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Varicose veins are a chronic peripheral venous disease with an estimated prevalence of 20% to 30% in the adult population worldwide. People with varicose veins frequently experience pain, lower limb oedema, skin changes, venous leg ulceration, and impaired quality of life, with symptoms that may progress over time []. The most widely used framework for categorising clinical manifestations and disease severity (from mild to advanced stages) of varicose veins is called the Clinical–Etiological–Anatomical–Pathophysiological (CEAP) classification [, ]. The tool is validated in clinical practice and focuses primarily on clinical classification, as presented in .

Endovenous thermal ablation techniques have become the standard of care for treating symptomatic truncal reflux, largely replacing conventional surgical stripping. Guidelines recommend these procedures particularly for people with clinically significant disease, typically classified as CEAP C2 or higher, in whom truncal reflux (where blood flows backward down the main, deep superficial veins of the legs) contributes to symptoms and disease progression. These minimally invasive procedures aim to eliminate pathological reflux by delivering controlled thermal energy to the target vein, resulting in vein closure (ablation) and symptom relief. Clinical practice guidelines consistently recommend thermal ablation as a first‐line treatment because it achieves high occlusion rates, rapid recovery, and favourable participant‐reported outcomes compared with traditional surgery [, , , , ].

This review will evaluate the effects of different tumescent solutions used in thermal ablation (including laser, radiofrequency, microwave, and steam ablation) for the treatment of lower limb varicose veins. Tumescent anaesthesia consists of infiltrating large volumes of fluid into the perivenous or subcutaneous space, a technique designed to optimise procedural safety and efficacy by modifying the local tissue environment [, ]. The fluid absorbs the intense heat produced by the thermal device, protecting adjacent tissues. It also compresses the vein, forcing it to collapse around the optical fibre and thus improving the efficiency of energy transmission. For thermal ablation procedures without neuraxial (spinal or epidural) anaesthesia, the solution may also provide effective local analgesia, helping the patient feel more comfortable during the procedure and potentially influencing early recovery and postprocedural pain.

The role of tumescent anaesthesia has become increasingly important as endovenous techniques have evolved, incorporating advances in fibre design, longer and more selective wavelengths, and the extension of thermal ablation to superficial venous tributaries. Beyond providing precise tissue protection, vein compression, and pain control, tumescence also contributes to local haemostasis through mechanical compression. Collectively, these functions position tumescent anaesthesia as a key technical component for ensuring the success of contemporary minimally invasive endovenous treatments [, , , , ].

In current clinical practice, tumescent solution is routinely used in adults undergoing endovenous thermal ablation for symptomatic varicose veins, particularly those classified as CEAP C2 or higher. The intervention consists of perivenous infiltration of a fluid solution that may vary in composition, including diluent (normal saline or Ringer's lactate), buffering strategies, anaesthetic content, temperature, and adjunct agents. These variations may be compared with alternative formulations or, in some cases, with procedures performed without tumescent anaesthesia. In contrast, non‐thermal, non‐tumescent techniques such as mechanochemical ablation (MOCA) have been developed to avoid the need for perivenous thermal protection. However, tumescent anaesthesia may still be required in selected cases to improve patient comfort, particularly in ambulatory settings or when treating more extensive venous segments. Potential adverse effects of tumescent anaesthesia include local pain, bleeding, infection, and, rarely, systemic toxicity associated with anaesthetic agents [, , , ].

The tumescent solutions used in thermal ablation vary widely in their composition and technical characteristics. This variability has resulted in substantial heterogeneity in clinical practice. Clinicians have widely adopted tumescent anaesthesia, and major guidelines endorse the technique, including those of the Brazilian Society of Angiology and Vascular Surgery (SBACV) [], European Society for Vascular Surgery (ESVS) [], and Society for Vascular Surgery/American Venous Forum/American Vein and Lymphatic Society (SVS/AVF/AVLS) []. However, the physiological rationale for routine infiltration and the optimal formulation remain incompletely defined.

