Effect of sugammadex on postoperative pulmonary complications in patients with respiratory dysfunction after laparoscopic gastric or intestinal surgery: A retrospective study

Use of sugammadex is associated with fewer postoperative pulmonary complications. This study investigated the relationship between sugammadex and postoperative pulmonary complications (PPC) in specic patients with respiratory dysfunction. The authors reviewed the electronic medical and anesthesia records of patients with respiratory dysfunction who had laparoscopic gastric or intestinal surgery at a single center between May 01, 2018, and December 31, 2019. The patients were divided into the sugammadex group and the non-sugammadex group, based on whether or not they received sugammadex. Binary logistic regression analyses were used to characterize the differences in incidence of PPC. pleural effusion, incidence of massive pleural effusion after operation, and rate of postoperative dyspnea, between the two groups after propensity score matching. A rank-sum test was performed on variables that were non-normally distributed, including infusion volume, urine output, bleeding volume, length of hospital stay, length of hospitalization after operation, hospital cost, spontaneous recovery time, awakening time, and exhaustion time.


Background
Respiratory function is impaired during general anesthesia [1]. Respiratory complications are associated with longer hospitalization and increased nancial cost [2]. Numerous studies have explored strategies for effectively protecting respiratory function [3][4]. The use of neuromuscular blockade (NMB) drugs is related to adverse respiratory events after anesthesia. Patients with a history of pulmonary disease have increased risk of postoperative pulmonary complications (PPC) [5][6]. Neostigmine, which is a cholinesterase inhibitor reversal agent, may increase airway resistance and airway secretions. Muscarinic antagonists are often used to reduce side effects, but adverse pulmonary effects cannot be prevented in speci c patients, such as asthmatic patients.
Sugammadex is a modi ed gamma-cyclodextrin, which is used for the reversal of NMB induced by aminosteroid neuromuscular blocking agents, particularly rocuronium [7][8][9]. It facilitated the clinical application of a high-dose muscle relaxant anesthetic technique aimed at maintaining deep NMB throughout the surgical procedure. Maintaining deep NMB improves surgical working conditions in selected laparoscopic procedures [10][11]. Sugammadex can rapidly reverse NMB, regardless of the depth of the block, and is associated with a lower risk of postoperative residual curarization after extubation [12][13][14]. A recent study showed that spontaneous recovery of NMB was an independent risk factor for PPC in intermediate-to-high risk patients undergoing abdominal surgery [15].
This study aimed to evaluate the relationship between sugammadex and PPC in patients with respiratory dysfunction following laparoscopic gastric or intestinal surgery.

Methods
This retrospective observational study was approved by the department of anesthesiology at Ningbo First Hospital (Approval number: 2020-R020, Approval date: February 24, 2020, Ethical committee: Ningbo First Hospital, Zhejiang-Province, China).

Study population
All laparoscopic gastric or intestinal surgery patients with respiratory dysfunction operated between May 01, 2018, and December 31, 2019, were included in this retrospective study. The requirement for informed patient consent was waived because of the retrospective non-interventional study design. The exclusion criteria were as follows: American Society of Anesthesiologists (ASA) physical status ≥ IV, incomplete medical documentation, without pulmonary function tests or with no history of pulmonary disease before operation. Fig. 1. After exclusion, a total of 112 patients were enrolled and available for analysis (Fig. 1). Patients in the S group received sugammadex (n = 46), while patients in the N group did not receive injection of sugammadex (n = 66). Patient characteristics were compared between the sugammadex and nonsugammadex groups before propensity score matching in patients who underwent laparoscopic gastric cancer surgery (Table 1).
1 Patient characteristics Table 1 shows the demographic and pre-operative data. There were signi cant differences in preoperative medications between the sugammadex and non-sugammadex groups. Table 2 shows the intraoperative data. There were signi cant differences in the anesthesia depth monitoring between the sugammadex and non-sugammadex groups. The data are presented as mean ± SD or number (percentage).
ASA, americansociety of anesthesiologists; BMI, body mass index .    The data are presented number (percentage).

