This study assessed the effect of a single bolus administration of lidocaine on the prevention of tourniquet-induced hypertension (TIH) and compared the effect of lidocaine to that of ketamine in patients undergoing general anesthesia.
This randomized, controlled, double-blind study included 75 patients who underwent lower limb surgery using a tourniquet. The patients were administered lidocaine (1.5 mg/kg, n = 25), ketamine (0.2 mg/kg, n = 25) or placebo (n = 25). The study drugs were administered intravenously 10 min before tourniquet inflation. Systolic blood pressure (SBP), diastolic blood pressure (DBP), and heart rate (HR) were measured before tourniquet inflation, after tourniquet inflation for 60 min at 10 min intervals, and immediately after tourniquet deflation. The incidence of TIH, defined as an increase of 30% or more in SBP or DBP during tourniquet inflation, was also recorded.
SBP, DBP, and HR increased significantly over time in the control group compared to those in the lidocaine and ketamine groups for 60 min after tourniquet inflation (P < 0.001, P < 0.001, and P = 0.007, respectively). The incidence of TIH was significantly lower in the lidocaine (n = 4, 16%) and ketamine (n = 3, 12%) group than in the control group (n = 14, 56%) (P = 0.001).
Single-bolus lidocaine effectively attenuated blood pressure increase due to tourniquet inflation, with an effect comparable to that of bolus ketamine.
Arterial tourniquets are widely used in the operative field to prevent bleeding during surgery [
Although the mechanism of TIH development remains unclear, its onset is considered to be associated with the activation of C fibers that cause N-methyl-D-aspartate (NMDA) receptor activation associated with the central sensitization mechanism [
Lidocaine is a local anesthetic with well-known anti-inflammatory and analgesic properties [
However, whether a bolus administration of lidocaine without a continuous infusion can prevent TIH development in patients undergoing lower limb surgery remains unknown. Accordingly, we hypothesized that a bolus administration of lidocaine would also be effective in preventing TIH. To confirm this hypothesis, we investigated whether a bolus administration of lidocaine before tourniquet inflation could reduce the incidence of TIH in patients undergoing lower limb surgery under general anesthesia. Additionally, we compared the effect of bolus lidocaine on TIH prevention to that of bolus ketamine.
The protocol for this randomized, double-blind, prospective study was reviewed and approved by the Institutional Review Board (no. UUHIRB-2019-01-015) and written informed consent was obtained from all study participants.
The study included 75 patients aged 18–75 years, with American Society of Anesthesiologists physical status grade I or II who underwent lower limb surgery using a tourniquet under general anesthesia. Patients with a medical history of ischemic heart disease, peripheral vascular disease, deep vein thrombosis, or a history of allergic reactions or seizures triggered by local anesthetics were excluded from this study.
Patients were randomly assigned to one of three groups (lidocaine, ketamine, and control; allocation ratio 1:1:1) using a random number table generated by online randomization software (
No preoperative medications were administered to any patient. After entering the operating room, the patients were administered 5 ml/kg lactated Ringer’s solution before anesthesia induction, and patient monitoring was initiated by attaching a basic monitor (electrocardiogram, pulse oximeter, noninvasive blood pressure [NIBP]). Invasive blood pressure monitoring was applied for patients aged ≥ 65 years, and the bispectral index (BIS; BIS VISTA™ monitor, Aspect Medical Systems, USA) was monitored to assess the adequacy of anesthetic depth during surgery. Tracheal intubation was performed with propofol (2 mg/kg), rocuronium (0.8 mg/kg), or remifentanil (1 μg/kg). The patients were ventilated in volume control mode with a tidal volume of 7 ml/kg, positive end-expiratory pressure of 6 cmH2O, and fraction of inspired oxygen of 0.5. The respiratory rate was controlled to maintain an end-tidal CO2 pressure of 35–40 mmHg. After inducing anesthesia, remifentanil was continuously administered, along with 1.5–2.5% sevoflurane. The sevoflurane concentration was adjusted to maintain a BIS value between 40 and 60. After tracheal intubation, the dose of remifentanil was maintained at 0.05 μg/kg/min. When the SBP changed by more than 10% from that measured before anesthesia induction, the dose of remifentanil was increased or decreased by 0.03 μg/kg/min. If the SBP increased to > 180 mmHg, 300 μg nicardipine was administered intravenously. A tourniquet (20 cm wide) was placed on the upper thigh of the surgical side and inflated to 300 mmHg after the lower limb was lifted to an angle of 45° for 5 min.
