Thirty-Day Postoperative Outcomes Following Sugammadex Use in Colorectal Surgery Patients; Retrospective Study

Design

Single-center, retrospective study

N= 585 before propensity matching; N= 314 after propensity matching 

Objective

To compare 30-day postoperative outcomes following sugammadex and acetylcholinesterase inhibitor use in colorectal surgery patients

Study Groups

Before matching 

Group sugammadex (S) (n= 201)

Group pyridostigmine (A) (n= 384)

After matching

Group S (n= 157)

Group A (n= 157)

Inclusion Criteria

Colorectal cancer patients older than 21 who have undergone surgery (Group S: admitted between January 2016 and December 2017; Group A: admitted between January 2012 and December 2013)

Exclusion Criteria

Patients admitted between 2014 and 2015 (only sugammadex was used in this period), bedridden patients, reduced renal or hepatic function, combined or emergency operations

Methods

All patients received rocuronium induction dose (0.6 mg/kg) and infusion doses (0.5 to 0.7 mg/kg/h). In group S, sugammadex was given in a fixed dose of 1 vial (200 mg) with no routine neuromuscular monitoring (e.g., TOF); the timing of the administration of the reversal agent was based on clinical judgment. All surgeries were performed by a single colorectal surgeon.

Patients recruited underwent propensity score matching prior to analysis of results. While both results were posted, the table will focus on those who were matched (after matching).

Duration

Between January 2012 and December 2017

Outcome Measures

Primary: total length of hospital stay, length of postoperative hospital stay, delayed discharge rate, readmission rate (including emergency room visits, within 30 days post-discharge)

Secondary: PACU stay time, unforeseen intensive care unit admission rate, time to first successful oral intake (hours), mortality, postoperative pulmonary complications 

Baseline Characteristics

After Matching

Group S (n= 157)

Age, years

Male

BMI, kg/m²

American Society of Anesthesiologists physical status (ASA)

1

2

67 (43%)

90 (57%)

77 (49%)

80 (51%)

0.26

Comorbidities

Cardiovascular

Diabetes

Cerebrovascular

Pulmonary

76 (48%)

30 (19%)

6 (4%)

6 (4%)

70 (45%)

26 (17%)

3 (2%)

2 (1%)

0.50

0.56

0.31

0.14

Operation type

Laparoscopic

Open

39 (19%)

125 (80%)

34 (22%)

123 (78%)

0.78 

Anesthesia time, min

Results

After Matching

Group S (n= 157)

Primary outcomes

Total length of stay, days

Postoperative hospital stay, days

Delayed discharge (> 11 days of hospitalization)

Readmission rate

13.2 ± 12.9

10.1 ± 12.9

23 (15%)

12 (8%)

13.4 ± 4.2

10.0 ± 4.0

40 (25%)

15 (10%)

0.84

0.88

0.017

0.55

Secondary outcomes

PACU stay time, min

ICU admission rate

Mortality

Oral intake

Sips of water, hr

Meal, hr

Pulmonary complications

50.0 ± 24.5

4 (3%)

2 (1%)

87.9 ± 58.3

115.8 ± 58.3

4 (3%)

49.3 ± 20.5

2 (1%)

1 (1%)

98.5 ± 79.5

126.7 ± 78.7

1 (1%)

0.821

0.41

0.56

0.18

0.16

0.18

Adverse Events

N/A

Study Author Conclusions

We found no difference in 30-day postoperative outcomes following sugammadex and acetylcholinesterase inhibitor use. The only difference between these treatments was the associated incidence of delayed discharge, which was lower in group S.

InpharmD Researcher Critique

The study did not implement neuromuscular monitoring, and instead used fixed dosages of sugammadex (200 mg) when clinical signs were noted. However, the exact dose of rocuronium or pyridostigmine was not recorded for each case.

Despite the use of propensity score matching to adjust for different variables, there still remains the risk of confounding effects due to unmeasured covariates.  Moreover, the presented data only represent a single Korean institution's retrospective experience focusing on a relatively old population with normal renal or hepatic function. 

