Safety and effectiveness of opioid-free anesthesia in thoracoscopic surgery: a propensity-score matching analysis

doi:10.21203/rs.3.rs-2737393/v1

Background: The aim of this study was to observe the effect of opioid-free anesthesia (OFA) on intraoperative hemodynamics and postoperative analgesia in thoracoscopic surgery.

Methods: A total of 101 thoracoscopic surgery patients who received the OFA technique were compared with 101 thoracoscopic surgery patients who received standard opioid-containing anesthesia(SOA),. Heart rate (HR) and mean arterial blood pressure (MAP) were measured before anesthesia induction, immediately after endotracheal intubation, at the beginning of surgery, and 10, 20, and 30 min after the beginning of surgery. Total amount of intraoperative infusion, frequency of vasoactive drug use, morphine ingested via the patient-controlled intravenous analgesia(PCIA) 24 h post-surgery, and visual analogue scale (VAS) scores at rest and activity on the first day after surgery were analyzed.

Results: There was no significant difference in intraoperative HR between the two groups (F=0.889, P=0.347); however, there was significant difference in intraoperative MAP (F=16.709, P<0.001), which was lower in SOA patients than in OFA patients. The frequency of vasoactive drug use and the amount of infusion was less in OFA patients (P=0.001). The amount of morphine used by the PCIA 24 h after surgery was significantly lower in OFA patients (OFA, 1.8 [0, 4.8] mg vs. STD, 3.6 [0.6, 23] mg, P<0.001). There was no significant difference in VAS scores at rest (P=0.745) or during activity (P=0.792) on the first day after surgery.

Conclusions: Compared with SOA, OFA can effectively maintain the stability of intraoperative MAP, reduce the incidence of hypotension, and effectively reduce the consumption of opioids after surgery.

intraoperative haemodynamics

opioid-free anaesthesia

thoracoscopic surgery

postoperative analgesia

Owing to its advantages of minimal trauma, quick recovery, and short hospital stay [1], thoracoscopic surgery has undergone rapid development in clinical practice; consequently, the demand for analgesia has decreased. However, postoperative pain following thoracoscopic surgery is still severe. In recent years, the concept of enhanced recovery after surgery (ERAS) has been promoted and applied in many surgical fields, including general surgery and orthopedics [2]. During the implementation of ERAS, perioperative pain control is the most important goal, and opioids have been the main drugs used for perioperative pain management [3]. However, opioids are not without drawbacks. While they do control pain, they also produce many adverse reactions, including nausea, vomiting [4], gastrointestinal peristalsis inhibition [5], urinary retention, respiratory inhibition, pain sensitization [6,7],and tolerance,. The opioid addiction epidemic, which caused more than 200,000 deaths in the United States between 1999 and 2016, is another drawback of opioids [8]. Reducing the use of perioperative opioids reduces the incidence of perioperative adverse reactions and facilitates rapid postoperative recovery. Therefore, reduction of opioid dosage and the development of de-opiating opioids have become research hotspots in recent decades [9-11].

Opioid-free anesthesia (OFA) is a multi-mode anesthesia that combines sedatives, N-methyl-D-aspartate antagonists [12], local anesthetics, anti-inflammatory drugs, α-2 agonists, and regional block techniques [7,13]. Relevant literature has reported that OFA is feasible and effective compared with traditional opioid-based anesthesia [14]. However, there are few studies on the application of OFA in thoracoscopic surgery. Therefore, patients undergoing thoracoscopic surgery in the Department of Thoracic Surgery at our hospital were selected as the research participants in this study. We reviewed the effects of OFA and traditional opioid-containing anesthesia on intraoperative hemodynamic changes and postoperative analgesia, and aimed to provide more evidence supporting the safety and efficacy of OFA techniques.

Patient selection and study design

This study was approved by our institutional review board and informed consent was obtained (2020PHB308-01). Patients who underwent thoracoscopic surgery from January 2017 to June 2020 were retrospectively analyzed. Ultimately, 4572 patients who underwent thoracoscopic surgery, including 68 patients younger than 18 years and 4504 patients older than 18 years, were included. All 4504 adult patients received nerve block analgesia before surgery, of which 32 received thoracic epidural anesthesia (TEA), 67 received intercostal nerve block, 102 received erector spinae nerve block, and 4303 received thoracic paravertebral block (TPVB). Among the 4303 patients who received TPVB, the block effect was judged to have failed in 56 patients, and 4247 patients received successful TPVB before surgery. According to the anesthesia method, 4247 patients were divided into two groups: an OFA group and standard opioid-containing anesthesia(SOA) group. Finally, 101 patients were included in the OFA group, and 1:1 propensity-score matching was performed, resulting in 101 patients who comprised the SOA group (Fig. 1).

