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Effect of intravenous lidocaine on the transcerebral inflammatory response during cardiac surgery: a randomized-controlled trial.

ABSTRACT: PURPOSE:Postoperative cognitive dysfunction (POCD) occurs frequently after cardiac surgery. The pathophysiology of POCD remains elusive, but previous work showed that intravenous lidocaine may be protective against POCD, possibly by modulating cerebral inflammation. We hypothesized that intravenous lidocaine would attenuate the cerebral inflammatory response to cardiopulmonary bypass (CPB) by reducing the transcerebral activation gradients of platelets, leukocytes, and/or platelet-leukocyte conjugates. METHODS:We studied 202 patients undergoing cardiac surgery with CPB in this prospective randomized double-blinded placebo-controlled trial. Subjects were randomized to receive either intravenous lidocaine (bolus + 48-hr infusion) or placebo (identical infusion volume and duration). Paired jugular venous and radial arterial blood samples were drawn at several time points and analyzed by fluorescence-activated cell sorting to identify activated platelets and platelet-leukocyte conjugates. Transcerebral activation gradients were calculated by subtracting arterial values from venous values and were compared between groups using repeated measures regression models with covariate adjustment for age, sex, surgery type, and CPB duration. RESULTS:Beginning after aortic cross-clamp release and peaking ten minutes after the termination of CPB, the mean (SD) transcerebral activation gradient of platelet-monocyte conjugates decreased in lidocaine-treated vs placebo-treated patients [-1.84 (11.47) mean linear fluorescence intensity (MLFI) vs 1.46 (13.88) MLFI, respectively; mean difference, -4.08 MLFI; 95% confidence interval, -7.86 to -0.29; P = 0.03). No difference was seen at any time point for activated platelets or for platelet-neutrophil conjugates. CONCLUSION:While lidocaine did not affect the systemic or transcerebral activation of platelets or leukocytes, we did observe a reduction in the transcerebral activation of platelet-monocyte conjugates after aortic cross-clamp release. This may be a manifestation of reduced cerebral inflammation during cardiopulmonary bypass in response to treatment with lidocaine. This trial was registered at ClinicalTrials.gov (NCT00938964).

SUBMITTER: Klinger RY

PROVIDER: S-EPMC7097969 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature

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Effect of intravenous lidocaine on the transcerebral inflammatory response during cardiac surgery: a randomized-controlled trial.

Klinger Rebecca Y RY Cooter Mary M Berger Miles M Podgoreanu Mihai V MV Stafford-Smith Mark M Ortel Thomas L TL Welsby Ian J IJ Levy Jerrold H JH Rinder Henry M HM Newman Mark F MF Mathew Joseph P JP

Canadian journal of anaesthesia = Journal canadien d'anesthesie 20160728 11

<h4>Purpose</h4>Postoperative cognitive dysfunction (POCD) occurs frequently after cardiac surgery. The pathophysiology of POCD remains elusive, but previous work showed that intravenous lidocaine may be protective against POCD, possibly by modulating cerebral inflammation. We hypothesized that intravenous lidocaine would attenuate the cerebral inflammatory response to cardiopulmonary bypass (CPB) by reducing the transcerebral activation gradients of platelets, leukocytes, and/or platelet-leukoc ...[more]

PMID: 27470233

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Project description:BACKGROUND:Cognitive decline after cardiac surgery occurs frequently and persists in a significant proportion of patients. Preclinical studies and human trials suggest that intravenous lidocaine may confer protection in the setting of neurologic injury. It was hypothesized that lidocaine administration would reduce cognitive decline after cardiac surgery compared to placebo. METHODS:After institutional review board approval, 478 patients undergoing cardiac surgery were enrolled into this multicenter, prospective, randomized, double-blinded, placebo-controlled, parallel group trial. Subjects were randomized to lidocaine 1?mg/kg bolus after the induction of anesthesia followed by a continuous infusion (48 ?g · kg · min for the first hour, 24 ?g · kg · min for the second hour, and 10 ?g · kg · min for the next 46?h) or saline with identical volume and rate changes to preserve blinding. Cognitive function was assessed preoperatively and at 6 weeks and 1 yr postoperatively using a standard neurocognitive test battery. The primary outcome was change in cognitive function between baseline and 6 weeks postoperatively, adjusting for age, years of education, baseline cognition, race, and procedure type. RESULTS:Among the 420 allocated subjects who returned for 6-week follow-up (lidocaine: N = 211; placebo: N = 209), there was no difference in the continuous cognitive score change (adjusted mean difference [95% CI], 0.02 (-0.05, 0.08); P = 0.626). Cognitive deficit (greater than 1 SD decline in at least one cognitive domain) at 6 weeks occurred in 41% (87 of 211) in the lidocaine group versus 40% (83 of 209) in the placebo group (adjusted odds ratio [95% CI], 0.94 [0.63, 1.41]; P = 0.766). There were no differences in any quality of life outcomes between treatment groups. At the 1-yr follow-up, there continued to be no difference in cognitive score change, cognitive deficit, or quality of life. CONCLUSIONS:Intravenous lidocaine administered during and after cardiac surgery did not reduce postoperative cognitive decline at 6 weeks.