The anesthesiologists who participated in anesthesia management, the orthopedic surgeons, and the patients were all blinded to patient allocation. Another anesthesiologist, who did not participate in the patient's anesthesia, was given a group of randomly assigned patients through sealed opaque envelopes and prepared the “study drug”. All syringes used in the study were the same and were labeled as “study drug”. The anesthesiologist who participated in each patient's anesthesia management recorded the following values: the incidence of TIH, defined as an SBP or DBP increase ≥ 30% of the baseline value; SBP, DBP, and heart rate (HR) measured before tourniquet inflation (baseline value), after tourniquet inflation for 60 min at 10-min intervals, and immediately after tourniquet deflation; duration of anesthesia, surgery, tourniquet inflation; total dose of remifentanil administered during anesthesia; number of patients nicardipine administration during anesthesia; number of patients receiving fentanyl administration in the post-anesthesia care unit (PACU). The numerical rating scale (NRS, 0–10) score was measured immediately after transfer to the PACU and after 20 min, and again 24 h after surgery.
The administration of all anesthetics was discontinued at the conclusion of surgery. For neuromuscular block reversal, glycopyrrolate (0.008 mg/kg) and pyridostigmine (0.1 mg/kg) were administrated. After confirming proper neuromuscular recovery, the patients were extubated and transferred to the PACU.
This study aimed to determine whether a single IV dose of lidocaine (1.5 mg/kg) could prevent an increase in blood pressure caused by tourniquet inflation and to compare the single IV dose of lidocaine to that of ketamine, which is already known for its preventive effects. Satsumae et al. [
IBM SPSS Statistics for Windows, version 25.0 (IBM Corp., USA) was used to perform all the statistical analyses. For continuous variables, we used Kolmogorov-Smirnov tests to evaluate the distributions for normality. Normally distributed variables are expressed as means and standard deviations. Continuous variables with normal distribution were compared between the three groups using one-way Analyses of variance (ANOVA) with Tukey’s post-hoc tests. Continuous variables including SBP, DBP, and HR were analyzed using repeated-measures ANOVA with Bonferroni's post-tests to determine intra-group comparisons over time. For repeated measures ANOVA models, sphericity was assessed by Mauchly test and Greenhouse–Geisser correction was applied when required. Categorical variables (such as the incidence of TIH, nicardipine administration during anesthesia, and fentanyl administration in the PACU) were analyzed by chi-square or Fisher's exact tests, as applicable. Categorical data were expressed as numbers or percentages.
Statistical significance was set at P < 0.05, except for pairwise between-group comparisons. For the problem of multiple comparisons (each group versus each other group = 3 comparisons), a Bonferroni-corrected significance level of 0.05/3 = 0.017 was used. We have showed Bonferroni-corrected P values.
While 82 patients were considered eligible, seven patients declined to participate in this study. Thus, a total of 75 patients were randomized, with each group including 25 patients (
TIH was observed in 14 of 25 patients (56%) in the control group, occurring significantly more often compared to the lidocaine (four patients, 16%) and ketamine (three patients, 12%) groups (P = 0.001) (
There was a significant interaction between the three groups over time in SBP and DBP (all P < 0.001) (
During tourniquet inflation, changes in HR between the three groups also showed a significant interaction with time (P = 0.007) (
As shown in
The results of this study demonstrated that the bolus administration of 1.5 mg/kg lidocaine 10 min before tourniquet inflation prevented an increase in blood pressure caused by tourniquet inflation in patients undergoing general anesthesia, an effect similar to that for single 0.2 mg/kg dose of ketamine.
After 30–60 min of tourniquet inflation, patients may develop an increase in SBP and HR that persists until tourniquet deflation, a phenomenon known as 'tourniquet pain'. An increase in blood pressure due to tourniquet application may occur despite an adequate depth of anesthesia [
The present study compared a single bolus of lidocaine to that of ketamine, which is known for its TIH-preventing effect. Several studies have assessed the effect of preventing TIH using ketamine, an NHDA receptor antagonist. Satsumae et al. reported that preoperative IV ketamine (0.25 mg/kg or more) significantly prevented tourniquet-induced systemic arterial pressure increase in patients under general anesthesia [
Patients treated with lidocaine and ketamine had a lower NRS score 24 h after surgery compared to the score in patients receiving normal saline. Several studies have suggested that lidocaine and ketamine have beneficial preemptive analgesic effects in patients undergoing surgery [
In our study, anesthesia was maintained using sevoflurane, an inhalation anesthetic, and remifentanil, a synthetic opioid. Remifentanil is believed to contribute to hemodynamic stabilization by preventing the release of stress hormones when patients are exposed to stressful situations during surgery [
This study has several limitations. First, as mentioned before, the amount of analgesic, including patient-controlled analgesia (PCA), used for 24 h after surgery was not measured; therefore, it was not possible to assess the difference in NRS scores between the three groups 24 h after surgery. Second, the infusion rate of remifentanil was adjusted by increasing or decreasing according to the changes in the patient blood pressure after the induction of anesthesia. During the design process of this study, we thought that the adjustment of the infusion rate of remifentanil according to changes in patient blood pressure was commonly performed in actual clinical practice, and this was reflected in this study. However, considering the pure effect of lidocaine or ketamine on SBP, which we wanted to evaluate in this study, this could be a limitation of this study. Since this study aimed to evaluate the changes in blood pressure during surgery, it is important to measure blood pressure in the same way for all patients regardless of age. However, we measured blood pressure with NIBP if a patient’s age was under 65 and conducted invasive blood pressure measurement if a patient’s age was over 65 in this study. The use of different BP measurement methods depending on the patient's age may be another limitation of this study.