Anesthesia method and management

All patients received ultrasound-guided TPVB at the T3 and T6 segments of the surgical side before surgery, and 15 mL of 0.4% ropivacaine was injected into the thoracic paravertebral space at the corresponding segments. With the diffusion of the drug solution, the pleura was evidently depressed, which confirmed that the local anesthetic was well diffused. The blocking effect was determined by acupuncture 15 min after the start of the procedure. Successful thoracic paravertebral block using the two-point method was confirmed when the head side reached T3 or higher, and the tail side reached T8 or lower. If the above-mentioned levels were not reached, remediation and re-evaluation were performed. If this failed, the block was considered a failure, and the patient was excluded from the analysis.

Patients in the OFA group were given a 1-μg/kg load dose of dexmedetomidine hydrochloride by intravenous pump within 15 min of entering the operating room; subsequently, a rate of 0.4 μg/kg/h was maintained until 30 min before the end of surgery. Before anesthesia induction, 0.5% tetracaine hydrochloride was used for laryngeal surface anesthesia, and 0.2–0.4 mg/kg etomidate, 1.5–2 mg/kg lidocaine, and 1 mg/kg esmolol were injected intravenously to obtund the pressor response to intubation in the absence of opioids. During the operation, propofol was continuously administered intravenously to maintain the bispectral index (BIS) value between 40–60, and lidocaine (1.0–1.5 mg/kg) was injected intravenously to maintain the analgesic effect. Patients in the SOA group did not receive any intravenous lidocaine, and opioids such as sufentanil, fentanyl, or remifentanil were routinely given for induction of anesthesia and maintenance of intraoperative analgesia. After induction of anesthesia, double-lumen endotracheal intubation was performed in both groups to achieve one-lung ventilation.

Based on the premise of maintaining satisfactory anesthesia depth, if hypotension occurred (MAP decrease ≥20% of the basic value or MAP <60 mmHg), 6 mg intravenous ephedrine or 50 μg deoxyepinephrine was injected intravenously, and if bradycardia (HR <50 times/min) occurred for 1 min, 0.5 mg atropine was injected intravenously.

Postoperative patient-controlled intravenous analgesia (PCIA) was used for postoperative analgesia, and the formula used was 50 mg oxycodone plus normal saline to 100 mL without a background dose. PCIA was delivered in 2-mL doses with an interval of 5 min. At the end of the operation, all patients in both groups were transferred to the postoperative anesthesia recovery care unit with tracheal intubation.

Data collection

The clinical data and surgical anesthesia data of patients were collected by consulting the electronic medical record system. The data collected included general patient information; HR and MAP before anesthesia (T0), immediately after endotracheal intubation (T1), at the beginning of surgery (T2), and 10 min (T3), 20 min (T4), and 30 min (T5) after surgery; intraoperative infusion volume and frequency of vasoactive drugs; dosage of opioids in the PCIA pump 24 h after surgery (expressed by equivalent morphine dose: 1 mg oxycodone = 1.5 mg morphine); and visual analogue scale (VAS) score at rest and during activity on the first day after surgery.

Statistical analysis

SPSS 25.0 software was used for date analysis. The patients were included in the logistic model tendency score according to the relevant covariables including age, sex, American Society of Anesthesiologists (ASA) grade, body mass index (BMI), presence or absence of hypertension, surgical type, and intraoperative blood loss. Nearest-neighbor matching (NNM) was adopted, the caliper value was set at 0.1, and matching was performed in a 1:1 ratio. Continuous data were tested for normality with the Shapiro–Wilk test. Continuous variables with normal distribution are presented as mean±standard deviation (SD) and the independent sample t-test was used for inter-group comparisons. Non-normal variables are reported as median (interquartile range) and the Kruskal–Wallis H test was used for comparison between groups. The counting data are expressed as percentage (%), and the chi-square test was used for comparison between groups. The Kruskal–Wallis H test was used for grade data. A repeated-measurement analysis of variance was used for data of repeated measurements of the same index between groups. P<0.05 indicated a statistically significant difference.

