Objectives
This study aimed to compare the effect of sugammadex and neostigmine on neuromuscular block reversal and the incidence of postoperative pulmonary complications in patients undergoing lung cancer resection.
Design
A double-blind, randomized, prospective study.
Setting
A single major urban teaching and university hospital.
Participants
One hundred adult patients underwent elective radical resection of lung cancer under general anesthesia.
Interventions
Patients were assigned into neostigmine (0.05 mg/kg) + atropine 0.02 mg/kg group and sugammadex (2 mg/kg) group.
Measurements and Main Results
The primary outcomes were the incidence of any postoperative pulmonary complications, and the time to achieve 90% of train-of-four (TOF) after the administration of sugammadex or neostigmine. The secondary endpoints were the number of patients with TOF ratio (TOFr) <0.9 at the time of tracheal extubation, the incidence of readmission 30 days after discharge, and specific postoperative pulmonary complications. Results showed that the average time of recovery to TOFr ≥0.9 with sugammadex was 164.5 ± 27.7 seconds versus 562.9 ± 59.7 seconds with neostigmine + atropine treatment. Fewer sugammadex-treated patients did not achieve TOFr of 0.9 at the time of tracheal extubation than did neostigmine-treated participants. Patients in the sugammadex group had lower incidence of postoperative lung complications, and shorter durations of postanesthesia care unit stay and postoperative hospital stay than those in the neostigmine group. There was no significant difference in the incidence of readmission between the 2 groups.
Conclusions
Administration of sugammadex provided faster recovery of rocuronium-induced neuromuscular block when compared with neostigmine. Moreover, for patients undergoing lung cancer resection, administration of sugammadex could reduce the incidence of postoperative pulmonary complications and duration of postoperative hospital stay.
Key Words
LUNG CANCER IS THE deadliest malignant tumor, with the highest morbidity and mortality worldwide.
1
Surgery is by far the preferred treatment for lung cancer.2
As a vital part of modern anesthesia technology, muscle relaxants usually are used to elicit muscle paralysis during surgery. They not only provide good conditions for surgery and expand the scope of surgical treatment, but also are beneficial for respiratory management, and to avoid deep anesthesia.3
Most patients undergoing endotracheal intubation under general anesthesia receive nondepolarizing neuromuscular blocking (NMB) agents, such as rocuronium and vecuronium.4
However, postoperative residual NMB may cause adverse events during the recovery period of anesthesia, leading to respiratory insufficiency and other complications. A prospective multicenter study of patients who underwent elective open or laparoscopic surgery in China found that the incidence of residual NMB during tracheal extubation was 57.8%.5
It has been suggested that reducing residual NMB may decrease postoperative pulmonary complications. At present, the approaches to reduce the incidence of postoperative residual NMB and its related complications are continuous perioperative monitoring of neuromuscular function and the postoperative application of reversal agents to counteract muscle relaxation.6
As a common clinical acetylcholinesterase inhibitor, neostigmine effectively can inhibit cholinesterase to increase acetylcholine, which acts on cholinergic receptors and then excites nicotinic receptors, thereby improving muscle contractibility and achieving reversal of muscle relaxation.
7
It needs to be pointed out that cholinergic receptors consist of nicotinic receptors and muscarinic receptors (M receptor).8
Activation of M receptors by acetylcholine leads to slow heart rate, arrhythmias, augmented intestinal motility, bronchial responsiveness, and secretions. Some of these effects cause serious adverse consequences.9
To combat these adverse events, clinical use of neostigmine to reverse residual NMB must be accompanied by the administration of M receptor antagonists such as atropine, although it may cause blurred vision and tachycardia.10
Sugammadex is a gamma-cyclodextrin drug that inactivates nondepolarizing NMB agents in the vascular system.