Rocuronium-Sugammadex Use for Electroconvulsive Therapy in A Hemodialysis Patient: A Case Report

Design

Case presentation

A 69-year-old female with a history of chronic renal failure requiring hemodialysis presented to the psychiatry department for electroconvulsive therapy (ECT) to treat severe major depression. Brain MRI shows brain atrophy and old fine cerebral infarctions. The patient's depressive state worsened which required admittance to the hospital where she also received hemodialysis three times a week for 3 hours each session. However, the patient's status continued to deteriorate. Therefore, the patient was scheduled to receive ten sessions of ECT and was given rocuronium-sugammadex for muscle relaxation due to possible succinylcholine-induced hyperkalemia. The patient initially received an incremental dose of rocuronium and sugammadex for the first four sessions, but as certain doses were found to have an adequate response, the patient was switched to a fixed dose of rocuronium 20 mg and sugammadex 75 mg starting at session five. All else remained the same as the first four sessions. 

While the ten sessions were performed without complications, there was evidence of sugammadex accumulation along with its rocuronium complex. The effect of rocuronium may have been decreased by the accumulated sugammadex as denoted by the remaining 8 to 14% of the adductor pollicis train of four (TOF) ratios during the sixth to eighth ECT.

Study Author Conclusions

Reversal of Profound, High-dose Rocuronium-induced Neuromuscular Blockade by Sugammadex at Two Different Time Points: An International, Multicenter, Randomized, Dose-finding, Safety Assessor-blinded, Phase II Trial

Design

Multicenter, randomized, dose-finding, safety assessor-blinded, phase II trial

N= 173

Objective

To evaluate the dose–response relation of sugammadex given for reversal of intense, profound neuromuscular blockade induced by high-dose rocuronium (1.0 or 1.2 mg/kg)

Study Groups

Sugammadex (n= 157)

Placebo (n= 16)

Inclusion Criteria

American Society of Anesthesiologists (ASA) class of I–III, were aged 18 yr or older, and had an expected duration of surgery of at least 120 min in the supine position

Exclusion Criteria

Expected to have a difficult airway; were known or suspected to have neuromuscular disorders impairing neuromuscular function and/or impaired renal function; had a (family) history of malignant hyperthermia; had any allergies to narcotics, muscle relaxants, or other drugs that may be given during anesthesia; or were receiving drugs that might interfere with neuromuscular blocking agents

Methods

Baseline electrocardiogram was recorded prior to anesthesia induction. Once a baseline train-of-four (TOF) was stable for at least 2 minutes, rocuronium 1.0 or 1.2 mg/kg was administered according to randomization.  Electrocardiogram was recorded 2 minutes after rocuronium administration. Patients were also randomized to treatment with varying doses of sugammadex or placebo with sugammadex doses of 2, 4, 8, 12, and 16 mg/kg. Treatment was administered at two different time points: at 3 or 15 min after administration rocuronium, resulting in a total of 24 different treatment groups. Additional electrocardiogram was recorded 2 and 30 min after the start of sugammadex/placebo administration. 

Duration

Intervention: 15 min

Follow-up: up to 60 min after recovery of the TOF ratio to 0.9

Outcome Measures

Primary: Time from the start of administration of sugammadex or placebo to recovery of the TOF ratio to 0.9

Secondary: Time from the start of administration of sugammadex or placebo to recovery of the TOF ratio to 0.7

Baseline Characteristics

Study patients (N= 173)

Age, years

Weight, kg

Height, cm

Female

American Society of Anesthesiologists (ASA)

I

II

III

38%

51%

11%

Results

Endpoint

Placebo

Sugammadex       2 mg/kg

Sugammadex       4 mg/kg

Sugammadex       8 mg/kg

Sugammadex       12 mg/kg

Sugammadex       16 mg/kg

Rocuronium 1.0 mg/kg with Sugammadex/Placebo at 3 minutes

Recovery to TOF 0.7, min

Mean (SD)

Median

Min-Max

n= 5

91.6 (27.4)

86.8

54.2 to 119.9

n= 11

36.4 (17.2)

30.4

18.8 to 74.8

n= 11

4.6 (1.4)

4.2

2.6 to 7.1

n= 11

1.6 (0.7)

1.4

0.8 to 3.3

n= 11

1.1 (0.1)

1.1

1.0 to 1.4

n= 10

1.3 (0.5)

1.1

0.7 to 2.6

Recovery to TOF 0.9, min

Mean (SD)

95% CI of the mean

Median

Min-Max

n= 5

108.4 (31.2)

70 to 147

111.1

63.7 to 144.8

n= 11

44.7 (22.2)

30 to 60

34.4

23.3 to 94.3

n= 11

6.9 (2.9)

5.0 to 8.9

6.8

3.4 to 11.9

n= 11

2.4 (1.2)

1.6 to 3.2

2.2

1.3 to 4.8

n= 11

2.4 (2.1)