From January 2017 to June 2020, 4247 patients underwent thoracoscopic surgery and received successful TPVB before the operation. OFA was administered to 101 patients and 4146 patients were administered standard opioid-based anesthesia. After 1:1 NNM, all 101 patients in the OFA group were matched with 101 patients from the SOA group. The baseline level of clinicopathological characteristics of patients in the two groups before matching is shown in Table 1. After matching, there were no significant differences in clinicopathological characteristics between the two groups (Table 2). In the SOA group, the opioids consumed were remifentanil (81.6±28.38 μg) and sufentanil (23.2±8.85 μg).

Fig.2 and Fig.3 show the changes in HR and MAP in both groups, respectively. There was no significant difference in the changes in HR between the two groups (P=0.347). There was a significant difference in the changes in MAP between the two groups (P<0.001). Compared with SOA group, the fluctuation of MAP in the OFA group was smaller, and significantly lower than that in the OFA group.

Table 3 shows that 43.6% of patients in the SOA group did not use vasoactive drugs during surgery, while 69.3% of patients in the OFA group did not use vasoactive drugs during surgery. There was a significant difference in the frequency of vasoactive drug use between the two groups (P=0.001) and in the difference in intraoperative infusion volume between the two groups (P=0.001). There was a significant difference in the morphine dosage in the PCIA pump 24 h after surgery between the two groups (1.8 [0, 4.8] mg vs. 3.6 [0.6, 23] mg, P<0.001). There was no significant difference in VAS scores (P=0.745) at rest or during activity (P=0.792) between groups on the first day after surgery.

Opioids have been an integral part of balanced anesthesia because of their strong analgesic effect. Opioids can also inhibit sympathetic nerve excitation and do not cause histamine release. Therefore, they can inhibit the stress response caused by various noxious stimuli brought about by surgery during general anesthesia [3], so as to maintain the stability of hemodynamics in patients during surgery. However, with the recognition of adverse reactions to opioids and the promotion of the ERAS concept, OFA has been increasingly studied and reported, and the safety and effectiveness of OFA has always been the focus of attention. It is necessary to collect further relevant data to clearly evaluate OFA’s benefit–risk ratio.

Many factors affect hemodynamic changes during surgery. Therefore, we adopted NNM and included basic characteristics of the patients such as sex, age, BMI, ASA grade, the presence or absence of hypertension, the type of operation, and the amount of intraoperative bleeding in the matching factors. After matching, there were no significant differences between the two groups in these characteristics. In a review on OFA in thoracic surgery, Tempe and Sawhney [3] reported that an important factor contributing to successful OFA is regional anesthesia or nerve block, such as TEA, TPVB, or intercostal nerve block. TEA was once considered the gold standard for postoperative analgesia in thoracic surgery [15], but it has significant side effects, including hypotension, respiratory depression and urinary retention; moreover, rare and related complications may result in permanent nerve damage.Several studies [16-19] have shown that TPVB can provide the same analgesic effect as TEA, and side effects such as hypotension and respiratory depression are mild. A review [20] found that for patients with normal blood volume, the occurrence of hypotension with TPVB was less common compared with TEA, which was attributed to unilateral sympathetic block. Scarci and colleagues [21] both found that TPVB reduced the incidence of hypotension and bradycardia compared with TEA.

In this study, the patients in both groups received TPVB before surgery, which affected intraoperative blood pressure less while reducing the stress response and providing a superior analgesic effect [15]. However, compared with the patients in the SOA group, those in the OFA group had less fluctuation in intraoperative MAP (Fig. 3).In addition, patients in the SOA group had a higher rate of intraoperative hypotension and used pressor drugs more frequently. Therefore, the influence of other intraoperative factors on blood pressure should be considered, and the most important difference between the two groups was the use of opioids.

Previous studies have shown that sufentanil and remifentanil can directly expand peripheral blood vessels while inhibiting the sympathetic nerve [22], and these effects are in a dose-dependent manner; this may be why the incidence of intraoperative hypotension in the SOA group was higher than that in the OFA group. In addition, it is worth mentioning that there was a significant difference in intraoperative infusion volume between groups. For patients who have been fasting for a long time, the anesthesiologist accelerates the infusion speed and supplements blood volume as treatment measures to ensure the stability of the patient’s hemodynamics, in addition to using vasoactive drugs.

