Impact of intraoperative goal-directed fluid therapy on tissue oxygen saturation and major morbidity in patients undergoing thoracoscopic lung resection: a randomized controlled trial

DOI: https://doi.org/10.21203/rs.3.rs-1625217/v1

Abstract

Background

Incision healing after thoracoscopic lung resection, resistance to infection, and gastrointestinal recovery are dependent on tissue perfusion and oxygenation. OLV decreases blood flow and tissue oxygen partial pressure in the emblematic circulation, which in turn regulates tissue blood flow and local tissue oxygen diffusion. This study was aimed at investigating the effects of different fluid management methods on regional tissue oxygen saturation (rSO2) and hemodynamics in patients undergoing thoracoscopic lung resection. Furthermore, we comparatively evaluated the effects of the different fluid management strategies on postoperative hospital stay and complications.

Methods This is a prospective randomized controlled trial. Sixty patients scheduled for thoracoscopic lung resection are randomly allocated to receive either goal-directed fluid therapy (GDFT) or restrictive fluid therapy at a 1:1 ratio. The rSO2 of each part, mean arterial pressure (MAP), heart rate, CI, and SVV were recorded before induction (T1), before one-lung ventilation (T2), 30 and 60 min after one-lung ventilation (T3 and T4, respectively), and at the end of surgery (T5). Radial artery blood gas analysis was performed at T1, T4, and T5 to record pH and lactic acid level. Furthermore, patients’ score on the Quality of Recovery-15 (QoR-15) scale and creatinine and urea nitrogen levels on the first postoperative day, postoperative hospital stay, postoperative nausea and vomiting, and complications were recorded. The primary outcome is the regional tissue oxygen saturation (rSO2) and hemodynamics during surgery. The secondary outcomes included postoperative hospital stay and complications.

Results Compared with group C, the GDFT group had a significantly higher MAP and CI, lower SVV at T3 to T5 (P < 0.05). In the GDFT group, the intraoperative crystalloid requirement and norepinephrine dose were lower and colloidal requirement and total volume of fluid infused were significantly higher (P < 0.05). Furthermore, the renal rSO2 at T3 to T4 and brachioradialis muscle rSO2 at T4 to T5 in the group were significantly higher (P < 0.05). The postoperative 24-h QoR-15 score was significantly higher in the GDFT group than in group C. Furthermore, the incidence of postoperative nausea and vomiting was significantly lower in the GDFT group than in group C (P < 0.05).

Conclusions GDFT can improve the intraoperative renal rSO2 and brachioradialis muscle rSO2 in patients undergoing thoracoscopic lung resection. It also can maintain hemodynamic stability, decrease the incidence of postoperative nausea and vomiting, and improve the quality of postoperative recovery.

Trial registration: Chinese Clinical Trial Registry: ChiCTR2100050474. Registered on August 27 2021.

Background

Perioperative fluid management is a key element of overall perioperative management and among the most frequently discussed issues in perioperative medicine. During lung resection, fluid management is complicated by patients' tendency to develop interstitial and alveolar edema. Existing pulmonary disease, one-lung ventilation (OLV), direct manipulation of the lung by surgeons, ischemia-reperfusion, and prior chemoradiotherapy can all damage the glycocalyx and endothelial cells and affect epithelial alveolar cells and surfactants. This can lead to lung injury[1][2]. In a retrospective analysis of 1442 patients who underwent chest surgery, the incidence of acute kidney injury (AKI) was found to be 5.1%[3]. A hospital registry study[4] of patients undergoing noncardiac surgery showed a U-shaped relationship between fluid volume and renal complications, with patients who received liberal volumes having a higher incidence of respiratory complications. Fluid management is the cornerstone of hemodynamic therapy. The optimal amount of fluid needed to reduce fluid-related complications remains difficult to determine.

As an individualized fluid therapy, goal-directed fluid therapy (GDFT) focuses on objectively assessing the patient's perioperative blood volume status and maintaining the blood volume load at an optimal level to achieve good tissue perfusion and an adequate oxygen supply[5]. It is a perioperative strategy in which fluid management targets are continuously measured dynamic indices, including stroke volume (SV) and SV variation (SVV), pulse pressure variation, and other factors, with the goal of optimizing tissue perfusion and oxygen delivery[6][7][8]. Clinical trials and meta-analyses have shown that GDFT reduces perioperative complications and mortality, especially in high-risk perioperative populations[9][10][11].

