Defining the optimum tumescent anaesthesia solution in endovenous laser ablation

Abstract

Objectives

To produce a tumescent anaesthesia solution with physiological pH for endovenous thermal ablation and evaluate its influence on peri- and postoperative pain, clinical and quality of life outcomes, and technical success.

Methods

Tumescent anaesthetic solution (0.1% lidocaine with 1:2,000,000 epinephrine) was titrated to physiological pH by buffering with 2 ml incremental aliquots of 8.4% sodium bicarbonate. Patients undergoing great saphenous vein endovenous laser ablation and ambulatory phlebectomy were studied before and after introduction of buffered tumescent anaesthetic. Primary outcome was perioperative pain measured on a 10 cm visual analogue scale. Secondary outcomes were daily pain scores during the first postoperative week, complications, time to return to normal activity, patient satisfaction, generic and disease-specific quality of life, and technical success. Patients were assessed at baseline, and at 1, 6 and 12 weeks following the procedure.

Results

A physiological pH was achieved with the addition of 10 ml of 8.4% sodium bicarbonate to 1 l of standard tumescent anaesthetic solution. Sixty-two patients undergoing great saphenous vein endovenous laser ablation with phlebectomy were recruited before and after the introduction of buffered tumescent anaesthetic solution. Baseline and operative characteristics were well matched. The buffered solution was associated with significantly lower (median (interquartile range)) periprocedural pain scores (1 (0.25–2.25) versus 4 (3–6), p < 0.001) and postoperative pain score at the end of the treatment day (1.8 (0.3–2.8) versus 3.0 (1.2–5.2), p = 0.033). There were no significant differences in postoperative pain scores between the groups at any other time. There were no significant differences in other clinical outcomes between the groups. Both groups demonstrated significant improvements in generic and disease-specific quality of life, with no intergroup differences. Both groups demonstrated 100% ultrasonographic technical success at all time points.

Conclusions

Buffering of tumescent anaesthetic solution during endovenous thermal ablation is a simple, safe, inexpensive and effective means of reducing perioperative and early postoperative pain.

Keywords

Endovenous laser treatment varicose veins patient-reported outcomes quality of life assessment great saphenous vein

Introduction

Endovenous thermal ablation (EVTA) is recommended as the first-line treatment for superficial venous insufficiency by the National Institute for Health and Care Excellence,¹ with significant benefits over conventional surgery.^2–5 Optimisation of the EVTA technique may further improve patient outcomes.

EVTA is almost universally performed utilising perivenous tumescent anaesthesia which provides: local anaesthetic, hydrodissection of surrounding tissues away from the vein, a heat sink protecting surrounding tissues from thermal damage, and vein compression maximising heat source/vein contact promoting treatment uniformity. However, patients frequently report the infiltration of tumescent anaesthetic to be the most painful aspect of EVTA.^6,7

The tumescent anaesthetic is typically a crystalloid solution containing local anaesthetic and epinephrine. However, the precise constituents vary considerably, with specific formulations rarely reported.

The addition of sodium bicarbonate to buffer the acidic pH of local anaesthetic solutions used for skin and subcutaneous infiltration (such as prior to epidural, venous and arterial catheterisation, for local anaesthetic day-case procedures and prior to suturing lacerations) reduces patient reported pain.^10–14 However this is an ‘off label’ use of sodium bicarbonate, and there is currently no evidence to support its use in tumescent anaesthesia for EVTA.

Objectives

Laboratory study

To produce a physiological pH tumescent anaesthetic solution for EVTA.

Clinical cohort study

To evaluate the effect of a physiological pH tumescent anaesthetic solution on peri- and postoperative pain, clinical and quality of life (QoL) outcomes, and technical success assessed on duplex ultrasonography (DUS).

