Effect of intravenous lidocaine infusion on postoperative pain and inflammatory factors in patients undergoing thoracic surgery

doi:10.21203/rs.3.rs-5267125/v1

Objective

To observe the effects of intravenous lidocaine infusion on postoperative pain and inflammatory factors in patients undergoing thoracic surgery.

Methods 120 patients undergoing thoracoscopic lobectomy were randomly divided into groups A, B and C, with 40 cases in each group. Group A received intravenous lidocaine 1.0 mg/kg during anesthesia induction, continued to pump lidocaine 1.5 mg/kg•h during the operation until the end of the operation, and continued to pump lidocaine 0.2 mg/kg•h after surgery until 48 hours after surgery; Group B received intravenous lidocaine 1.0 mg/kg during induction of anesthesia and continued to pump lidocaine 1.5 mg/kg•h during operation until the end of operation; Group C was given equal volume of normal saline. VAS pain scores were recorded after extubation, 30 min after extubation, when leaving PACU, 24 h after surgery and 48 h after surgery. Coughing during extubation, postoperative nausea and vomiting, additional postoperative analgesics, number of analgesic pump compressions, first time to exhaust gas, first time to get out of bed, length of hospital stay and postoperative QoR15 score were measured. Serum levels of procalcitonin and IL-6 were measured by intravenous blood samples before and 48 h after operation.

Results Compared with group C, VAS scores in group A and group B were significantly decreased 30min after extubation, after leaving PACU, 24h and 48h after surgery (P < 0.017). The incidence of coughing during extubation was decreased (P < 0.05), the first time of getting out of bed was significantly shortened (P < 0.017), the levels of procalcitonin and IL-6 were significantly decreased 24h after extubation (P < 0.017), and the score of QoR15 was significantly increased (P < 0.017). There were no significant differences in VAS score after extubation, incidence of postoperative nausea and vomiting, additional analgesic drugs and the number of analgesic pump compression, first postoperative exhaust time and postoperative hospital stay among three groups (P > 0.05).

Conclusion

Intravenous infusion of lidocaine can effectively relieve postoperative pain and reduce the level of postoperative inflammatory factors in patients undergoing thoracic surgery.

Trial registration Chinese Clinical Trial Registry, ChiCTR2300078858, 20/12/2023.

Lidocaine

Thoracic surgery

Postoperative pain

Inflammatory factors

Trauma and stress caused by surgery often lead to acute postoperative pain, seriously affect the prognosis of patients, increase the incidence of postoperative complications and prolong^[1] hospital stay. In various types of surgery, the pain of thoracic surgery is more intense. Opioids are commonly used as analgesic drugs at present, but they have adverse reactions such as respiratory depression and affect the recovery of gastrointestinal function. With the development of the concept of enhanced recovery after surgery (ERAS), perioperative multimodal analgesia and the reduction of opioid use have become a widespread consensus. ^[2-5]Lidocaine, as an amide local anesthetic, is commonly used for local anesthesia and anti-arrhythmic use. Numerous studies have shown that continuous intraoperative infusion of lidocaine can effectively relieve postoperative pain after laparoscopic surgery. However^[6-7], the optimal infusion strategy of lidocaine and its analgesic effect in thoracic surgery remain unclear. In this study, patients undergoing thoracoscopic surgery were selected as the study objects to explore the effects of intraoperative lidocaine infusion on postoperative pain and inflammatory factors of patients, so as to provide clinical reference.

General information This study was a randomized, double-blind, controlled clinical trial approved by the hospital ethics committee and with the informed consent of the patients. This study was approved by the Ethics Committee of the Nanjing Gaochun People's Hospital (IRB 2023-107-01) and registered with the Chinese Clinical Trials Registry prior to patient enrollment (ChiCTR2300078858, 20/12/2023). Written informed consent was obtained from all patients. Inclusion criteria: 120 patients with elective thoracoscopic lobectomy, male or female, aged 18-75 years old, ASA grade I-III, liver and kidney function basically normal. Exclusion criteria: Patients with a history of chronic pain and use of related drugs before surgery, changes in surgical modalities (including only wedge resection of lung lobectomy or intraoperative thoracotomy), history of related drug allergies, pre-existing arrhythmias, serious cardiac or mental diseases, liver and kidney dysfunction before surgery, and refused to participate in the trial. A total of 120 patients were randomly divided into group A, group B and group C according to numerical table method, with 40 patients in each group.

