Does Deep Neuromuscular Blockade Improve Operating Conditions During Total Hip Replacements?

• Sponsor: Craig Curry (Other)
• Overall Status: Completed
• CT.gov ID: NCT03219294
• Collaborator: MaineHealth (Other), Spectrum Medical Group Anesthesiology (Other)
• Enrollment: 116
• Location: 1
• Arms: 2
• Actual Duration (Months): 12
• Patients Per Site Per Month: 9.7

Study Details

Study Description

Brief Summary

During many surgeries, increased muscle tension makes it harder for the surgeon to expose the site of surgery and work within the incision. Neuromuscular blockade (NMB) drugs such as Vecuronium bind to neurotransmitter (acetyl choline) receptors at the neuromuscular junction, blocking their action and producing muscle relaxation. This muscle relaxation allows easier retraction of muscle tissues and manipulation of structures in the wound. Improved surgical conditions are likely to result in improved patient outcomes. While increased depths of NMB have been shown to optimize surgical conditions during intra-abdominal and retroperitoneal procedures, the impact of NMB depth has not been reported for orthopedic surgeries.1 To address this, we propose to study the effect of NMB depth on surgical conditions during total hip replacement (THR).

Condition or Disease	Intervention/Treatment	Phase
Arthropathy of Hip	Drug: Vecuronium 0.1 mg/kg; Drug: Vecuronium 0.2mg/kg	Phase 4

Detailed Description

Specific Aims

1. Assess difference in surgical conditions between moderate and deep NMB groups. Enrolled patients will be randomized to receive moderate (n=58) or deep (n=58) NMB. Difference in surgical conditions will be evaluated by:

2. The number of requests from the surgeon for additional relaxation (NMB) during the procedure. At any time during the operation if the surgeon feels the muscle tension is interfering with ease of operation he will ask for additional muscle relaxation. If the patient is moderately relaxed they will be converted to deep relaxation with additional muscle relaxants. If they are already deeply relaxed no additional relaxants will be administered (as is our current practice). All requests will be recorded.

3. Rating by the surgeon after each surgery using an internally developed satisfaction scale. The scale was developed by modifying a scale used in a previous study of muscle relaxation in intra-abdominal surgery1 to specify two key elements identified by our surgeon: ease of muscle retraction and femur manipulation.

4. Assess the impact of deep vs moderate NMB on time of surgery, measured from the time of incision to joint reduction.

SIGNIFICANCE If we identify improved surgical conditions with deeper relaxation we will incorporate deep NMB into our routine anesthesia practice for THR.

Vecuronium will be used as NMB drug in all study patients; this agent is currently used in over 90% of THR cases at Maine Medical Center (MMC). As is currently routine Vecuronium will be given after initiation of general anesthesia with propofol to facilitate intubation and further doses of Vecuronium will be given throughout the case as noted below to maintain NMB at the desired depth until the femoral implant is reduced. After the intubating dose of Vecuronium, NMB depth will be monitored every 5 minutes and dosing will be adjusted as needed to maintain a constant depth of NMB according to our current routine practice.

Group 1: Moderate NMB: Intubating dose of Vecuronium of 0.1 mg/kg (IBW) and re-dosing with 0.0125 to 0.05 mg/kg as needed to achieve and maintain 1 to 2 train of four (TOF) contractions. Redosing in this manner is a current clinical practice.

Group 2: Deep NMB: Intubating dose of Vecuronium of 0.2 mg/kg (IBW) and re-dosing with 0.025 to 0.1 mg/kg to achieve and maintain zero twitches in the TOF, and post tetanic count (PTC) of 1 to 2 contractions. This level of blockade is new to the practice since approval of the drug for use at MMC but is in common use since the advent of Sugammadex.

The surgeon may request additional relaxation at anytime for inadequate surgical conditions thought to be related to muscle tension. All requests will be recorded. Patients in the moderate NMB group will receive additional doses of vecuronium to achieve deep NMB (PTC of 1- 2). In the deep NMB group with PTC of 1-2, a saline dose without NMB will be given.

NMB reversal Sugammadex will be given for reversal of NMB after the prosthesis has been reduced, using routine dosing of 2 mg/kg for the moderate group and 4 mg/kg for the deep group, per package insert by Merck.