Discussion
This was the rst study on sugammadex use in patients with respiratory dysfunction diagnosed by pulmonary function test before surgery, which had more clinical signi cance than patients diagnosed with existing or a previous history of pulmonary disease [16]. In this study, sugammadex was associated with superior recovery of respiratory function after anesthesia compared with neostigmine in patients with pulmonary dysfunction, including consciousness recovery time, and tracheal extubation time. In this study, we de ned awakening, orientation, and cooperation as consciousness recovery, and de ned the time between study drug administration and consciousness recovery as consciousness recovery time. This retrospective study found that sugammdex achieved a shorter consciousness recovery time than neostigmine in patients with pulmonary dysfunction, which was similar to Jones et al. study [17]. The mechanism by which sugammadex reduces consciousness recovery time remains unclear, and a potential explanation is the afferenttation (muscle spindle) theory [18][19]. This theory states that afferent signals generated in muscle stretch receptors reach arousal centers in the brain to induce arousal via afferent nerve pathways. This implies that NMB has a sedative effect by decreasing afferent input and subsequent stimulation of brain arousal centers [19][20]. Tracheal extubation time was de ned as the time between study drug administration to extubation, which was much shorter in the sugammadex group, as shown in a previous study [21], including in the elderly or pediatric population [22][23], because of a different mechanism than neostigmine by directly binding and rapidly inactivating steroidal neuromuscular blockers [24].
Numerous studies have investigated the in uence of NMB in respiratory outcome after anesthesia, and neostigmine was shown to have direct detrimental effects [25]. In contrast, other studies reported that after administration of NMB, sugammadex was associated with fewer postoperative adverse respiratory events [26][27]. In this study, administration of sugammadex was associated with fewer PPCs, such as postoperative cough, pleural effusion (all), massive pleural effusion and breathing failure in patients with pulmonary dysfunction before operation. However, the relationship between administration of NMB and postoperative complications remains controversial [28][29][30]. This study showed that sugammadex administration lowered the rate of transfer to ICU in patients with pulmonary dysfunction, which was related to a lower incidence of residual NMB, which was in agreement with the ndings of Yea-Ji Lee [31].
In this study, more PPCs were observed in the neostigmine group, which may result in higher rate of ICU treatment, such as ventilator therapy and the environment of ICU, and basic pulmonary disease. These factors increased the risks of pneumonia, atelectasis and other pulmonary dysfunction in these speci c patients. These ndings were in agreement with the results of a retrospective study, which showed that RNMB reversal with sugammadex reduced the risk of pulmonary complications in elderly ASA 3/4 patients [32]. Sugammadex usage facilitated rapid reversal of deep NMB, and the early recovery of spontaneous breathing obviously reduced the rate of unplanned admissions and transfers to the ICU after operation, especially in these pulmonary dysfunction patients, in whom the main concern was the recovery of respiratory function. A signi cantly higher incidence of pulmonary complications such as cough and pneumonia was observed in the non-sugammadex group. However, there was no evidence of fewer occurrence of postoperative fever in the non-sugammadex group, which may be due to some infections related to surgery, such as incision infection, intra-abdominal infection, anastomotic stula, etc.
These infections may lead to high fever.
In this study, we monitored detailed PPCs, including cough, pneumonia, pleural effusion (all), pleural effusion (little), pleural effusion (massive), di culty in breathing, re-intubation, and atelectasis. The incidence of postoperative cough, pleural effusion (all), massive pleural effusion and breathing failure were signi cantly lower in the patients with pulmonary dysfunction before operation who received sugammadex. In addition, the sugammadex group tended to have a slightly lower rate of fever and total pleural effusion. However, there was no difference in CT diagnosis of pneumonia, and a small volume of pleural effusion was observed. In the future, a prospective study is needed to investigate the effects of sugammadex on patients with different levels of pulmonary dysfunction before operation, which will bring deeper guiding signi cance to clinical work in the future.
Our study also has some limitations: Firstly, previous studies have shown that PPCs are associated with higher hospital costs. This study found that administration of sugammadex was associated with fewer respiratory system complications, which was in turn closely associated with lower rate of transfer to ICU, and length of stay in hospital after surgery. Length of stay in hospital, postoperative hospitalization, and hospital costs showed no signi cant differences between the groups. One reason for this nding may have been the small sample size, which is a limitation of this study. The second limitation of this study was the absence of records on the costs after surgery. In the future, we will design more complete prospective studies to compare postoperative hospitalization costs. No complication related to sugammadex was observed in the sugammadex group, while the complications related to ERAS showed no difference between the two groups, which may be due to the retrospective study design. Another important reason for these negative results could be the small sample size of speci c patients.

Conclusions
In conclusion, we found sugammadex can reduce PPCs and postoperative ICU admission in patients with pulmonary dysfunction, including postoperative cough, pleural effusion (all), massive pleural effusion and breathing failure. sugammadex was associated with superior recovery of respiratory function after anesthesia.

Declarations
Ethics approval and consent to participate This retrospective observational study was approved by the department of anesthesiology at Ningbo First Hospital (Approval number: 2020-R020, Approval date: February 24, 2020, Ethical committee: Ningbo First Hospital, Zhejiang-Province, China). The requirement for informed patient consent was waived because of the retrospective non-interventional study design.

Consent for publication
Not applicable.

Availability of data and materials
The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request. Flow chart depicting patient selection protocol in this study.