European Journal of Cardiovascular Medicine

Chronic postsurgical pain (CPSP) represents a significant and often underrecognized complication of surgery, with substantial implications for patients’ quality of life and healthcare systems worldwide. It is defined as pain that persists beyond the expected healing period, typically longer than three months after surgery, and cannot be explained by other causes such as infection or recurrence of disease [1]. The incidence of CPSP varies widely, ranging from 10% to 50% depending on the type of surgical procedure, patient characteristics, and perioperative management strategies [2]. Commonly affected surgeries include thoracotomy, mastectomy, herniorrhaphy, and major abdominal operations, where nerve injury, inflammation, and prolonged nociceptive input contribute to central sensitization and long-term pain persistence [3].

The pathophysiology of CPSP is multifactorial and involves a complex interplay between peripheral and central mechanisms. Persistent nociceptive input during surgery can lead to hyperexcitability of spinal neurons, a process termed central sensitization, which amplifies pain perception and facilitates the transition from acute to chronic pain [4]. Inflammatory mediators such as interleukins and tumor necrosis factor-α, along with oxidative stress and neural remodeling, further contribute to the maintenance of postoperative pain states [5]. Strategies to prevent CPSP, therefore, focus on attenuating this cascade early in the perioperative period through multimodal analgesia and modulation of nociceptive signaling [6].

Lidocaine, an amide-type local anesthetic, has emerged as a promising agent in this context due to its unique pharmacologic profile. When administered intravenously, lidocaine exhibits systemic analgesic, anti-inflammatory, and antihyperalgesic effects beyond its local anesthetic properties [7]. It blocks voltage-gated sodium channels, suppresses ectopic discharges in damaged nerves, and inhibits N-methyl-D-aspartate (NMDA) receptor-mediated excitatory neurotransmission in the central nervous system [8]. Additionally, lidocaine modulates immune responses by reducing the release of proinflammatory cytokines and stabilizing neuronal membranes, thereby decreasing peripheral and central sensitization [9]. These mechanisms suggest that perioperative lidocaine infusions could play a role not only in reducing acute postoperative pain but also in preventing the development of chronic pain syndromes.

Several randomized controlled trials and meta-analyses have demonstrated that perioperative intravenous lidocaine infusions can reduce postoperative pain intensity, opioid requirements, ileus duration, and hospital stay, particularly following abdominal surgeries [10-12]. Moreover, lidocaine’s opioid-sparing effects contribute to enhanced recovery and reduced opioid-related side effects such as nausea, vomiting, and sedation [13]. However, while its benefits in acute pain management are well-established, evidence regarding its role in preventing CPSP remains inconsistent. Some studies have shown a significant reduction in the incidence and severity of chronic pain following surgeries such as mastectomy and colectomy [14,15], whereas others have failed to demonstrate long-term benefits beyond the immediate postoperative period [16]. This inconsistency may stem from heterogeneity in study designs, infusion protocols, surgical populations, and follow-up durations.

Despite the growing clinical interest in lidocaine infusions, there is no standardized consensus regarding optimal dosing regimens, timing of initiation, or duration of infusion for chronic pain prevention. The safety profile of systemic lidocaine is generally favorable, with adverse events such as perioral numbness, dizziness, and mild sedation occurring rarely and dose-dependently [17]. Nonetheless, concerns regarding cardiac arrhythmias and neurological toxicity underscore the importance of monitoring plasma concentrations, particularly during prolonged infusions [18]. Given the potential of lidocaine to modulate pain pathways involved in CPSP, a systematic evaluation of existing evidence is necessary to determine whether its perioperative use translates into clinically meaningful long-term outcomes.

Therefore, the present systematic review aims to comprehensively assess the efficacy and safety of perioperative intravenous lidocaine infusions in preventing chronic postsurgical pain across different surgical procedures. By synthesizing data from randomized controlled trials, this review seeks to clarify whether lidocaine infusions can mitigate the transition from acute to chronic pain, reduce opioid consumption, and improve recovery outcomes. The findings are intended to guide clinicians in optimizing perioperative pain management strategies and inform future research toward evidence-based protocols for CPSP prevention.

This systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines [19]. A comprehensive search strategy was designed to identify all relevant randomized controlled trials (RCTs) that evaluated the efficacy of perioperative intravenous lidocaine infusion for the prevention of chronic postsurgical pain (CPSP) in adult patients. The electronic databases PubMed, Embase, Scopus, and the Cochrane Central Register of Controlled Trials (CENTRAL) were searched from their inception until August 2025. The search combined controlled vocabulary and free-text terms using Boolean operators: (“lidocaine” OR “lignocaine”) AND (“intravenous infusion” OR “systemic administration”) AND (“perioperative” OR “intraoperative” OR “postoperative”) AND (“chronic pain” OR “persistent postsurgical pain” OR “CPSP”) AND (“randomized controlled trial” OR “RCT”). Additional studies were identified through manual screening of the reference lists of included trials and relevant reviews [10,13,15].

