Insler 1995.

Methods	Randomized, placebo‐controlled trial. Sequence generation based on date of admission. No information provided on allocation concealment. Participants and personnel were blinded. No statement on blinding of outcome assessors. This study was designed to evaluate whether a continuous low‐dose lidocaine infusion reduces postoperative pain and anxiety in patients undergoing CABG and to retrospectively examine time to extubation, ICU stay, and hospital length of stay. The study was conducted in the USA. Date not published.
Participants	Number assessed for eligibility: N/A Number randomized: 100 → 50:50 Number analysed: 44:45 Inclusion criteria Hospital patients undergoing first‐time CABG Exclusion criteria Patients > 75 years, hepatic dysfunction, vitamin K deficiency, serum albumin < 3.0 mg/dl, serum bilirubin > 2.0 mg/dl. Renal impairment, serum creatinine > 1.8 mg/dl, severe left ventricular dysfunction, concomitant valvular surgery, CABG reoperation, patients with pacemakers or atrial and/or ventricular arrhythmias Baseline details Experimental group (n = 44) Mean age (years): 62.65 (mean age of all experimental and control patients) M = 81%, F = 19% Mean weight (kg): 64.5 to 85.3 kg (range of weight for all experimental and control patients) ASA I/II: N/A Duration of surgery (min): N/A Main surgical procedure: CABG Control group (n = 45) Mean age (years): 62.65 (mean age of all experimental and control patients) M = 75%, F = 25% Mean weight (kg): 64.5 to 85.3 kg (range of weight for all experimental and control patients) ASA I/II: N/A Duration of surgery (min): N/A Main surgical procedure: CABG
Interventions	Experimental group (44 patients) An infusion was begun after induction of anaesthesia and before surgical incision. An intravenous dose of 1.5 mg/kg was administered over a 10‐minute period, followed by an infusion of 30 µg/kg/min throughout surgery and for up to 48 hours in the ICU unless discharged earlier. Control group (45 patients) The control group received a placebo substitute.
Outcomes	The primary endpoint of the study was postsurgical pain. Dichotomous Adverse events (hospital mortality, exploration for re‐bleeding, myocardial infarction) Continuous Heart rate at 16 hrs, central venous pressure at 2 hrs and 8 hrs, pulmonary artery pressure at 2 hrs Length of hospital stay (days), (data were presented as median with IQR) Length of ICU stay (hrs) Pain score (visual analogue pain scoring system 0 to 10) at 4 hrs, 8 hrs, 16 hrs, 24 hrs, 48 hrs, and 96 hrs (data presented graphically) Sedation score at 1 hrs, 2 hrs, 4 hrs, 8 hrs, 16 hrs, 24 hrs, 48 hrs, and 96 hrs (data presented graphically) Total postoperative fentanyl consumption (µg) Total postoperative midazolam consumption (mg) Total postoperative propranolol consumption (mg)
Notes	Small trial sample size (< 200 patients) Power analysis performed (pain, n = 44) Medication "If the patient experienced pain, residual neuromuscular blockade or anxiety as evidenced by hypertension (systolic blood pressure greater than 150 mmHg), or tachycardia (heart rate greater than 100 beats per minute), if a conscious patient was unable to maintain a sustained 5‐second head lift, or if a patient experienced a direct communication of pain or discomfort in response to questioning, he or she was treated with intravenous fentanyl and/or midazolam via the following standardized regimen. Fentanyl was administered an 250‐1xg intravenous increments every 15 minutes until a total of I mg was reached. If these demonstrated features were still evident, then intravenous midazolam was administered in 0.5‐mg increments every 5 minutes until the patient was judged comfortable according to the previously cited criteria or a total of 5 mg was reached. If a hyperdynamic situation persisted, then propranolol was administered in 0.25‐rag intravenous increments until the situation abated or a total of 1.0 mg was administered." Anaesthesia The anaesthesia regime was standardized in both groups. Funding No funding mentioned
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	High risk	Quote: "a double‐blinded, randomized, and prospective approach." "Patients accepted into the study were numbered sequentially 1 through 100."
Allocation concealment (selection bias)	Unclear risk	No statement on allocation concealment.
Blinding of participants and personnel (performance bias) All outcomes	Unclear risk	Quote: "…pharmacy‐prepared lidocaine infusion (L) in an 8 mg/ml concentration, or placebo substitute (P), numbered 1 through 100, was sent to the operating room on the day of surgery…" It is not clear who was responsible for randomisation and informed the pharmacy how to prepare the study drugs (i. e. which number referred to which group). Therefore, it is unclear if blinding of personnel and participants was adequate.
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	No statement on blinding of outcome assessors.
Incomplete outcome data (attrition bias) All outcomes	High risk	Dropout rate (experimental/control): 12%:10% Eleven patients were excluded and reasons were described. Reasons for exclusion (e.g. ventricular arrhythmia) may be related to the intervention. One patient in the lidocaine group was excluded due to death (multi‐organ system failure).
Selective reporting (reporting bias)	Unclear risk	There is no reference to a trial registry and no published study protocol.
Other bias	High risk	Patients in the placebo group received an intravenous bolus of lidocaine (1.5 mg/kg) if ventricular ectopy or fibrillation occurred during surgery (CABG).