Clinical trial NCT03112993: Speed of Recovery of Reversal of Neuromuscular Blockade in Geriatric Patients Undergoing Spine Surgery
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Spine Surgery
Keywords: spine surgery
neuromuscular blockade
sugammadex
elderly
reversal
neostigmine
recovery
Lead sponsor: University of Missouri-Columbia
Sponsor class: OTHER
Collaborators: name: Merck Sharp & Dohme LLC
First posted: 2017-04-13
Enrollment: 40
Sex: ALL
Minimum age (years): 65
Standard ages: OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
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.
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Difference in Time of Neuromuscular Recovery From a Neuromuscular Moderate Blockade
timeFrame: Day 1
measure: Difference in Time From Neuromuscular Reversal to Exit From OR
timeFrame: Day 1
Secondary outcomes:
measure: Difference in Time From Neuromuscular Reversal to Tracheal Extubation
timeFrame: Day 1
measure: Difference in Length of Stay in PACU
timeFrame: Day 1
Other outcomes:
measure: Difference in Time to First Ambulation After Surgery
timeFrame: From Day 1 up to 1 week, depending on individual recovery time
Locations:
city: Columbia
country: United States
facility: University on Missouri Hospital
state: Missouri
Study officials:
affiliation: Univesity of Missouri-Columbia
name: Boris Mraovic, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Mraovic B, Timko NJ, Choma TJ. Comparison of recovery after sugammadex or neostigmine reversal of rocuronium in geriatric patients undergoing spine surgery: a randomized controlled trial. Croat Med J. 2021 Dec 31;62(6):606-613. doi: 10.3325/cmj.2021.62.606.