Perioperative Intravenous Lidocaine

The management of postoperative pain and recovery is still unsatisfactory in a number of cases in clinical practice. Opioids used for postoperative analgesia are frequently associated with adverse effects, including nausea and constipation, preventing smooth postoperative recovery. Not all patients are suitable for, and benefit from, epidural analgesia that is used to improve postoperative recovery. The non-opioid, lidocaine, was investigated in several studies for its use in multimodal management strategies to reduce postoperative pain and enhance recovery. This review was published in 2015 and updated in January 2017. To assess the effects (benefits and risks) of perioperative intravenous (IV) lidocaine infusion compared to placebo/no treatment or compared to epidural analgesia on postoperative pain and recovery in adults undergoing various surgical procedures. We searched CENTRAL, MEDLINE, Embase, CINAHL, and reference lists of articles in January 2017. We searched one trial registry contacted researchers in the field, and handsearched journals and congress proceedings. We updated this search in February 2018, but have not yet incorporated these results into the review. We included randomized controlled trials comparing the effect of continuous perioperative IV lidocaine infusion either with placebo, or no treatment, or with thoracic epidural analgesia (TEA) in adults undergoing elective or urgent surgery under general anaesthesia. The IV lidocaine infusion must have been started intraoperatively, prior to incision, and continued at least until the end of surgery. We used Cochrane's standard methodological procedures. Our primary outcomes were: pain score at rest; gastrointestinal recovery and adverse events. Secondary outcomes included: postoperative nausea and postoperative opioid consumption. We used GRADE to assess the quality of evidence for each outcome. We included 23 new trials in the update. In total, the review included 68 trials (4525 randomized participants). Two trials compared IV lidocaine with TEA. In all remaining trials, placebo or no treatment was used as a comparator. Trials involved participants undergoing open abdominal (22), laparoscopic abdominal (20), or various other surgical procedures (26). The application scheme of systemic lidocaine strongly varies between the studies related to both dose (1 mg/kg/h to 5 mg/kg/h) and termination of the infusion (from the end of surgery until several days after).The risk of bias was low with respect to selection bias (random sequence generation), performance bias, attrition bias, and detection bias in more than 50% of the included studies. For allocation concealment and selective reporting, the quality assessment yielded low risk of bias for only approximately 20% of the included studies.IV Lidocaine compared to placebo or no treatment We are uncertain whether IV lidocaine improves postoperative pain compared to placebo or no treatment at early time points (1 to 4 hours) (standardized mean difference (SMD) -0.50, 95% confidence interval (CI) -0.72 to -0.28; 29 studies, 1656 participants; very low-quality evidence) after surgery. Due to variation in the standard deviation (SD) in the studies, this would equate to an average pain reduction of between 0.37 cm and 2.48 cm on a 0 to 10 cm visual analogue scale . Assuming approximately 1 cm on a 0 to 10 cm pain scale is clinically meaningful, we ruled out a clinically relevant reduction in pain with lidocaine at intermediate (24 hours) (SMD -0.14, 95% CI -0.25 to -0.04; 33 studies, 1847 participants; moderate-quality evidence), and at late time points (48 hours) (SMD -0.11, 95% CI -0.25 to 0.04; 24 studies, 1404 participants; moderate-quality evidence). Due to variation in the SD in the studies, this would equate to an average pain reduction of between 0.10 cm to 0.48 cm at 24 hours and 0.08 cm to 0.42 cm at 48 hours. In contrast to the original review in 2015, we did not find any significant subgroup differences for different surgical procedures.We are uncertain whether lidocaine reduces the risk of ileus (risk ratio (RR) 0.37, 95% CI 0.15 to 0.87; 4 studies, 273 participants), time to first defaecation/bowel movement (mean difference (MD) -7.92 hours, 95% CI -12.71 to -3.13; 12 studies, 684 participants), risk of postoperative nausea (overall, i.e. 0 up to 72 hours) (RR 0.78, 95% CI 0.67 to 0.91; 35 studies, 1903 participants), and opioid consumption (overall) (MD -4.52 mg morphine equivalents , 95% CI -6.25 to -2.79; 40 studies, 2201 participants); quality of evidence was very low for all these outcomes.The effect of IV lidocaine on adverse effects compared to placebo treatment is uncertain, as only a small number of studies systematically analysed the occurrence of adverse effects (very low-quality evidence).IV Lidocaine compared to TEAThe effects of IV lidocaine compared with TEA are unclear (pain at 24 hours (MD 1.51, 95% CI -0.29 to 3.32; 2 studies, 102 participants), pain at 48 hours (MD 0.98, 95% CI -1.19 to 3.16; 2 studies, 102 participants), time to first bowel movement (MD -1.66, 95% CI -10.88 to 7.56; 2 studies, 102 participants); all very low-quality evidence). The risk for ileus and for postoperative nausea (overall) is also unclear, as only one small trial assessed these outcomes (very low-quality evidence). No trial assessed the outcomes, 'pain at early time points' and 'opioid consumption (overall)'. The effect of IV lidocaine on adverse effects compared to TEA is uncertain (very low-quality evidence). We are uncertain whether IV perioperative lidocaine, when compared to placebo or no treatment, has a beneficial impact on pain scores in the early postoperative phase, and on gastrointestinal recovery, postoperative nausea, and opioid consumption. The quality of evidence was limited due to inconsistency, imprecision, and study quality. Lidocaine probably has no clinically relevant effect on pain scores later than 24 hours. Few studies have systematically assessed the incidence of adverse effects. There is a lack of evidence about the effects of IV lidocaine compared with epidural anaesthesia in terms of the optimal dose and timing (including the duration) of the administration. We identified three ongoing studies, and 18 studies are awaiting classification; the results of the review may change when these studies are published and included in the review.

