Yardeni 2009.

Methods	Randomized, placebo‐controlled trial. No detailed information on adequate sequence generation and allocation concealment provided. The anaesthesiologist in charge was blinded. No statement on blinding of participants and outcome assessors. The study focused on the effects of pre‐incisional and intraoperative IV lidocaine on pain intensity and immune reactivity in the postoperative period in patients undergoing abdominal hysterectomy. The study was conducted in Israel. Date not published.
Participants	Number assessed for eligibility: N/A Number randomized: 65 → 32:33 Number analysed: 30:30 Inclusion criteria Female patients (ASA physical status I to II) scheduled for transabdominal hysterectomy, age 45 to 70. Exclusion criteria Hypertension, arrhythmia, diabetes, and patients with previous medication with immunosuppressive drugs, nonsteroidal anti‐inflammatory drugs, or steroids. Baseline details Experimental group (n = 30) Mean age (years): 55.9 M = 0%, F = 100% Mean weight (kg): 71.2 ASA I/II: N/A Duration of surgery (min): 109 Main surgical procedure: abdominal hysterectomy Control group (n = 30) Mean age (years): 53.4 M = 0%, F = 100% Mean weight (kg): 70.0 ASA I/II: N/A Duration of surgery (min): 106 Main surgical procedure: abdominal hysterectomy
Interventions	Experimental group (32 patients) Patients received IV lidocaine (bolus 2 mg/kg, continuous infusion 1.5 mg/kg/hr), starting 20 min before the beginning of surgery and continued during the operation. Control group (33 patients) Patients in the second group were given an equal volume of saline infusion.
Outcomes	Dichotomous no outcomes reported. Continuous Intraoperative fentanyl consumption (µg) PCEA consumption in 24 hrs (ml), PCEA boluses in 24 hrs (ml) Postoperative pain score (VAS 0 to 10) at rest and during coughing at 4 hrs, 8 hrs, 12 hrs, 24 hrs, 48 hrs, and 72 hrs PHA‐M‐induced proliferation of peripheral blood mononuclear cells isolated from venous blood samples taken on the morning of surgery, 24 hrs, 48 hrs, and 72 hrs after surgery Ex vivo cytokine production (IL‐1ra, IL‐6) of peripheral blood mononuclear cells isolated from venous blood samples taken on the morning of surgery, 24 hrs, 48 hrs, and 72 hrs after surgery
Notes	Only female patients Small trial sample size (< 200 patients) The authors performed a 'post hoc' sample size calculation (no statement concerning the outcome) Medication "On arrival to the PACU, patients of both groups were connected to a PCEA pump and received an initial loading dose of 3–5 ml 0.1% bupivacaine 2 g/ml fentanyl and a bolus of 3 ml 0.1% bupivacaine 2 g/ml fentanyl on demand (lockout time 10 min), with continuous background infusion of 6 ml/hr. The total doses of intraoperative fentanyl and PCEA during the 24 hrs after surgery for both groups are detailed in Table 1. Postoperative analgesia was given only by PCEA to avoid nonsteroidal anti‐inflammatory drugs or opiates that may have affected the study outcome. 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)	Unclear risk	Quote: "at the preoperative anesthesiology visit, the patients were randomly assigned to 1 of 2 perioperative pain management techniques:…" No method described.
Allocation concealment (selection bias)	Unclear risk	No statement on allocation concealment.
Blinding of participants and personnel (performance bias) All outcomes	Unclear risk	Quote: "...anaesthesiologist who did not participate in the study was instructed to prepare 2% lidocaine or saline solution in a syringe pump labelled number 1 or 2, respectively, and hand it to the anaesthesiologist in charge without notifying him of the content." In consideration of the fact that "label 1" and "label 2" are not true random numbers for each patient, we judged that this is not sufficient as an adequate blinding method.
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	No statement on blinding of outcome assessors.
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	Dropout rate (experimental/control): 6%:9% Exclusions were described. Group assignment unclear.
Selective reporting (reporting bias)	Unclear risk	There is no reference to a trial registry. No published study protocol.
Other bias	Low risk	The study appears to be free of other sources of bias.