title: Effect of intravenous lidocaine on the transcerebral inflammatory response during cardiac surgery: a randomized-controlled trial.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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).
authors.affiliation: Department of Anesthesiology, Duke University Medical Center, Box 3094, Durham, NC, 27710, USA. kling004@mc.duke.edu.
authors.forename: Rebecca Y
authors.initials: RY
authors.lastname: Klinger
authors.affiliation: Department of Anesthesiology, Duke University Medical Center, Box 3094, Durham, NC, 27710, USA.
authors.forename: Mary
authors.initials: M
authors.lastname: Cooter
authors.affiliation: Department of Anesthesiology, Duke University Medical Center, Box 3094, Durham, NC, 27710, USA.
authors.forename: Miles
authors.initials: M
authors.lastname: Berger
authors.affiliation: Department of Anesthesiology, Duke University Medical Center, Box 3094, Durham, NC, 27710, USA.
authors.forename: Mihai V
authors.initials: MV
authors.lastname: Podgoreanu
authors.affiliation: Department of Anesthesiology, Duke University Medical Center, Box 3094, Durham, NC, 27710, USA.
authors.forename: Mark
authors.initials: M
authors.lastname: Stafford-Smith
authors.affiliation: Departments of Pathology, Hematology, and Medicine, Duke University Medical Center, Durham, NC, USA.
authors.forename: Thomas L
authors.initials: TL
authors.lastname: Ortel
authors.affiliation: Department of Anesthesiology, Duke University Medical Center, Box 3094, Durham, NC, 27710, USA.
authors.forename: Ian J
authors.initials: IJ
authors.lastname: Welsby
authors.affiliation: Department of Anesthesiology, Duke University Medical Center, Box 3094, Durham, NC, 27710, USA.
authors.forename: Jerrold H
authors.initials: JH
authors.lastname: Levy
authors.affiliation: Departments of Medicine and Laboratory Medicine, Yale University, New Haven, CT, USA.
authors.forename: Henry M
authors.initials: HM
authors.lastname: Rinder
authors.affiliation: Department of Anesthesiology, Duke University Medical Center, Box 3094, Durham, NC, 27710, USA.
authors.forename: Mark F
authors.initials: MF
authors.lastname: Newman
authors.affiliation: Department of Anesthesiology, Duke University Medical Center, Box 3094, Durham, NC, 27710, USA.
authors.forename: Joseph P
authors.initials: JP
authors.lastname: Mathew
mesh_terms: D000328:Adult; D000368:Aged; D000779:Anesthetics, Local / Q000008:administration & dosage / Q000627:therapeutic use*; D001927:Brain Diseases / Q000188:drug therapy*; D006348:Cardiac Surgical Procedures / Q000379:methods*; D002315:Cardiopulmonary Bypass / Q000009:adverse effects; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007249:Inflammation / Q000188:drug therapy*; D007262:Infusions, Intravenous; D007962:Leukocytes; D008012:Lidocaine / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009000:Monocytes; D015539:Platelet Activation; D011446:Prospective Studies
chemical_list: D000779:Anesthetics, Local; D008012:Lidocaine