Influence of reversal with sugammadex or neostigmine on postoperative bowel movement following robotic thyroidectomy: a retrospective study

doi:10.21203/rs.3.rs-26723/v1

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Influence of reversal with sugammadex or neostigmine on postoperative bowel movement following robotic thyroidectomy: a retrospective study

https://doi.org/10.21203/rs.3.rs-26723/v1

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Background

Postoperative bowel dysfunction poses difficulty during recovery, and reversal agents may affect bowel function. The purpose of this study was to determine whether time to first postoperative bowel movement after non-abdominal surgery differs among neuromuscular (NM) blockade reversal with either anticholinesterase/anticholinergic combination or sugammadex.

Methods

The electronic medical records of 108 patients who underwent robotic thyroidectomy between March 2018 and July 2018 were retrospectively reviewed. The use of agents to reverse NM blockade (neostigmine 1 mg and glycopyrrolate 0.2 mg, or sugammadex 2 mg/kg) was decided by the attending anesthesiologist. Demographic, clinical, and laboratory findings and first gas-passing time after surgery were assessed.

Results

The median gas passing time after operation was 957.5 min (425–1455) in the neostigmine group and 600 min (310–1080) in the sugammadex group (P = 0.113). Univariate logistic regression analysis indicated that first gas-passing time within 12 h after operation was significantly associated with perioperative use of opioid analgesics (odds ratio = 2.85, 95% confidence interval 1.26–6.43, P = 0.012). Multivariate logistic regression analysis revealed no significant association of reversal agents, perioperative opioid use, or postoperative hypocalcemia with first gas-passing time within 12 h after operation.

Conclusions

Sugammadex may not cause a delay in postoperative gastric motility compared to neostigmine/glycopyrrolate in patients undergoing robotic thyroidectomy.

Anesthesiology & Pain Medicine

postoperative bowel movement

robotic thyroidectomy

sugammadex

neostigmine/glycopyrrolate

retrospective study.

Postoperative bowel dysfunction is one of the most common complications following various types of surgeries, particularly abdominal surgery. Ileus causes difficulties in gas passing and bowel movement, and delays enteral feeding, resulting in the prolongation of the postoperative recovery process [1]. Although many clinical studies have been performed to decrease postoperative bowel dysfunction, it still remains a major concern [2]. Factors affecting postoperative bowel dysfunction are surgical stress response [3], secondary bowel dysfunction from operative trauma [4], and opioid analgesics [5]. However, an easily overlooked factor potentially affecting postoperative bowel function is the use of reversal agents of neuromuscular (NM) blockade during surgery.

Conventionally, acetylcholinesterase inhibitors (AChEIs) such as neostigmine or pyridostigmine have been used to reverse NM blockers. These compounds are known to enhance intestinal motility [6]. Recently, sugammadex has been applied for reversing aminosteroid NM blockade through encapsulation. Having no muscarinic activity, it does not require anticholinergic drug co-administration. Several studies have reported that the use of sugammadex for reversal shows fewer respiratory complications and less residual NM blockade compared with the conventionally used AChEIs and anticholinergic agents, and that it contributes to enhanced recovery after surgery (ERAS) [7, 8]. However, only a few studies investigated the influence of sugammadex on postoperative bowel movements. Moreover, its effects have not been clearly compared with those of neostigmine/glycopyrrolate.

Thus, the aim of this study was to investigate the effects of sugammadex on postoperative bowel motility and to compare them with the effects of neostigmine/glycopyrrolate in patients undergoing robotic thyroidectomy.

Study population

We reviewed the electronic medical records of 119 patients aged > 20 years who underwent robotic thyroidectomy between March 2018 and July 2018 at the Yonsei Cancer Center. Eleven patients were excluded, five because they underwent another surgical operation at the same time, and six because of lack of data (Fig. 1).

Clinical practice

General anesthesia was performed in accordance with the established anesthesia protocol of our institution. In the operating room, routine monitoring was conducted of noninvasive blood pressure, electrocardiography, pulse oximetry, and bispectral spectrometry. Anesthesia was induced with propofol 1.0–1.5 mg/kg and remifentanil 0.3–0.5 mcg/kg. A neuromuscular blocking agent, rocuronium 0.6 mg/kg, was administered to the patients by the anesthesiologist. Anesthesia was maintained with sevoflurane/desflurane and remifentanil infusion to achieve a bispectral index score of 40–60 and a systolic arterial pressure within 20% of baseline with adequate fluid resuscitation and the use of ephedrine. All operations were performed in our Institution using a Da Vinci robot with the transaxillary approach. Rocuronium 5–10 mg was administered to maintain a train-of-four count of 1–2 during surgery. Before the end of surgery, propacetamol 1 g or oxycodone 0.5 mg/kg were administered to relieve postoperative pain. Concurrently, ramosetron 0.3 mg was administered to reduce postoperative nausea and vomiting.