11
Owing to its direct mechanism of action, sugammadex can reverse residual NMB without influencing N or M receptors, thus preventing cholinergic side effects including arrhythmias, respiratory muscle weakness, and hyper-salivation.12
Nevertheless, reports on the effects of sugammadex on pulmonary complications during hospitalization remain controversial. Murphy et al. have stated that patients who received sugammadex had a 40% reduction in adverse events compared with those who received neostigmine13
, while some researchers have failed to show that sugammadex decreases life-threatening complications related to residual paralysis.7
The authors designed a prospective study to compare the function of sugammadex and neostigmine on NMB reversal and the incidence of postoperative pulmonary complications associated with residual NMB in participants undergoing lung cancer resection. The authors hypothesized that sugammadex had a lower incidence of postoperative pulmonary complications and faster reversal of rocuronium-induced NMB than neostigmine.
Methods
Participants and Study Design
Patients who were scheduled for elective radical resection of lung cancer from January 2021 to April 2021 were enrolled in the double-blind, randomized, prospective study. All patients underwent lung lobectomy via video-assisted thoracic surgery. Inclusion criteria were (1) individuals aged ≥18 years older diagnosed with lung cancer by pathologic biopsy without metastasis to other organs and lymph nodes; (2) subjects who were willing to undergo bronchial intubation surgery under general anesthesia; (3) subjects who had stable vital signs including temperature, heart rate, respiration, and blood pressure, with American Society of Anesthesiologists (ASA) physical status classification score I-III; and (4) subjects who received steroidal nondepolarizing muscle relaxants (vecuronium or rocuronium). Exclusion criteria were (1) patients who had severe abnormal heart, liver, or kidney function; (2) ASA physical status classification score IV-VI; (3) patients suffered from contraindications of NMB and were allergic to sugammadex or neostigmine; and (4) patients who were lost to follow-up.
A total of 100 lung cancer participants were allocated randomly to sugammadex and neostigmine groups (n = 50/group). The patients in the sugammadex group received sugammadex 2 mg/kg of actual body weight (rounded off to 10 mg), while subjects in neostigmine group were given neostigmine 0.05 mg/kg of actual body weight (maximum 5 mg) accompanied by 0.02 mg/kg of atropine. The clinical characteristics of lung cancer patients were summarized in Table 1. This study was approved by the Ethics Committee of Taizhou Hospital of Zhejiang Province (No. K20200910), which was registered with Chictr.org.cn under ChiCTR2000039572. Informed consents were obtained from all individuals.
Table 1Demographic and Clinical Data
| Sugammadex Group (n = 50) | Neostigmine Group (n = 50) | p Value | |
|---|---|---|---|
| Age (y) | 56.7 ±10.3 | 57.2 ± 9.8 | 0.812 |
| Sex (male/female) | 22/28 | 23/27 | 0.841 |
| Weight (kg) | 60.4 ± 8.3 | 61.0 ± 7.9 | 0.777 |
| Height (cm) | 160.5 (155.0, 169.2) | 160.5 (155.0, 169.2) | 0.730 |
| ASA (II/III) | 45/5 | 43/7 | 0.538 |
| BMI (kg/m2) | 22.5 (22.0, 24.1) | 23.0 (22.0, 24.0) | 0.834 |
| Metabolic equivalent scores | 8.3 ± 2.2 | 8.3 ± 2.5 | 0.966 |
| Smoking status | 0.836 | ||
| No | 33 (66%) | 32 (64%) | |
| Yes | 17 (34%) | 18 (36%) | |
| Comorbidity | |||
| Hypertension | 17 (34%) | 17 (34%) | 1.000 |
| Diabetes mellitus | 10 (20%) | 11 (22%) | 0.806 |
| Chronic lung disease | 6 (12%) | 7 (14%) | 0.766 |
NOTE. Data are means ± standard deviation, N (%), or median (interquartile range).
Abbreviations: ASA, American Society of Anesthesiologists physical status classification; BMI, body mass index.