Methods Intravenous access was opened after admission. NIBP, ECG and SpO₂ were routinely monitored. Hydroxyethyl starch solution was pre-injected with 5mL/kg, radial artery puncture was performed under local anesthesia, and invasive arterial pressure was monitored. Induction of anesthesia: Intravenous injection of midazolam 0.05mg /kg, sufentanil 0.3-0.5ug /kg, cisatracuramide benzoate 0.2mg /kg, etomidate 0.3mg/kg. After the patient's consciousness disappeared and the muscle relaxation was satisfied, a suitable double-lumen tracheal catheter was selected for bronchial intubation according to the measurement of trachea diameter in chest CT. After intubation, fiberoptic bronchoscope was used to locate the double-lumen tube. Anesthesia maintenance: Propofol 4~12 mg/kg·h and remifentanil 0.05~0.15 μg/kg·min were pumped continuously during the operation. The dosage was adjusted according to intraoperative hemodynamic parameters and anesthesia depth. The fluctuation ranges of MAP and heart rate were less than ±20% of the basic values, and the Narcotrend index was maintained at 40~60. Cisatracurium benzenesulfonate was added as needed. In group A, 1.0 mg/kg lidocaine was injected intravenously during anesthesia induction, 1.5 mg/kg•h lidocaine was pumped continuously during the operation until the end of the operation, 0.2 mg/kg•h lidocaine was pumped continuously after the operation until 48 hours after the operation; Group B received intravenous lidocaine 1.0 mg/kg during induction of anesthesia and continued to pump lidocaine 1.5 mg/kg•h during operation until the end of operation; Group C was given equal volume of normal saline. Propofol and remifentanil were stopped at the end of the operation. After the patient was awake and the muscle strength recovered, the tracheal catheter was removed, and the Aldrete recovery score was > 9. Formula of postoperative analgesic pump: Sufentanil 100ug+ normal saline to 100ml. All patients were given a load dose of 5ml, a background infusion of 2ml /h, an additional dose of 2ml, and a locking time of 10 min. The goal of pain management was to ensure that patients had a postoperative NRS score of < 3.

VAS pain scores after extubation, 30 min after extubation, 24 h after surgery, and 48 h after surgery were recorded by an unknown anesthesiologist, as well as postoperative nausea and vomiting, first time to exhaust gas, first time to get out of bed, and postoperative length of hospital stay. At the same time, 15⁃item Quality of Recovery Score (QOR-15 scale) was used to evaluate the patients' postoperative recovery at 24h after surgery. 5 mL of venous blood samples were collected before surgery and 48 h after surgery and divided into blood collection tubes. Serum levels of procalcitonin and IL-6 were measured.

Statistical analysis was performed by SPSS 24.0 statistical software. The measurement data of normal distribution were expressed as mean ± standard deviation (x±s), and one-way analysis of variance was used for comparison between groups. The measurement data of non-normal distribution were expressed by M (Q1, Q3), and the comparison between groups was performed by non-parametric test. Counting data were represented by the number of cases (percentage), χ-test or Fisher exact probability method were² used for comparison between groups, and the difference was statistically significant at P < 0.05. If the difference was statistically significant, SNK method was used for pairwise comparison, combined with the joint probability for segmentation, and the test level was reduced to 0.05/3, that is, P < 0.017 was statistically significant.

In this study, 120 patients were initially included, one case was excluded due to lack of data, and 2 cases were lost to follow-up after surgery. A total of 117 patients were finally included in the analysis, including 40 cases in group A, 39 cases in group B, and 38 cases in group C. There were no statistically significant differences in gender, age, BMI, ASA grade, operation duration and anesthesia duration among the three groups.