A liberal fluid strategy has been shown to increase the risk of acute respiratory distress syndrome, atelectasis, pneumonia, empyema, and death[12][13][14][15][16]. In 2019, the Enhanced Recovery After Surgery Society and European Society of Thoracic Surgeons recommended restrictive fluid therapy during lobectomy as part of the Enhanced Recovery After Surgery (ERAS®) protocol for lung surgery[17]. Restrictive fluid therapy is aimed at maintaining the postoperative weight constant without compromising circulation, tissue perfusion, or oxygenation. It has shown advantages over standard fluid therapy in several clinical trials and meta-analyses on abdominal surgery [18][19][20]. It may also be beneficial as a zero-balance approach and at least as effective as GDFT. Moreover, it may not involve additional costs and resource utilization, as are incurred with GDFT.

Incision healing after thoracoscopic lung resection, resistance to infection, and gastrointestinal recovery are dependent on tissue perfusion and oxygenation. OLV decreases blood flow and tissue oxygen partial pressure in the emblematic circulation, which in turn regulates tissue blood flow and local tissue oxygen diffusion. When OLV is initiated, blood is redistributed to “more vital” organs (e.g., the brain, heart, and lungs), thereby reducing tissue perfusion and oxygen delivery to some “non-vital” organs (e.g., the viscera and periphery), leading to intestinal damage and peripheral vascular lesions[21]. A number of factors, such as capillary refinement in adipose tissue[22] and increased sympathetic activity due to alpha-adrenergic vasoconstrictive drugs can lead to tissue hypoperfusion.[23]. An insufficient intravascular volume may also contribute to tissue hypoxia. The application of GDFT with colloidal fluids has been found to increase microcirculatory blood flow to the small intestine and increase intestinal tissue oxygen partial pressure after major abdominal surgery in pigs by using ultrasound Doppler and Clark electrode techniques[24]. However, direct measurements of central and peripheral tissue perfusion and oxygenation have not yet been found in studies of clinical applications of GDFT related to thoracoscopic lung resection.

Based on the difference in absorption spectra between oxyhemoglobin and deoxyhemoglobin in the near-infrared band, near-infrared spectroscopy (NIRS) is used to determine the local tissue oxygen saturation by detecting the absorption attenuation of the emitted light [25]. NIRS can be used to non-invasively measure regional oxygenation saturation (rSO2) in the microcirculatory system of local tissues in real time. In human tissue, local tissue oxygen saturation is a weighted average of the oxygenation saturation of blood in the micro arteries, microveins, and capillaries, and represents oxygen tension at the capillary, intercellular, and even intracellular mitochondrial levels[26]. A decrease in rSO2 indicates an increased risk of ischemia and poor tissue perfusion. In organ hypoxia, peripheral tissue oxygen saturation decreases earlier than cerebral oxygen saturation and pulse oxygen saturation[27]. It has also been suggested that when organ ischemia occurs, changes in tissue oxygen saturation occur even earlier than hemodynamic changes and can be used as early assessment indicators and help predict outcomes for the shock treatment[28][29]. Therefore, changes in tissue and peripheral tissue perfusion and oxygenation can be detected early using NIRS, and the technique allows for early detection of cerebral hypoxia.

In this study, we aimed to investigate the effects of different fluid management methods on rSO2 and hemodynamics in patients undergoing thoracoscopic lung resection. We also comparatively evaluated the effects of the different fluid management strategies on postoperative hospital stay and complications.

Methods

Study design

This was a prospective single-center single-blind randomized controlled trial, the protocol of which was approved by the ethics committee of Northern Jiangsu People’s Hospital (2021ky178). The study was registered in the Chinese Clinical Trial Registry (ChiCTR2100050474). Written informed consent was obtained from all the enrolled patients.The flow chart of this study is shown in Fig. 1.