Despite the recovery advantages of minimally invasive surgical techniques, delayed return of gut function after colectomy is a common barrier to timely discharge from hospital. To evaluate the effect of 2% perioperative intravenous lidocaine infusion on return of gut function after elective minimally invasive colon resection. The ALLEGRO trial was a randomized, placebo-controlled, double-blind trial conducted in 27 UK hospitals. A total of 590 adults scheduled for elective minimally invasive colon resection for benign or malignant disease were randomized 1:1 to 2% intravenous lidocaine or saline placebo. Enrollment occurred from August 13, 2018, to April 11, 2023, with a pause in recruitment from March 20, 2020, through July 6, 2020; final follow-up was on August 10, 2023. The intervention patients received 2% intravenous lidocaine administered as 1.5-mg/kg bolus at induction of anesthesia followed by 1.5 mg/kg/h for 6 or 12 hours. Control patients received 0.9% saline placebo for 6 or 12 hours. The primary outcome was the proportion of patients with return of gut function at 72 hours after surgery, defined by the GI-3 composite end point of tolerating diet (ingestion of food and drink without significant nausea or vomiting for 3 consecutive meals) and passage of flatus or stool. There were 11 secondary outcomes, including time to GI-3 recovery, time to GI-2 recovery (tolerance of oral diet and passage of stool), prolonged postoperative ileus, postoperative nausea and vomiting score, Overall Benefit of Analgesia Score, postoperative opioid consumption, Quality of Recovery-15, quality of life (EuroQol 5-Dimension 5-Level), enhanced recovery protocol adherence, time to meeting medically defined criteria for discharge, and time to patient self-assessed readiness for discharge. The trial enrolled 590 patients (295 intervention, 295 control); after 33 postrandomization exclusions, 557 patients were included (279 intervention, 278 control; 249 female patients [44.7%]; mean [SD] age, 66 [10.9] years); 532 (96%) received the randomized treatment. Return of gut function as defined by the GI-3 composite outcome was achieved at 72 hours by 160 patients (57.3%) in the intravenous lidocaine group vs 164 patients (59.0%) in the placebo group (adjusted absolute difference, -1.9% [95% CI, -8.0% to 4.2%]; relative risk, 0.97 [95% CI, 0.88 to 1.07]). There was no significant difference between the intervention and control groups in any of the 11 secondary end points. Among patients undergoing elective minimally invasive colon resection, perioperative administration of 2% intravenous lidocaine did not improve return of gut function at 72 hours. isrctn.org Identifier: ISRCTN52352431.

Systemic administration of the local anaesthetic lidocaine is antinociceptive in both acute and chronic pain states, especially in acute postoperative and chronic neuropathic pain. These effects cannot be explained by its voltage-gated sodium channel blocking properties alone, but the responsible mechanisms are still elusive. This narrative review focuses on available experimental evidence of the molecular mechanisms by which systemic lidocaine exerts its clinically documented analgesic effects. These include effects on the peripheral nervous system and CNS, where lidocaine acts via silencing ectopic discharges, suppression of inflammatory processes, and modulation of inhibitory and excitatory neurotransmission. We highlight promising objectives for future research to further unravel these antinociceptive mechanisms, which subsequently may facilitate the development of new analgesic strategies and therapies for acute and chronic pain.