Methods

Laboratory study

A 1000 ml bag of 0.9% sodium chloride for intravenous infusion (Baxter Healthcare, Newbury, Berkshire, UK) had 100 ml extracted to leave 900 ml. To this, 100 ml of 1% lidocaine with 1:200,000 epinephrine (Xylocaine, AstraZeneca UK Ltd, Luton, UK) was added. This was our standard tumescent anaesthetic solution. Commercially available solutions of 0.9% sodium chloride (Baxter Healthcare, Newbury, Berkshire, UK), 1% lidocaine (B. Braun Medical Ltd, Sheffield, UK), 1% lidocaine with 1:200,000 epinephrine (Xylocaine, AstraZeneca UK Ltd, Luton, UK) and 2% lidocaine with 1:200,000 epinephrine (Xylocaine, AstraZeneca UK Ltd, Luton, UK) were also prepared for pH testing.

pH testing was performed using an Oakton/Eutech instruments pH 11 meter (Oakton Instruments, Vernon Hills, Illinois, USA), after two-point calibration with buffers at pH 4.01 and pH 7.00. Analyses were undertaken in the biochemistry laboratory at Hull Royal Infirmary, temperature controlled at 21℃; the surgical outpatient theatre, where endovenous laser ablation (EVLA) is performed, is also temperature-controlled to 21℃. The test solutions were slowly stirred with the fully immersed probe, in order to ensure a homogenous solution, allowing sufficient time for the pH reading to stabilise. Between each test, the pH probe was rinsed thoroughly in distilled water. Three measurements were undertaken on three separate occasions, giving a total of nine pH readings for each solution to account for subtle variations in ambient temperature or slight inaccuracies in preparation.

The standard tumescent anaesthetic solution was titrated to physiological pH (pH 7.40) by buffering with 2 ml incremental aliquots of 8.4% sodium bicarbonate (Martindale Pharmaceuticals Ltd, Wooburn Green, UK). Mean (SD) pH values were calculated, along with hypothesis testing to confirm that the pH figures obtained for each solution were significantly different.

Clinical cohort study

A consecutive series of patients with unilateral primary, symptomatic, varicose veins secondary to great saphenous vein (GSV) insufficiency, undergoing EVLA with concomitant phlebectomy before and after the introduction of the optimal pH tumescent anaesthetic solution were studied.

Each participant provided written informed consent to undergo the procedure and take part in the study. Baseline clinical demographics including age, sex, body mass index, clinical etiology anatomy pathophysiology (CEAP) and Venous Clinical Severity Scores (VCSS) were recorded. Pretreatment QoL was assessed using generic (Short-form 36, (SF36) and EuroQol 5-domain (EQ5D)) and disease-specific (Aberdeen Varicose Vein Questionnaire (AVVQ)) tools. DUS characteristics of interest included presence of saphenofemoral junction (SFJ) reflux and GSV diameters.

EVLA was performed on a day-case, outpatient basis as per our standard practice. Preoperative DUS examination was performed by the operating surgeon to identify the SFJ and the lowest point of GSV reflux. Varicosities for phlebectomy were marked. Under standard aseptic conditions, an ultrasound-guided Seldinger technique was employed to cannulate the GSV at the lowest point of demonstrable reflux and place the tip of the EVLA catheter at the SFJ. Local anaesthesia to skin was 1% lidocaine with 1:200,000 epinephrine, buffered with 8.4% NaHCO₃ in a 10:1 ratio.

With the patient in Trendelenburg position, ultrasound-guided perivenous tumescent anaesthesia was administered using a pedal-operated peristaltic pump (Nouvag DP-20, Nouvag, Goldach, Switzerland) via a spinal needle, at a target of 10 ml per cm length of GSV. The first cohort of patients received the unbuffered standard tumescent anaesthetic solution (no bicarbonate), while the second cohort of patients received the buffered, optimal pH tumescent anaesthetic solution.

A 600 µm jacket-tipped laser fibre (NeverTouch, AngioDynamics, Cambridge, UK) was introduced, the catheter withdrawn leaving the laser fibre tip at the junction, aiming for a flush occlusion; the catheter and fibre were then locked together. An 810 nm laser (AngioDynamics, Cambridge, UK) delivered a 14 W continuous beam with a withdrawal rate of 2 mm sec⁻¹, giving a target linear endovenous energy density (LEED) of 100 Jcm⁻¹.

Phlebectomy was performed through 2 mm stab incisions, following infiltration of the same tumescent anaesthesia. Incisions were dressed with Steri-Strips™ (3 M UK PLC, Bracknell, UK), cotton wool, gauze and an elasticated self-adhesive compression bandage applied from foot to groin. Patients were encouraged to mobilise immediately and were discharged home the same day.