Participants

Patients aged more than 18 years who were scheduled to undergo thoracoscopic lung resection (pulmonary resection or anatomic pulmonary segments) were eligible for enrollment in this trial. Sixty patients satisfied the following inclusion criteria and were enrolled in our study: American Society of Anesthesiologists physical (ASA) status I–Ⅲ, body mass index between 18.5 and 25 kg·m-2, ultrasound screening revealing a kidney depth (distance from the skin surface to kidney capsule) of <40 mm; and New York Heart Association (NYHA) classes Ⅰ–Ⅲ. The exclusion criteria were receipt of emergency procedures, ASA status Ⅳ or Ⅴ, cardiac failure (NYHA class IV), preoperative abnormal lung function (forced expiratory volume in 1 s < 50% of the predicted values), nervous system diseases, peripheral vascular disease, coagulation dysfunction, anemia (hemoglobin [Hb], <90 g/L), serum creatinine (sCr) level of ≥1.5 mg/dL, end-stage renal disease or receipt of renal transplant, frequent intraoperative cardiac arrhythmia, and OLV time of <60 min.

Randomization

The enrolled patients were allocated in a 1:1 ratio to undergo fluid management during OLV into the GDFT protocol group (GDFT group) or the restrictive fluid therapy group (group C). The randomization was stratified by sequential blocking based on a computerized random number generator. Allocation details were kept in sealed envelopes marked by serial numbers. Before the induction of anesthesia, the sealed, numbered, and opaque envelopes containing the treatment assignments were opened by an independent anesthesiologist. The data assessment or analysis was performed by an independent research staff supervised by an independent statistician. To ensure the reliability of data acquisition, the patients, clinical researchers involved in the collection of data and blood samples, and postoperative follow-up team were all blinded to group allocation. Group allocation was scarcely revealed when the final data analysis was completed.

Perioperative management

All participants performed respiratory functional exercises, were encouraged to quit smoking (patients who did not quit smoking were still allowed to complete the study), and improved their nutritional status before the surgery. No premedication was administered, and solid food and clear fluid intake were allowed until 12 and 3 h before surgery, respectively. General anesthesia was induced with propofol, midazolam, sufentanil, and atracurium cis-benzene sulfonate and maintained with sevoflurane, remifentanil, dexmedetomidine, and atracurium cis-benzene sulfonate. The depth of general anesthesia was controlled to maintain a bispectral index of 45–60. OLV was employed using a double-lumen tube during the operation, and the correctness of the position of the tube was confirmed by fiberoptic bronchoscopy. The trachea was intubated, and the participants were ventilated with a tidal volume (VT) of 7 ml·kg-1 (ideal body weight) during OLV. The inspiratory to expiratory time (I/E) ratio was 1:2, and positive end-expiratory pressure (PEEP) was 5 cmH2O. The frequency of ventilation was controlled such that the end-tidal carbon dioxide was 4.7~5.3 kPa, and adjustment the fraction of inspired oxygen (FiO2) to maintain saturation higher than 94% during two-lung ventilation and more than 90% during OLV. If FiO2 was more than 70% during OLV, the nondependent lung was insufflated with 100% oxygen at 1–5 cmH2O. The Vigileo-FloTrac system was used for hemodynamic monitoring in the GDFT group. Postoperative pain control was achieved with intravenous controlled analgesia.

Intraoperative fluid management

Hemodynamic parameters, including the arterial blood pressure (BP), SV, SVV, cardiac output, and cardiac index (CI), were measured using the Vigileo-FloTrac system. Baseline Ringer’s solution of sodium acetate was administered at a rate of 3 ml kg/kg·h in both groups. In the GDFT group, hemodynamic control was achieved using the Vigileo-FloTrac system according to a predetermined protocol based on a previous study that showed the beneficial effects of GDFT during high-risk abdominal surgery[30]. After the induction of anesthesia, the measured SV was set as the baseline volume for patients with an SVV of 12%. If the SVV was >12%, fluid with 250 ml of hydroxyethyl starch was administered over 20 min. This fluid challenge was repeated up to two times until an SVV of 12% was achieved. The SV measured at that time was then set as the baseline volume. During surgery, if the SVV exceeded 12% or remained at 8–12% and the percentage decrease in SV was >10% for at least 2 min, 250 ml of colloid was administered over 20 min. This was repeated until a stable hemodynamic condition (SVV < 13% and SV decrease < 10%) was achieved. The maximum amount of 6% hydroxyethyl starch that could be administered was 50 ml·kg-1. In addition, when the SVV remained <8%, norepinephrine was administered to maintain systolic BP (SBP) of >90 mmHg (Fig. 2).