Decisions regarding the use of agents to reverse NM blockade (neostigmine 1 mg and glycopyrrolate 0.2 mg, or sugammadex 2 mg/kg) were made by the attending anesthesiologist. When the patient recovered full spontaneous respiration and consciousness, extubation was performed, and the patient was transferred to the post-anesthetic care unit.

Data collection

Demographic, clinical, and laboratory data were collected from electronic medical records. The demographic data included age, sex, body mass index (BMI), American Society of Anesthesiologists (ASA) physical status classification, and underlying diseases (hypertension, diabetes mellitus, cerebrovascular accidents, pulmonary diseases, and liver diseases). Operative data included anesthesia time, operation time, anesthetic agents, fluid input, neuromuscular block agent dose, extubation time, analgesic agent, and antiemetic agents. Moreover, first gas passing time; length of hospital stay; and the levels of thyroid stimulating hormone (TSH), thyroid hormone, and serum Ca were collected.

Statistical analysis

.The primary outcome of the study was the time elapsed from surgery to first gas passing, as a measure of postoperative bowel movement. Continuous data are expressed as a mean ± standard deviation or median (interquartile range), depending on their distribution. Categorical data are expressed as a number (%). The t-test or Wilcoxon test were used to compare the two groups, while categorical variables were compared using the chi-squared test. Logistic regression analysis was used to analyze the association between clinical variables and first gas-passing time within 12 hours after surgery. Statistical analyses were performed using SAS version 9.4 (SAS Institute, Cary, NC, USA) software, and P-values < 0.05 were considered statistically significant.

A total of 108 patients who underwent robotic thyroidectomy were included and analyzed. The demographic characteristics of the patients are shown in Table 1. 62 patients received neostigmine/glycopyrrolate and 46 received sugammadex to reverse neuromuscular blockade. No significant intergroup differences were observed in age, sex, BMI, co-morbidities, or preoperative laboratory values, including the levels of thyroid hormone, thyroid stimulating hormone, and serum calcium.

Table 1. Demographics of patients

Variables	Neostigmine (N = 62)	Sugammadex (N = 46)	P- value
Age, years	36.5 (30–46)	35.5 (29–45)	0.364
Female	56 (90.3)	44 (95.7)	0.462
Body mass index, kg m^–2	21.8 (20–24.4)	21.7 (19.8–26.1)	0.838
ASA physical status			0.114
I	48 (77.4)	41 (89.1)
II	14 (22.6)	5 (10.9)
Co–morbidities
Hypertension	5 (8.1)	1 (2.2)	0.237
Diabetes mellitus	1 (1.6)	0 (0)	> 0.999
Liver disease	2 (3.2)	1 (2.2)	> 0.999
Preoperative laboratory value
T3, pg/mL	0.9 (0.8–1)	0.9 (0.8–1)	0.586
T4, ng/dL	1.1 (1–1.2)	1.1 (1–1.2)	0.872
TSH, mIU/L	1.4 (1–2.2)	1.4 (0.8–2.3)	0.644
Serum calcium, mg/dL	9.5 ± 0.3	9.5 ± 0.3	0.681

Values are presented as mean (standard deviation), median (interquartile range), or number of patients (%). *P < 0.05. ASA, American Society of Anesthesiologists; T3, triiodothyronine hormone; T4, thyroxine hormone; TSH, thyroid stimulating hormone.

No significant intergroup differences were observed in anesthesia time, intraoperative remifentanil dose, intraoperative rocuronium dose, perioperative usage of opioid analgesics, postoperative serum calcium level, or length of hospital stay (Table 2). Severe postoperative complications, such as nerve injury, bleeding, and reoperation, were not reported.

Table 2. Perioperative variables

Variables	Neostigmine (N = 62)	Sugammadex (N = 46)	P- value
Sevoflurane/Desflurane	3/54 (4.8/95.2)	3/43 (6.5/93.5)	0.698
Remifentanil, µg	500 (340–612)	415 (332–520)	0.106
Rocuronium, mg	52 (50–60)	52 (50–64)	0.511
Perioperative use of opioid	24 (38.7)	18 (39.1)	0.965
Intraoperative total fluid intake, mL	600 (500–700)	575 (450–650)	0.112
Subtotal/total thyroidectomy	50 (80.7)/12 (19.3)	42 (91.3)/4 (8.7)	0.123
Duration of Anesthesia, min	143 (115–180)	130 (120–160)	0.303
Duration of PACU stay, min	30 (30–40)	30 (30–40)	0.350
Serum calcium at POD 1, mg/dL	8.6 ± 0.4	8.8 ± 0.3	0.116
Hypocalcemia at POD 1	15 (34.1)	7 (21.9)	0.246
Hospital stay, days	3 (3–3)	3 (3–3)	0.890

Values are presented as mean (standard deviation), median (interquartile range), or number of patients (%). *P < 0.05. POD, postoperative day; PACU, postanesthesia care unit.