Project description:BackgroundMajor abdominal surgery is associated with endothelial glycocalyx disruption. The anti-inflammatory effects of lidocaine were recently associated with endothelial barrier protection.MethodsThis was a single-centre, parallel group, randomized, controlled, double blind, pilot trial. Forty adult patients scheduled for major abdominal surgery were included between December 2016 and March 2017 in the setting of a University Hospital in Brussels (Belgium); reasons for non-inclusion were planned liver resection and conditions associated to increased risk of local anesthetics systemic toxicity. Patients were randomized to receive either lidocaine by continuous intravenous administration or an equivalent volume of 0.9% saline. The primary endpoint was the postoperative syndecan-1 concentration (difference between groups). Near-infrared spectroscopy of the thenar eminence in association with the vascular occlusion test, and contemporary analysis of flow-mediated dilation of the brachial artery were the secondary outcomes, along with haemodynamic data. Blood samples and data were collected before surgery (T0), and at 1-3 h (T1) and 24 h (T2) post-surgery.ResultsSyndecan-1 concentration increased significantly post-surgery (P < 0.001), but without any difference between groups. The near-infrared spectroscopy-derived and flow-mediated dilation-derived variables showed minor changes unrelated to group assignment. Compared with the placebo group, the intervention group had a significantly lower peri-operative mean arterial pressure and cardiac index, despite equally conducted goal-directed haemodynamic management. Postoperative lactate concentrations were similar between groups.ConclusionsLidocaine failed to have any effect on endothelial function. Since in comparisons to other types of clinical situations, syndecan-1 was only slightly upregulated, endothelial dysfunction after major abdominal surgery might be overestimated.Trial registration« ISRCTN Registry » identifier: ISRCTN63417725. Date: 15/06/2020. Retrospectively registered.

Project description:BACKGROUND:Use of minimally invasive surgical techniques for lung resection surgery (LRS), such as video-assisted thoracoscopy (VATS), has increased in recent years. However, there is little information about the best anesthetic technique in this context. This surgical approach is associated with a lower intensity of postoperative pain, and its use has been proposed in programs for enhanced recovery after surgery (ERAS). This study compares the severity of postoperative complications in patients undergoing LRS who have received lidocaine intraoperatively either intravenously or via paravertebral administration versus saline. METHODS/DESIGN:We will conduct a single-center randomized controlled trial involving 153 patients undergoing LRS through a thoracoscopic approach. The patients will be randomly assigned to one of the following study groups: intravenous lidocaine with more paravertebral thoracic (PVT) saline, PVT lidocaine with more intravenous saline, or intravenous remifentanil with more PVT saline. The primary outcome will be the comparison of the postoperative course through Clavien-Dindo classification. Furthermore, we will compare the perioperative pulmonary and systemic inflammatory response by monitoring biomarkers in the bronchoalveolar lavage fluid and blood, as well as postoperative analgesic consumption between the three groups of patients. We will use an ANOVA to compare quantitative variables and a chi-squared test to compare qualitative variables. DISCUSSION:The development of less invasive surgical techniques means that anesthesiologists must adapt their perioperative management protocols and look for anesthetic techniques that provide good analgesic quality and allow rapid rehabilitation of the patient, as proposed in the ERAS protocols. The administration of a continuous infusion of intravenous lidocaine has proven to be useful and safe for the management of other types of surgery, as demonstrated in colorectal cancer. We want to know whether the continuous administration of lidocaine by a paravertebral route can be substituted with the intravenous administration of this local anesthetic in a safe and effective way while avoiding the risks inherent in the use of regional anesthetic techniques. In this way, this technique could be used in a safe and effective way in ERAS programs for pulmonary resection. TRIAL REGISTRATION:EudraCT, 2016-004271-52; ClinicalTrials.gov, NCT03905837 . Protocol number IGGFGG-2016 version 4.0, 27th April 2017.