The length of GSV treated, volume of tumescent anaesthetic and LEED were documented. Immediately following the procedure, patients were asked to score the maximum periprocedural pain they experienced by marking a line on a 10 cm unmarked visual analogue scale (VAS) from 0, ‘No pain’ to 10 ‘Worst imaginable pain’. A one-week VAS pain diary, again using an unmarked 10 cm VAS was provided to each patient with a request to complete the pain score at the end of each day.

Follow-up

Follow-up visits were scheduled for 1, 6 and 12 weeks. At each visit, patients independently completed the same QoL tools prior to meeting with an investigator.

At the first visit, the bandaging was removed and exchanged for a full-length graduated compression stocking, (T.E.D.™, Tyco Healthcare, Gosport, UK), giving 18 mmHg compression at the ankle, to be worn during the day for a further five weeks until the next follow-up visit.

Each visit we recorded: QoL using SF36, EQ5D and AVVQ; adverse events/reactions/complications in accordance with the Society of Interventional Radiology Standards of Practice Committee Guidelines on reporting complications;⁸ patient satisfaction scores on a 10 cm VAS; and findings of DUS assessment of the deep and superficial venous systems specifically looking for DVT and GSV occlusion.

Outcome measures

The primary outcome measure was periprocedural pain, scored on an unmarked 10 cm VAS. Based on an α of 0.05, it was calculated that 31 patients in each group would give 80% power to detect a medium effect size.

Secondary outcome measures included: daily postprocedural pain during week 1, time to return to normal activity, complications, patient satisfaction, QoL assessed by generic (SF36 and EQ5D) and disease-specific (AVVQ) tools, and technical success on DUS.

Data analyses were undertaken using IBM® SPSS® Statistics v19.0. Continuous data were checked for normality using histograms and tests for kurtosis and skewness; parametric, non-parametric and ordinal data were handled appropriately. A p-value < 0.05 was taken to indicate statistical significance. Univariate regression analyses were performed to assess for any confounding effect of the baseline parameters.

Results

Laboratory study

The pH of the commercially available solutions and of the standard tumescent solution was significantly acidic (Table 1). Increasing 2 ml aliquots of sodium bicarbonate resulted in buffering of the tumescent solution and a more neutral pH. Optimum ‘physiological’ pH was achieved with the addition of 10 ml sodium bicarbonate to the standard tumescent solution, and this was selected as the solution of choice for the clinical evaluation (Figure 1).

Figure 1.

pH analyses of tumescent anaesthetic solution, buffering with incremental 2 ml aliquots of 8.4% sodium bicarbonate (NaHCO₃). (a) Standard unbuffered solution (0.1% lidocaine with 1:200,0000 epinephrine).(b) solution A plus 2 ml 8.4% NaHCO₃, (c) solution A plus 4 ml 8.4% NaHCO₃, (d) solution A plus 6 ml 8.4% NaHCO₃, (e) solution A plus 8 ml 8.4% NaHCO₃, (f): solution A plus 10 ml 8.4% NaHCO₃ and (g) solution A plus 12 ml 8.4% NaHCO₃.

Table 1.

pH analyses of 0.9% sodium chloride, typical local anaesthetic solutions and standard unbuffered tumescent anaesthetic solution.

Solution	pH
0.9% sodium chloride	6.55 (0.02)
1% Lidocaine	6.46 (0.01)
1% Lidocaine + 1:200,000 epinephrine	4.38 (0.01)
2% Lidocaine + 1:200,000 epinephrine	4.58 (0.01)
Standard tumescent anaesthetic solution	6.32 (0.01)

Note: pH reported as mean (SD). Analyses performed at 21℃.

Clinical cohort study

A cohort of 62 consecutive patients undergoing unilateral EVLA and phlebectomy were studied, 31 patients prior to and 31 patients following the introduction of buffered tumescent anaesthesia. The unbuffered and buffered groups had equivalent baseline characteristics in terms of clinical, QoL, and DUS features (Table 2) and treatment parameters (Table 3).