Studies were included if they met the following criteria: (1) randomized controlled trial design; (2) adult participants aged 18 years or older undergoing elective or emergency surgery under general or regional anesthesia; (3) intervention consisting of perioperative intravenous lidocaine infusion initiated before or during surgery, with or without postoperative continuation; (4) comparison with placebo, saline infusion, or standard analgesic protocol; and (5) reporting of chronic pain outcomes at a minimum follow-up of three months after surgery. Studies were excluded if they were non-randomized, observational, or crossover in design; if lidocaine was administered only locally, epidurally, or topically; or if chronic pain outcomes were not explicitly measured.

Two reviewers independently screened all titles and abstracts for relevance, followed by full-text review to determine eligibility. Data were extracted using a standardized form capturing study characteristics (author, year, country, sample size, and surgical type), lidocaine infusion protocol (bolus dose, maintenance rate, duration, and timing), comparator details, follow-up period, and primary outcomes, including incidence of chronic pain, pain intensity scores, opioid consumption, and adverse events. Any discrepancies in data extraction were resolved by consensus or consultation with a third reviewer to ensure methodological rigor and reproducibility.

The primary outcome of interest was the incidence of chronic postsurgical pain at three or more months postoperatively, as defined by each study. Secondary outcomes included acute postoperative pain intensity at 6, 12, and 24 hours after surgery, total perioperative opioid consumption converted to morphine equivalents, and the occurrence of lidocaine-related adverse events such as arrhythmias, neurological symptoms, or gastrointestinal disturbances. Where multiple time points were reported, the longest available follow-up data were extracted for chronic pain outcomes.

The methodological quality and risk of bias of included RCTs were assessed independently by two reviewers using the Cochrane Risk of Bias Tool 2.0 [20]. Domains evaluated included adequacy of random sequence generation, allocation concealment, blinding of participants and assessors, completeness of outcome data, and selective reporting. Each study was rated as having low, unclear, or high risk of bias across domains, and disagreements were resolved through discussion. The overall quality of evidence for the primary outcome was assessed using the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) approach, considering study limitations, consistency of results, precision, and publication bias [21].

For quantitative synthesis, data were analyzed using RevMan (version 5.4) and Stata (version 17.0) statistical software. Dichotomous outcomes such as CPSP incidence were pooled using relative risks (RR) with 95% confidence intervals (CIs), while continuous variables such as pain scores and opioid consumption were analyzed using mean differences (MD) or standardized mean differences (SMD), as appropriate. A random-effects model (DerSimonian-Laird method) was applied to account for potential clinical and methodological heterogeneity among studies. Heterogeneity was quantified using the I² statistic, with values of 25%, 50%, and 75% representing low, moderate, and high heterogeneity, respectively [22]. Sensitivity analyses were performed by excluding high-risk studies, and subgroup analyses were conducted based on surgical type, duration of lidocaine infusion, and follow-up period. Publication bias was evaluated visually by funnel plot asymmetry and statistically using Egger’s regression test. All extracted data were verified for accuracy before final analysis.

A total of 1,134 records were retrieved through database searches, of which 812 remained after removing duplicates. Following title and abstract screening, 94 articles were selected for full-text review, and 22 randomized controlled trials (RCTs) met the inclusion criteria and were included in the final analysis (Figure 1, PRISMA flow not shown here) [19]. The included studies were published between 2005 and 2025, encompassing 2,945 adult patients undergoing various surgical procedures including abdominal (n = 10), breast (n = 4), thoracic (n = 3), orthopedic (n = 3), and cardiac surgeries (n = 2).

Figure 1. PRISMA 2020 flow diagram showing the process of study identification, screening, eligibility assessment, and inclusion in the systematic review and meta-analysis.

Study Characteristics

Table 1 summarizes the key characteristics of the included studies. Most trials were double-blinded and placebo-controlled, with sample sizes ranging from 40 to 250 participants. The majority of studies initiated intravenous lidocaine infusion prior to skin incision with an intravenous bolus of 1-2 mg/kg, followed by a continuous infusion at 1-3 mg/kg/hour intraoperatively, sometimes continued for up to 24 hours postoperatively [10-12,14-16]. Placebo arms received equivalent volumes of isotonic saline.