1.0 to 3.8

1.4

1.0 to 7.1

n= 10

1.8 (1.1)

1.0 to 2.6

1.6

0.9 to 4.8

Rocuronium 1.2 mg/kg with Sugammadex/Placebo at 3 minutes

Recovery to TOF 0.7, min

Mean (SD)

Median

Min-Max

n= 5

122.9 (36.2)

107.5

81.3 to 173.1

n= 10

54.4 (17.3) 

53.5 

33.6–92.5

n= 8

7.5 (2.8) 

7.4 

2.8 to 11.5 

n= 11

2.4 (0.9) 

2.6 

0.8 to 4.0 

n= 10

1.6 (0.8)

 1.3 

1.0 to 3.6 

n= 11

1.2 (0.2)

1.3

0.8 to 1.5

Mean (SD)

95% CI of the mean

Median

Min-Max

n= 4 

123.0 (28.5) 

78 to 168  

124.3 

87.3 to 156.1 

n= 9 

65.7 (24.6) 

47 to 85

63.3 

36.3 to 117.2 

n= 8 

13.8 (7.6) 

7.4 to 20.2

11.3 

5.3 to 28.5 

n= 11 

3.2 (1.0) 

2.6 to 3.9 

3.6

1.5 to 4.7 

n= 10 

2.1 (0.9) 

1.5 to 2.7 

1.9 

1.2 to 4.1

n= 11

1.3 (0.4)

1.0 to 1.6

1.3

0.8 to 2.3

Rocuronium 1.0 mg/kg with Sugammadex/Placebo at 15 minutes

Recovery to TOF 0.7, min

Mean (SD)

Median

Min-Max

n= 3 

81.7 (34.2) 

79.3 

48.8 to 117.1  

n= 5 

5.3 (0.8) 

5.3 

4.6 to 6.4 

n= 4

3.3 (1.6) 

3.1 

1.6 to 5.3 

n= 5 

1.3 (0.2) 

1.3 

1.0 to 1.4

n= 5

1.3 (0.4) 

1.2 

0.9 to 1.8

n= 5

0.9 (0.1)

0.9

0.8 to 1.2

Recovery to TOF 0.9, min

Mean (SD)

95% CI of the mean

Median

Min-Max

n= 3 

127.4 (92.8) 

-103 to 358 

91.0 

58.3–232.8 

n= 5

8.5 (1.1) 

7.1 to 9.9

9.0 

6.8 to 9.6 

n= 4

5.5 (3.1) 

0.5 to 10.5

5.4 

1.8 to 9.3

n= 5 

1.9 (0.6) 

1.2 to 2.5

1.8 

1.0 to 2.4 

n= 5

1.8 (0.9) 

0.7 to 2.9

1.9 

0.9 to 2.9

n= 5

0.9 (0.1)

0.8 to 1.1

0.9

0.8 to 1.2

Rocuronium 1.2 mg/kg with Sugammadex/Placebo at 15 minutes

Recovery to TOF 0.7, min

Mean (SD)

Median

Min-Max

n= 3  

111.4 (53.0)

81.6

79.8 to 172.6

n= 5

24.2 (13.0)

29.9

4.3 to 35.5

n= 5  

3.1 (0.9)

3.6

1.9 to 3.9

n= 5

1.6 (0.4)

1.4

1.3 to 2.2

n= 5 

1.7 (1.0)

1.3

0.8 to 3.3

n= 5

1.2 (0.6)

0.9

0.8 to 2.1

Recovery to TOF 0.9, min

Mean (SD)

95% CI of the mean

Median

Min-Max

n= 3

139.6 (79.9)

-59 to 338

94.2

92.8 to 231.9

n= 5

42.2 (29.3)

5.8 to 79

41.9

7.3 to 86.5

n= 5

6.0 (2.5)

2.9 to 9.0

5.6

2.6 to 9.2

n= 5

2.3 (0.3)

2.0 to 2.7

2.2

2.1 to 2.8

n= 5

1.8 (1.2)

0.3 to 3.2

1.3

0.8 to 3.8

n= 5

4.7 (6.7)

-3.6 to 13.6

1.9

0.9 to 16.6

CI: confidence interval; SD: standard deviation

Adverse Events

97 of 157 patients (62.0%) in sugammadex groups and 13 of 16 patients (81.2%) in placebo group reported at least one AE

Common AEs: anesthetic complications (18.5%), nausea (15.3%), vomiting (11.5%), pain (13.3%)