Table 2.

Baseline patient characteristics.

		Unbuffered, n = 31	Buffered, n = 31	p
Clinical parameters
Age (years)		54 (14.8)	49 (18)	0.194^a
Female sex		15/31	21/31	0.123^b
Left leg		13/31	19/31	0.127^b
BMI (kgm⁻²)		26.31 (24.54–29.71)	30.01 (27.82–32.87)	0.794^c
VCSS		5 (4–7)	5 (4–6)	0.542^c
CEAP Clinical grade	C2	17	20	0.078^b
	C3	0	4
	C4	13	6
	C5	1	1
	C6	0	0
Quality of life
SF36
Physical functioning		95 (70–100)	90 (70–100)	0.669^c
Role – physical		100 (50–100)	100 (0–100)	0.649^c
Bodily pain		72 (51–100)	67 (41–84)	0.144^c
General health		72 (60–82)	72 (57–83.25)	0.817^c
Vitality		70 (50–85)	70 (43.75–85)	0.482^c
Social functioning		100 (75–100)	93.75 (62.5–100)	0.279^c
Role – emotional		100 (66–100)	100	0.517^c
Mental health		88 (60–92)	88 (72–92)	0.884^c
EQ5D		0.806 (0.796–1.000)	0.796 (0.620–1.000)	0.068^c
AVVQ		12.00 (8.97–15.54)	14.28 (9.99–19.10)	0.160^c
DUS characteristics
SFJ reflux present		31/31	31/31	1.00^d
GSV diameter (mm) 2 cm from SFJ		9.0 (7.4–10.1)	8.5 (6.8–11.6)	0.688^c
At knee		7.0 (5.3–8.6)	5.9 (4.4–8.0)	0.276^c

Note: Age is quoted as mean (SD); BMI, VCSS, QoL values and GSV diameters are quoted as median (IQR).

DUS: duplex ultrasonography; VCSS: Venous Clinical Severity Scores; BMI: body mass index; SFJ: saphenofemoral junction; GSV: great saphenous vein; AVVQ: Aberdeen Varicose Vein Questionnaire; EQ5D: EuroQol 5-domain; SF36: Short-form 36.

Student’s independent samples t-test.

Chi square test.

Mann-Whitney U test.

Fisher’s exact test.

Table 3.

Treatment data.

Treatment data	Unbuffered	Buffered	p
Length of vein treated (cm)	51.0 (34–58)	44.5 (38.5–59.3)	0.941^a
Volume of tumescent anaesthesia (ml)^b	800 (700–937)	775 (575–925)	0.285^a
LEED (Jcm⁻¹)	106 (92–120.9)	99 (73.4–121)	0.198^a

LEED: linear endovenous energy density.

Mann-Whitney U test.

Volume of tumescent is total used for axial ablation and ambulatory phlebectomy.

Primary outcome

Periprocedural pain, recorded on patient-reported 10 cm VAS at the conclusion of the procedure, was significantly lower in the buffered group (median 1 (interquartile range (IQR) 0.25–2.25) versus 4 (3–6), p < 0.001) (Figure 2).

Figure 2.

Periprocedural pain scores, unbuffered versus buffered tumescent anaesthesia. p < 0.001.

Secondary outcomes

Clinical outcomes

Daily pain scores recorded on a 10 cm VAS at the end of each day were significantly lower in the buffered group on the treatment day (median 1.8 (IQR 0.3–2.8) versus 3.0 (1.2–5.2), p = 0.033, Figure 3). There were no differences between the two groups in daily pain scores at any other time point. Univariate regression analysis demonstrated no confounding effect from any baseline or procedural parameter on either periprocedural or postprocedural pain scores.

Figure 3.

Postprocedural pain scores, unbuffered versus buffered tumescent anaesthesia.

There was no difference between the groups in time to return to normal activities, at a median (IQR) of 1 (0–2) versus 1 (1–2) day (p = 0.541) in the unbuffered and buffered groups, respectively.

Complications were low in each group, with no instances of infection, venous thromboembolism or thrombophlebitis. At one week, two patients in the unbuffered group and one patient in the buffered group reported sensory disturbance (p = 1.000). At six weeks, all three cases of sensory disturbance had resolved.