There was no significant difference in VAS score between the three groups after extubation. Compared with group C, VAS scores in group A and group B were significantly lower at 30min after extubation, after leaving PACU, 24h and 48h after surgery, and the incidence of coughing during extubation was reduced. There was no significant difference in intraoperative hypotension, hypoxemia, postoperative nausea and vomiting, additional postoperative analgesic drugs and the number of analgesic pump compressions among the three groups.

Compared with group C, the first time of getting out of bed was significantly shorter in group A and group B, and the postoperative QoR15 score was significantly increased. There was no significant difference in the time of first exhalation and postoperative hospital stay among the three groups.

There was no significant difference in preoperative procalcitonin and IL-6 levels among the three groups. Compared with group C, the levels of procalcitonin and IL-6 in group A and group B were significantly decreased 24h after surgery, and the difference between group A and group B was not statistically significant.

Table 1 Comparison of general conditions among the three groups

Indicators	Group A (n=40)	Group B (n=39)	Group C (n=38)	P value
Male/female (ex.)	23/17	16/23	18/20	0.335
Age (years)	58.5 (53.25, 69.75)	55.0 (51.0, 62.0)	57.0 (51.5, 70.25)	0.197
BMI(kg/m²)	22.55±2.93	23.38±2.85	22.89±3.01	0.450
ASA Class I/II/III (example)	1/30/9	2/31/6	0/26/12	0.344
Operation time (min)	95 (56.25, 130.0)	70.0 (50.0, 139.0)	65.0 (45.0, 102.5)	0.085
Duration of anesthesia (min)	115 (71.25, 150.0)	85.0 (65.0, 150.0)	84.5 (60.0, 126.0)	0.117

Table 2 VAS scores (score, M(Q1,Q3)) at different time points in the three groups

Groups	After extubation	30min after extubation	When leaving PACU		24h after surgery	48h after surgery
Group A (n=40)	1 (0, 2)	1 (0, 2)		1 (0,1.75)	2 (1, 3)	0 (0, 1)
Group B (n=39)	1 (0, 2)	1 (1, 2)		1 (1, 2)	2 (1, 2)	0 (0, 1)
Group C (n=38)	1 (0, 2)	3 (2, 4)		2 (2, 3)	3 (2, 4)	2 (2, 3)

Note: Compared with group A,^a P < 0.017; Compared with group B, P < 0^b.017

Table 3 Comparison of intraoperative anesthetic drug dosage and adverse reactions among the three groups

Groups	Sufentanil (ug)	Remifentanil (mg/h)	Propofol (mg/h)	Low blood pressure (ex.)		Hypoxemia (ex.)
Group A (n=40)	41.88±9.59	0.41±0.11	136.75±39.96		17	0
Group B (n=39)	40.77±10.73	0.40±0.14	149.74±85.33		16	2
Group C (n=38)	43.42±10.14	0.39±0.13	136.32±55.63		11	0

Table 4 Comparison of coughing during extubation and postoperative analgesic use among the three groups

Subgroups	Coughing during extubation (case)	Additional administration of pain medication (ex.)	Number of postoperative analgesic pump compressions
Group A (n=40)	4	8		0 (0, 1)
Group B (n=39)	4	5		0 (0, 2)
Group C (n=38)	11^ab	10		0 (0, 2)

Note: Compared with group A,^a P < 0.05; Compared with group B, P < 0^b.05

Table 5 Comparison of postoperative adverse reactions and recovery quality among the three groups

Groups	Nausea and vomiting (ex.)	Exhaust time (h)	Time to get out of bed and move (h)	QoR15 rating	Postoperative hospital stay (days)
Group A (n=40)	6	20.0 (18.3, 22.0)	21.0 (19.0, 22.0)	145 (135149).	7 (6, 8)
Group B (n=39)	8	20.0 (18.0, 24.0)	22.0 (17.0, 25.0)	144 (135148).	7 (6, 8)
Group C (n=38)	6	22.0 (20.0, 24.0)	26.0 (24.0, 28.0)	135 (123141).	7 (6, 8)