Kamdar [23] and Mulier [24] suggested that OFA can effectively reduce the postoperative dosage of opioids. In terms of postoperative analgesia, the present study also conducted a correlation analysis. There was a significant difference between groups in the consumption of morphine by the PCIA pump 24 h after surgery (OFA, 1.8 [0, 4.8] mg vs. SOA, 3.6 [0.6, 23] mg, P<0.001). Consumption in the OFA group was significantly lower than in the SOA group, indicating that OFA could improve early postoperative analgesia and reduce the dose of postoperative opioids; the reason may be the pain sensitization caused by intraoperative opioids. Joly and colleagues [25] found that opioids might increase the area of secondary hyperalgesia around the surgical wound, thus increasing the demand for opioids after surgery, even if they did not improve the postoperative pain score. In addition, the acute tolerance of postoperative opioids (opioid-induced hyperalgesia) is correlated with the dosage of intraoperative opioids, which may aggravate the demand for opioid analgesics for postoperative pain [9], and studies have shown that high-dose remifentanil [26] or sufentanil [27] during surgery can aggravate postoperative pain. Relevant clinical trials have shown that intravenous lidocaine can reduce postoperative pain, and the combination of dexmedetomidine can further enhance this effect [28,29]. This may be another reason why the OFA group can effectively reduce the dosage of postoperative analgesic drugs

Because the present study was a retrospective cohort study, it was limited by a lack of blinding; therefore, there was potential for bias. In addition, a large clinical effect would be required from any intervention to demonstrate a statistically significant difference between study groups.Although propensity-score matching may have assisted in accounting for observed differences between the two groups, it cannot account for unobserved differences and therefore leaves room for residual confounding. However, the findings of this study provide a basis for further prospective randomized controlled trials.

This study demonstrated that during thoracoscopic surgery, patients managed with OFA were more stable in terms of MAP than patients who were managed with standard techniques using opioids. On the other hand, OFA reduced morphine consumption via the PCIA pump 24 h after surgery. In conclusion, OFA is a safe and feasible technology in thoracoscopic surgery.

OFA: Opioid-free anesthesia; SOA: Standard opioid-containing anesthesia; HR: Heart rate; MAP: Mean arterial blood pressure; PCIA: Patient-controlled intravenous analgesia; VAS: visual analogue scale; ERAS: Enhanced recovery after surgery; TEA: Thoracic epidural anesthesia; TPVB: Thoracic paravertebral block; BIS: Bispectral index; ASA: American Society of Anesthesiologists; BMI: Body mass index; NNM: Nearest-neighbor matching;D1, First day after surgery; HBP, High blood pressure

Acknowledgments

The authors thank Zehao Wu for his assistance in date analysis and technical support during the study. The authors also thank Guo Xu for his assistance in data collection.

Authors’ contributions

All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by Shanshan Zhang, Jianmin Zhang and Ran Zhang. The first draft of the manuscript was written by Shanshan Zhang and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Funding

None.

Declaration of interests

The authors declare no conflicts of interest.

Availability of data and materials

The datasets used and analysed during the current study are available from the corresponding author on reasonable request.

Ethics approval and consent to participate

The study protocol was established, according to the ethical guidelines of the Helsinki Declaration and was approved by the Institutional Review Board of Peking University People’s Hospital (2020PHB308-01).

Consent to publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.