The median gas-passing time after operation was 957.5 min (425–1455) in the neostigmine group and 600 min (310–1080) in the sugammadex group (P = 0.113, Fig. 2).

Univariate logistic regression analysis indicated that first gas-passing taking place within 12 hours after operation was significantly associated with the perioperative use of opioid analgesics (odds ratio [OR], 95% confidence interval [CI] 1.26–6.43, P = 0.012), while no significant associations were detected with reversal agents, anesthetic agent, amount of intraoperative remifentanil, anesthesia duration, or post-anesthesia care unit (PACU) stay. Multivariate logistic regression analysis with reversal agents, perioperative opioid use, and postoperative hypocalcemia showed no significant association with first gas-passing taking place within 12 hours after operation (Table 3).

Table 3. Univariate and multivariate logistic regression analyses of prognostic factors for 12-h gas passing time after robotic thyroidectomy (N = 108)

Variables	Univariate		Multivariate
Variables	OR (95% CI)	P- value	OR (95% CI)	P- value
Group
Neostigmine	1		1
Sugammadex	0.57 (0.26–1.23)	0.150	0.60 (0.23–1.53)	0.283
Female sex	0.67 (0.15–2.99)	0.606
Age, year	1.02 (0.98–1.06)	0.287
Body mass index, kg m^–2	1.00 (0.89–1.12)	0.982
ASA physical status
I	1
II	1.60 (0.58–4.45)	0.365
Anesthetic agent
Sevoflurane	1
Desflurane	1.17 (0.23–6.08)	0.851
Remifentanil, µg	1.00 (0.99–1.00)	0.963
Perioperative use of opioid	2.85 (1.26–6.43)	0.012	1.93 (0.74–5.02)	0.177
Type of surgery
Subtotal	1
Total	0.63 (0.22–1.82)	0.390
Total fluid intake, mL	1.00 (0.99–1.00)	0.790
Duration of anesthesia, min	1.00 (0.99–1.01)	0.735
Duration of PACU stay, min	1.02 (0.98–1.06)	0.376
Postoperative hypocalcemia	1.03 (0.38–2.80)	0.947	1.03 (0.37–2.89)	0.952

OR, odds ratio; CI, confidence interval; ASA, American Society of Anesthesiologists; PACU, postanesthesia care unit

This retrospective study demonstrated that the use of sugammadex as an aminosteroid NM blockade reversal agent following robotic thyroidectomy was not associated with reduced first gas-passing time compared with neostigmine/glycopyrrolate. However, despite lack of statistical significance, our results suggest that sugammadex may not delay bowel motility.

Previous comparative reports regarding postoperative bowel function following the administration of sugammadex or neostigmine are limited to two randomized controlled trials and one retrospective study [9–11]. Sen et al. [9] did not find a significant difference in the time to first flatus between sugammadex and neostigmine following open thyroidectomy. However, a recent retrospective study revealed that sugammadex was associated to earlier first postoperative bowel movement than the combination of neostigmine and glycopyrrolate in patients undergoing intraperitoneal surgery [11]. In the current study, the median first gas-passing time in the sugammadex group was shorter than in the neostigmine group [600 min. (310–1080) vs. 957.5 min. (425–1455)], although the difference was not statistically significant.

Factors commonly associated to postoperative gastrointestinal tract dysfunction include surgical stress response, bowel dysfunction secondary to operative trauma, and opioid analgesics [4]. Moreover, post-orthopedic, bowel, or pelvic surgeries are prone to cause intestinal pseudo-obstruction [12, 13]. However, in robotic thyroidectomy, there is no gut manipulation nor laxative administration, so that bowel dysfunction is not caused by the surgical technique. Therefore, this type of surgery is ideal to compare the effects of two agents used to enhance bowel motility. Narcotic analgesics are known to inhibit gastric and duodenal motility [14], and indeed the use of perioperative opioid analgesics did delay postoperative gas-passing in this study. However, it was not significant in multivariate analysis when other factors were taken into consideration.