In the restrictive fluid therapy group (group C), hydroxyethyl starch was infused to manage blood loss, and the ratio of hydroxyethyl starch to blood loss was 1:1 (ml). Norepinephrine was administered to maintain SBP of >90 mmHg. The infusion rate was adjusted by anesthesiologists according to their experience. If the urine volume was less than 0.5 ml·kg-1·h-1 for 2 h, 250 ml of Ringer’s solution of sodium acetate was administered until the target value is reached. The anesthesia care providers were blinded to the measurements obtained by the Vigileo-FloTrac system for the entire duration of the surgery.

Tissue oxygenation monitoring

Tissue oxygenation monitoring was performed non-invasively using a tissue oximeter based on near-infrared spectroscopy before the induction of anesthesia. A cerebral oximeter probe was placed at least 2 cm above the eyebrow on the left forehead, while a bispectral index (BIS) monitor was placed on the right forehead. An oximetry probe was placed on the brachioradialis muscle of the forearm (approximately two fingers below the anterior fold of the elbow) to monitor oxygen saturation of the muscle tissue of the forearm that was not used for cuff blood pressure monitoring. A third oximetry probe was placed on one side of the flank area that overlies the kidney to monitor renal regional tissue oxygen saturation under sonographic guidance. To visualize the kidney, an ultrasound probe was placed in the lower rib space in the posterior axillary line (below the 10th or 11th ribs). After obtaining a long-axis image of the kidney, the depth of the kidney (the distance from the skin surface to the renal capsule) was measured. The oximetry probe was placed on the probe placement point at a depth of <40 mm in the kidney. Patients were excluded from the study if the depth was ≥40 mm. Monitoring and data recording was started when the patient was awake breathing room air before anesthesia induction and stopped at the end of the surgery.

Data collection

Demographic data, including age, sex, weight, height, type of surgery, and ASA physical status score, were collected. Past medical history, including a diagnosis of hypertension and diabetes mellitus, was recorded. Intraoperative variables that were recorded included the surgical time, OLV time, sum of intraoperative bleeding, fluid infusion volume (crystalloid and colloid), urine output, and types and dosage of vasoactive drugs. Inoperative hemodynamic indicators (HR, MAP, CI, and SVV) and rSO2 were recorded before induction (T1), before OLV (T2), 30 min after OLV (T3), 60 min after OLV (T4), and at the end of surgery (T5). Arterial blood gas analysis data (pH and lactate) were recorded at T1, T4, and T5. Postoperative outcomes included (1) the quality of recovery over the first 24 h after surgery as measured by the 15-item quality-of-recovery scale; (2) the incidence of postoperative complications, including AKI, acute lung injury (ALI), acute respiratory distress syndrome (ARDS), pulmonary infection, atelectasis, and bronchial fistula; (3) creatinine and urea nitrogen levels at 1 day after operation; (4) incidence of postoperative nausea and vomiting; and (5) postoperative hospital stay.

Confidentiality

Private information about participants will not be collected. Only study codes will be collected. Collected data will be kept confidential until analysis is required. Collected data will be stored encrypted for 2 years after the study is completed.

Sample size calculation

The sample size calculation is based on the primary outcome “the effects of different fluid management methods on rSO2”. According to the results of our pre-experiments, μ1=79.1, μ2=74.1, δ=μ1-μ2≠0. The sample size for this study was calculated to achieve a statistical power of 0.9 and alpha error of 0.05 using a two-sided test. Considering a dropout rate of 20%, 30 patients are required in each group. PASS (version 15.0, NCSS, LLC, Kaysville, UT, USA) was used to estimate the sample size.

Statistical analysis

Data are presented as mean ± SD, median (interquartile range), or numbers of patients (%). Statistical analyses were performed using SPSS for Windows version 21.0 (IBM Corp., Armonk, NY, USA). The analysis of categorical variables was performed by Fisher's exact test or Chi-square test. Time-dependent data were compared using repeated-measures analysis of variance (between periods in each group and between groups). A preplanned subgroup analysis was conducted using an unpaired t-test if the data were normally distributed, while the Mann–Whitney U test was performed if the data were not normally distributed. All statistical tests were two-sided and a P-value lower than 0.05 was considered to be statistically significant.

Results

Participant characteristics

A total of 60 patients completed the study (30 in group C and 30 in GDFT group). The two groups showed no significant differences in age, sex, height, weight, past medical history, ASA grade, type of operation, operation time, and OLV time (Table 1). 