Fischer GW, Cohen E. An update on anesthesia for thoracoscopic surgery. Curr Opin Anaesthesiol 2010; 23: 7-11.
Kehlet H, Wilmore DW. Multimodal strategies to improve surgical outcome. Am J Surg 2002; 183: 630-41.
Tempe DK, Sawhney C. Opioid-free anesthesia for thoracic surgery: a step forward. J Cardiothorac Vasc Anesth 2020; 34: 3041-3.
Salomé A, Harkouk H, Fletcher D, Martinez V. Opioid-free anesthesia benefit–risk balance: A systematic review and meta-analysis of randomized controlled trials. J Clin Med 2021; 10: 2069.
Koepke EJ, Manning EL, Miller TE, Ganesh A, Williams DGA, Manning MW. The rising tide of opioid use and abuse: the role of the anesthesiologist. Perioper Med (Lond) 2018; 7: 16.
Colvin LA, Bull F, Hales TG. Perioperative opioid analgesia-when is enough too much? A review of opioid-induced tolerance and hyperalgesia. Lancet 2019; 393:1558-68.
Forget P. Opioid-free anaesthesia. Why and how? A contextual analysis. Anaesth Crit Care Pain Med 2019; 38: 169-72.
Seth P, Rudd RA, Noonan RK, Haegerich TM. Quantifying the epidemic of prescription opioid overdose deaths. Am J Public Health 2018; 108: 500-2.
Lavand'homme P, Estebe JP. Opioid-free anesthesia: a different regard to anesthesia practice. Curr Opin Anaesthesiol 2018; 31: 556-61.
Brandal D, Keller MS, Lee C,Grogan T, Fujimoto Y, Gricourt Y, et al. Impact of enhanced recovery after surgery and opioid-free anesthesia on opioid prescriptions at discharge from the hospital: a historical-prospective study. Anesth Analg 2017; 125: 1784-92.
Friedberg BL. Opioid free anesthesia with BIS/EMG monitored propofol-ketamine. Rev Esp Anestesiol Reanim (Engl Ed) 2018; 65: 243-5.
Forget P, Cata J. Stable anesthesia with alternative to opioids: are ketamine and magnesium helpful in stabilizing hemodynamics during surgery? A systematic review and meta-analyses of randomized controlled trials. Best Pract Res Clin Anaesthesiol 2017; 31: 523-31.
Boysen PG 2nd, Pappas MM, Evans B. An evidence-based opioid-free anesthetic technique to manage perioperative and periprocedural pain. Ochsner J 2018; 18: 121-5.
Devine G, Cheng M, Martinez G, Patvardhan C, Aresu G, Peryt A, et al. Opioid-free anesthesia for lung cancer resection: a case-control study. J Cardiothorac Vasc Anesth 2020; 34: 3036-40.
D'Ercole F, Arora H, Kumar PA. Paravertebral block for thoracic surgery. J Cardiothorac Vasc Anesth 2018; 32: 915-27.
Davies RG, Myles PS, Graham JM. A comparison of the analgesic efficacy and side effects of paravertebral vs epidural blockade for thoracotomy-a systematic review and meta-analysis of randomized trials. Br J Anaesth 2006; 96: 418-26.
Conlon NP, Shaw AD, Grichnik KP. Postthoracotomy paravertebral analgesia: will it replace epidural analgesia? Anesthesiol Clin 2008; 26: 369-80.
Daly DJ, Myles PS. Update on the role of paravertebral blocks for thoracic surgery: are they worth it? Curr Opin Anaesthesiol 2009; 22: 38-43.
Yeung JH, Gates S, Naidu BV, Wilson MJ, Gao Smith F. Paravertebral block versus thoracic epidural for patients undergoing thoracotomy. Cochrane Database Syst Rev 2016; 2: CD009121.
D'Ercole F, Arora H, Kumar PA. Paravertebral Block for Thoracic Surgery. J Cardiothorac Vasc Anesth.2018;32(2):915-27.
Scarci M, Joshi A, Attia R. In patients undergoing thoracic surgery is paravertebral block as effective as epidural analgesia for pain management? Interact Cardiovasc Thorac Surg 2010; 10: 92-6.
Baldo BA. Toxicities of opioid analgesics: respiratory depression, histamine release, hemodynamic changes, hypersensitivity, serotonin toxicity. Arch Toxicol 2021; 95: 2627-42.
Kamdar NV, Hoftman N, Rahman S, Cannesson M. Opioid-free analgesia in the era of enhanced recovery after surgery and the surgical home: implications for postoperative outcomes and population health. Anesth Analg. 2017; 125: 1089-91.
Mulier J, Dekock M. Opioid free general anesthesia, a new paradigm? Best Pract Res Clin Anaesthesiol 2017; 31: 441-3.
Joly V, Richebe P, Guignard B, Fletcher D, Maurette P, Sessler DI, et al. Remifentanil-induced postoperative hyperalgesia and its prevention with small-dose ketamine. Anesthesiology 2005; 103: 147-55.
Fletcher D, Martinez V. Opioid-induced hyperalgesia in patients after surgery: a systematic review and a meta-analysis. Br J Anaesth 2014; 112: 991-1004.
Aubrun F, Valade N, Coriat P, Riou B. Predictive factors of severe postoperative pain in the postanesthesia care unit. Anesth Analg 2008; 106: 1535-41.
Weibel S, Jokinen J, Pace NL, Schnabel A, Hollmann MW, Hahnenkamp K, et al. Efficacy and safety of intravenous lidocaine for postoperative analgesia and recovery after surgery: a systematic review with trial sequential analysis. Br J Anaesth 2016; 116: 770-83.
Sivaji P, Agrawal S, Kumar A, Bahadur A. Evaluation of lignocaine, dexmedetomidine, lignocaine-dexmedetomidine infusion on pain and quality of recovery for robotic abdominal hysterectomy: a prospective randomized controlled trial. Braz J Anesthesiol. 2022; 72: 593-8.