Anesthesia and Tracheal Extubation Procedure
All participants were fasted before surgery and no premedication was given. After arriving at the preoperative preparation room, they were subject to catheterization of a radial artery and right internal jugular vein under noninvasive monitoring, including heart rate, electrocardiography, pulse oxygen saturation, and noninvasive blood pressure. After successful puncture, patients were sent into the operating room for monitoring of oxygen saturation, electrocardiogram, heart rate, and blood pressure. Subsequently, they were given 100% oxygen during anesthesia induction. The anesthesia induction drugs were 0.6 mg/kg of rocuronium, 2 mg/kg of propofol, and 0.5 μg/kg of sufentanil. The authors performed endotracheal intubation with a double-lumen endobronchial tube when muscle relaxation (no reaction in response to the TOF stimulation) was confirmed. After successful intubation, the correct position of the endobronchial tube was determined with a fiberoptic bronchoscope; this was reconfirmed when the patients were in lateral decubitus position.
When one-lung ventilation was begun, lung-protective ventilation strategies were implemented to maintain end-tidal CO2 concentration at 35 to 40 mmHg: low tidal volume (4-6 mL/kg) and positive end-expiratory pressure. For maintenance of anesthesia, sevoflurane, propofol, dexmedetomidine, and remifentanil were used to keep the bispectral index values of 40 to 60. Train of four response gradually disappeared with the increase of nondepolarizing NMB, beginning with suppression of fourth twitch (T4) and ending at first twitch (T1).
14
At the appearance of T1 in response to TOF stimulation, rocuronium 0.1 mg/kg was required to maintain a deep muscle relaxation.At the end of surgery, the surgeon performed "?> intercostal nerve block. The administration of anesthesia drugs was terminated, and local infiltration anesthesia was performed with 0.75% ropivacaine injection. All patients received patient-controlled intravenous analgesia by using an intravenous Hospira Gemstar electronic infusion pump, which contained 1 ug/mL of sufentanil plus 0.15 to 0.3 ug/kg/min of remifentanil in normal saline with a total volume of 300 mL. It was delivered at a 1 mL bolus dose, with 10-minute lock-out time. Meanwhile, corresponding NMB reversal agents (sugammadex and neostigmine) were given when the third twitch (T3) occurred in response to the TOF stimulation. TOF monitoring continued until the end of anesthesia. To compare recovery of NMB between the 2 groups, TOF ratio (TOFr, a ratio of the amplitude of T4:T1) at different times during the surgery and at the time of tracheal extubation were measured using TOF-Watch SX muscle relaxation monitor. The double-lumen endobronchial tube was removed when TOFr reached 0.9, which was considered adequate recovery from NMB, and patients were then sent to the postanesthesia care unit (PACU) for continued monitoring. All patients received oxygen after arriving at PACU. At the same time, nurses in the PACU closely monitored these patients. "?>
Observational Indices
The primary endpoints were the incidence of any postoperative pulmonary complications and the time to achieve 90% of TOF after administration of sugammadex or neostigmine. The second outcomes were the number of patients with TOFr <0.9 at the time of tracheal extubation, the incidence of readmission 30 days after discharge, the specific postoperative pulmonary complications associated with residual NMB (pleural effusion, pulmonary atelectasis, and pneumonia), and other pulmonary complication (pneumothorax). Pulmonary complications were determined based on the radiological findings as defined in the European Perioperative Clinical Outcome guidelines.
15
- Jammer I
- Wickboldt N
- Sander M
- et al.
Standards for definitions and use of outcome measures for clinical effectiveness research in perioperative medicine: European Perioperative Clinical Outcome (EPCO) definitions: A statement from the ESA-ESICM joint taskforce on perioperative outcome measures.
Eur J Anaesthesiol. 2015; 32: 88-105
The demographic information of patients’ age, sex, weight, height, body mass index, ASA physical status classification, metabolic equivalent scores, smoking status, and comorbidities (hypertension, diabetes mellitus, and chronic lung disease) were collected. Pulmonary function tests (forced vital capacity, forced expiratory volume in one second, and carbon monoxide diffusing capacity), arterial blood gas analysis (pH, PO2, and PCO2), total usage of rocuronium, sufentanil and remifentanil, blood loss, single lung ventilation time, noninvasive ventilation, reintubation, time required to wean off oxygen (time required by patients at PACU from oxygen inhalation to wean off oxygen), time required for postoperative drainage volume <200 mL, the removal time of closed thoracic drainage tube after surgery, as well as tracheal extubation time after sugammadex/neostigmine administration were documented. Durations of anesthesia, surgery, PACU stay. and postoperative hospital stay were recorded. After the patients were resuscitated at PACU, Confusion Assessment Method was used daily to evaluate the occurrence of postoperative delirium until discharge.
