned to receive either general anesthesia plus epidural (GAE [n = 36]) or general anesthesia only (GA [n = 38]). Troponin I, 8-isoprostane, cortisol, C3alpha, interleukin (IL)-6, IL-8, and IL-10 were measured preoperatively, at 30 minutes, and 4, 12, 24, and 48 hours postoperatively. RESULTS: Baseline characteristics were similar in the two groups. One patient died in the GAE group, but no other major postoperative complications were recorded in either group. The IL-6 and IL-8 levels were lower in the GAE group (ratio 0.83, 95% confidence interval: 0.68 to 1.02; p = 0.070) than in the GA group (ratio 0.90, 95% confidence interval: 0.78 to 1.02; p = 0.090). The difference in levels of IL-10 between the GAE and GA groups varied over time (p greater, similar 0.001). The C3alpha, troponin I, 8-isoprostane, and cortisol release was similar in the two groups throughout (p > or = 0.12). CONCLUSIONS: Thoracic epidural anesthesia does not provide any additional benefits in terms of reducing myocardial damage, inflammatory, and stress response compared with general anesthesia only in patients undergoing OPCABG surgery.

A placebo-controlled trial of mirtazapine for the management of methamphetamine withdrawal.

INTRODUCTION AND AIMS: As an antidepressant with sedative and anxiolytic properties, mirtazapine may be an appropriate pharmacotherapy for methamphetamine withdrawal. This study sought to examine whether mirtazapine improves retention and alleviates methamphetamine withdrawal symptoms in an out-patient setting. DESIGN AND METHODS: An out-patient double-blind, randomised placebo-controlled trial of mirtazapine for the treatment of methamphetamine withdrawal was conducted (15 mg nocte for 2 days, 30 mg nocte for 12 days). Both groups were offered narrative therapy counselling. Measures recorded on days 0, 3, 7, 14 and 35 included: treatment retention, Amphetamine Cessation Symptoms Assessment, the Athens Insomnia Scale, the Brief Symptom Inventory, the Depression-Anxiety-Stress Scale (DASS), Severity of Dependence scale and the Opiate Treatment Index Drug Use subscale. RESULTS: Thirty-one participants were recruited (18 placebo, 13 mirtazapine) and 52% completed the 2-week medication phase. No significant differences between the mirtazapine and placebo groups in retention, or any symptom measure were observed, except greater DASS-anxiety and longer sleep duration were measured at baseline among the mirtazapine group. DISCUSSION AND CONCLUSIONS: Results suggest that mirtazapine does not facilitate retention or recruitment in out-patient methamphetamine withdrawal treatment, although recruitment may have been insufficient to identify a significant treatment effect. The potential role of narrative therapy for methamphetamine dependent patients deserves further exploration.