Table 1: Baseline patient characteristics before nearest-neighbor propensity-score matching

	SOA Group (n=4146)	OFA Group (n=101)	P-value
Age (years)	58.00±15.00	57.07±11.41	0.960
Male/female	1894/2252	52/49	0.248
BMI (kg/m²)	24.03±4.04	24.04±3.07	0.518
ASA (n (%))			0.122
I	786 (19.0)	13 (12.9)
II	3147 (76.0)	86 (85.1)
III	211 (5.0)	2 (2.0)
IV	2 (0.0)	0 (0.0)
HBP (yes/no)	1164/2982	28/73	0.938
Classification of surgery (n (%))			0.297
Wedge resection	1251 (30.2)	40 (39.60)
Segmentectomy	149 (3.6)	3 (2.97)
Lobectomy	2277 (54.9)	50 (49.51)
Sleeve pneumonectomy	13 (0.3)	0 (0)
Unilateral pneumonectomy	15 (0.4)	1 (0.99)
Thymic mediastinal surgery	441 (10.6)	7 (6.93)
Intraoperative bleeding volume (mL)	30 [20, 50]	20 [20, 50]	0.024

Data are presented as median [Interquartile range] or mean ± standard deviation or number (%) of patients.

BMI, body mass index; ASA, American Society of Anesthesiologists; OFA, opioid-free anesthesia; HBP, high blood pressure; SOA, standard opioid-containing anesthesia

Table 2: Patient characteristics after nearest-neighbor propensity-score matching

	SOA Group (n=101)	OFA Group (n=101)	P-value
Age (years)	58.05±11.27	57.07±11.41	0.540
Male/female	51/50	52/49	0.888
BMI (kg/m²)	23.87±2.80	24.04±3.07	0.684
ASA (n (%))			0.489
I	17 (16.8)	13 (12.9)
II	80 (79.2)	86 (85.1)
III	4 (4.0)	2 (2.0)
IV	0 (0.0)	0 (0.0)
HBP (yes/no)	27/74	28/73	0.874
Classification of surgery (n (%))			0.807
Wedge resection	39 (38.61)	40 (39.60)
Segmentectomy	4 (3.96)	3 (2.97)
Lobectomy	50 (49.51)	50 (49.51)
Sleeve pneumonectomy	0 (0)	0 (0)
Unilateral pneumonectomy	0 (0)	1 (0.99)
Thymic mediastinal surgery	8 (7.92)	7 (6.93)
Intraoperative bleeding volume (mL)	20 [15, 30]	20 [20, 50]	0.356

Data are presented as median [Interquartile range] or mean ± standard deviation or number (%) of patients.

BMI, body mass index; ASA, American Society of Anesthesiologists; OFA, opioid-free anesthesia; HBP, high blood pressure; SOA, standard opioid-containing anesthesia

Table 3: Clinical results

	SOA Group (n=101)	OFA Group (n=101)	Z/χ² Value	P-value
Frequency of vasoactive drugs			19.623	0.001
0	44 (43.6)	70 (69.3)
1	36 (35.6)	24 (23.8)
2	18 (17.8)	4 (3.9)
3	3 (3.0)	2 (2.0)
4	0 (0.0)	1 (1.0)
Intraoperative infusion volume (mL)	1000 [1000, 1500]	1000 [1000, 1000]	3.353	0.001
24-h morphine PCIA use (mg)	3.6 [0.6, 23]	1.8 [0, 4.8]	3.537	<0.001
VAS score on D1
VAS (at rest)	1 [0, 2]	1 [0, 1]	0.325	0.745
VAS (at activity)	3 [2, 4]	3 [2, 3]	0.264	0.792

Data are presented as median [Interquartile range] or mean ± standard deviation or number (%) of patients.

PCIA, patient-controlled intravenous analgesia; VAS, visual analogue score; D1, first day after surgery

No competing interests reported.

Safety and effectiveness of opioid-free anesthesia in thoracoscopic surgery: a propensity-score matching analysis

Status:

Journal Publication

Version 1

Abstract

Figures

Introduction

Methods

Results

Discussion

Abbreviations

Declarations

References

Tables

Additional Declarations

Status:

Journal Publication

Version 1