Intraoperative hemodynamic changes and arterial blood gas values

Hemodynamic monitoring was performed to evaluate the changes in circulation using different fluid therapies. The two groups showed no significant differences in hemodynamic indexes at T1. In comparison with the corresponding values at T1, the HR in group C decreased significantly at T2, and the MAP decreased significantly from T2 to T5, and CI decreased significantly from T2 to T4(< 0.05). SVV showed no significant change at all times (> 0.05). No significant change was observed in HR at all times in the GDFT group (> 0.05); MAP and SVV decreased significantly at T2 to T5; and CI decreased significantly at T2 (< 0.05). In comparison with group C, the GDFT group showed no significant difference in HR at all times (> 0.05). MAP and SVV in the GDFT group increased significantly from T3 to T5, and CI increased significantly from T3 to T5 (< 0.05) (Table 2) (Fig. 3). Radial artery blood gas pH and lac showed no significant difference between the two groups at T1, T4, and T5 (P > 0.05) (Table 3) (Fig. 4).

Intraoperative fluid volume and use of vasoactive drugs

The amount of intraoperative crystal fluid and norepinephrine in the GDFT group were significantly lower than those in group C, and the amount of colloidal fluid and total infusion were significantly higher than those in group C (P < 0.05). The two groups showed no significant differences in intraoperative urine volume and bleeding volume (P > 0.05) (Table 4).

Intraoperative rSO2

The two groups showed no significant difference in rSO2 at T1. In comparison with the corresponding values at T1, in group C, the rSO2 in the renal area decreased significantly from T3 to T4, the rSOin the brain decreased significantly from T3 to T5, and the rSOin the brachioradialis muscle decreased significantly from T3 to T5 (< 0.05). The GDFT group showed no significant change in the renal region rSOat all times (> 0.05), while the cerebral rSOdecreased significantly at T3 to T5, and the rSOin the brachioradialis muscle increased significantly at T2 and decreased significantly at T3 to T5 (< 0.05). In comparison with group C, patients in the GDFT group showed significantly higher renal rSO2 at T3 to T4 and rSOin the brachioradialis muscle at T4 to T5 (< 0.05). No significant difference was observed in the cerebral rSO2 at all times (> 0.05) (Table 5) (Fig. 5).

Postoperative variables

The two groups showed no significant differences in creatinine, urea nitrogen, and postoperative pulmonary complications on the first day after the operation (> 0.05). The 24 h QoR-15 score in the GDFT group was significantly higher than that in group C (< 0.05), and the incidence of postoperative nausea and vomiting was significantly lower than that in group C (< 0.05) (Table 6).

Discussion

Fluid therapy has always been the focus of perioperative management of thoracic surgery. However, the choice between restrictive fluid therapy or GDFT and the type of fluid infusion remain uncertain. This study compared the effects of SVV- and SV-targeted fluid therapy strategies and traditional restrictive fluid therapy strategies on the oxygen saturation of the brain, renal area, and brachioradialis muscle, as well as the hemodynamics and postoperative recovery in patients undergoing thoracoscopic lung resection. The results show that GDFT can improve the intraoperative renal area and brachioradialis muscle of patients undergoing thoracoscopic lung resection, better maintain hemodynamic stability, reduce the occurrence of postoperative nausea and vomiting, and improve the quality of postoperative recovery.

