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Speed of Recovery of Reversal of Neuromuscular Blockade in Geriatric Patients Undergoing Spine Surgery

A Prospective, Randomized, Double-Blind Clinical Trial Evaluating the Speed of Recovery and Safety of Reversal of Neuromuscular Blockade With Sugammadex (Bridion™) Versus Neostigmine in Geriatric Patients Undergoing Spine Surgery

Status
Completed
Phases
Phase 4
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT03112993
Enrollment
40
Registered
2017-04-13
Start date
2017-05-30
Completion date
2018-08-14
Last updated
2022-04-01

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Spine Surgery

Keywords

spine surgery, neuromuscular blockade, sugammadex, elderly, reversal, neostigmine, recovery

Brief summary

Spine surgery is one of the most common operative procedures in the United States. It is performed in the prone position (a patient laying on belly). Muscle relaxants are given for neuromuscular blockade often referred as paralysis for surgical exposure which is maintained until the patient is returned to the supine position (a patient laying on back) at the end of surgery. At the end of the surgery the paralysis is reversed with a drug (neostigmine). A new drug (sugammadex) has the ability to rapidly reverse the paralysis but it is not well investigated in elderly. This study will investigate speed of recovery and complications of the two reversal drugs in elderly patients (age ≥ 65 years) undergoing posterior spine surgery.

Detailed description

The elderly (age ≥ 65 years) population is the fastest growing segment of the American population. Spine surgery is one of the most common operative procedures in the United States and, as the population ages, a larger percentage of geriatric patients will require this procedure. In addition, spinal surgery is often more complex in the elderly population, resulting in longer surgical times. A previous study reported that the rate of complex procedures increased 15-fold in Medicare recipients. Spine surgery is performed in the prone position and neuromuscular blockade (NMB) is maintained until the patient is returned to the supine position at the end of surgery to avoid the risk of patient movement, injury, and inadvertent tracheal extubation while prone. Currently, NMB is reversed with neostigmine immediately after turning the patients back to the supine position at the end of the procedure. Rocuronium bromide, an intermediate-acting neuromuscular blocking agent (NMBA), is used in approximately 60% of surgical cases in the United States and is commonly used for muscle relaxation during spinal surgery. With aging, the clearance and half-life of rocuronium is prolonged resulting in a wide variability in the duration of action and time to reversal. Until recently, the only medication available for the reversal of neuromuscular blockade was neostigmine and postoperative residual neuromuscular block (PRNB) was common, especially in elderly patients. A recent study reported that PRNB occurred in 58% of elderly patients who were maintained at a moderate level (2 twitches in the TOF) of muscle relaxation with rocuronium during elective surgery. As a result, these older adults experienced an increased incidence of airway obstruction, hypoxemic events, muscle weakness, postoperative pulmonary complications, and increased PACU and hospital lengths of stay. A new neuromuscular reversal agent sugammadex (Bridion®) has the ability to rapidly reverse both moderate and deep rocuronium-induced NMB. Another study reported that the mean time to complete reversal (TOF ratio ≥ 0.9) of a moderate block (2 twitches in the TOF) with sugammadex in geriatric patients was 2.9 minutes, which was only 1 minute longer than in younger patients. Reversal of NMB with neostigmine is much slower and it is reported to take approximately 19 minutes to achieve complete reversal in middle-aged patients. There is little available data on the NMB reversal time in older adults, but it will likely be even longer because the age-related physiologic changes prolong neuromuscular recovery. Thus, sugammadex has the potential to more rapidly reverse NMB in geriatric patients at the end of surgery. As a result, the use of sugammadex should decrease time in the OR and possibly PACU time and result in cost savings. Neostigmine has cardiac muscarinic effects and, therefore, has to be administered with an anticholinergic agent such as glycopyrrolate to counteract these effects. A previous study found a 16% incidence of cardiac dysrhythmias in elderly patients who received neostigmine/glycopyrrolate NMB reversal. The ability of sugammadex to completely reverse NMB without the addition of an anticholinesterase agent should result in an improved safety profile in elderly patients. The goal of this prospective, randomized, double-blinded controlled trial is to test the hypothesis that the reversal of neuromuscular blockage with sugammadex as compared to neostigmine in geriatric patients will provide a shorter time to complete recovery of neuromuscular function, improve the workflow in the operating room and decrease operative costs.