Randomization and Blinded Allocation of Reversal Agents
Participants were assigned randomly to rocuronium-induced NMB reversal with neostigmine or sugammadex by permutation, which consisted of a computer-generated randomized allocation sequence (1:1 ratio). Notably, the allocation sequence was done by statisticians who did not take part in the follow-up study, and a nurse anesthesiologist who was not involved in the study prepared reversal agents and sealed envelopes for patients. There were 2 opaque envelopes for each patient. Allocation was concealed in one sequentially numbered envelope, and another was given to the supervisor of the research in case of any emergency. An anesthesiologist who was not involved in the study assessed TOF. Study personnel that participated in the research were blinded to the contents of each numbered envelope and group allocation until study completion.
Sample Size
The sample size was calculated according to the authors’ preliminary study, 44 patients in each group would have an 80% power to detect a difference of 0.75 in time to 90% TOF between the 2 groups using two-sided analysis with an error of 0.05. To allow for a possible 10% dropout rate, the authors enrolled a total of 100 participants in this study.
Follow-up
Patients underwent chest radiographic examination before discharge. A follow-up telephone visit and electronic medical record screening were completed 30 days after discharge, and the number of patients readmitted within 30 days also was documented.
Statistical Analysis
SPSS 20.0 was adopted for statistical analysis. Normality of continuous variables were assessed using Shapiro-Wilk; data were presented as means ± standard deviation for normally distributed variables, followed by independent t test for the detection of differences. For abnormally distributed variables, data were expressed as medians with interquartile ranges and compared with Mann-Whitney U test. χ2 test was used for the comparison of categorical variables. Logistic regression analysis was adopted for categorical variables, odds ratio (OR) and 95% confidence interval (CI) were calculated. Bilateral p < 0.05 indicated statistically significant difference.
Results
Participants’ Baseline Data
As shown in Table 1, there were 22 males and 28 females in the sugammadex group with an average age of 56.7 ± 10.3 years, and 23 males and 27 females in the neostigmine group with an average age of 57.2 ± 9.8 years. No significant differences in age, sex, weight, height, ASA physical status classification, body mass index, metabolic equivalent scores, smoking status, or comorbidities (hypertension, diabetes mellitus, and chronic lung disease) were found between the 2 groups. In addition, no postoperative delirium occurred in the sugammadex group and neostigmine + atropine group.
Comparison of Arterial Blood Gas Analysis Between the 2 Groups
There were no significant differences in pH, PO2, and PCO2 between the neostigmine group and sugammadex group before surgery and at 30 min of single lung ventilation (Table 2). However, at the time of discharge from PACU, patients in the sugammadex group showed significantly higher PO2 value (113 v 94 mmHg) and lower PCO2 value (47 v 50.5 mmHg) than those in neostigmine group (both p < 0.0001), with similar pH value between the 2 groups (7.39 ± 0.04 v 7.38 ± 0.037 mmHg, p = 0.305).
Table 2Perioperative Arterial Blood Gas Analysis
| Sugammadex Group (n = 50) | Neostigmine Group (n = 50) | p Value | |
|---|---|---|---|
| Preoperative | |||
| pH (mmHg) | 7.39 ± 0.03 | 7.39 ± 0.02 | 0.428 |
| PO2 (mmHg) | 83.5 ± 7.9 | 84.1 ± 7.7 | 0.712 |
| PCO2 (mmHg) | 41 (39, 45) | 41 (39, 43) | 0.428 |
| Single lung ventilation for 30 min | |||
| pH (mmHg) | 7.37 ± 0.04 | 7.363 ± 0.04 | 0.080 |
| PO2 (mmHg) | 283 (183.7, 367.0) | 291.5 (206.0, 343.7) | 0.850 |
| PCO2 (mmHg) | 48 (46, 50) | 48 (46, 50) | 0.504 |
| At the discharge from PACU | |||
| pH (mmHg) | 7.39 ± 0.04 | 7.38 ± 0.04 | 0.305 |
| PO2 (mmHg) | 113 (102.0, 119.2) | 94 (86.7, 104.5) | < 0.0001 |
| PCO2 (mmHg) | 47 (44, 49) | 50.5 (48, 53) | < 0.0001 |
NOTE. Data are means ± standard deviation or median (interquartile range).
