Introduction

Chronic rhinosinusitis is a common ENT disease in adults. Mean overall incidence of chronic rhinosinusitis is 11.61 ± 5.47% [1]. Functional endoscopic sinus surgery (FESS) is a gold standard for the treatment of chronic rhinosinusitis [2, 3]. These procedures are currently effective and safe. However, certain complications including damage to the optic nerve, dura mater with subsequent meningitis and severe blood loss following injury of the great vessels can occur [4]. Considering the features of FESS, even mild bleeding in small nasal cavity and paranasal sinuses can significantly complicate visualization of anatomical structures and surgery per se [2].

There are various approaches to reduce intraoperative bleeding [5 — 8]. Controlled hypotension can significantly reduce intensity of bleeding. However, there are medical and technical limitations. Contraindications for significant decrease of intraoperative blood pressure are coronary artery disease, atherosclerosis, diabetes mellitus, advanced age and some other comorbidities. Hemostatic agents are ineffective and even contraindicated in some cases of significant damage to tissues and vessels, as well as extended surgery [2, 8, 9]. Some authors reported that intraoperative intravenous administration of lidocaine reduces the doses of narcotic analgesics and general anesthetics [10, 11], intensity of bleeding and improves visualization during sinus surgery [5, 7]. Some studies demonstrate that anti-inflammatory effect [12, 13] and vasoconstriction underlie lidocaine-induced decrease of intensity of bleeding. These effects depend on serum concentration of the drug [14].

Maximum lidocaine infusion rate is 300 mg/hour [15] and limited by serum concentration 5 µg/L [16]. Lidocaine has a biphasic effect on smooth muscles and peripheral blood vessels. Vasoconstriction occurs at low serum concentrations while vasodilation is a result of high serum concentration [10, 14]. Serum concentration of lidocaine over 6-8 µg/L is toxic and can cause such side effects as psychomotor agitation, general weakness, blood pressure decrease, seizures, coma, collapse, atrioventricular blockade, respiratory arrest and others [15, 16]. Efficacy and safety of intravenous lidocaine in FESS is not well understood, and further research is required.

The purpose of the study was to evaluate the effectiveness of intravenous lidocaine for reducing the intensity of intraoperative bleeding in functional endoscopic sinus surgery.

Material and methods

A prospective randomized cohort single-center study included 76 FESS procedures under general anesthesia and mechanical ventilation. The study was performed at the Pavlov First Saint Petersburg State Medical University. Our research complies with international and ethical standards set out in the Declaration of Helsinki of the World Medical Association "Recommendations guiding physicians in biomedical research involving human subjects". Local ethics committee approved the study. All patients signed an informed consent. Elective surgical interventions were performed after standard previous examination.

Inclusion criteria: age over 18 years, lesion of nasal cavity and/or paranasal sinuses eligible for minimally invasive surgery, no coagulation abnormalities and uncontrolled arterial hypertension. Exclusion criteria: uncontrolled hypertension, severe coronary artery disease with frequent pain attacks, severe widespread atherosclerosis, previous allergic reactions to local anesthetics, anticoagulant or antiplatelet agent intake, clinical and laboratory data on coagulation abnormalities, systemic diseases accompanied by vascular diseases (vasculitis, Wegener's granulomatosis and others).

All patients underwent general anesthesia with invasive mechanical ventilation. Patients were randomized into 2 groups: no intraoperative intravenous administration of lidocaine (NL) (n=40); intraoperative intravenous infusion of lidocaine (L) (n=36) via a syringe pump to reduce intensity of intraoperative bleeding. In the NL group, saline was injected through a syringe pump instead of lidocaine. In this group, we reduced intensity of intraoperative bleeding via decrease of mean blood pressure (MBP) (controlled hypotension) using the components of general anesthesia (increase of minimum alveolar concentration (MAC) and dose of fentanyl).

The same surgeon performed all interventions and assessed intensity of intraoperative bleeding every 5 minutes using a 6-point Fromme-Boezaart Scale (Table 1) [6]. Surgeon was not informed about intravenous injection of lidocaine.