Study Design

• Study Type: Interventional
• Actual Enrollment: 116 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Outcomes Assessor)
• Masking Description: The anesthesiologist will NOT be blinded, but the orthopedic surgeon performing the hip replacement surgery will be.
• Primary Purpose: Other
• Official Title: Does Deep Neuromuscular Blockade Improve Operating Conditions During Total Hip Replacements?
• Actual Study Start Date: May 1, 2017
• Actual Primary Completion Date: Apr 30, 2018
• Actual Study Completion Date: May 1, 2018

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Moderate Neuromuscular Blockade (NMB) Intubating dose of Vecuronium 0.1 mg/kg (IBW) and re-dosing with 0.0125 to 0.05 mg/kg as needed to achieve and maintain 1 to 2 train-of-four (TOF) contractions. Redosing in this manner is a current clinical practice.	Drug: Vecuronium 0.1 mg/kg; Vecuronium will be administered to achieve and maintain 1 to 2 TOF contractions.; Other Names: vecuronium bromide
Active Comparator: Deep NMB Deep NMB: Intubating dose of Vecuronium 0.2 mg/kg (IBW) and re-dosing with 0.025 to 0.1 mg/kg to achieve and maintain zero twitches in the TOF, and post tetanic count (PTC) of 1 to 2 contractions. This level of blockade is new to the practice since approval of the drug for use at Maine Medical Center (MMC) but is in common use since the advent of Sugammadex.	Drug: Vecuronium 0.2mg/kg; Vecuronium will be administered to achieve and 0 TOF/PTC 1-2.; Other Names: vecuronium bromide

Outcome Measures

Primary Outcome Measures

1. Surgical Conditions [Through study completion, an average of 24 hours.]

   The surgeon graded the overall surgical conditions on a 5 point Likert scale, that was taken into account along with requests for additional muscle relaxation. The Likert scale went from 1 (extremely poor conditions: muscles resistant to retraction and obscure view, implant difficult to insert into socket, requires assist) to 5 (optimal conditions: muscles relaxed, excellent view, implant easy to insert).

Secondary Outcome Measures

1. Duration of Surgery [Through study completion, an average of 24 hours for each patient and up to one year for the whole study.]

   Time from incision to joint reduction

Eligibility Criteria

Criteria

• Ages Eligible for Study: 50 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• American Society of Anesthesiologists (ASA) Physical status 1-3

• age 50-75

• English speaking

• able to provide informed consent

• BMI equal to less than 30

• non-emergent THR by anterolateral minimally invasive non-cemented total hip arthroplasty

Exclusion Criteria:

• Revision surgery

• Bilateral THR

• ASA 4+

• age less than 50 or greater than 75

• BMI greater than 30

• unable to provide informed consent

• women taking oral contraceptives (Sugammadex used for reversal interferes with their efficacy

• contraindications to general inhalation anesthesia (such as malignant hyperthermia)

• contraindications to NMB (known allergy to NMB)

• chronic kidney disease

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Maine Medical Center	Portland	Maine	United States	04102

Sponsors and Collaborators

• Craig Curry
• MaineHealth
• Spectrum Medical Group Anesthesiology

Investigators

• Principal Investigator: Craig Curry, MD, Maine Medical Center/Spectrum Medical Group