Randomised controlled trials (RCTs) have investigated several modifications of standard tumescent anaesthesia, including buffered lidocaine, cooled or warmed solutions, combinations of lidocaine and bupivacaine, the addition of dexamethasone to reduce postoperative inflammation, and the use of tranexamic acid or adrenaline to minimise periprocedural bleeding [, , , , ]. In addition, some studies have directly compared thermal ablation performed with standard tumescence to procedures conducted without tumescence, raising important questions about its absolute necessity and the potential role of alternative approaches. However, no comprehensive synthesis of this evidence currently exists, leaving uncertainty about how best to maximise procedural safety, treatment efficacy, and patient comfort. The effects of different tumescent solutions may vary across populations. For example, older individuals may have increased tissue fragility and altered vascular structure, potentially influencing both safety and treatment response. Similarly, individuals with a higher body mass index (BMI) may experience differences in the distribution and effectiveness of the tumescent solution due to increased adipose tissue. These factors may contribute to differences in outcomes such as pain, recovery time, and complication rates.

The findings of this review will be highly relevant to people seeking safer and more comfortable procedures, clinicians who require evidence‐based guidance for optimal practice, and health systems and policymakers aiming to implement cost‐effective and standardised care pathways. Moreover, identifying effective and safe tumescent formulations may promote equitable access to treatment in low‐resource settings by highlighting effective low‐cost alternatives [, ].

To evaluate the benefits and harms of different tumescent solutions for adults with lower limb varicose veins undergoing thermal ablation (laser, radiofrequency, microwave, or steam ablation), compared with other tumescent formulations or no tumescent anaesthesia.

We will include only parallel‐group RCTs with individual allocation. We will exclude cross‐over trials, cluster‐randomised trials, and quasi‐RCTs. Cluster‐randomised trials are ineligible because the unit of randomisation (e.g. centres or hospitals) may introduce additional sources of bias and analytical complexity, including issues related to intracluster correlation. As our outcomes are primarily measured at the individual participant or limb level, and we do not expect to identify cluster‐randomised trials addressing our research question, their inclusion is unlikely to contribute meaningful evidence to this review [, ]. We will include studies reported as full‐text articles, those published as abstracts only, and unpublished data.

We will include participants of any sex and any age with lower limb varicose veins undergoing thermal ablation with any energy modality, including endovenous laser ablation, radiofrequency ablation, microwave ablation, or steam ablation (water vapour therapy), in an ambulatory or inpatient setting. The diagnosis of varicose veins should be based on an objective test demonstrating pathological reflux, such as duplex ultrasound or venography. We will exclude participants treated for other conditions (e.g. venous malformations) or exclusively with non‐thermal methods (e.g. mechanochemical ablation or cyanoacrylate closure). If we identify studies with mixed populations in which only a subset of participants meets our inclusion criteria, we will attempt to obtain subgroup data from the study authors. For studies with mixed populations where subgroup data are unavailable but at least 50% of participants meet our criteria, we will include all participants in the analysis and explore the impact of this decision in a sensitivity analysis. We will exclude studies in which fewer than 50% of participants are eligible and subgroup data are unavailable.

The primary comparison of interest will be tumescent anaesthesia versus no tumescent anaesthesia. In addition, we will explore comparisons between different tumescent solution characteristics (e.g. diluents, temperature, buffering, anaesthetic content, adjunct medications). We will analyse these secondary comparisons where sufficient data are available. All variations in the preparation or administration of the tumescent solution will be eligible for comparison. Only studies in which all participants underwent the same thermal ablation technique (e.g. endovenous laser ablation, radiofrequency ablation, microwave ablation, or steam ablation) will be eligible. The sole distinction between comparison groups must be the use or characteristics of the tumescent solution. This restriction ensures that the type of thermal ablation procedure remains constant across groups, thereby isolating the effect of tumescent anaesthesia as the variable of interest.

