Mathew 2009.

Methods	Randomized, placebo‐controlled trail. No statement on blinding of personnel. Participants and outcome assessors were blinded. This study assessed the potential of intravenously administered lidocaine to reduce postoperative cognitive dysfunction following cardiac surgery employing cardiopulmonary bypass. The study was conducted in the USA from March 1999 to April 2003.
Participants	Number assessed for eligibility: 2681 Number randomized: 277 → 133:144 Number analysed: 88:94 Inclusion criteria Patients scheduled to undergo CABG and/or an open chamber procedure with CPB. Exclusion criteria Patients undergoing circulatory arrest or had a history of symptomatic cerebrovascular disease (e.g. stroke with a residual deficit), psychiatric illness (any clinical diagnoses requiring therapy), renal failure (serum creatinine > 2 mg/dl), liver disease (liver function tests > 1.5 times the upper limit of normal), higher alcohol consumption (> 2 drinks/day), or were unable to read or had less than a seventh grade education. Baseline details Experimental group (n = 114) Mean age (years): 61.7 M = 72.8%, F = 27.2% Mean weight (kg): 86.1 ASA I/II: N/A Duration of surgery (min): N/A Main surgical procedure (n): CABG (51), CABG with valve (22), valve (40), other (1) Control group (n = 127) Mean age (years): 61.4 M = 66.9%, F = 33.1% Mean weight (kg): 81.6 ASA I/II: N/A Duration of surgery (min): N/A Main surgical procedure (n): CABG (52), CABG with valve (23), valve (47), other (5)
Interventions	Experimental group (114 patients) Lidocaine was administered after induction of anaesthesia as a 1 mg/kg bolus followed by a continuous infusion (4 mg/min for 1 hr, 2 mg/min for the second hr, 1 mg/min for the rest) through 48 hours postoperatively. Control group (127 patients) Placebo bolus and infusion for 48 hrs.
Outcomes	The primary endpoint of the study was incidence of cognitive deficit. Dichotomous Number of patients with cognitive deficits at 6 weeks and 1 year after surgery Serious adverse events (mortality) Continuous Cognitive score (5 cognitive tests producing 10 scores) at 6 weeks and 1 year after surgery Length of hospital stay (days), (data presented as median with IQR, asymmetric distribution) Plasma level of caspase‐3, C‐reactive protein, IL‐8, matrix metalloproteinase‐9, vascular endothelial growth factor, S‐100ß at baseline, at end of CPB, 4.5 hrs and 24 hrs after CPB
Notes	Large trial sample size (> 200 patients) Power analysis performed (incidence of cognitive deficit, n = 112) Medication N/A Anaesthesia Standardization of the anaesthesia regime is unclear. Funding "Supported in part by grants #9970128N (Dr. Newman) from the American Heart Association, Dallas, TX, USA, #M01‐RR‐30 from the National Institutes of Health, Washington, D.C., USA, and by the Division of Cardiothoracic Anesthesiology and Critical Care Medicine, Department of Anesthesiology, Duke University Medical Center, Durham, NC, USA." Conflict Of Interest "Dr. Laskowitz is a consultant for Biosite Diagnostics."
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "a group assignment schedule was prepared using a randomization function in sedation‐agitation status…"
Allocation concealment (selection bias)	Unclear risk	Quote: "...and stored in consecutively numbered sealed envelopes until allocation." Not mentioned if envelopes were opaque.
Blinding of participants and personnel (performance bias) All outcomes	Unclear risk	Quote: "...identical volume and rate changes as the treatment group such that blinding was preserved." No statement on blinding of personnel and participants.
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Quote: "experienced psychometricians blinded to the treatment group examined subjects..."
Incomplete outcome data (attrition bias) All outcomes	High risk	Dropout rate after received intervention (experimental/control): 23%:26% Exclusions, withdrawals, and dropouts were described. It is unclear from the description whether the reasons (e.g. lack of interest, health, other) may be related to true outcome.
Selective reporting (reporting bias)	Unclear risk	There is no reference to a trial registry and no published study protocol.
Other bias	Low risk	The study appears to be free of other sources of bias.