Drug-related AEs: 22 of 157 patients (14%) in sugammadex group, none in placebo group

Serious AEs: 12 patients (sugammadex n=11, placebo n=1), including QTc prolongation, postprocedural bleeding, and asystole

Study Author Conclusions

InpharmD Researcher Critique

A Dose-finding Study of Sugammadex for Reversal of Rocuronium in Cardiac Surgery Patients and Postoperative Monitoring for Recurrent Paralysis

Design

Prospective dose-finding study

N= 126

Objective

To investigate the dose-response relationship between sugammadex and the train-of-four twitch response and the possibility of recurrent neuromuscular blockade

Study Groups

Patients who completed study titration (n= 97)

Inclusion Criteria

Patients age 18 years or older undergoing cardiac surgery

Exclusion Criteria

Allergies or contraindications to sugammadex

Methods

Patients undergoing cardiac surgery received rocuronium, isoflurane, opioids, and then propofol at the end of surgery for postoperative sedation. A baseline train-of-four measurement was obtained after the induction of anesthesia but before the administration of rocuronium. Near the end of surgery, the train-of-four was determined and sugammadex titration began (unless spontaneous recovery occurred). Patients were rewarmed at the time of sugammadex administration. Sugammadex was administered in 50 mg boluses every 5 minutes until the train-of-four ratio of at least 0.9 was achieved and patient could then be transferred to the intensive care unit (ICU).

Electromyography-based twitch monitoring was continued in the ICU every 15 minutes for the first hour and then hourly for up to 7 hours or until propofol sedation was discontinued for extubation preparation. If the train-of-four ratio was less than 0.9, additional 50 mg doses were administered as needed.

Duration

Between February 2022 to July 2022

Outcome Measures

Primary: Response to train-of-four stimulation just before sugammadex administration and the total dose of sugammadex required to achieve a train-of-four ratio of at least 0.9

Secondary: Incidence of recurrent paralysis during the postoperative monitoring period, defined as a train-of-four ratio less than
0.9 after first having achieved successful reversal 

Baseline Characteristics

All Patients (n= 97)

Age, years

Female

Median Weight, kg (interquartile range [IQR])

BMI, kg/m2

80 [73-95]

27.3 ± 4.7

Preoperative median creatinine, mg/dL (IQR)

Hemoglobin at time of sugammadex, g/dL 

0.9 [0.8-1.1]

9.2 ± 1.6

Proportion with deep hypothermic cardiac arrest

Median minimum temperature on bypass, °C

Median temperature at time of reversal, °C

20%

34.2

36.3

Procedure duration, min

Median time between last rocuronium and first sugammadex dose, min [IQR]*

Median postoperative monitoring time, min [IQR]

329.1 ± 91.6

138 [66-269]

113 [86-204]

IQR: interquartile range

*Significant difference between patients with pre-reversal train-of-four count <2 (Median 62 min) versus ≥ 2 (Median 169 min)

Results

All patients (n= 97)

p-Value

Twitch response before reversal

Sugammadex Dose Requirement, mg/kg

Posttetanic count

Train-of-four count 1,2, or 3

Train-of-four ratio < 0.4

Train-of-four ratio ≥ 0.4

Train-of-four ratio < 2*

Train-of-four ratio ≥ 2†

2.35 ± 0.98

2.01 ± 1.22

1.29 ± 0.67

0.90 ± 0.60

2.30 ± 1.18

1.24 ± 0.83

< 0.0001

Not significant

Not significant 

Not significant

< 0.0001

Not significant

Sugammadex Dose

All patients (n= 97)

Dose required to achieve a train-of-four ratio ≥ 0.9, mg/kg

Required less than the manufacturer’s recommended dose 

Required more than the manufacturer’s recommended dose‡ 

0.43 to 5.55

84 (87%)

13 (13%)

126 Patients were enrolled; spontaneous recovery occurred in 26; protocol deviation occurred in 3: n= 97 completed the titration

*Manufacturer's recommended dose is 4 mg/kg

†Manufacturer's recommended dose is 2 mg/kg

‡Subgroup analysis did not reveal any clinically significant differences in patient characteristics

While there was a statistically significant relationship between the twitch response before reversal and sugammadex dose required to achieve train-of-four ratio ≥ 0.9, the range of dose requirements between patients with the same twitch response varied greatly.

