Randomized, Double-Blinded, Placebo Controlled Study of Neuroprotection With Lidocaine in Cardiac Surgery

Abstract

Background and Purpose Cognitive decline after cardiac surgery remains common and diminishes patients’ quality of life. Based on experimental and clinical evidence, this study assessed the potential of intravenously administered lidocaine to reduce postoperative cognitive dysfunction following cardiac surgery employing cardiopulmonary bypass. Methods Following IRB approval, 277 patients undergoing cardiac surgery were enrolled into this prospective, randomized, double-blinded placebo controlled clinical trial. Subjects were randomized to receive: 1) Lidocaine as a 1 mg/kg bolus followed by a continuous infusion through 48 hours postoperatively or 2) Placebo bolus and infusion. Cognitive function was assessed preoperatively and again at 6 weeks and 1 year postoperatively. The effect of lidocaine on postoperative cognition was tested using multivariable regression modeling; p <0.05 was considered significant. Results Among the 241 allocated subjects (Lidocaine: N=114; Placebo: N=127), the incidence of cognitive deficit in the lidocaine group was 45.5% versus 45.7% in the placebo group (p=0.97). Multivariable analysis revealed a significant interaction between treatment group and diabetes, such that diabetic subjects receiving lidocaine were more likely to suffer cognitive decline (p=0.004). Secondary analysis identified total lidocaine dose (mg/kg) as a significant predictor of cognitive decline and also revealed a protective effect of lower dose lidocaine in nondiabetic subjects. Conclusions Lidocaine administered during and after cardiac surgery does not reduce the high rate of postoperative cognitive dysfunction. Higher doses of lidocaine and diabetic status were independent predictors of cognitive decline. Protective effects of lower dose lidocaine in nondiabetic subjects need to be further evaluated.

Perioperative intravenous lidocaine infusion for postoperative pain control: a meta-analysis of randomized controlled trials

“…26,28,30,36,41,50 Mortality in the IVLI group (0.4%) was not significantly different from that in the control group (0.5%) (six studies, n = 611, RR: 0.87, 95% CI 0.42-1.80; I 2 = 0%). …”

“…24 Seven studies originated in the USA, [25][26][27][28][29][30][31] one in Belgium, 32 two in Taiwan, 14,33 three in Germany, 23,34,35 one in New Zealand, 36 three in Sweden, [37][38][39] two in China, 40,41 one in France, 42 three in Canada, [43][44][45] one in Mexico, 24 two in Saudi Arabia, 46,47 one in Israel, 48 one in the Republic of Korea 49 and one in Finland. 50 Studies were conducted in patients undergoing abdominal, cardiac, thoracic, orthopedic, or urologic surgery ( Table 1).…”

“…51 Twenty-six (90%) studies were placebo-controlled blinded studies. 14,[23][24][25][26][27][29][30][31][32][33][34][35][36][37][38][39][40][41][42][43][45][46][47][48][49] Primary outcomes…”

“…Nineteen studies calculated plasma lidocaine levels. 23,[25][26][27][28][29][30][31][32][34][35][36]38,[40][41][42]46,47,50 A plasma concentration of [5 lgÁmL -1 of lidocaine was observed in eight studies, 25,26,28,29,35,36,41,50 six in cardiac surgery 26,28,29,36,41,50 and two in abdominal surgery. 25,35 Only three studies reported the number of patients involved (three patients in total).…”

Developmental Disability in the Young and Postoperative Cognitive Dysfunction in the Elderly After Anesthesia and Surgery: Do Data Justify Changing Clinical Practice?

“…154 What about EPO, melatonin, memantine, and statins in the elderly? Xiong et al report that delayed administration of EPO reduced hippocampal cell loss, enhanced angiogenesis and neurogenesis, and improved functional outcome after traumatic brain injury in rats.…”