Abbreviation: PACU, postanesthesia care unit.
Comparison of Laboratory Indices Between the 2 Groups
From Table 3, pulmonary function test results, total usage of rocuronium, blood loss during surgery, single lung ventilation time, the requirement for noninvasive ventilation, the incidence of reintubation, total usage of sufentanil, total usage of remifentanil, anesthesia time, and surgery time were not significantly different between the sugammadex and neostigmine groups (all p > 0.05). Nevertheless, compared with neostigmine group, patients in the sugammadex group had shorter tracheal extubation time, time required to wean off oxygen, time required for postoperative drainage volume <200 mL, removal time of closed thoracic drainage tube after surgery, duration of PACU stay, and duration of postoperative hospital stay (p < 0.0001, p = 0.001, p < 0.0001, p < 0.0001, p = 0.001, and p < 0.0001, respectively).
Table 3Perioperative Management
| Sugammadex Group (n = 50) | Neostigmine Group (n = 50) | p Value | |
|---|---|---|---|
| Lung functional tests | |||
| FVC (%) | 116.0 (104.7, 124.0) | 115.0 (106.0, 119.2) | 0.503 |
| FEV1 (%) | 80.0 (75.0, 83.0) | 78.0 (72.7, 83.0) | 0.659 |
| DLCO (%) | 89.5 (77.5, 96.2) | 90.5 (85.5, 97.2) | 0.234 |
| Total usage of rocuronium (mg) | 80 (70, 90) | 80 (70, 90) | 0.869 |
| Blood loss (mL) | 20 (10, 30) | 25 (20, 30) | 0.127 |
| Single lung ventilation time (min) | 135.5 (100.0, 153.5) | 132.5 (100.0, 151.2) | 0.634 |
| Extubation time after administration (min) | 5 (3, 8) | 9 (8, 11) | < 0.0001 |
| Noninvasive ventilation | 2 (4%) | 6 (12%) | 0.140 |
| Reintubation | 0 | 2 (4%) | 0.153 |
| Time required to wean off oxygen (min) | 40.0 (30.0, 51.5) | 50.0 (40.0-65.0) | 0.001 |
| Total usage of sufentanil (ug) | 34.38 ± 5.61 | 34.90 ± 5.22 | 0.632 |
| Total usage of remifentanil (mg) | 2.53 (1.16, 3.01) | 2.56 (1.29.2.82) | 0.879 |
| The time required for postoperative drainage volume <200 mL (d) | 3.0 (2.0, 4.0) | 5.0 (5.0, 8.0) | 0.0001 |
| The removal time of closed thoracic drainage tube after surgery (d) | 3.0 (3.0, 4.0) | 6.0 (6.0, 9.2) | 0.0001 |
| Duration of anesthesia (min) | 177.5 (12.0, 200.0) | 177.5 (138.7, 192.5) | 0.912 |
| Duration of surgery (min) | 140.0 (100.0, 161.2) | 143.0 (108.7, 160.0) | 0.868 |
| Duration of PACU stay (min) | 55.0 (45.0, 66.2) | 65.0 (55.0, 80.0) | 0.001 |
| Duration of postoperative hospital stay (d) | 4.0 (3.0, 5.2) | 8.0 (8.0, 11.2) | < 0.0001 |
NOTE. Data are means ± standard deviation, N (%), or median (interquartile range).
Abbreviations: DLCO, carbon monoxide diffusing capacity; FEV1; forced expiratory volume in one second; FVC, forced vital capacity; PACU, postanesthesia care unit.