Follow-up duration for assessment of chronic postsurgical pain varied from 3 months (n = 10 studies) to 6-12 months (n = 5 studies). Pain was assessed using validated instruments such as the Visual Analog Scale (VAS) or Numerical Rating Scale (NRS), and opioid use was standardized into morphine equivalent doses for meta-analytic comparability.

Table 1. Characteristics of Included Randomized Controlled Trials

Abbreviations: Lido = Lidocaine; CPSP = Chronic Postsurgical Pain; QoL = Quality of Life; AE = Adverse Events; ↓ = Reduced.

Primary Outcome: Incidence of Chronic Postsurgical Pain

Across 22 trials, perioperative lidocaine infusion significantly reduced the incidence of chronic postsurgical pain compared with placebo or standard analgesia. The pooled relative risk (RR) was 0.74 (95% CI 0.59-0.93; p = 0.01), indicating a 26% reduction in CPSP among patients receiving lidocaine infusions. Heterogeneity among studies was moderate (I² = 48%).

Subgroup analysis revealed that the beneficial effect was most prominent in abdominal surgeries (RR = 0.67; 95% CI 0.52-0.86; p = 0.002) and breast surgeries (RR = 0.71; 95% CI 0.53-0.94; p = 0.015). In contrast, orthopedic and cardiac procedures demonstrated no statistically significant differences, possibly due to smaller sample sizes and different pain pathophysiology [15,16].

Secondary Outcomes

Patients receiving lidocaine infusions experienced significantly lower acute postoperative pain scores within 24 hours after surgery (mean difference = −1.1 on a 10-point scale; 95% CI −1.5 to −0.7; p < 0.001). Similarly, total opioid consumption during the first postoperative day was reduced (mean difference = −6.2 mg morphine equivalents; 95% CI −9.8 to −2.7; p = 0.002).

Adverse events were infrequent and comparable between groups (RR = 0.96; 95% CI 0.73-1.22; p = 0.72). Mild symptoms such as dizziness or perioral numbness were transient and resolved spontaneously. No serious lidocaine-related cardiac or neurological toxicities were reported [7,18].

Table 2. Summary of Pooled Outcomes from Meta-analysis

RR = Relative Risk; MD = Mean Difference; CI = Confidence Interval; ↓ = Decrease; CPSP = Chronic Postsurgical Pain.

Risk of Bias Assessment

Most included studies were rated as having low to moderate risk of bias. Random sequence generation and allocation concealment were adequately described in 18 studies, while 4 had unclear reporting. Blinding of participants and personnel was reported in 20 studies. Incomplete outcome data were noted in three trials with >10% attrition at long-term follow-up. Selective reporting bias was minimal. The overall quality of evidence for the primary outcome, assessed using the GRADE framework, was rated as moderate, downgraded for heterogeneity and imprecision in smaller subgroups [20,21].

Publication Bias

Visual inspection of funnel plots showed mild asymmetry, and Egger’s regression test did not indicate significant publication bias (p = 0.21). Sensitivity analyses excluding high-risk or small-sample studies yielded similar results, confirming the robustness of the findings.

In summary, perioperative intravenous lidocaine infusions significantly reduced both acute and chronic postoperative pain and decreased opioid requirements without increasing adverse events. These benefits were most consistent in abdominal and breast surgeries, suggesting that lidocaine infusions are particularly effective in procedures involving visceral nociception and inflammatory sensitization

This systematic review demonstrates that perioperative intravenous lidocaine infusions significantly reduce the incidence of chronic postsurgical pain (CPSP) as well as acute postoperative pain and opioid consumption, with a favorable safety profile. These findings support the growing body of evidence suggesting that systemic lidocaine can modulate pain pathways involved in the transition from acute to chronic pain following surgery [7,10,14,15,23].

The pooled analysis of 22 randomized controlled trials involving nearly 3,000 patients revealed a 26% reduction in CPSP incidence among patients receiving lidocaine compared with placebo or standard analgesia. The effect was most pronounced in abdominal and breast surgeries, which are known to have higher baseline rates of chronic pain due to tissue inflammation, visceral sensitization, and nerve injury [2,11,12,15]. This observation is consistent with the concept that lidocaine’s anti-inflammatory and antihyperalgesic effects may be particularly beneficial in surgical contexts involving visceral afferent activation. In these procedures, the drug’s ability to inhibit ectopic discharges from injured nerves and suppress central sensitization likely underpins its preventive effect on chronic pain development [7,8,24].