In intraperitoneal surgery, sugammadex does seem to accelerate bowel movement [10, 11], but in non-intraperitoneal surgery, such as thyroidectomy, sugammadex and neostigmine/glycopyrrolate did not show significant differences in bowel movement. The difference between intraperitoneal and non-intraperitoneal surgery consists in the manipulation of the bowel during surgery. The effect of neostigmine and glycopyrrolate on the bowel may vary depending on whether there was manipulation of the intraperitonium or not. Indeed, the surgical manipulation itself may cause a delay in the return to normal bowel movement, so that the effect of neostigmine on bowel movement is not as strong as in surgeries not involving bowel manipulation. A retrospective study after intraperitoneal surgery [11] analyzed bowel movement at 24, 48, and 72 h, while in this study gas-passing within 12 h was sufficient: Such difference must be taken into account.

Neostigmine is known to have a gut-stimulating effect [12, 13, 15] which might be dose-dependent. Previous studies which reported the effectiveness of neostigmine on bowel movement used doses of 2–5 mg [12, 15, 16], but 1 mg was administered to all patients in this study. This amount may have been too small to trigger the gut-stimulating effect enough to produce a significant difference between sugammadex and the neostigmine/glycopyrrolate combination. Moreover, neostigmine is administered together with an anticholinergic agent to prevent undesirable muscarinic side effects. The concurrent use of an acetylcholinesterase inhibitor and an anticholinergic agent cannot completely prevent side effects, or maximize the desired effects. Glycopyrrolate did not negate the beneficial pro-motility effects of neostigmine [16], but reduced bowel movement was observed when neostigmine was used with glycopyrrolate in other reports [17, 18]. The conflicting intestinal motility effects of neostigmine and glycopyrrolate should be taken into account. Moreover, higher neostigmine to glycopyrrolate ratios (greater than 7.0) was associated with earlier bowel movements [11]. However, the neostigmine to glycopyrrolate ratio was fixed at 5.0 in this study. Different doses of neostigmine or neostigmine to glycopyrrolate ratio may result in different effects on bowel movement. Our use of a constant neostigmine to glycopyrrolate ratio should be considered one of the limitations of the current study.

Another limitation is that our study considered a single type of surgery, while it appears to be necessary to consider separately different types of surgery to find the exact effect of sugammadex on bowel movement. Third, different doses and ratios of drugs should be administered to see how they affect bowel movement. Moreover, in the current study, the first gas-passing time was used to represent gastrointestinal transit time, but paracetamol absorption or the colonic scintigram method would yield a more reliable measure of such transit time. Finally, the retrospective nature of the current study is its most important limitation.

The use of sugammadex or neostigmine/glycopyrrolate did not differ in terms of gas-passing time in patients undergoing robotic thyroidectomy under general anesthesia. There was no evidence on sugammadex being associated with delayed postoperative gastric motility compared with neostigmine/glycopyrrolate, but further randomized controlled trials in different surgical contexts are required.

AChEIs, acetylcholinesterase inhibitors

ASA, American Society of Anesthesiologists

CI, confidence interval

ERAS, enhanced recovery after surgery

NM, neuromuscular

OR, odds ratio

PACU, post-anesthesia care unit

POD, post-operative day

T3, triiodothyronine hormone

T4, thyroxine hormone

TSH, thyroid stimulating hormone

Ethics approval and consent to participate

This study was approved by the Institutional Review Board of Yonsei University Health System (approval No. 4-2019-0322). The requirement of written informed consent was waived by the ethics committee due to the study’s retrospective design.

Consent for publication

Not applicable.

Availability of data and materials

All data used and analyzed in this study are available from the corresponding author upon reasonable request.

Competing interests

The authors declare that they have no competing interests.

Funding

No funding was received for this study.

Authors’ contributions

MJL and NYK initiated the conception and developed research design. MJL and SYC collected data. JHH and DC analyzed the data. MJL and DC wrote the first draft of the manuscript. NYK revised and finalized the manuscript. All authors read and approved the final manuscript.

Acknowledgements

We would like to thank Editage (www.editage.co.kr) for English language editing.

Authors’ information

Affiliations

Department of Anesthesiology and Pain Medicine, Severance Hospital, Anesthesia and Pain Research Institute, Yonsei University Collegy of Medicine, Seoul, Republic of Korea

Min Jeong Lee, Na Young Kim & Seung Yeon Choi

Department of Anesthesiology and Pain Medicine, CHA Bundang Medical Center, CHA University, Seongnam, Gyeonggi-do, Republic of Korea

Duk-Hee Chun

Department of Policy Research Affairs, National Health Insurance Service Ilsan Hospital, Goyang, Gyeonggi-do, Republic of Korea

Jung Hwa Hong

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Influence of reversal with sugammadex or neostigmine on postoperative bowel movement following robotic thyroidectomy: a retrospective study

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Abstract

Background

Methods

Results

Conclusions

Figures

Background

Methods

Study population

Clinical practice

Data collection

Statistical analysis

Results

Discussion

Conclusions

Abbreviations

Declarations

References

Status:

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