Interventions

DRUGsugammadex

once at the end of the surgery

DRUGNeostigmine

once at the end of the surgery

Sponsors

Merck Sharp & Dohme LLC
CollaboratorINDUSTRY
University of Missouri-Columbia
Lead SponsorOTHER

Study design

Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)

Masking description

The surgeon, anesthesiologist, operating room staff, patients, personnel in the postanesthesia care unit (PACU) as well as the investigators collecting the postoperative data will be blinded to the group allocation.

Intervention model description

Participants will receive (per a randomization schedule) either sugammadex, or neostigmine/glycopyrrolate to reverse neuromuscular blockade at the end of the surgery. The reversal agent will be prepared in a blinded fashion.

Eligibility

Sex/Gender
ALL
Age
65 Years to No maximum
Healthy volunteers
No

Inclusion criteria

1. Posterior spinal surgery 2. Age ≥ 65 years 3. American Society of Anesthesiologists (ASA) grade I-III

Exclusion criteria

1. Inability to obtain written informed consent 2. Allergy to rocuronium or anesthetic agents used in the protocol 3. Known or suspected neuromuscular disorders 4. Significant renal disease with a serum creatinine ≥ 2 mg/dl 5. Significant liver disease 6. A family history of malignant hyperthermia

Design outcomes

Primary

MeasureTime frameDescription
Difference in Time of Neuromuscular Recovery From a Neuromuscular Moderate BlockadeDay 1Speed of neuromuscular recovery in minutes measured by recovery of the T4:T1 ratio ≥ 0.9 (measured with a TOF-Watch SX)
Difference in Time From Neuromuscular Reversal to Exit From ORDay 1Difference in time from neuromuscular reversal to exit from OR was measured in minutes.

Secondary

MeasureTime frameDescription
Difference in Time From Neuromuscular Reversal to Tracheal ExtubationDay 1Difference in time from neuromuscular reversal to tracheal extubation was measured in minutes.
Difference in Length of Stay in PACUDay 1Length of PACU stay measured in minutes.

Other

MeasureTime frameDescription
Difference in Time to First Ambulation After SurgeryFrom Day 1 up to 1 week, depending on individual recovery timeTime from end of anesthesia to the first subject ambulation in hours.

Countries

United States

Participant flow

Recruitment details

Recruitment Period First subject on study: 30/MAY/2017; Last subject off study: 14/AUG/2018. Locations: University Hospital and Missouri Orthopaedic Institute, University of Missouri, Columbia, Missouri, United States of America.

Participants by arm

ArmCount
Sugammadex Group
2 mg/kg of sugammadex, IV once at the end of the surgery. Dosing will be based on actual body weight not ideal body weight. sugammadex: once at the end of the surgery
19
Neostigmine Group
50 micrograms/kg (not to exceed 5 mg) and glycopyrrolate, 10 micrograms/kg (not to exceed 1 mg), IV once at the end of the surgery. Dosing will be based on actual body weight not ideal body weight. Neostigmine: once at the end of the surgery
21
Total40