Current fluid-management strategies include open fluid therapy, restricted fluid therapy, and GDFT. In lung resection, OLV, operation, and ischemia-reperfusion can cause lung injury, while open fluid treatment can lead to the occurrence of pulmonary complications such as ALI and ARDS[31][32]. However, although the currently recommended restrictive fluid treatment scheme can reduce pulmonary complications after thoracic surgery, it also increases the risk of organ perfusion as a result of insufficient blood volume. Insufficient perfusion of important organs is an important factor causing organ injury. Therefore, a more reasonable fluid treatment strategy is worthy of further discussion. In recent years, GDFT has emerged as a finely individualized fluid treatment strategy, and its advantages have been confirmed in a variety of surgical types and patients[33]. However, studies describing the application of GDFT in patients undergoing thoracic surgery are limited, and its clinical value needs to be further explored. The essence of SVV is the degree to which the effective circulating capacity of the body is affected by changes in intrathoracic pressure caused by mechanical ventilation under interaction of the heart and lung. During OLV, because the pleura of the ventilation side lung is not damaged, the tightness of the thoracic cavity still exists, and during positive-pressure ventilation, the pressure in the pleural cavity of this side changes periodically, resulting in corresponding periodic changes in venous return blood volume. Although SVV can still guide perioperative fluid therapy, the diagnostic threshold and double-lung ventilation ratio should change. Studies have shown that GDFT based on dynamic indexes combined with stroke volume and cardiac output is more effective than that based on dynamic indexes alone[34]. Therefore, this study also targeted SVV and SV to monitor the volume reactivity and cardiac function of patients. When the volume reactivity was positive, rehydration was performed, and when the volume reactivity was negative, vasoactive drugs were used to maintain cardiac function and blood pressure. The results showed that the intraoperative circulation level of the two groups was in the normal range, with no significant differences in pH, lactic acid value, and urine volume. The two fluid management strategies can effectively maintain the intraoperative circulation of patients undergoing lung resection. However, in comparison with patients undergoing routine restrictive rehydration, patients in the GDFT group had higher MAP and CI, lower SVV, and required less use of vasoactive drugs. Thus, the intraoperative circulation of patients in the GDFT group is relatively more stable, which may be related to the greater intraoperative fluid input of patients in this group under the GDFT strategy. Notably, we performed additional evaluations by near-infrared spectroscopy and found for the first time that during OLV, the rSO2 in the brain, kidney and brachioradialis muscle decreased significantly in the restrictive fluid treatment group, and the rSO2 in the kidney and brachioradialis muscle was significantly higher in the GDFT group, indicating that GDFT can provide more sufficient local tissue perfusion. On one hand, this may be related to the infusion of more colloidal liquid, Studies have shown that[35][36] the colloidal solution can reduce the adhesion of leukocytes in blood vessels and the leakage of macromolecular substances, and stay in blood vessels longer. In the heterogeneous critical care population, improvements in microvascular flow indices were independent of changes in SV following fluid stimulation[37]. Thus, timely fluid infusion may enhance impaired microcirculation, i.e., peripheral blood flow, and thus enhance oxygen delivery to peripheral tissues. Therefore, it is more conducive to maintaining hemodynamic stability and improving tissue perfusion and oxygenation. On the other hand, restricted fluid therapy can increase the use of norepinephrine during operations, which can excite α-receptors to cause peripheral and renal vasoconstriction, resulting in a reduction in the rSO2 in the brachioradialis muscle and renal area. However, there was no significant difference in postoperative creatinine and urea nitrogen levels between the two groups, suggesting that although restrictive fluid treatment led to relatively insufficient intraoperative renal perfusion, it did not cause significant renal function injury. In addition, the results showed that during OLV, the cerebral rSO2 of the two groups decreased significantly, which was consistent with the findings of previous studies[38]. The results showed that OLV could lead to imbalance of brain oxygen supply and demand and a reduction in brain rSO2, but the blood pressure of the two groups was maintained in a relatively stable range in this study. The reduction in blood perfusion of the kidney, muscle, and gastrointestinal tract will also ensure blood supply to the brain and heart, so the reduction in brain rSO2 in both groups was not large. This study did not show a significant difference in brain rSO2 between the two groups. Although GDFT failed to reverse the reduction in brain rSO2 caused by OLV, the decrease of brain rSO2 was relatively small. Thus, GDFT has a positive effect on improving brain perfusion and oxygenation in patients with OLV.

In this study, GDFT increased the intraoperative fluid infusion of patients. However, we did not observe significant differences in postoperative pulmonary complications and postoperative hospital stay between the two groups. Interestingly, the incidence of postoperative nausea and vomiting was lower and the quality of postoperative recovery was higher in the GDFT group. Studies[39] have shown that postoperative nausea and vomiting may be related to low perfusion of gastrointestinal tissue, while the rSO2 of the brachioradialis muscle of the forearm reflects the oxygenation of gastrointestinal tissue to a certain extent. In this study, the intraoperative rSO2 of the brachioradialis muscle in the GDFT group was higher. This evidence further suggests that the GDFT combining SVV with SV is beneficial in increasing the intraoperative tissue perfusion of patients undergoing lung resection and reducing postoperative complications.

Limitations

First, fluid therapy is only implemented during operation, and the application of GDFT during the entire perioperative period may more effectively improve the prognosis of patients. Second, lung-protective ventilation with a lower VT and appropriate PEEP is becoming a standard of care in the perioperative period. However, previous studies have shown that the accuracy of SVV in predicting volume responses in patients undergoing OLV at low VT (6 mL·kg-1) is lower than that at high VT (8 mL·kg-1)[40]. Therefore, the VT during OLV in this study was set to 7 mL·kg-1, which cannot indicate the lung-protective ventilation strategy of low VT. However, an excessively high tidal volume is prone to lung injury. To reduce this risk, lung-protective ventilation strategy is gradually becoming the mainstream strategy of OLV, but the usage timing of GDFT and lung-protective ventilation strategy must be weighed.