Postoperative pain continues to be inadequately managed. While opioids remain the mainstay for postoperative analgesia, their use can be associated with adverse effects, including ileus, which can prolong hospital stay. A number of studies have investigated the use of perioperative intravenous lidocaine infusion for improving postoperative analgesia and enhancing recovery of bowel function. This systematic review was performed to determine the overall efficacy of intravenous lidocaine infusion on postoperative analgesia and recovery from surgery in patients undergoing various surgical procedures. We searched the databases of MEDLINE, CINAHL and the Cochrane Library from 1966 to December 2009. We searched for randomized controlled comparisons of lidocaine infusion with placebo in the surgical setting and reporting on postoperative analgesia and other aspects of patient recovery from surgery. The quality of all included studies was assessed using the Modified Oxford Scale. Information on postoperative pain intensity and analgesic requirements was extracted from the trials and compared qualitatively. Other relevant data such as return of bowel function, length of hospital stay, intraoperative anaesthetic requirement and adverse effects were also compared. Sixteen trials were included. A total of 395 patients received intravenous lidocaine with 369 controls. In open and laparoscopic abdominal surgery, as well as in ambulatory surgery patients, intravenous perioperative infusion of lidocaine resulted in significant reductions in postoperative pain intensity and opioid consumption. Pain scores were reduced at rest and with cough or movement for up to 48 hours postoperatively. Opioid consumption was reduced by up to 85% in lidocaine-treated patients when compared with controls. Infusion of lidocaine also resulted in earlier return of bowel function, allowing for earlier rehabilitation and shorter duration of hospital stay. First flatus occurred up to 23 hours earlier, while first bowel movement occurred up to 28 hours earlier in the lidocaine-treated patients. Duration of hospital stay was reduced by an average of 1.1 days in the lidocaine-treated patients. Administration of intravenous lidocaine infusion did not result in toxicity or clinically significant adverse events. Lidocaine had no impact on postoperative analgesia in patients undergoing tonsillectomy, total hip arthroplasty or coronary artery bypass surgery. In conclusion, intravenous lidocaine infusion in the perioperative period is safe and has clear advantages in patients undergoing abdominal surgery. Patients receiving lidocaine infusion had lower pain scores, reduced postoperative analgesic requirements and decreased intraoperative anaesthetic requirements, as well as faster return of bowel function and decreased length of hospital stay. Further studies are needed to assess whether lidocaine has a beneficial effect in patients undergoing other types of surgery and to determine the optimum dose, timing and duration of infusion of lidocaine in this setting.

Breast cancer surgery is associated with a high incidence of persistent postsurgical pain (PPSP). The aim of this study was to evaluate the impact of intravenous (IV) lidocaine on acute and PPSP, analgesic requirements, and sensation abnormalities in patients undergoing surgery for breast cancer. Thirty-six patients participated in this randomized, double-blinded study. Before induction of general anesthesia, patients received a bolus of intravenous lidocaine 1.5 mg/kg followed by a continuous infusion of lidocaine 1.5 mg/kgh (lidocaine group) or an equal volume of saline (control group). The infusion was stopped 1 hour after the skin closure. Pain scores and analgesic consumption were recorded at 2, 4, 24 hours, and then daily for 1 week postoperatively. Three months later, patients were assessed for PPSP and secondary hyperalgesia. Two (11.8%) patients in the lidocaine group and 9 (47.4%) patients in the control group reported PPSP at 3 months follow-up (P=0.031). McGill Pain Questionnaire revealed greater present pain intensity-visual analog scale in the control group (14.6 ± 22.5 vs. 2.6 ± 7.5; P=0.025). Secondary hyperalgesia (area of hyperalgesia/length of surgical incision) was significantly less in the lidocaine group compared with control group (0.2 ± 0.8 vs. 3.2 ± 4.5 cm; P=0.002). The 2 groups were similar in terms of analgesic consumption during the early postoperative period. Intravenous perioperative lidocaine decreases the incidence and severity of PPSP after breast cancer surgery. Prevention of the induction of central hyperalgesia is a potential mechanism.

Lidocaine is an amide local anaesthetic initially used intravenously as an antiarrhythmic agent. At some point it was proposed that intravenous lidocaine (IVL) had an analgesic effect that could be potentially beneficial in perioperative settings. Since these preliminary reports, a large body of evidence confirmed that IVL had anti-inflammatory and opiate-sparing effects, a combination of characteristics leading to an array of effects such as a decrease in postoperative pain and opiate consumption, and a reduction in the duration of digestive ileus. Additional studies demonstrated IVL to possess antithrombotic, antimicrobial and antitumoral effects. Beneficial effects of IVL have been characterized in abdominal surgery but remain controversial in other types of surgeries. Because the quality of evidence was limited, due to inconsistency, imprecision and study quality, recent conclusions from meta-analysis pooling together all types of surgery stated the uncertainty about IVL benefits. Additional indications such as the prevention of propofol-induced injection pain, prevention of hyperalgesia, protection against bronchial reactivity by bronchotracheal relaxation during surgery, and the increase in depth of general anaesthesia have since emerged. IVL is rapidly distributed in the body and metabolized by the liver. With the commonly recommended doses, lidocaine's therapeutic index remains very high and the plasma concentrations stay largely below the cardiotoxic and neurotoxic threshold levels, a notion that may be used by clinicians to draw conclusions on the benefit-risk profile of IVL in comparison to other analgesic strategies. The purpose of this review is to address the pharmacokinetic and pharmacodynamic properties of lidocaine in healthy and pathological conditions.