Table 1. Scale for assessing the bleeding in surgical site

In both groups, we performed premedication with fentanyl 0.002-0.003 mg/kg and, if necessary, atropine 0.005 mg/kg. Anesthesia was induced with propofol 2-3 mg/kg. Muscle relaxation required injection of rocuronium bromide 0.4-0.6 mg/kg. After insertion of laryngeal mask (LMA Classic), mechanical ventilation was started with a tidal volume of 6-8 ml/kg with control of exhaled carbon dioxide at a minimum fresh gas flow of 0.5-1 l/min. Anesthesia was maintained with desflurane (4-12 vol%) up to minimum alveolar concentration of 0.8-1.4. Additional bolus doses of fentanyl (50-100 μg) were administered intravenously depending on stages of surgery. At the beginning of surgery, we performed infiltration anesthesia of nasal cavity using a standard solution of articaine hydrochloride with epinephrine hydrochloride 1:100,000 (3.4 ml).

In the L group, we injected bolus of lidocaine IV 1-1.5 mg/kg at a rate of 1 mg/s prior to the main surgical stage and then used infusion through a syringe pump (1-2 mg/kg/hour) considering surgical trauma and hemodynamic reactions (not more than 300 mg/min). In the NL group, saline was administered instead of lidocaine according to the same scheme.

Intraoperative monitoring included the following parameters: heart rate (HR), non-invasive blood pressure with registration of MBP, electrocardiography (ECG), pulse oximetry (SpO₂) and MAC. Venous blood sampling was intraoperatively performed to quantify lidocaine at three points: 1) after intravenous bolus injection; 2) after 15 minutes; 3) after 60 minutes of microfluidic injection through a syringe pump. After awakening, we assessed patient condition using a 10-point Aldrete scale (post anesthetic recovery score, PARS) [17]. Postoperative monitoring lasted for at least 2 hours with control of heart rate, non-invasive blood pressure, ECG and SpO₂. Statistical analysis was performed using the StatTech v. 2.2.0 software (Stattech LLC, Russia). Intensity of bleeding, MBP, MAC and dose of fentanyl were assessed after 10, 30 and 60 minutes.

Results and discussion

Distribution of patients depending on gender (p=0.235), age and BMI was similar in both groups. Surgery time, severity of polyposis according to Friedman scale and number of septum-surgeries were similar in both groups (Table 2).

Table 2. Characteristics of patients in the study groups

Note. * — significant differences (p <0.05); NL — group without lidocaine; L — group with lidocaine; M — arithmetic mean; SD — standard deviation; 95% CI — 95% confidence interval; Me — median; Q1 — Q3 — upper and lower quartiles; n — number of patients, PARS — Aldrete scale.

Awakening time and PARS score were significantly higher in the L group, since intraoperative infusion of lidocaine provides effective long-term pain relief in postoperative period [11] and decreases reflexes from upper respiratory tract [10]. It is also known that high serum concentrations of lidocaine (> 15 µg/ml) can cause delayed awakening [18]. Mean concentration of lidocaine did not exceed the upper limit (Table 3).

Table 3. Intraoperative concentrations of lidocaine

Note. M — arithmetic mean; SD — standard deviation; 95% CI — 95% confidence interval; n — number of patients.

Concentrations of lidocaine chosen by us for intravenous bolus and subsequent infusion are not accompanied by excess of permissible serum concentrations and toxic effect of lidocaine (excitation, agitation, perioral paresthesia, visual impairment and other more severe symptoms) in intraoperative and postoperative periods. Statistical analysis of bleeding intensity was performed after 10, 30 and 60 minutes of surgery (Table 4).

Table 4. Intensity of intraoperative bleeding at various stages of surgery

Note. * — significant differences (p <0.05); p_30-10 — differences after 30 and 10 minutes; p_60-10 — differences after 60 and 10 minutes.

In the L group, intensity of bleeding was significantly lower after 10, 30 and 60 minutes compared to another group. Injection of lidocaine was characterized by similar intensity of bleeding throughout the entire surgery. At the same time, intensity of bleeding after 30 and 60 minutes was significantly higher compared to the 10^th minute in the NL group. Thus, mild-to-moderate bleeding persisted throughout the entire surgery in the L group while bleeding became significantly more intense after 30 and 60 minutes in the NL group.