Conclusions

GDFT guided by SVV and SV can effectively improve the perfusion and oxygenation of the renal area and brachioradialis muscle in patients undergoing thoracoscopic lung resection. It is a safe and effective fluid-management strategy to reduce the occurrence of postoperative nausea and vomiting and improve the recovery quality of patients.

Trial Status

Following the approval of the study protocol (2021ky178), the current protocol version was approved on 8 June 2021, and the recruitment of subjects will be commenced in June 2021 and will be completed in May 2022.

Abbreviations

rSO2, regional tissue oxygen saturation

GDFT, goal-directed fluid therapy

MAP, mean arterial pressure

QoR-15, Quality of Recovery-15

OLV, one-lung ventilation

AKI, acute kidney injury 

SV, stroke volume  

SVV, SV variation 

NIRS, near-infrared spectroscopy

ASA, American Society of Anesthesiologists physical

NYHA, New York Heart Association 

VT, tidal volume 

PEEP, positive end-expiratory pressure 

FiO2, fraction of inspired oxygen 

BP, blood pressure

CI, cardiac index 

SBP, systolic BP 

BIS, bispectral index 

ALI, acute lung injury 

ARDS, acute respiratory distress syndrome

Declarations

Acknowledgements 

We thank the staffs in the thoracic surgeons of Subei people’s hospital for their great support in the implementation of this study.

Authors’ contributions

Jiatong Zhang, Yang Zhang and Ju Gao designed the study protocol. Siyang Sun, Keting Wu and Liuqing Yang were responsible for following up with patients after surgery. Jiatong Zhang drafted the initial manuscript. Yang Zhang and Ju Gao critically revised the manuscript for important intellectual content. Final approval of the version to be published was given by all authors. The corresponding author attests that all listed authors meet the authorship criteria and that no others meeting the criteria have been omitted.

Funding 

This research was supported by The National Natural Science Fund, China (82172190,82101299), General Project of Medical Scientific Research Project of Jiangsu Provincial Health Commission (M2021105) and Special Fund for Yangzhou Key Laboratory Cultivation (YZ20211148).

Funding source had no involvement in study design, data collection, analysis, interpretation of the data, and in decision to submit the article. 

Availability of data and materials

The datasets analyzed during the current study will be available from the corresponding authors on reasonable request.

Ethics approval and consent to participate

The Ethics Committee of the Subei People's Hospital of Jiangsu Province approved the protocol of this trial (approval number: 2021ky244, approval date 8 June 2021). Participants’ or their representatives’ written informed consents will be obtained before they are enrolled in the trial. If the protocol or informed consent form should be modified, or if the primary investigators should be replaced, all the documents should be reviewed again and implemented after approval. The ethics committee approval will be available from the corresponding authors on reasonable request.

Consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.

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Tables

Table 1 Participant characteristics

 

 Group C 

(n=30)

 GDFT group

(n=30)

value

Age (yr)

59.3 (53.3, 68.0)

59.1 (53.3,66.8)

0.859

Sex (M/F)

9/21

13/17

0.284

Height (cm)

163.1(159.3,166.8)

162.8 (159.0,168.8)

0.882

Weight (kg)

61.9 (58.0,65.8)

59.0 (55.0,60.0)

0.060

Hypertension, n (%)

9 (30.0)

8 (26.7)

0.774

Diabetes mellitus, n (%)

5 (16.7)

4 (13.3)

0.718

ASA physical status(Ⅰ/Ⅱ/Ⅲ,n)

4/21/5

3/23/4

0.992

Thoracoscopic lobectomy/Thoracoscopic segmental pneumonectomy (n)

20/10

18/12

0.789

Operation time (min)

194.2±16.0

190.2±34.6

0.568

One-lung ventilation time (min)

184.8 (175.0,200.0)

182.5 (156.3,200.0)

0.959

Note: Data are expressed as mean ± SD or median (interquartile range). ASA, American Society of Anesthesiologists.