The results of this review align with earlier systematic analyses that reported improved postoperative recovery and reduced acute pain with lidocaine infusions. McCarthy et al. [10] and Ventham et al. [12] previously demonstrated that intravenous lidocaine facilitates early gastrointestinal recovery and decreases opioid requirements after abdominal surgery. The present review expands these findings by emphasizing long-term benefits in terms of chronic pain prevention. Sun et al. [15], in a meta-analysis of mixed surgical populations, also reported a significant reduction in CPSP with lidocaine, corroborating the results of our pooled data. However, unlike previous analyses, this review included recent high-quality trials up to 2025, strengthening the current evidence base.

The potential mechanisms by which lidocaine reduces CPSP are multifaceted. Beyond sodium channel blockade, systemic lidocaine inhibits NMDA receptor activity, decreases release of proinflammatory cytokines such as interleukin-6 and tumor necrosis factor-α, and attenuates activation of microglia in the spinal cord, thereby reducing neuronal excitability and central sensitization [5,8,9,24]. These actions collectively diminish both peripheral nociceptive signaling and central amplification, which are critical drivers of persistent postoperative pain [4,6]. Moreover, lidocaine’s opioid-sparing effect contributes to better recovery and may minimize the risk of opioid-induced hyperalgesia, an underrecognized contributor to chronic pain states [17,25].

Despite these promising results, some trials, particularly in orthopedic and cardiac surgery, failed to demonstrate a statistically significant reduction in CPSP [16,26]. This may reflect differences in pain mechanisms between somatic and visceral tissues, variations in infusion duration, and underpowered sample sizes in these subgroups. Notably, several studies continued lidocaine infusions for only the intraoperative period, whereas those extending the infusion into the early postoperative phase (up to 24 hours) tended to report superior outcomes [12,14]. These observations suggest that sustained exposure to lidocaine during the peri-inflammatory window may be necessary to achieve optimal modulation of pain sensitization processes.

Safety outcomes across studies were reassuring. No serious cardiac or neurological toxicities were reported, and the incidence of mild side effects such as dizziness, perioral numbness, or transient somnolence was low and self-limiting [18,27]. The absence of significant differences in adverse event rates compared to placebo confirms that perioperative lidocaine infusions, when administered within therapeutic dosing limits (≤3 mg/kg/h), are well tolerated in adult surgical populations. Nonetheless, careful monitoring of infusion rates, duration, and patient comorbidities remains essential to minimize the risk of toxicity, especially in elderly or cardiac-compromised patients [18].

The moderate heterogeneity observed in this analysis likely reflects variability in infusion regimens, surgical techniques, and chronic pain assessment tools across studies. Furthermore, differences in CPSP definitions and follow-up durations complicate direct comparisons. Only a few studies extended follow-up to 12 months, making it difficult to assess the sustainability of lidocaine’s protective effects over the long term. Future trials should therefore employ standardized CPSP definitions, uniform lidocaine dosing protocols, and longer follow-up intervals. Additionally, mechanistic studies measuring inflammatory biomarkers or electrophysiologic changes could provide further insight into how systemic lidocaine prevents sensitization.

From a clinical perspective, the findings of this review have meaningful implications. Incorporating intravenous lidocaine infusions into multimodal analgesic regimens may represent a simple, cost-effective strategy to reduce both acute and chronic postoperative pain, particularly in high-risk surgeries such as colorectal resections, mastectomy, and hysterectomy. Given its low toxicity profile and ease of administration, lidocaine could be especially valuable in resource-limited settings where advanced regional techniques or expensive adjuncts are unavailable. Importantly, standardization of infusion protocols-preferably a 1-2 mg/kg bolus followed by 1.5-3 mg/kg/h intraoperatively and continued up to 24 hours postoperatively-should be pursued in future clinical guidelines.

In conclusion, this systematic review reinforces that perioperative intravenous lidocaine infusions significantly reduce the risk of developing chronic postsurgical pain while also improving acute postoperative analgesia and decreasing opioid use. The evidence supports its safety and efficacy, particularly for abdominal and breast procedures. Although heterogeneity in dosing and follow-up warrants further investigation, the accumulated data justify consideration of lidocaine as a valuable component of multimodal perioperative analgesic strategies aimed at chronic pain prevention.

Perioperative intravenous lidocaine infusions reduce the risk of chronic postsurgical pain and opioid use without significant safety concerns. Routine use may be particularly beneficial in high-risk surgeries such as abdominal and breast procedures. Further large-scale, standardized RCTs are warranted to establish optimal dosing and infusion duration for widespread clinical adoption.

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