Project description:BACKGROUND:Pain after major head and neck cancer surgery is underestimated and has both nociceptive and neuropathic characteristics. Extended resection, flap coverage, nerve lesions, inflammation, and high-dose opioid administration can also lead to hyperalgesia and chronic postoperative pain. Opioids are frequently associated with adverse events such as dizziness, drowsiness, nausea and vomiting, or constipation disturbing postoperative recovery and extending the length of hospital stay. Patients eligible for major head and neck cancer surgery cannot benefit from full multimodal pain management with locoregional anesthesia. Intravenous lidocaine, investigated in several studies, has been found to decrease acute pain and morphine consumption. Some data suggest also that it can prevent chronic postsurgical pain. Evidence supporting its use varies between surgical procedures, and there is no published study regarding systemic lidocaine administration in major head and neck cancer surgery. We hypothesized that intravenous lidocaine infused in the perioperative period would lead to opioid sparing and chronic postsurgical pain reduction. METHODS/DESIGN:A total of 128 patients undergoing major head and neck surgery will be included in this prospective two-center, double-blind, randomized controlled trial. Patients will be randomly assigned to lidocaine or placebo treatment. After induction of general anesthesia, an intravenous lidocaine bolus will be administered (1.5?mg.kg-?1), followed by a continuous infusion (2?mg.kg-?1.h-?1) which will be reduced in the postanesthesia care unit (1?mg.kg-?1.h-?1). The primary outcome measure is morphine consumption 48?h after surgery. The secondary outcomes include intraoperative remifentanil consumption, morphine consumption 24?h after surgery, and chronic postsurgical pain that will be assessed 3-6?months after surgery. DISCUSSION:Recent evidence suggests that intravenous lidocaine can lead to opioid sparing and chronic postsurgical pain reduction for certain types of surgery. This is the first trial to prospectively investigate the efficacy and safety of intravenous lidocaine in major head and neck cancer surgery. TRIAL REGISTRATION:ClinicalTrials.gov, NCT02894710 . Registered on 11 August 2016.

Project description:BackgroundChronic postoperative pain (CPSP) is one of the common complications of breast cancer patients, which can seriously affect the quality of life and long-term prognosis of patients. The purpose of this study was to investigate whether perioperative intravenous lidocaine infusion could reduce the incidence of CPSP in patients with breast cancer.MethodsFemale patients undergoing radical breast cancer surgery were randomly assigned to the 2% lidocaine group (L) and the control group (S). group L received an intravenous infusion of 1.5 mg/kg lidocaine 10 minutes prior to induction, followed by a continuous infusion of 2 mg/kg/h until the end of surgery. The control group received an equal amount of saline. The primary outcome was the incidence of CPSP at 3 months. Secondary outcomes included VAS pain scores and frequency of remedial analgesia within 24 hours postoperatively; incidence of CPSP at 1 and 6 months; and scores on the Brief Pain Inventory (BPI), Simplified McGill Pain Questionnaire (SF-MPQ), and Neuropathic Pain Score (DN-4) at 1, 3, and 6 months postoperatively.ResultsEighty-two patients participated in this study. A total of 78 patients completed the 3-month postoperative follow-up (39 in group S and 39 in group L). At 3 months, the incidence of CPSP was significantly lower in the L group than in the S group (33.3% in the S group and 12.8% in the L group, P=0.032). Pain scores at rest and during exercise were significantly lower in the L group than in the S group at different time points (P≤0.001 and P<0.001). The need for remedial analgesia at 24 hours postoperatively also differed significantly between the two groups (P=0.036). At 6 months, the incidence of CPSP was also lower in the L group than in the S group (29.7% in the S group and 10.5% in the L group, P=0.038). The differences in SF-MPQ scores were statistically significant at both 3 and 6 months postoperatively (P=0.022, P=0.037).ConclusionsIntravenous infusion of lidocaine reduces the incidence of CPSP in breast cancer patients at 3 and 6 months and is effective in relieving acute postoperative pain.Trial registrationChinese Clinical Trial Registry ChiCTR2100050445.

Dataset Information

Effect of intravenous lidocaine on the transcerebral inflammatory response during cardiac surgery: a randomized-controlled trial.

Publications

Effect of intravenous lidocaine on the transcerebral inflammatory response during cardiac surgery: a randomized-controlled trial.

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