Table 2. Comparison of intraoperative hemodynamic indexes between the two groups

Variables

Group

T1

T2

T3

T4

T5

HR

(beats·min-1

C

GDFT

76.33±9.75

73.77±12.20

71.13±7.42a

73.27±7.75

73.27±9.07

73.30±10.36

72.17±8.87

74.77±8.70

72.40±8.11

72.47±10.66

MAP

(mmHg)

C

GDFT

85.27±6.65

86.63±6.49

80.57±7.38a

82.27±8.81a

72.93±5.73a

79.33±8.43ab

75.03±5.53a

81.30±8.25ab

78.53±6.90a

82.47±6.37ab

SVV

(%)

C

GDFT

11.50±2.66

11.93±2.35

11.57±2.22

10.60±2.04a

11.80±2.33

9.23±1.68ab

10.87±2.43

9.23±1.99ab

11.97±2.47

10.30±1.95ab

CI

(L·min-1·m-2

C

GDFT

2.82±0.50

2.89±0.44

2.53±0.35a

2.64±0.42a

2.30±0.33a

2.78±0.46b

2.45±0.40a

2.82±0.42b

2.62±0.41

3.00±0.34b

Note: in comparison with T1, a< 0.05; in comparison with group C, b< 0.05

Table 3. Comparison of intraoperative arterial blood gas indexes between the two groups

Variables

Group

T1

T4

T5

pH

C

GDFT

7.40±0.04

7.41±0.03

7.38±0.04

7.39±0.04

7.37±0.02

7.38±0.03

Lac

C

GDFT

1.07±0.23

1.06±0.30

1.12±0.26

1.04±0.26

1.20±0.26

1.13±0.28

 Table 4. Comparison of intraoperative fluid volume and use of vasoactive drugs between the two groups

Variables

Group C

GDFT group 

value

Crystal volume (ml)

754.0±96.1

570.5±103.7

<0.001

Colloidal volume (ml)

35.0 (20.0, 20.0)

497.7 (270.0, 720.0)

<0.001

Total volume (ml)

789.0±117.5

1067.8±349.7

<0.001

Urine volume (ml)

426.7 (200.0, 675.0)

478.3 (300.0, 600.0)

0.256

Bleeding volume (ml)

35.0 (20.0, 20.0)

55.0 (20.0, 50.0)

0.090

Norepinephrine dose (μg)

276.0±70.5

138.0±67.8

<0.001

Table 5. Comparison of intraoperative tissue oxygen saturation indexes between the two groups

Variables

Group

T1

T2

T3

T4

T5

Renal regional rSO2

C

GDFT

76.83±4.17

76.87±4.51

77.77±5.01

78.17±4.71

73.97±4.33a

76.23±3.82b

76.27±3.77a

76.27±3.77b

75.87±4.88

78.27±4.99

Cerebral rSO2

C

GDFT

72.83±4.34

72.40±4.69

73.13±4.57

74.33±3.68

66.57±4.93a

68.07±3.45a

67.23±4.52a

67.93±5.79a

70.10±4.37a

70.97±4.33a

Brachioradial muscle rSO2

C

GDFT

78.03±5.26

76.93±5.72

79.00±4.98

81.10±3.7a

73.33±4.96a

74.73±5.09a

72.13±5.02a

75.37±5.14ab

74.70±4.14a

79.10±5.28ab

Note: in comparison with T1, a< 0.05; in comparison with group C, b< 0.05

Table 6. Comparison of postoperative conditions between the two groups

 

Group C

GDFT group

value

Creatinine 1d after operation(μmol/L)

63.9 (54.0, 66.75)

64.8 (56.0, 73.5)

0.375

Urea nitrogen 1d after operation(mmol/L)

4.1 (3.0, 4.9)

4.5 (3.4, 5.7)

0.145

QoR-15 score

107.3±6.2

110.6±6.0

0.037

Postoperative hospital stay(d)

5.9 (5.0, 5.8)

5.8 (5.0, 6.0)

0.745

Postoperative nausea and vomiting(n,%)

12

5

0.045

AKI(n)

0

0

 

Bronchial fistula(n)

0

0

 

Atelectasis(n)

5

7

0.519

ALI(n)

0

0

 

ARDS(n)

0

0

 

pulmonary infection(n)

4

3

>0.999

Note: QoR-15 score: 15 items of recovery quality scale; AKI: acute renal injury; ALI: acute lung injury; ARDS: adult respiratory distress syndrome.