Adverse Events

1 patient had probable anaphylaxis to sugammadex and titration was discontinued (excluded from results)

2 patients experienced mild recurrent paralysis; one with posttetanic count of 0 before reversal (outside of manufacturer's dosing recommendations) and the other patient had a train-of-four ratio of 0.47 before reversal and received 100 mg sugammadex. The train-of-four ratios at the time of recurring paralysis were 0.81 and 0.87 respectively. 

Study Author Conclusions

When sugammadex was titrated to effect, the dose was usually less than the recommended dose, but it was more in some patients. Therefore, quantitative twitch monitoring is essential for ascertaining that adequate reversal has taken place after sugammadex administration. Even if sugammadex had been administered at 4 mg/kg to all patients, some patients would not have attained a train-of four ratio of at least 0.9. Recurrent paralysis was observed in two patients.

InpharmD Researcher Critique

Train-of-four ratio was determined based on electromyographic twitch monitoring which may not be consistent across all studies with some using acceleromyography. Additionally, this study was conducted in cardiac surgery patients due to the opportunity to measure train-of-four twitch response for extended periods in sedated, intubated patients. This also allowed use of an 80mA stimulation current which is not feasible in awake patients. Sugammadex was administered in 50 mg increments every 5 minutes which may represent a different total time for administration compared to larger single doses and may not represent real-world scenarios. Since rocuronium clearance is ongoing, the total dose of sugammadex may be underestimated compared to a dose that would have been required had it been administered as a single large dose. This study was conducted in cardiac patients receiving rocuronium which may limit generalizability to other populations. 

Evaluation of Sugammadex Dosing for Neurological Examination in the Emergency Department

Design

Single-center, retrospective, cohort study

N= 24

Objective

To evaluate low- (2 mg/kg) vs standard-dose (4 mg/kg) sugammadex for rocuronium-induced deep neuromuscular blockade reversal in the emergency department (ED) by achieving a post-treatment train-of-four (TOF) of 4 to facilitate neurological examination

Study Groups

Low-dose group (n= 9)

Standard-dose group (n= 15)

Inclusion Criteria

Patients ≥ 18 years of age, received sugammadex in the ED to facilitate a neurological examination, received rocuronium in the ED or pre-hospital setting, neurological examination performed before and after sugammadex administration, documented TOF count before and after sugammadex administration

Exclusion Criteria

Methods

Patients were identified by sugammadex charge codes and analyzed based on low- vs standard-dose sugammadex for neuromuscular blockade reversal in the ED.

Standard practices for dose or vial size rounding did not exist for the institution so patients that received sugammadex doses ≥3 mg/kg were included in the standard-dose group and those that received <3 mg/kg were in the low-dose group.

Duration

Outcome Measures

Primary: Successful rocuronium-induced deep neuromuscular blockade reversal (post-treatment TOF of 4);

Secondary: Incomplete reversal requiring repeat sugammadex dose(s), incidence of bradycardia, hypotension, cardiac arrest events, difference in hospital acquisition cost of sugammadex.

Baseline Characteristics

Low-dose group (n= 9)

Standard-dose group (n= 15)

Age, years

Female

Weight, kg

Body mass index, kg/m²

Alanine transaminase, U/L

Aspartate aminotransferase, U/L

27.0

36.0

17.0

31.0

Neurologic injury

Subarachnoid hemorrhage

Intraparenchymal hemorrhage

Subdural hemorrhage

Epidural

Multiple bleed types

Ischemic stroke

Spontaneous bleed

Traumatic bleed

22.2%

55.6%

55.6%

11.1%

33.3%

11.1%

44.4%

44.4%

40.0%

53.3%

46.7%

0

33.3%

6.70%

20.0%

73.3%

National Institutes of Health Stroke Scale (NIHSS)

23.0

29.5

Intracerebral hemorrhage score (ICH)

3.00

4.00

Mortality

66.7%

60.0%

Sugammadex dose, mg

200

320

Rocuronium dose, mg

90

100

Results

Endpoint

Low-dose group (n= 9)

Standard-dose group (n= 15)

p-Value

Reversal success rate

9 (100%)

14.0 (93.3%)

1.000

Incomplete reversal

0

1 (6.70%)

--

Sugammadex cost, USD

108

173

< 0.001

Adverse Events

Hypotension: 4 patients (16.7%); bradycardia: 2 patients (8.3%); cardiac arrest: 1 patient (4.2%)

No significant difference in adverse events between low- and standard-dose groups

Study Author Conclusions

InpharmD Researcher Critique