Baseline characteristics

CharacteristicNeostigmine GroupTotalSugammadex Group
Age, Continuous71.2 years
STANDARD_DEVIATION 4.8
70.8 years
STANDARD_DEVIATION 4.75
70.4 years
STANDARD_DEVIATION 4.7
ASA Physical Status Classification
ASA PS 2
5 Participants13 Participants8 Participants
ASA Physical Status Classification
ASA PS 3
16 Participants27 Participants11 Participants
Duration of surgery196 minutes
STANDARD_DEVIATION 96
185.5 minutes
STANDARD_DEVIATION 112
175 minutes
STANDARD_DEVIATION 128
End of surgery to administration of reversal (min)4.8 minutes
STANDARD_DEVIATION 1.4
5.15 minutes
STANDARD_DEVIATION 1.7
5.5 minutes
STANDARD_DEVIATION 2
Race (NIH/OMB)
American Indian or Alaska Native
0 Participants0 Participants0 Participants
Race (NIH/OMB)
Asian
0 Participants0 Participants0 Participants
Race (NIH/OMB)
Black or African American
1 Participants2 Participants1 Participants
Race (NIH/OMB)
More than one race
0 Participants0 Participants0 Participants
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
0 Participants0 Participants0 Participants
Race (NIH/OMB)
Unknown or Not Reported
0 Participants0 Participants0 Participants
Race (NIH/OMB)
White
20 Participants38 Participants18 Participants
Sex: Female, Male
Female
4 Participants13 Participants9 Participants
Sex: Female, Male
Male
17 Participants27 Participants10 Participants

Adverse events

Event typeEG000
affected / at risk
EG001
affected / at risk
deaths
Total, all-cause mortality
0 / 190 / 21
other
Total, other adverse events
0 / 190 / 21
serious
Total, serious adverse events
2 / 194 / 21

Outcome results

Primary

Difference in Time From Neuromuscular Reversal to Exit From OR

Difference in time from neuromuscular reversal to exit from OR was measured in minutes.

Time frame: Day 1

ArmMeasureValue (MEAN)Dispersion
Sugammadex GroupDifference in Time From Neuromuscular Reversal to Exit From OR3.9 minutesStandard Deviation 2.2
Neostigmine GroupDifference in Time From Neuromuscular Reversal to Exit From OR19.8 minutesStandard Deviation 13.8
Primary

Difference in Time of Neuromuscular Recovery From a Neuromuscular Moderate Blockade

Speed of neuromuscular recovery in minutes measured by recovery of the T4:T1 ratio ≥ 0.9 (measured with a TOF-Watch SX)

Time frame: Day 1

ArmMeasureValue (MEAN)Dispersion
Sugammadex GroupDifference in Time of Neuromuscular Recovery From a Neuromuscular Moderate Blockade3.9 MinutesStandard Deviation 2.2
Neostigmine GroupDifference in Time of Neuromuscular Recovery From a Neuromuscular Moderate Blockade26.29 MinutesStandard Deviation 17.51
Secondary

Difference in Length of Stay in PACU

Length of PACU stay measured in minutes.

Time frame: Day 1

ArmMeasureValue (MEAN)Dispersion
Sugammadex GroupDifference in Length of Stay in PACU81.4 minutesStandard Deviation 16.5
Neostigmine GroupDifference in Length of Stay in PACU85.3 minutesStandard Deviation 29.5
Secondary

Difference in Time From Neuromuscular Reversal to Tracheal Extubation

Difference in time from neuromuscular reversal to tracheal extubation was measured in minutes.

Time frame: Day 1

ArmMeasureValue (MEAN)Dispersion
Sugammadex GroupDifference in Time From Neuromuscular Reversal to Tracheal Extubation5.3 minutesStandard Deviation 2.5
Neostigmine GroupDifference in Time From Neuromuscular Reversal to Tracheal Extubation23.6 minutesStandard Deviation 18.7
Other Pre-specified

Difference in Time to First Ambulation After Surgery

Time from end of anesthesia to the first subject ambulation in hours.

Time frame: From Day 1 up to 1 week, depending on individual recovery time

ArmMeasureValue (MEAN)Dispersion
Sugammadex GroupDifference in Time to First Ambulation After Surgery17.4 hoursStandard Deviation 14.6
Neostigmine GroupDifference in Time to First Ambulation After Surgery17.8 hoursStandard Deviation 11.1

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026