Patient satisfaction was high in both groups, with a median (IQR) score on a 10 cm VAS of 10 (9–10) and 10 (10), in the unbuffered and buffered groups, respectively (p = 0.113).

QoL outcomes

There were significant improvements within both the unbuffered and buffered groups in the domains of physical functioning, role-physical, bodily pain, and social functioning (Figure 4). There were no significant intergroup differences in any of the SF36 domain scores between the unbuffered and buffered groups at any time point from baseline to 12 weeks.

Figure 4.

SF36 domain scores, unbuffered versus buffered tumescent anaesthesia, baseline to 12 weeks.

EQ5D utility index scores significantly improved in both groups over time (Figure 5); there were no significant intergroup differences.

Figure 5.

EQ5D utility index scores, unbuffered versus buffered tumescent anaesthesia, baseline to 12 weeks.

Intragroup analysis of AVVQ scores demonstrated significant improvement in both groups over time (Figure 6). There were no significant intergroup differences in AVVQ scores between the two groups at any time point.

Figure 6.

AVVQ scores, unbuffered versus buffered tumescent anaesthesia, baseline to 12 weeks.

Duplex ultrasound outcomes

All patients had successful eradication of reflux with occlusion of the treated GSV at one week, with no cases of recanalisation over the 12-week follow-up period.

Discussion

Tumescent anaesthesia is fundamental to the success of EVTA. The benefits of tumescent anaesthesia are related to its physical effects and the chemical properties of the constituents. Despite the significance of tumescent anaesthesia, there is very little evidence to guide selection of its constituents.

A Cochrane review of buffered lidocaine for intradermal injection found significantly reduced pain scores using a 10:1 ratio of lidocaine to 8.4% NaHCO₃. Our study is the first to test this concept within the practice of tumescent anaesthesia for EVTA.

This non-randomised study lends support to the practice of buffering of tumescent anaesthesia to reduce periprocedural pain. The significance of the difference in periprocedural pain scores between buffered and unbuffered tumescent anaesthesia in our study appears to be even greater than that reported in the Cochrane review, given that patients are receiving much larger volumes of perivenous tumescent anaesthesia over a more prolonged period of time. The Cochrane review also demonstrated that patients expressed a preference for buffered solutions, indicating that this difference in pain scores is clinically significant. The 30 mm difference in median periprocedural pain scores in this study is more than double that suggested to be clinically relevant.⁹

Pain during local anaesthetic (LA) infiltration is a common problem and can be sufficiently severe for patients to be dissatisfied and decline further laser ablation procedures.^10,11 The pain is predominantly due to the hydrogen ion concentration ((H⁺)) and acidic pH of the solution,¹² required to maintain a prolonged shelf-life. The data from the laboratory study demonstrate that ‘off-the-shelf’ 1% lidocaine with epinephrine has a pH of 4.38, and even when diluted to 0.1%, the solution remains significantly below physiological pH at 6.32.

Buffering lidocaine to a physiological pH using sodium bicarbonate was first reported in 1987,¹⁵ and has since become commonplace,^{13,15,16–20} with no reported associated complications, adverse events or drug precipitation. It does, however, remain an ‘off-license’ use of sodium bicarbonate.

A previous study¹³ found a pH of 4.46 for 1% lidocaine with 1:200,000 epinephrine, while buffering with 10:1 LA:8.4% sodium bicarbonate yielded a pH of 7.49. A Cochrane review¹⁴ reported the mean (SD) pH of 1% lidocaine buffered with 10:1 LA: 8.4% sodium bicarbonate was 7.3 (0.2). The manufacturers of the solutions used in these studies were different to those used in our study, but very similar pH results were observed for both the unbuffered and buffered solutions.

