Utilization Patterns of Perioperative Neuromuscular
Blockade Reversal in the United States
Tim Dubovoy, MD
Clinical Assistant Professor
Michigan Medicine
Introduction
• Sugammadex – a novel NMB reversal agent
– FDA approval December 2015
– Capable of reversing deeper levels of NMB
– Costs more than neostigmine
• Data on sugammadex use – largely based on international survey results
• Outcome studies focused primarily on measures of efficiency
– Limited evidence for reducing postoperative complications
• Adoption of a new drug may be hindered by cost concerns and arbitrary
restrictions on the use of sugammadex
Introduction
• Study aimed to identify practice changes in the management of
NMB reversal following FDA approval of sugammadex in the US
• Our hypotheses:
– There would be wide variation in adoption of sugammadex across individual hospitals
– Sugammadex would be used in a minority of eligible patients
Study Design
• Retrospective observational study
– 24 MPOG academic/private centers
– All had sugammadex on formulary at the time of the study
• Inclusions
– Surgical procedures between Jan 2014 and August 2018
– All adults (>18 years) receiving NMB agents
• Three distinct study periods:
– Before sugammadex was first used at each institution
– The transitional period – excluded from the primary analysis (0-6 months)
– After sugammadex – 6 months after first sugammadex use at each institution
Study Design
• Exclusions
– ASA ≥5; myasthenia gravis and/or pyridostigmine use
– CKD: preop GFR ≤ 30 mL/min or Elixhauser comorbidity
– Cardiac surgery, lung or liver transplantation
– Need for mechanical ventilation before or after surgery
– Median peep > 10 cm H
2
O
– Cases receiving both neostigmine and sugammadex
– Administration of reversal to facilitate intraoperative neurologic monitoring
Variables of Interest
• Primary outcome = administration of an NMB reversal agent
– Neostigmine, sugammadex, or spontaneous reversal
– Categorized by dose by dose ranges
• Covariates
– Patient level: demographic/anthropometric, ASA status, Elixhauser comorbidities
– Case level: CPT case grouping by body region, emergent
– NMB and monitoring: total dose of NMB agents (ED95 equivalents), train-of-four
counts (TOFc) before extubation
– Intraoperative timed events: time from last NMB to reversal, from reversal to
extubation, time from last NMB to extubation
– Type of institution and provider type
Statistical Analysis
• Descriptive and trend – normalized for each hospital to the
first documented sugammadex administration
– Categorical variables summarized with counts and frequencies
– Continuous variables summarized by medians and interquartile ranges
• Multivariable mixed-effects logistic regression model
controlling for institution to assess patient, procedure, and
provider factors associated with sugammadex administration
Patterns of Neuromuscular Blockade Reversal Across 24 Centers by Month
Patterns of Neuromuscular Blockade Reversal Across 24 Centers by Hospital
pattern = nonuniversity-affiliated institution
solid = university-affiliated institution
Before Sugammadex
N=421,754
Total Cases
N=934,798
Transitional
N=127,075
After Sugammadex
N=385,969
Neostigmine
N = 337,596
Sugammadex
N = 154,351
Neostigmine
N = 174,695
ED 95 of NMB per
hour of case
No documented TOF
TOF 0-1 at reversal
TOF 3-4 at reversal
1.1 [0.8, 1.5]
28.9%
3.4%
60.4%
1.2 [0.8, 1.5]
24.2%
2.1%
66.2%
1.3 [0.9, 1.7]
21.1%
7.5%
49.5%
Before Sugammadex
N=421,754
Total Cases
N=934,798
Transitional
N=127,075
After Sugammadex
N=385,969
Neostigmine
N = 337,596
Sugammadex
N = 154,351
Neostigmine
N = 174,695
Median
Neostigmine
Dose (mcg/kg)
41.2
(31.9-
50.4)
38.8 (29.9
-
48.3)
≤2 mg/kg
34.8%
>2 to ≤4
52.6%
>4 to <12 6.1%
*36% of Sugammadex cases received a dose of exactly 200 mg
Sugammadex Dose*
(mg/kg)
Covariate
Adjusted Odds Ratio
(95% Confidence Interval)
Adjusted p-value
Last
TOFc before extubation 0 or 1
twitches (ref
3/4)
4.06 (3.83 – 4.31) <0.001
Resident/Fellow In
-Room Provider
(reference Faculty Only)
1.29 (1.23 – 1.35) <0.001
CRNA
0.79 (0.76 – 0.83) <0.001
ED
95 of NMB per hour of case
duration (
ref Quartile 1)
Quartile 2
1.23 (1.18 – 1.28) <0.001
Quartile 3
1.65 (1.58 – 1.72) <0.001
Quartile 4 (high)
3.01 (2.88 – 3.16) <0.001
Non
-university medical center 0.06 (0.02 – 0.23) <0.001
Lessons Learned
• Our hypotheses:
– There would be wide variation in adoption of sugammadex across individual hospitals
– Sugammadex would be used in a minority of eligible patients
• Overall, across all centers, sugammadex was used preferentially in
patients with known risk factors for residual NMB or postoperative
pulmonary complications
– Higher degree of NMB prior for reversal
– Limited physiologic reserves and medical comorbidities
– Surgical procedures that present high risk for postoperative respiratory complications
Limitations
• Scope was limited to FDA-approved indications and doses
– Did not examine uses outside of standard guidelines or special clinical scenarios
– Pediatric populations, CKD, “rescue”
• We did no examine the effects of policy or practice restrictions that may
have existed at the individual institutions
– Compliance with restrictions?
Thank You