Note: Compared with group A,^a P < 0.017; Compared with group B, P < 0^b.017

Table 6 Comparison of IL-6 and procalcitonin before and after operation among the three groups

Indicators	Grouping		Pre-operation	24 hours after surgery
	Group A (n=40)	1.50 (1.50, 3.57)			14.03 (7.74, 41.67)
IL6	Group B (n=39)	1.82 (1.50, 3.44)			15.35 (6.20, 35.59)
	Group C (n=38)	1.50 (1.50, 3.39)			35.64 (19.97, 56.94)
Procalcitonin	Group A (n=40) Group B (n=39) Group C (n=38)	0.02 (0.02, 0.03) 0.02 (0.02, 0.03) 0.02 (0.02, 0.04)			0.10 (0.05, 0.25) 0.10(0.03,0.20) 0.35(0.10,0.66)^ab

Note: Compared with group A,^a P < 0.017; Compared with group B, P < 0^b.017

Thoracoscopic surgery has the characteristics of less trauma and quick recovery, but due to surgical incision trauma, pleural stretch and postoperative indentation of drainage tube, the degree of acute postoperative pain in patients is still relatively severe. Relevant data show^[8] that about 78% of thoracoscopic surgery patients have severe acute pain within 48 hours after surgery, which seriously affects sleep and postoperative recovery quality, increases the occurrence of postoperative lung complications, and prolongs hospital stay. Therefore, perfect postoperative analgesia is very important for postoperative recovery of thoracic surgery patients.

Opioids are the most commonly used analgesic drugs in clinical practice. Their analgesic effect is exact and effective, but they also have adverse reactions such as respiratory depression, nausea and vomiting, and inhibition of gastrointestinal function recovery. Lidocaine, as an amide local anesthetic, is commonly used in local anesthesia and anti-arrhythmic drugs. A large number of studies have shown that intravenous infusion of lidocaine can produce analgesic effects, and its mechanism may be related to inhibiting ectopic discharge of sensory nerve, inhibiting inflammatory response, regulating excitatory/inhibitory neuro^[9-12]transmitter release, etc.

The results of this study showed that compared with the group without lidocaine, the VAS pain scores of group A and group B were significantly reduced 30min after extubation, at the time of leaving PACU, 24h and 48h after surgery, indicating that intravenous infusion of lidocaine could reduce postoperative acute pain in patients undergoing thoracic surgery, which was similar to the results of Fan Zheng et al. ^[13]Zhang Liang et al. showed that the addition of lidocaine to suf^[14]entanil PCIA after surgery could enhance postoperative analgesia. This study showed that compared with intraoperative lidocaine infusion, continuous infusion of lidocaine 48h after surgery did not significantly improve postoperative acute pain, which may be related to the pharmacokinetic characteristics of lidocaine. Studies have shown that the half-life of continuous infusion of lidocaine can reach 1.5-2h, and with the extension of infusion time, its pharmacokinetics are non-linear and time-dependent. Koppert et al. showed that the analgesic effect of intravenous lidocaine infusion from 1h after^[15] surgery could be maintained until 72h after surgery, which may be the reason why there was no significant difference in postoperative pain scores between the two groups. In addition, the analgesic effect of lidocaine is also related to the blood concentration, and the study found that the analgesic effect was obvious when the blood concentration of lidocaine was maintained at 2-5mg/L. This study did not monitor the blood concentration of lidocaine in the two groups, so the relationship between the blood concentration and the postoperative analgesic effect could not be clarified.