In addition to ameliorating the painful effects of an acidic pH, sodium bicarbonate also potentiates LA activity. It increases the proportion of the non-ionised, lipid-soluble, component, which more readily crosses neuron cell membranes, resulting in a quicker onset of action,^16–18 without affecting depth or duration of anaesthesia.¹³

The pH testing in this study was performed at a stable temperature corresponding to the ambient temperature (21℃) in the EVLA procedure room. The effect of temperature on pH is important. The pH of acidic solutions tends to increase with increasing temperature, while the opposite is true for alkali solutions, and neutral pH solutions tend to remain stable.¹⁹ Warmed anaesthetic solutions are thus less acidic and better tolerated.^21–23 Therefore, warming the tumescent solution to 37℃ may be an alternative to buffering; however, this would require a warming cabinet and advance tumescent preparation, which may not be practical or time efficient. Additionally, a warmed solution will cool, and any increased analgesic effects will consequently diminish with time. Furthermore, a cooler solution is potentially more protective against EVTA heat-induced tissue damage than warmer solutions.

The effect of tumescent solution temperature on outcomes after EVLA has been studied.

Pannier et al.²⁰ reported a randomised controlled trial (RCT) of cold (5℃) versus warmed (37℃) tumescent anaesthesia during 1470 nm EVLA. There were no differences between the groups in terms of postprocedural pain, as measured on a VAS of 0–4 up to day 10. Periprocedural pain was not assessed.

A recent in vitro study compared the vein perforation rates of 980 nm and 1470 nm wavelength lasers, using both room-temperature and cooled tumescent anesthesia.²⁴ There were significantly fewer vein perforations with both wavelengths using cold (4℃) tumescent in comparison to room temperature (24℃) tumescent. A subsequent RCT from the same unit,²⁵ using 1470 nm laser with a radial fibre, demonstrated a benefit of cold tumescent over a room temperature solution in terms of lower periprocedural and postproceduralpain. The authors also reported significantly fewer complications with cold tumescent, in terms of ecchymosis, induration and paraesthesia, but overall the warm complications reported appear significantly more prevalent than in our experience and the findings of a 2013 meta-analysis.²⁶ The tumescent solution comprised 500 ml 0.9% saline, containing 20 ml 0.5% bupivacaine, 1 ml 1:1000 epinephrine and 20 mEq sodium bicarbonate. The pH of the solutions was not reported. All patients underwent EVLA under intravenous midazolam sedation with oxygen supplementation, and so clearly the perioperative pain scores must be interpreted with this in mind. Patients underwent concomitant phlebectomy under separate local anaesthetic, the temperature and constituents of which were not reported. Extrapolation from the published data would suggest a mean of around 6 ml tumescent solution was infiltrated per cm of GSV, which is well below our target of 10 ml per cm.

It may be that more accurate titration of sodium bicarbonate at other specific temperatures reveals an even more optimal pH. In practical terms, however, the addition of 10 ml of sodium for every 1000 ml 0.1% Xylocaine with 1:2,000,000 epinephrine at room temperature is convenient given that this equates to one full vial per preparation. The cost of sodium bicarbonate is almost negligible²⁷ relative to the overall expense of an EVTA procedure.

The addition of epinephrine is highly advantageous in tumescent anaesthesia, particularly in the context of ambulatory phlebectomy. Epinephrine promotes vasoconstriction, reducing the incidence of postoperative bruising, haematoma and hyperpigmentation²⁸ and delays the absorption of local anaesthetic, thus prolonging its effects.

This was a pragmatic study designed to assess for any potential benefit in buffering of tumescent anaesthesia. The extent of ambulatory phlebectomy could not be controlled and was, therefore, not recorded; the aim was to treat all visible symptomatic varicosities, which were marked preoperatively with the patient standing and providing their input. Thus, there is potential for this procedure to act as a confounder for any peri- or postoperative pain, patient satisfaction and QoL. However, all included patients within the study were taken from routine NHS referrals without prejudice, and so there is no significant concern that the treatment groups were different or not representative of typical practice.