Reporting of our prespecified outcomes will not be an inclusion criterion for this review. When a publication reports none of these outcomes, we will access the trial protocol and contact the trial authors to ascertain whether the outcomes were measured but not reported. We will present the characteristics of eligible trials with no reported review‐relevant outcomes (i.e. unusable data) in the narrative findings. In line with other Cochrane Vascular reviews, if data are available, we will present outcomes at three time points [, , , , ]. Short term: within six weeks of the intervention. Medium‐term: more than six weeks to less than five years after the intervention. Long term: five years or more after the intervention. Our primary time point of interest is within six weeks of the intervention. We intend to report short‐term outcomes in summary of findings tables, while also reporting medium‐term and long‐term outcomes at the longest available follow‐up.

Technical success: defined as complete anatomical obliteration or absence of reflux on duplex ultrasound, using the standard criterion of 0.5 seconds of reflux Pain: intraoperative or early postoperative pain, measured using validated scales (e.g. visual analogue scale (VAS) or numeric rating scale (NRS))

Complications: including nerve injury, skin burns, haematoma, bleeding, and thromboembolic events Recovery time: return to normal daily activities or work, measured in days Quality of life: assessed using validated disease‐specific instruments (e.g. Aberdeen Varicose Vein Questionnaire (AVVQ), Chronic Venous Insufficiency Questionnaire (CIVIQ)) Hospitalisation time: length of hospital stay, measured in hours, distinguishing day‐case admissions (< 24 hours) from inpatient admissions (≥ 24 hours). Participant satisfaction: measured using standardised or study‐specific questionnaires, when available (e.g. Likert scale‐based surveys or validated participant satisfaction instruments).

We aim to identify all relevant RCTs, regardless of language or publication status (published, unpublished, in press, or in progress). We will search the following databases for relevant trials. Cochrane Central Register of Controlled Trials (CENTRAL) via the Cochrane Register of Studies Web (CRS Web). MEDLINE (PubMed MEDLINE Epub Ahead of Print, In‐Process & Other Non‐Indexed Citations, PubMed MEDLINE Daily, and PubMed MEDLINE; 1946 onwards). Latin American and Caribbean Health Science Information database (LILACS; https://lilacs.bvsalud.org/ ; 1982 onwards). We will draft a preliminary search strategy for MEDLINE, which will be presented in . We then adapt this strategy to the other databases. The search strategy will incorporate the Cochrane Highly Sensitive Search Strategy for identifying randomised controlled trials and controlled clinical trials, as described in the Cochrane Handbook for Systematic Reviews of Interventions []. We will search the following trials registries. World Health Organization (WHO) International Clinical Trials Registry Platform ( https://trialsearch.who.int ). US National Institutes of Health Ongoing Trials Register ClinicalTrials.gov ( https://clinicaltrials.gov ). We will search all databases from their inception to the present and will impose no restrictions on publication language or status.

To identify additional published, unpublished, and ongoing trials for inclusion in this review, we will take the following additional steps. Checking the reference lists of included studies and any relevant systematic reviews identified for further potentially eligible trials. Contacting experts, trialists, and relevant organisations in the field to enquire about ongoing or unpublished trials. Checking for any postpublication amendments to included or eligible studies, including retractions, expressions of concern, errata, and corrigenda, using relevant sources (e.g. journal websites and databases such as Retraction Watch).

We will merge the search results to remove duplicate records. Two review authors (LYTT, LCUN) will then independently examine the titles and abstracts of the retrieved records in Covidence, eliminating those that are clearly irrelevant []. The same two review authors will then retrieve and independently assess the full‐text articles of the remaining references to determine eligibility for inclusion, recording any excluded studies and the reasons for exclusion. We will contact the authors of included trials to request any relevant unpublished data. Disagreements will be resolved through discussion or, if necessary, by consultation with a third review author (RLGF). We will collate multiple reports of the same study so that each study, rather than each reference, represents the unit of interest in the review. We will document the study selection process and present it in a PRISMA flow diagram () [].

Two review authors (LYTT, FCM) will independently extract data from the included studies and enter them into an electronic data extraction form. We will extract the following study characteristics. Publication details: year, country, and authors. Methods: study design, total study duration, number of study centres and locations, study setting, total number enroled, number lost to follow‐up or withdrawn, exclusions after randomisation, number analysed, and use of intention‐to‐treat (ITT) analysis. Participants: mean age, age range, sex, comorbidities, diagnostic criteria, and inclusion and exclusion criteria. Interventions: characteristics of the intervention and comparator. Outcomes: specified and collected critical and important outcome measures. Notes: trial funding, conflicts of interest of study authors, and trial registration.