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Apr 13, 2017

More Information

Publications

• Basad E, Ishaque B, Stürz H, Jerosch J. The anterolateral minimally invasive approach for total hip arthroplasty: technique, pitfalls, and way out. Orthop Clin North Am. 2009 Oct;40(4):473-8, viii. doi: 10.1016/j.ocl.2009.05.001. Review.
• Brueckmann B, Sasaki N, Grobara P, Li MK, Woo T, de Bie J, Maktabi M, Lee J, Kwo J, Pino R, Sabouri AS, McGovern F, Staehr-Rye AK, Eikermann M. Effects of sugammadex on incidence of postoperative residual neuromuscular blockade: a randomized, controlled study. Br J Anaesth. 2015 Nov;115(5):743-51. doi: 10.1093/bja/aev104. Epub 2015 May 2.
• Chambers D, Paulden M, Paton F, Heirs M, Duffy S, Craig D, Hunter J, Wilson J, Sculpher M, Woolacott N. Sugammadex for the reversal of muscle relaxation in general anaesthesia: a systematic review and economic assessment. Health Technol Assess. 2010 Jul;14(39):1-211. doi: 10.3310/hta14390. Review.
• Madsen MV, Staehr-Rye AK, Gätke MR, Claudius C. Neuromuscular blockade for optimising surgical conditions during abdominal and gynaecological surgery: a systematic review. Acta Anaesthesiol Scand. 2015 Jan;59(1):1-16. doi: 10.1111/aas.12419. Epub 2014 Oct 19. Review.
• Paton F, Paulden M, Chambers D, Heirs M, Duffy S, Hunter JM, Sculpher M, Woolacott N. Sugammadex compared with neostigmine/glycopyrrolate for routine reversal of neuromuscular block: a systematic review and economic evaluation. Br J Anaesth. 2010 Nov;105(5):558-67. doi: 10.1093/bja/aeq269. Epub 2010 Oct 8. Review.

• Responsible Party: Craig Curry, Anesthesiologist, MaineHealth
• ClinicalTrials.gov Identifier: NCT03219294
• Other Study ID Numbers: 988210-2
• First Posted: Jul 17, 2017
• Last Update Posted: Sep 18, 2019
• Last Verified: Sep 1, 2019

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No
• Keywords provided by Craig Curry, Anesthesiologist, MaineHealth: neuromuscular blockade; sugammadex
• Additional relevant MeSH terms: Joint Diseases; Bromides; Vecuronium Bromide

Study Results

Participant Flow

Arm/Group Title	Moderate NMB	Deep NMB
Arm/Group Description	Intubating dose of Vecuronium 0.1 mg/kg (IBW) and re-dosing with 0.0125 to 0.05 mg/kg as needed to achieve and maintain 1 to 2 TOF contractions. Redosing in this manner is a current clinical practice. Vecuronium 0.1 mg/kg: Vecuronium will be administered to achieve and maintain 1 to 2 TOF contractions.	Deep NMB: Intubating dose of Vecuronium 0.2 mg/kg (IBW) and re-dosing with 0.025 to 0.1 mg/kg to achieve and maintain zero twitches in the TOF, and post tetanic count (PTC) of 1 to 2 contractions. This level of blockade is new to the practice since approval of the drug for use at MMC but is in common use since the advent of Sugammadex. Vecuronium 0.2mg/kg: Vecuronium will be administered to achieve and 0 TOF/PTC 1-2.
Period Title: Overall Study
STARTED	58	58
COMPLETED	58	58
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Moderate NMB	Deep NMB	Total
Arm/Group Description	Intubating dose of Vecuronium 0.1 mg/kg (IBW) and re-dosing with 0.0125 to 0.05 mg/kg as needed to achieve and maintain 1 to 2 TOF contractions. Redosing in this manner is a current clinical practice. Vecuronium 0.1 mg/kg: Vecuronium will be administered to achieve and maintain 1 to 2 TOF contractions.	Deep NMB: Intubating dose of Vecuronium 0.2 mg/kg (IBW) and re-dosing with 0.025 to 0.1 mg/kg to achieve and maintain zero twitches in the TOF, and post tetanic count (PTC) of 1 to 2 contractions. This level of blockade is new to the practice since approval of the drug for use at MMC but is in common use since the advent of Sugammadex. Vecuronium 0.2mg/kg: Vecuronium will be administered to achieve and 0 TOF/PTC 1-2.	Total of all reporting groups
Overall Participants	58	58	116
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	63.1 (6.7)	62.9 (7.4)	63 (7.04)
Sex: Female, Male (Count of Participants)
Female	29 50%	30 51.7%	59 50.9%
Male	29 50%	28 48.3%	57 49.1%
Race and Ethnicity Not Collected (Count of Participants)
Count of Participants [Participants]	0 0%
Region of Enrollment (participants) [Number]
United States	58 100%	58 100%	116 100%