The results of this study showed that intravenous infusion of lidocaine could shorten the time for patients to get out of bed for the first time after surgery, but there was no significant difference in the time for the first postoperative exhaust. Li Yaxing et^[16] al. showed that intravenous infusion of lidocaine could significantly shorten the time of first anal exhaust in elderly patients after laparoscopic radical resection of colon cancer, and promote the recovery of postoperative intestinal function, which may be related to reducing the dosage of opioids, alleviating intestinal inflammation and reducing sympathetic nerve excitability. In this study, there were no significant differences in intraoperative and postoperative opioid use among the three groups of patients. Meanwhile, thoracic surgery may have less impact on patients' intestinal function than abdominal surgery, so there was no significant difference in the first postoperative exhaust time among the three groups of patients. Intraoperative lidocaine infusion can significantly improve patients' postoperative acute pain, which may be the reason for shortening patients' first postoperative activity time.

Choking reaction is prone to occur during anesthesia and recovery, causing hypertension, tachycardia and other adverse reactions. Previous studies have shown^[17] that intravenous infusion of lidocaine can effectively inhibit the choking reaction during extubation, which may be related to the stabilization and inhibition of neuronal transmission by lidocaine. The results of this study indicated that intraoperative intravenous infusion of lidocaine could reduce the incidence of coughing during extubation to a certain extent, but there was no statistical difference between the two groups, which may be related to the small sample size. QoR15 scale, as A simple scale to evaluate the quality of postoperative recovery of patients, has been widely used in clinical patients with different types of surgery. It is divided into two volumes A and B, including physical comfort, appetite, breathing, emotion, psychology and pain, etc., covering a total of 15 specific items^[18]. The results of this study showed that the QoR15 score of patients who received intravenous lidocaine was significantly higher than that of patients who did not receive intravenous lidocaine, which may be related to the effective relief of postoperative acute pain of patients and the promotion of early ambulation of patients.

The stress response caused by surgical trauma and pain is easy to induce the inflammatory response of the body, thus causing damage to normal tissues. IL-6 and procalcitonin are commonly used clinical inflammatory indicators. In this study, venous blood of patients was collected before and 24 hours after surgery to detect the levels of inflammatory factors. The results showed that intravenous infusion of lidocaine could significantly reduce the levels of procalcitonin and procalcitonin and procalcitonin 6 inflammatory factors 24 hours after surgery. It is suggested that lidocaine can inhibit the inflammatory response and reduce the level of inflammatory factors, which is consistent with the results of Afzal^[19] and other studies, and verifies the anti-inflammatory effect of lidocaine plays an important role in postoperative analgesia.

In summary, intravenous infusion of lidocaine can alleviate postoperative acute pain in patients undergoing thoracic surgery, shorten the time of getting out of bed for the first time after surgery, and significantly reduce the level of postoperative inflammatory factors. However, there are some limitations in this study: this study is a single-center, small-sample trial, and there are certain limitations in sample selection, which may have a certain impact on the results. In the future, large sample size and multi-center studies are needed to verify the effect of intravenous lidocaine infusion on acute pain after thoracic surgery.

Acknowledgements

Not Applicable.

Author contributions

F.C.N designed the research study. J.X.Q and N.J

performed the research. X.L.L and Z.Y analyzed the data. X.L.L and

F.C.N wrote the manuscript. F.C.N contributed to editorial changes

in the manuscript. All authors read and approved the final manuscript.

Funding

This study was supported by Jiangsu Health Vocational College "Medical Education Coordination, Chinese and Western Integration" special project (YJXTG202302).

Data availability

Corresponding authors may provide data and materials.

Consent for publication

Not applicable.

Competing interests

The authors declare no competing interests.

Human ethics and consent to participate

All subjects gave their informed consent for inclusion before they participated

in the study. The study was conducted in accordance with the Declaration of

Helsinki, and the protocol was approved by the Research Ethics Committee

of Nanjing Gaochun People's Hospital. Furthermore, the study was successfully

registered at the Chinese Clinical Trial Center (clinical trial number:

(ChiCTR2300078858, date of the registration: 20/12/2023).

Conflict of interest

There is no conflict of interest in this study.

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No competing interests reported.

Effect of intravenous lidocaine infusion on postoperative pain and inflammatory factors in patients undergoing thoracic surgery

Status:

Version 1

Abstract

Introduction

Materials and Methods

Results

Discussion

Declarations

References

Additional Declarations

Status:

Version 1