Any disagreements will be resolved by consensus or, if required, by consultation with a third review author (RLGF). We will use Covidence to support study selection, data extraction, data management, and the resolution of discrepancies among review authors []. One review author (LYTT) will enter the outcome data into RevMan [], and a second review author will independently verify the accuracy of the entered data against the original study reports. We will double‐check all entered data by comparing the information presented in the review with the original extraction forms. A second review author (RLGF) will independently spot‐check study characteristics for accuracy.

Two review authors (LYTT and FCM) will assess the risk of bias for each included study using the Cochrane tool RoB 1 []. We will resolve any disagreements by discussion or, if required, by involving a third review author (RLGF). RoB 1 covers the following domains. We will consider the potential impact of the lack of blinding differently for subjective and objective outcomes. In particular, we will consider outcomes such as pain, quality of life, and participant satisfaction more susceptible to bias due to lack of blinding, and outcomes such as technical success assessed by duplex ultrasound less prone to such bias []. For each domain, we will judge whether studies are at low, unclear, or high risk of bias and provide a supporting quotation from the study report, together with a justification for each judgement. We will summarise judgements across studies for each domain. When information relating to risk of bias comes from unpublished data or personal correspondence with trial authors, we will indicate this clearly. When considering treatment effects, we will take into account the risk of bias of the studies contributing data to each outcome.

For dichotomous outcomes, we will calculate risk ratios (RRs) with 95% confidence intervals (CIs). For continuous outcomes measured using the same instruments across studies, we will calculate mean differences (MDs) with 95% CIs. When outcomes are reported using different scales, we will calculate standardised mean differences (SMDs) with 95% CIs. If standard deviations (SDs) or standard errors (SEs) are not available, we will attempt to extract P values. We will enter results from outcome scales with a consistent direction of effect. When outcomes are reported as medians and interquartile ranges (IQRs), we will apply the method described by Wan and colleagues (2014) to convert these data to means and SDs, where appropriate. Skewed data reported as medians and IQRs will be described narratively []. To aid interpretation of SMDs, we will use the thresholds recommended in Section 15.5.3.1 of the Cochrane Handbook for Systematic Reviews of Interventions [].

We will calculate the number needed to treat for an additional beneficial outcome (NNTB) for the critical outcomes (vein occlusion and pain). For adverse outcomes, we will calculate the number needed to treat for an additional harmful outcome (NNTH), defined as 1 divided by the risk difference (RD), depending on the direction of effect, in accordance with the Cochrane Handbook for Systematic Reviews of Interventions []. We will calculate RDs using the RevMan calculator [].

For all included studies, the unit of analysis will follow the original study's reporting. For pain, recovery time, quality of life, hospitalisation time, and participant satisfaction, the unit of analysis will generally be the individual participant; however, pain may be analysed at the treated‐limb level when reported at that level. For technical success and complications, the unit of analysis will be the treated limb when reported per limb and the individual participant when reported per participant. In trials with multiple intervention arms, we will include only those arms that are relevant to the scope of this review. When studies include more than two relevant intervention arms, we will combine groups to create a single pairwise comparison, where appropriate. If combining groups is not appropriate, we will split the shared comparison group evenly across intervention arms to avoid double counting, in accordance with the Cochrane Handbook for Systematic Reviews of Interventions [].

For studies in which participants receive interventions on both limbs (within‐person or split‐body designs), we will account for the non‐independence of observations. Where appropriate methods have been used by the study authors (e.g. paired analyses), we will use the reported effect estimates. If such adjustments are not reported, we will consider using approximate methods as recommended in the Cochrane Handbook for Systematic Reviews of Interventions , or include the data in a narrative synthesis if appropriate adjustment is not possible []. We will not include cross‐over trials, as participants undergo the intervention only once rather than across multiple phases.