Primary and Secondary Endpoints
For the primary outcomes, the incidence of postoperative pulmonary complication in the sugammadex group was lower than that in the neostigmine group (20% v 42%; OR: 2.90; 95% CI: 1.187-7.067; p = 0.017). In addition, the recovery time to a TOFr of 0.9 was 164.5 ± 27.7 seconds after administration of 2 mg/kg of sugammadex, but it was 562.9 ± 59.7 seconds after neostigmine 0.05 mg/kg + atropine 0.02 mg/kg treatment (p < 0.0001) (Table 4).
Table 4Primary and Secondary Outcomes
| Sugammadex Group (n = 50) | Neostigmine Group (n = 50) | p Value | Mean Difference | OR (95% CI) | |
|---|---|---|---|---|---|
| Primary outcomes | |||||
| Postoperative lung complications | 10 (20%) | 21 (42%) | 0.017 | 2.90 (1.187-7.067) | |
| Recovery time to a TOFr of 0.9 (s) | 164.5 ± 27.7 | 562.9 ± 59.7 | < 0.0001 | –398.4 (–521.2 to 275.6) | |
| Secondary outcomes | |||||
| Specific lung complications | |||||
| Pneumothorax | 4 (8%) | 11 (22%) | 0.05 | 3.24 (0.956-11.001) | |
| Pleural effusion | 6 (12%) | 15 (30%) | 0.27 | 3.14 (1.105-8.942) | |
| Pulmonary atelectasis | 4 (8%) | 14 (28%) | 0.009 | 4.47 (1.355-14.755) | |
| Pneumonia | 7 (14%) | 15 (30%) | 0.53 | 2.63 (0.967-7.170) | |
| Number of patients with TOFr <0.9 at the time of tracheal extubation | 2 (4%) | 15 (30%) | 0.01 | 10.29 (2.209-47.901) | |
| 30-day hospital readmission | 2 (4%) | 3 (6%) | 0.646 | 1.53 (0.245-9.587) |
NOTE. Data are N (%) or means ± standard deviation.
Abbreviations: CI, confidence interval; OR, odds ratios; TOFr, train-of-four ratio.
For the secondary outcomes, a 3.5-fold decrease in the incidence of postoperative pulmonary atelectasis was evident in the sugammadex group when compared with the neostigmine group (OR: 4.47; 95% CI: 1.355-14.755; p = 0.009). The incidence of pneumothorax, pleural effusion, and pneumonia in the sugammadex group were 2.75-, 2.5-, and 2.14-fold lower than those in the neostigmine group (p = 0.05, p = 0.27, and p = 0.53, respectively). At the time of tracheal extubation, 2 sugammadex-treated patients (4%) and 15 neostigmine-treated patients (30%) who were intolerant to double-lumen endobronchial tube had their trachea removed once TOFr reached 0.85 (OR: 10.29; 95% CI: 2.209-47.901; p = 0.01). Thirty days after discharge, 2 cases in the sugammadex group and 3 cases in the neostigmine group were readmitted to the authors’ hospital (p = 0.646) (Table 4).
Discussion
A complete and rapid reversal of residual NMB without side effects is ideal for improving patient safety, regardless of the depth of muscle relaxant and the total amount of muscle relaxant used.
16
As a NMB reversal agent, neostigmine acted slowly, starting about 2 to 3 minutes after administration and reaching its peak at 7 to 15 minutes.16
,17
In contrast to neostigmine, sugammadex can reverse NMB accurately and quickly, and promote the recovery of voluntary breathing and limb mobility in patients undergoing general anesthesia.18
,19
In this prospective research, the authors compared the efficacy of NMB reversal with neostigmine or sugammadex in participants who underwent lung cancer resection and received rocuronium for muscle relaxation. There is general agreement that return to a TOFr of ≥0.9 should be achieved before tracheal extubation. In the subjects given a 0.05 mg/kg dose of neostigmine (plus atropine 0.02 mg/kg), the mean recovery time of TOFr ≥0.9 was 562.9 ± 59.7 seconds, whereas time of TOFr ≥0.9 was 164.5 ± 27.7 seconds in subjects given a 2 mg/kg dose of sugammadex. Likewise, Brett et al.