Conventionally, the maximum safe dosage of lidocaine with epinephrine for local injection is considered to be 7 mg kg⁻¹.²⁷ However, using the tumescent technique for liposuction, lidocaine doses of 35 mg kg⁻¹ were shown to be safe and effective,²⁹ and that dosages up to 55 mg kg⁻¹ can be used with minimal risk of lidocaine toxicity.³⁰ Objective clinical symptoms of lidocaine toxicity become apparent at plasma concentrations above 5 µg ml⁻¹.³¹ The peak plasma concentration of lidocaine after tumescent anaesthesia for liposuction has been demonstrated to be between 8 and 12 h after infusion. In a liposuction study where the mean (SD) dose of lidocaine was 33.2 (1.8) mg kg⁻¹,³² the maximum peak plasma concentration was 3.3 µg ml⁻¹. The dosage of lidocaine delivered to patients in our study was well below those values, ranging from 3.51 to 15.63 mg kg⁻¹. Similar data within the context of tumescent anaesthesia for EVTA are sparse. In a recent study,³³ administration of 3.57 to 10.7 mg kg⁻¹ of lidocaine in an EVLA tumescent solution (0.1% lidocaine without epinephrine, buffered with 25 mg sodium bicarbonate) resulted in peak lidocaine concentrations <1.8 µg ml⁻¹ at 60–120 min postadministration.

The target volume of tumescent infiltration in our practice is 10 ml per cm of GSV to be ablated, paying particular attention to the SFJ and proximal GSV, with an additional volume of typically 200 ml for ambulatory phlebectomy. Infiltration of this volume of fluid gives good ‘tumescence’ of the tissues, with a characteristic peu d’orange appearance of the skin. The very dilute nature of lidocaine in the tumescent solution, the relatively avascular compartment into which it is infiltrated (particularly given that the axial vein will be ablated), the vasoconstrictive effect of epinephrine, the high lipid solubility of lidocaine and its strong binding affinity to adipose tissue surrounding the superficial axial veins, and the vascular compression due to tissue tumescence all combine to delay systemic uptake of lidocaine.^21–23

Infiltration in EVTA is performed in two stages; firstly for the axial perivenous tumescence, followed approximately 5–10 min later by infiltration for ambulatory phlebectomy. This will further reduce the overall peak plasma concentration as the full LA dose is not administered in a single bolus.

Lidocaine is rapidly and efficiently eliminated through hepatic metabolism via the cytochrome P450 enzyme CYP3A4,³⁴ hence a degree of caution should be taken when considering very large volumes of this tumescent anaesthetic solution in patients who are taking known inhibitors of CYP3A4, or who have known significant liver disease.

Conclusions

The precise details of tumescent anaesthesia in EVTA have generally been poorly reported. This is the first study to investigate the pH of a tumescent anaesthetic solution, to define an optimal pH solution, and to assess its impact on periprocedural pain scores in the context of EVTA. We have shown that buffering tumescent anaesthesia results in lower perioperative pain scores. The pH results and clinical pain scores from this paper may not be generalisable to non-lidocaine based LA formulations, solutions at different temperatures or with different constituents.

The data on tumescent anaesthesia from our work, coupled with specific knowledge of the pharmacokinetics lend strong support to a policy of more accurate and open reporting of the technique used in future studies, such as the constituents of tumescent anaesthesia, use of buffering and corresponding pH, volumes infiltrated and temperature of the solution in order that studies can be compared.

While a small improvement in periprocedural pain may not in itself result in a significant QoL advantage, it is conceivable that as part of a wider picture of technique refinement and evolution, short-term QoL may benefit. Randomised clinical trials of technique modifications are required to ascertain the optimal procedure for improved patient outcomes.

Footnotes

Acknowledgements

We would like to thank Josie Hatfield for her assistance with study organisation and patient follow-up, and the Biochemistry department, Hull Royal Infirmary, for advice and assistance on pH analyses.

Declaration of Conflicting Interests

The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This research was funded by internal departmental funding.

Ethical approval

The study was conducted in accordance with principles laid down in the declaration of Helsinki, International Conference for Harmonisation of Good Clinical Practice guidelines, and the Research Governance Framework for Health and Social Care. All investigators associated with the study have undertaken Good Clinical Practice (GCP) training. The appropriate ethical and institutional R&D approvals were secured.

Guarantor

TW.

Contributorship

TW and ICC conceived the study. TW, NS and SN were involved in protocol development, gaining approvals, and acquisition of data through patient recruitment and follow-up. TW, CL and DC analysed the data. TW, CL and DC wrote the manuscript. TW, CL, SN, NS, DC and ICC all reviewed and edited the manuscript and approved the final version.

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