Lidocaine, widely recognized as the most commonly used amino-amide local anesthetic, is noted for its anti-inflammatory and neuroprotective properties. Clinical evidence shows that a continuous intravenous infusion of lidocaine over 48 hours can diminish the cerebral inflammatory response associated with cardiopulmonary bypass (CPB). A meta-analysis has suggested that perioperative lidocaine administration offers protective benefits against the occurrence of postoperative cognitive dysfunction (POCD) following cardiac surgery. These neuroprotective effects have also been observed in rat models of POCD. Research indicates that lidocaine's anti-inflammatory actions include inhibiting microglial activation through the TLR4/NF-κB and MAPK P38 pathways. Additionally, recent studies have shown that lidocaine reduces M1 polarization while promoting the anti-inflammatory M2 phenotype in microglial cells, with these findings replicated in a rat model of neuropathic pain.
Despite these positive findings, some clinical studies and individual animal research suggest conflicting results, with lidocaine sometimes failing to reduce POCD occurrence and potentially inducing neuroinflammation through other immune cell activations. The exact regulatory mechanism by which lidocaine influences the M1/M2 microglial ratio still requires further investigation. Given that the inhibitory effects on microglial activation have predominantly been identified in neuropathic pain models, additional validation in POCD models is necessary to clarify lidocaine's efficacy and mechanisms in this context.
| Agent or technique | Reported effect | Caveats and limitations |
|---|---|---|
| Propofol TIVA | May reduce POCD; odds ratio 0.52 (95% CI 0.31–0.87) | Low-certainty evidence with significant heterogeneity in methodology |
| BIS-guided anesthesia | Titrating to a BIS of 40–60 prevented POCD in 23 of every 1,000 patients at 3 months | A meta-analysis of four studies found no correlation between anesthetic depth and POCD; effects at 1 week and 1 year unclear |
| Sevoflurane | Higher POCD incidence than propofol at 7 days and 9 months; microglial activation and M1 polarization | Neuroprotective at sub-anesthetic doses; adverse effects are age-dependent and worsen with prolonged exposure |
| Desflurane | May offer advantages over sevoflurane and isoflurane; repeated exposures did not cause impairment or neuroinflammation | Less extensively studied; ischemia/reperfusion neuroprotection not replicated in other contexts |
| Dexmedetomidine | Significant reduction in POCD on postoperative day 7; odds ratio 0.34 (95% CI 0.19–0.61, p<0.001) | Trials used postoperative MMSE only, with no baseline cognitive assessment |
| Ketamine | Debated; clinical studies after cardiac surgery inconclusive | Dual anti-inflammatory and pro-inflammatory effects; high dose or prolonged exposure may worsen neuroinflammation |
| Dexamethasone | No significant effect on POCD incidence at 30 days | Based on limited, inconsistent data from only three studies; steroid-altered glucose metabolism may itself harm cognition |
| Parecoxib | Reduced POCD at 7 days across four RCTs (900 patients), with lower S100B and IL-6 | Three of the four RCTs assessed cognition with MMSE alone |
| Lidocaine | Continuous IV infusion over 48 hours diminished the cerebral inflammatory response associated with CPB; a meta-analysis suggests perioperative lidocaine may protect against POCD after cardiac surgery | Some clinical and animal studies conflict; mechanisms shown mainly in neuropathic pain models |