Fromme-Boezaart score 1 bleeding can be considered optimal for FESS, since even minor bleeding in a small space of nasal cavity impairs visibility and worsens surgical conditions [2, 5]. To assess the optimal surgical conditions, we additionally identified 2 groups depending on bleeding intensity: 1) mild bleeding (1 score), 2) moderate-to-severe bleeding (2-4 scores). The odds ratio of moderate-to-severe bleeding was significantly lower after 10, 30 and 60 minutes in the L group compared to the NL group: almost by 10 times after 10 minutes (OR 0.10; 95% CI 0.04–0.30), 4.3 times after 30 minutes (OR 0.23; 95% CI 0.09 — 0.61), 7.7 times after 60 minutes (OR 0.13; 95% CI 0.04 — 0.37) (Fig. 1).

Fig. 1. Bleeding intensity in both groups after 10, 30 and 60 minutes.

We also analyzed MBP for a complete assessment of the factors influencing bleeding intensity (Table 5).

Table 5. Mean blood pressure in both groups at various stages of surgery

Note. MBP — mean blood pressure; * — significant differences (p <0.05); Me — median; Q₁ — Q₃ — upper and lower quartiles.

MBP after 10 minutes was similar in both groups and slightly higher after 30 and 60 minutes in the L group. We observed stable MBP throughout the intervention in both groups (median 69 — 74.67 mm Hg). Some authors believe that intraoperative MBP 60-70 mm Hg provides favorable visualization of surgical field [19]. However, other authors consider decrease of MBP up to 50 mm Hg [20]. In our sample, general anesthesia was quite safe, since significant decrease of MBP has disadvantages including the risk of brain, myocardial and retinal ischemia, as well as renal perfusion impairment despite less intense bleeding [10].

We analyzed MAC after 10, 30 and 60 minutes of surgery (Fig. 2). There were significant between-group differences after 30 and 60 minutes (p <0.001). Lower MAC in the L group is due to potentiation of effects of general anesthetics by intravenous lidocaine. Intraoperative adjustment of MAC was performed individually for each patient depending on MBP, bleeding intensity, comorbidities and other factors. Inhalation anesthetics in high concentrations influence smooth muscles of vascular wall and can cause vasodilation of peripheral and cerebral vessels [21]. Therefore, bleeding may be intensified. MAC over 1.4 enhanced bleeding due to vasoplegia and peripheral blood flow intensification.

Fig. 2. MAC parameters in both groups after 10, 30 and 60 minutes.

We also assessed total intraoperative dose of fentanyl after 10, 30 and 60 minutes (Fig. 3). Statistical analysis revealed significant between-group differences (362.5 µg [337.5; 400] in the L group and 500 µg [500; 550] in the NL group, p<0.001). Some authors demonstrate that intravenous lidocaine can be used as co-analgesic [22]. Mechanisms of systemic analgesic effect of intravenous lidocaine in perioperative period are still unclear and unlikely to be based solely on the well-known effect of sodium channel blockade [23, 24]. Inhibition of N-methyl-D-aspartate receptors seems to be the main trigger for antihyperalgesic effect [25]. Intravenous infusion of lidocaine may also have an analgesic effect at the cerebral level [26]. Less total intraoperative dose of fentanyl through the use of intravenous lidocaine can reduce the risk of side effects of narcotic analgesics.

Fig. 3. Intraoperative dose of fentanyl in both groups.

Conclusions

1. Intravenous administration of lidocaine is favorable for visualization of surgical field in FESS.

2. Intravenous infusion of lidocaine 1-2 mg/kg/hour is not accompanied by excess of permissible serum concentrations and provides safe surgical intervention.

3. The applied doses of lidocaine made it possible to use lower MAC and doses of fentanyl, ensured stable intraoperative mean blood pressure and favorable visualization of surgical field.

The authors declare no conflicts of interest.