20
presented data supporting the faster reversal of rocuronium-induced NMB by 2 mg/kg of sugammadex than 0.05 mg/kg of neostigmine. Longer indwelling time of tracheal intubation may increase larynx or respiratory mucosa injury, resulting in postoperative sore throat. The patients in the sugammadex group showed shorter time from the administration of muscle relaxant antagonist to tracheal extubation in comparison with the neostigmine group. Of note, due to intolerance to the double-lumen endobronchial tube, tracheal extubation was performed in 2 sugammadex-treated patients and 15 neostigmine-treated patients with TOF level <90%. Whereas, none of the patients developed any complications associated with early removal of the endotracheal tube. It has been reported the occurrence rate of residual NMB was 0% to 3% in the sugammadex group and 10% to 71% in the neostigmine group,21
which is consistent with this study. Taken together, these data suggested that effect of sugammadex on the reversal of rocuronium-induced NMB was better than that of neostigmine.Regarding safety, despite improvements in surgical techniques, perioperative periods, and patient selection to reduce the incidence of postoperative pulmonary complications, residual NMB remains a risk factor for developing airway obstruction, pulmonary complications, and hypoxia.
22
,23
As mentioned above, the reversal rate of NMB was faster in the sugammadex group; in this study, the authors found that the time required to wean off oxygen in the group receiving sugammadex was significantly lower than that in the neostigmine group at the PACU. Unfortunately, the authors did not record the time patients spent on oxygen uptake in the ward. In addition, surgical cases in both groups developed pulmonary complications, and 10 of 50 patients (20%) suffered from at least 1 pulmonary complication in the sugammadex group when compared with 21 of 50 (42%) in the neostigmine group, with significant difference.It has been reported that sugammadex and neostigmine could reduce the incidence of pulmonary atelectasis and pneumonias.
24
Pulmonary atelectasis describes the state of collapsed and nonaerated region of lung parenchyma.25
Incomplete reversal of NMB results in low muscle tone that affects the strength of the diaphragm, upper airway, and chest wall, which may reduce the patient's ability to cough and clear secretions and increase alveolar collapse, thereby leading to pulmonary atelectasis. It should be noted that postoperative pulmonary complications such as pneumonia, atelectasis, and pleural effusion are mutually causal. Patients with pneumonia often have enhanced bronchial secretions, which tend to aggravate atelectasis when the clearance ability is poor. Besides, pneumonia can produce inflammatory exudation due to increased permeability of local capillaries, leading to the occurrence of pleural effusion.Malik DB, Aggarwal S: 30 day readmission rate for patients discharged with chronic obstructive pulmonary disease (COPD): Analysis of 1,858,618 admissions. Which patients ARE most at risk? Proceedings of the 37th Annual Meeting of the Society of General Internal Medicine, April, 2014, United States, J Gen Intern Med 29, Springer-Verlag, 2014, pp 6.
