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

Klinger, Rebecca Y.; Cooter, Mary; Berger, Miles; Podgoreanu, Mihai V.; Stafford‐Smith, Mark; Ortel, Thomas L.; Welsby, Ian J.; Levy, Jerrold H.; Rinder, Henry M.; Newman, Mark F.; Mathew, Joseph P.

doi:10.1007/s12630-016-0704-0

Cited by 23 publications

(18 citation statements)

References 54 publications

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“…39,40 In models of tissue injury, lidocaine has been shown to prevent leukocyte accumulation and endothelial adherence along with consequent microvascular thrombus when applied preventatively and to restore microvascular blood flood by disadhering leukocytes from the endothelium when applied postinjury. 41,42 As part of this study and reported elsewhere, 43 paired jugular venous and arterial samples were drawn on the first 202 randomized patients to measure transcerebral gradients of activated platelets and platelet-leukocyte conjugates. In that cohort, we observed a significant reduction in the transcerebral activation of platelet-monocyte conjugates after aortic cross-clamp release in patients who received lidocaine, which we hypothesized might reflect reduced cerebral inflammation during CPB.…”

Section: Perioperative Medicinementioning

confidence: 99%

Intravenous Lidocaine Does Not Improve Neurologic Outcomes after Cardiac Surgery

Klinger¹,

Cooter²,

Bisanar³

et al. 2019

Anesthesiology

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Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New 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 μg · kg−1 · min−1 for the first hour, 24 μg · kg−1 · min−1 for the second hour, and 10 μg · kg−1 · min−1 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.

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Section: Perioperative Medicinementioning

confidence: 99%

Intravenous Lidocaine Does Not Improve Neurologic Outcomes after Cardiac Surgery

Klinger¹,

Cooter²,

Bisanar³

et al. 2019

Anesthesiology

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“…Lidocaine has effects that depend on the total dose, and detrimental effects can be seen with elevated doses of lidocaine [27]. But lidocaine also has beneficial effects during surgery, providing (a) an anti-inflammatory effect; (b) an increase in the cardioprotective effect of cardioplegia; (c) a decrease in the risk of arrhythmias; and (d) a decrease in the risk of brain inflammation [15,16,28,29].…”

Section: Discussionmentioning

confidence: 99%

Effect of opioid-free anaesthesia on post-operative period in cardiac surgery: a retrospective matched case-control study

Guinot

Spitz

Berthoud

et al. 2019

Preprint

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Background: No study has been conducted to demonstrate the feasibility of an opioid-free anesthesia (OFA) protocol in cardiac surgery to improve patient care. The aim of the present study was to evaluate the effect of OFA on post-operative morphine consumption and the post-operative course. Methods: After retrospectively registering to clinicaltrial.gov (NCT03816592), we performed a retrospective matched cohort study (1:1) on cardiac surgery patients with cardiopulmonary bypass between 2018 and 2019. Patients were divided into two groups: OFA (lidocaine, dexamethasone and ketamine) or opioid anaesthesia (OA) (sufentanil). The main outcome was the total postoperative morphine consumption in the 48 hours after surgery. Secondary outcomes were rescue analgesic use, a major adverse event composite endpoint, and ICU and hospital length of stay (LOS). Results: 110 patients were matched (OFA: n=55; OA: n=55). On inclusion, demographic and surgical data for the OFA and OA groups were comparable. The total morphine consumption was higher in the OA group than in the OFA group (15 (6-34) vs 5 mg (2-18), p=0.001). The pain score during the first 48 post-operative hours did not differ between the two groups. Creatinine values did not differ on the first post-operative day (80 (IQR: 66-115) vs 77 mmol/l (IQR: 69-95), p=0.284). Incidence of the composite endpoint was lower in the OFA group (25 patients (43%) vs 38 patients (68%), p=0.021). The time to extubation and the ICU stays were shorter in the OFA group (3 (1-5) vs 5 (3-6) hours, p=0.001 and 2 (1-3) vs 3 (2-5) days, p=0.037). Conclusion: The use of OFA was associated with lower morphine consumption. OFA might be associated with shorter intubation time and ICU stays. Further randomized studies are needed to confirm these results.

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“…This approach derived four factor scores that corresponded to four cognitive domains: verbal memory; abstraction and visuospatial orientation; visual memory; and attention and concentration. Postoperative cognitive dysfunction was de ned as a ≥ 1 standard deviation decrease of factor scores in one or more of these four cognitive domain from baseline to 6 weeks after surgery as previously described [6,35,36,[38][39][40][41][42][43].…”

Section: Cognitive Testingmentioning

confidence: 99%

Cerebrospinal Fluid Proteomic Changes in Older Non-Cardiac Surgical Patients with Postoperative Cognitive Dysfunction

VanDusen

et al. 2020

Preprint

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Background: Postoperative cognitive dysfunction (POCD) is a syndrome of cognitive deficits that occurs in 10-40% of patients age > 60 within 1-12 months after surgery, hypothesized to be caused in part by neuroinflammation. However, the specific neuroinflammatory pathways involved remain unclear. Unbiased mass spectrometry-based proteomic analyses have been used to identify neuro-inflammatory pathways in multiple neurologic diseases and syndromes but have not yet been used in the POCD field. Thus, we used unbiased mass spectrometry-based proteomics to compare cerebrospinal fluid (CSF) samples from patients with and without POCD to identify potential neuroinflammatory pathways for further investigation in future studies. Methods: We performed unbiased LC-MS/MS proteomics on immunodepleted CSF samples obtained before, 24 hours, and 6 weeks after major non-cardiac surgery in older adults who developed (n=8) or did not develop POCD (n=6). General linear mixed models were used to identify peptides and proteins with intensity differences between groups or over time by groups. Kyoto Encyclopedia of Genes and Genomes analysis was used to identify pathways containing proteins/peptides with q values < 0.25 in the mixed model. Results: Mass spectrometry quantified 8258 peptides from 1222 proteins in >50% of patient samples at all three time points. Twelve peptides from 11 proteins showed differences in expression over time between groups (POCD vs non-POCD) at q < 0.05, including several from proteins previously implicated in neurodegenerative disease pathophysiology. Additionally, 283 peptides from 182 proteins were identified with trend-level differences (q < 0.25) in expression over time between these patient groups. Of these 283 peptides with trend-level significance, pathway analysis revealed that 50 of them were from 17 proteins that mapped to the complement and coagulation pathways (q=2.44*10-13).Conclusions: These data demonstrate the feasibility of performing unbiased mass spectrometry on perioperative CSF samples to identify peptides, proteins, and pathways associated with POCD. Additionally, they provide hypothesis-generating evidence for CSF complement and coagulation pathway changes in patients with POCD.

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

Cited by 23 publications

References 54 publications

Intravenous Lidocaine Does Not Improve Neurologic Outcomes after Cardiac Surgery

Intravenous Lidocaine Does Not Improve Neurologic Outcomes after Cardiac Surgery

Effect of opioid-free anaesthesia on post-operative period in cardiac surgery: a retrospective matched case-control study

Cerebrospinal Fluid Proteomic Changes in Older Non-Cardiac Surgical Patients with Postoperative Cognitive Dysfunction

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