In conclusion, the bolus administration of lidocaine (1.5 mg/kg) 10 min before tourniquet inflation reduced the incidence of TIH and postoperative pain, with a reduction comparable to that of bolus ketamine in patients undergoing lower limb surgery under general anesthesia.
None.
No potential conflict of interest relevant to this article was reported.
The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.
Conceptualization: Ji WooK Kim, A Ran Lee, Ju Deok Kim. Data curation: A Ran Lee. Formal analysis: Ji WooK Kim, Ju Deok Kim. Methodology: Dong Hee Kang. Project administration: Eun Sun Park, Min Su Yun, Sung Won Ryu, Uk Gwan Kim, Dong Hee Kang. Visualization: Min Su Yun, Sung Won Ryu, Uk Gwan Kim. Writing - original draft: Ji WooK Kim, A Ran Lee. Writing - review & editing: Ju Deok Kim. Investigation: A Ran Lee, Eun Sun Park. Resources: Sung Won Ryu, Uk Gwan Kim. Supervision: Dong Hee Kang, Ju Deok Kim.
Flowchart of the study participants.
Changes in blood pressure in the three groups during anesthesia. (A) Systolic blood pressure (SBP), (B) diastolic blood pressure (DBP). There was a significant interaction between the three groups over time in SBP and DBP by repeated-measures analysis of variance and Bonferroni post-hoc test (all P < 0.001). T0: immediately before tourniquet inflation, T10–T60: every 10 min after tourniquet inflation, respectively, Toff: after tourniquet deflation. *P < 0.05 compared to the ketamine group. †P < 0.05 compared to the ketamine and lidocaine groups.
Changes in heart rate (HR) in the three groups during anesthesia. There was a significant interaction in HR between the three groups over time by repeated-measures analysis of variance and Bonferroni post-hoc test (P < 0.001). T0: immediately before tourniquet inflation, T10–T60: every 10 min after tourniquet inflation, respectively, Toff: after tourniquet deflation.*P < 0.05 compared to the ketamine group.
Patient and Operation Data
Variable | Lidocaine group (n = 25) | Ketamine group (n = 25) | Control group (n = 25) | P value |
---|---|---|---|---|
Sex (M/F) | 9/16 | 6/19 | 8/17 | 0.654 |
Age (yr) | 55.2 ± 23.2 | 57.9 ± 20.0 | 56.9 ± 22.1 | 0.905 |
Height (cm) | 159.9 ± 13.4 | 158.0 ± 11.0 | 157.7 ± 12.6 | 0.789 |
Weight (kg) | 69.2 ± 11.4 | 65.5 ± 11.9 | 64.1 ± 9.2 | 0.245 |
Duration of surgery (min) | 83.0 ± 10.4 | 82.2 ± 10.0 | 87.4 ± 14.5 | 0.253 |
Duration of anesthesia (min) | 143.6 ± 22.0 | 142.0 ± 2.5 | 146.0 ± 20.9 | 0.809 |
Duration of tourniquet inflation (min) | 67.8 ± 4.6 | 66.8 ± 4.5 | 67.8 ± 4.1 | 0.653 |
Types of surgery | 0.607 | |||
TKRA | 15 | 15 | 14 | |
Arthroscopy evaluation | 1 | 4 | 4 | |
ACL reconstruction | 5 | 2 | 5 | |
Other | 4 | 4 | 2 |
Values are presented as number or mean ± SD. TKRA: total knee replacement arthroplasty, ACL: anterior cruciate ligament.
Intraoperative and Postoperative Data
Variable | Lidocaine group (n = 25) | Ketamine group (n = 25) | Control group (n = 25) | P value |
---|---|---|---|---|
Incidence of TIH | 4 (16) | 3 (12) | 14 (56) |
< 0.001 |
Total dose of remifentanil (μg) | 365.2 ± 92.4 | 347.3 ± 129.1 | 622.2 ± 109.0 |
< 0.001 |
Nicardipine administration during anesthesia | 1 (4) | 0 (0) | 4 (16) | 0.119 |
Fentanyl administration in the PACU | 18 (72) | 19 (76) | 16 (64) | 0.734 |
NRS immediately after entering the PACU | 6.1 ± 1.5 | 6.2 ± 1.3 | 6.1 ± 1.1 | 0.970 |
NRS after 20 min in the PACU | 3.9 ± 1.0 | 3.6 ± 0.8 | 5.0 ± 0.6 |
< 0.001 |
NRS 24 hours after the operation | 4.0 ± 0.8 | 4.1 ± 0.9 | 5.8 ± 1.1 |
< 0.001 |
Values are expressed as number (%) or mean ± SD. TIH: tourniquet-induced hypertension, NRS: numerical rating scale, PACU: post-anesthesia care unit.
Compared with lidocaine and ketamine groups.