Outcome Measures

1. Primary Outcome

Title	Surgical Conditions
Description	The surgeon graded the overall surgical conditions on a 5 point Likert scale, that was taken into account along with requests for additional muscle relaxation. The Likert scale went from 1 (extremely poor conditions: muscles resistant to retraction and obscure view, implant difficult to insert into socket, requires assist) to 5 (optimal conditions: muscles relaxed, excellent view, implant easy to insert).
Time Frame	Through study completion, an average of 24 hours.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Moderate NMB	Deep NMB
Arm/Group Description	Intubating dose of Vecuronium 0.1 mg/kg (IBW) and re-dosing with 0.0125 to 0.05 mg/kg as needed to achieve and maintain 1 to 2 TOF contractions. Redosing in this manner is a current clinical practice. Vecuronium 0.1 mg/kg: Vecuronium will be administered to achieve and maintain 1 to 2 TOF contractions.	Deep NMB: Intubating dose of Vecuronium 0.2 mg/kg (IBW) and re-dosing with 0.025 to 0.1 mg/kg to achieve and maintain zero twitches in the TOF, and post tetanic count (PTC) of 1 to 2 contractions. This level of blockade is new to the practice since approval of the drug for use at MMC but is in common use since the advent of Sugammadex. Vecuronium 0.2mg/kg: Vecuronium will be administered to achieve and 0 TOF/PTC 1-2.
Measure Participants	58	58
Extremely Poor Conditions	1 1.7%	2 3.4%
Poor Conditions	11 19%	10 17.2%
Acceptable Conditions	30 51.7%	29 50%
Good Conditions	15 25.9%	15 25.9%
Optimal Conditions	1 1.7%	2 3.4%

2. Secondary Outcome

Title	Duration of Surgery
Description	Time from incision to joint reduction
Time Frame	Through study completion, an average of 24 hours for each patient and up to one year for the whole study.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Moderate NMB	Deep NMB
Arm/Group Description	Intubating dose of Vecuronium 0.1 mg/kg (IBW) and re-dosing with 0.0125 to 0.05 mg/kg as needed to achieve and maintain 1 to 2 TOF contractions. Redosing in this manner is a current clinical practice. Vecuronium 0.1 mg/kg: Vecuronium will be administered to achieve and maintain 1 to 2 TOF contractions.	Deep NMB: Intubating dose of Vecuronium 0.2 mg/kg (IBW) and re-dosing with 0.025 to 0.1 mg/kg to achieve and maintain zero twitches in the TOF, and post tetanic count (PTC) of 1 to 2 contractions. This level of blockade is new to the practice since approval of the drug for use at MMC but is in common use since the advent of Sugammadex. Vecuronium 0.2mg/kg: Vecuronium will be administered to achieve and 0 TOF/PTC 1-2.
Measure Participants	58	58
Mean (Standard Deviation) [minutes]	32.6 (1.2)	33.8 (1.2)

Adverse Events

Time Frame	Patients were monitored for the duration of their surgical case and time in the post-anesthesia care unit until discharge from the hospital, usually 24 hours, and had a post-surgical follow-up several weeks after discharge.
Arm/Group Title	Moderate NMB		Deep NMB
Arm/Group Description	Intubating dose of Vecuronium 0.1 mg/kg (IBW) and re-dosing with 0.0125 to 0.05 mg/kg as needed to achieve and maintain 1 to 2 TOF contractions. Redosing in this manner is a current clinical practice. Vecuronium 0.1 mg/kg: Vecuronium will be administered to achieve and maintain 1 to 2 TOF contractions.		Deep NMB: Intubating dose of Vecuronium 0.2 mg/kg (IBW) and re-dosing with 0.025 to 0.1 mg/kg to achieve and maintain zero twitches in the TOF, and post tetanic count (PTC) of 1 to 2 contractions. This level of blockade is new to the practice since approval of the drug for use at MMC but is in common use since the advent of Sugammadex. Vecuronium 0.2mg/kg: Vecuronium will be administered to achieve and 0 TOF/PTC 1-2.
All Cause Mortality
	Moderate NMB		Deep NMB
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/58 (0%)		0/58 (0%)
Serious Adverse Events
	Moderate NMB		Deep NMB
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/58 (0%)		0/58 (0%)
Other (Not Including Serious) Adverse Events
	Moderate NMB		Deep NMB
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/58 (0%)		0/58 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.