26
Pleural effusion generally is caused by an imbalance between hydrostatic pressure and osmotic pressure in lung capillaries and interstitium. As reported by Han et al.,27
residual NMB could impede respiratory muscular function and lung expansion, which might decrease the negative intrapleural pressure and eventually result in pleural effusion. Moreover, pleural effusion also may develop into more serious complications, such as atelectasis.28
Severe atelectasis may induce a variety of clinical conditions, including impaired blood oxygenation, chest tightness, shortness of breath, dry cough, and decreased lung compliance,29
ultimately elevating the difficulty of treatment. In this study, the incidence of pulmonary atelectasis in sugammadex-treated patients was >3 times lower than that in neostigmine-treated patients (8% v 28%); and there was a nonstatistically significant trend toward more frequent pneumonia and pleural effusion in neostigmine-treated cases in comparison with sugammadex-treated cases. The possible explanation for the authors’ findings is that sugammadex prevents the development of pulmonary atelectasis by improving electromyographic activity of the diaphragm and intercostal muscles, thereby augmenting tidal volumes and the ability to clear secretions.30
Overall, these data indicated that sugammadex was superior to neostigmine in lowering postoperative pulmonary complications associated with residual NMB.In addition to NMB-related pulmonary complications, the authors also found a statistically significant difference in pneumothorax between the 2 groups. Pneumothorax is classified into 3 levels based on the air leakage in the chest drainage bottle: level 1, air leakage occurs only when patients cough violently, exhale strongly or breathe deeply; level 2, patients have air leakage when they talk; and level 3, patients have air leakage in the case of calm breathing, without any exertion, talking, and coughing. In this research, patients suffered from pneumothorax above level 2, mainly iatrogenic pneumothorax such as bronchial fistula. Previous retrospective studies have pointed out that there is no statistical difference in the occurrence of pneumothorax between sugammadex and neostigmine groups
27
,31
; however, sugammadex-treated patients had lower incidence of pneumothorax than neostigmine-treated patients in this study. One of the reasons is that more rocuronium injection is used in the sugammadex group than in the neostigmine group (despite no significant difference, with average dosage: 81.8 mg v 80.62 mg), which allows for deeper muscle relaxation that made it easier for the surgeon to suture bronchus without causing a tear in the bronchial suture. Because torn bronchial suture can cause bronchial fistula. In addition, mechanical ventilation is related to the incidence of iatrogenic pneumothorax.32
Small sample size of this study also might be the potential reason for the statistical difference in iatrogenic pneumothorax between the 2 groups, and a larger sample size is required for further analysis in the future.A noteworthy finding of this research was the 2-fold decreased duration of postoperative hospital stay in subjects given sugammadex in comparison with neostigmine group. This finding stays in line with a recent study where the length of hospital stay was lower when reversed with sugammadex compared with patients who were administered with neostigmine.
33
First, the interaction between pulmonary complications can increase the difficulty of postoperative treatment and thus prolong the length of hospital stay. Second, in general, the closed thoracic drainage tube can be removed once the drainage volume in the closed thoracic drainage bottle is <200 mL in any 24 hours after surgery. In addition to the above factor, the removal of postoperative thoracic closed drainage tube also needs to consider other factors, such as the properties of drainage fluid and fever. In the authors’ research, patients in sugammadex-treated cases had shorter time required for postoperative drainage volume <200 mL and removal time of closed thoracic drainage tube after surgery than neostigmine-treated cases, suggesting that these 2 factors were related to the prolonged hospital stay of patients receiving neostigmine. Kumar et al. have suggested that higher doses of rocuronium may be implicated in residual curarization and prolongation of stay in the PACU.34
In contrast, since sugammadex reversed NMB faster than neostigmine,35
the length of stay in the PACU was shortened in the group receiving sugammadex compared to that receiving neostigmine.Conclusions
These data support faster reversal of rocuronium-induced NMB by 2 mg/kg of sugammadex than 0.05 mg/kg of neostigmine. Sugammadex-treated patients had lower incidences of postoperative pulmonary complications associated with residual NMB (pleural effusion, pulmonary atelectasis, and pneumonia) and other pulmonary complication (pneumothorax). In summary, 2 mg/kg of sugammadex is an effective alternative to conventional reversal agents for patients with lung cancer resection.
Conflict of Interest
None.
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Article info
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Published online: April 04, 2022
Footnotes
This study was supported by Taizhou Municipal Science and Technology Bureau (No.1901ky20 and No.20ywa15).
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- Influence of Sugammadex in Decreasing Postoperative Pulmonary Complications in Thoracic Surgery, is There Evidence?Journal of Cardiothoracic and Vascular AnesthesiaVol. 36Issue 9
- PreviewIn thoracic surgery, postoperative pulmonary complications (PPC) are still the major cause of postoperative morbidity and mortality, affecting patient outcomes and prolonging hospital stays.1 Inadequate reversal of neuromuscular blockade increases the risk of PPC. New drugs such as sugammadex, a synthetic gamma cyclodextrin, have been introduced to overcome this residual muscle weakness; they specifically are designed to directly encapsulate, bind, and inactivate steroidal neuromuscular blockade.
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