Neuromuscular Monitoring After Administration of Neuromuscular Blocking Agents in Different Types of Surgery
Conditions
Keywords
neuromuscular blockade, NMBA, sugammadex, Bridion, TOF,
Brief summary
The intent of this observational study is to collect prospective data regarding neuromuscular monitoring practices and extubation standards (Train-Of-Four \[TOF\] value) during surgery, in countries of Central and Eastern Europe, Middle East and Africa (CEE/EEMEA countries). Secondarily the study will observe, for which surgical procedures neuromuscular blocking agents (NMBAs), and reversal agents to such, are used. This study is a non-interventional clinical trial, and administration of NMBAs, and respective reversal agents, (as well as all drugs used during anesthesia) will be done in accordance with routine anesthesiology practice, and labeling guidelines. Neuromuscular transmission will be monitored according to routine anesthesiology practice by means of acceleromyography. The assignment of the participant to a particular therapeutic strategy is not decided in advance by a trial protocol, but falls within current practice and the prescription of the medicine is clearly separated from the decision to include the patient in the study.
Interventions
OTHERNo neuromuscular blockade (NMB)-reversal agent used
Participants whose reversal from NMB is spontaneous (no reversal agent used)
DRUGSugammadex
Participants receive NMB-reversal agents at the discretion of the treating physician per label according to local guidelines, in accordance with routine anesthesiology practice. As this is a prospective observational study designed to collect data as part of routine clinical practice, the protocol does not assign which reversal agents, if any, are to be used. This intervention is associated with a cohort that is intended to include participants who receive the NMB-reversal agent sugammadex, administered according to the local clinical practice and drug product labeling.
DRUGOther NMB-Reversal Agents Used in Routine Anesthesiology Practice
Participants receive NMB-reversal agents at the discretion of the treating physician per label according to local guidelines, in accordance with routine anesthesiology practice. As this is a prospective observational study designed to collect data as part of routine clinical practice, the protocol does not assign which reversal agents, if any, are to be used. This intervention is associated with a cohort that is intended to include participants who receive any NMB-reversal agent other than sugammadex, and represents multiple drugs whose use and administration may vary according to local clinical practice, product availability and product labeling.
Sponsors
Merck Sharp & Dohme LLC
Study design
Observational model
CASE_CONTROL
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
All of the criteria below must be met for a participant to be eligible for study participation. The prospective participant: * Is an adult, 18 to 65 years-of-age; * Is to undergo surgery requiring general anesthesia with non-depolarizing NMBA administration, with or without NMB reversal; * Meets the inclusion criteria listed on the NMBA label in each country; * Is willing to participate and sign an informed consent form (ICF).
Exclusion criteria
Exclusion from the study will be determined by the treating physician. In addition the criteria below should be considered in determining those participants who should be excluded from the study. The prospective participant: * Is pregnant or breast feeding; * Has a neuromuscular disorder; * Has severe hepatic impairment; * Has severe renal impairment.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With a Train-Of-Four (TOF)-Ratio <0.9 at Extubation | At extubation (approximately <1 to 125 minutes after end of surgery) | Neuromuscular function assessment was performed according to routine anesthesiology practice. This typically involves application of repetitive Train-Of-Four (TOF) electrical stimulations to the ulnar nerve and assessment of twitch response at the adductor pollicis muscle. The TOF-ratio, expressed as a decimal from 0.0 up to 1.0, is the ratio of the magnitude of the fourth twitch (T4) to that of the first twitch (T1). The greater the T4/T1 ratio the greater the recovery from neuromuscular blockade. The TOF-ratio was measured at the time of post-surgical extubation. TOF-ratio at time of extubation was to be recorded for each participant, if available, irrespective of the criteria used to make the decision to extubate the participant. TOF-ratio \<0.9 at extubation is considered to indicate a high risk for development of postoperative residual curarization (i.e, residual neuromuscular blockade), which can result in respiratory complications. |
| Time From End of Surgery (End of Last Stitch) to Extubation | From end of surgery (end of last stitch) to extubation (duration of approximately <1 to 62 minutes) | This measure is the duration from the last surgical wound stitch to the post-surgical extubation of the participant. The time of extubation was to be recorded for each participant, irrespective of the criteria used to make the decision to extubate the participant. Data are presented by TOF-ratio \<0.9 and ≥0.9 at extubation. The TOF-ratio is a measure of neuromuscular function ranging from 0.0 to 1.0. The greater the T4/T1 ratio the greater the recovery from neuromuscular blockade. TOF-ratio \<0.9 at extubation is considered to indicate a high risk for development of postoperative residual curarization (i.e, residual neuromuscular blockade), which can result in respiratory complications. |
| Type of Surgical Procedure Performed in Study Participants | Day of surgery (Day 1) | The type of surgical procedure performed in each study participant was recorded. |
| Type of NMB-reversal Agent Administered to Study Participants | At administration of NMB-reversal agent (up to approximately 395 minutes after start of surgery) | For all participants who received an NMB-reversal agent, the specific agent administered was recorded. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time From NMB-reversal Agent Administration to Recovery Room Dismissal | Post-surgical and recovery period (up to approximately 170 hours post-surgery) | This measure is the duration from NMB-reversal agent administration to dismissal of the participant from the Recovery Room. The time of dismissal from the Recovery Room was to be recorded for each participant, irrespective of the criteria used to make the decision to dismiss the participant. |
| Time From NMB-reversal Agent Administration to Operating Room Dismissal | Post-surgical period (up to approximately 24 hours post-surgery) | This measure is the duration from NMB-reversal agent administration to dismissal of the participant from the Operating Room. The time of dismissal from the Operating Room was to be recorded for each participant, irrespective of the criteria used to make the decision to dismiss the participant. |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Spontaneous Reversal Participants whose reversal from NMB was spontaneous (no reversal agent used) | 155 |
| Sugammadex Participants administered sugammadex for NMB reversal | 177 |
| Other Reversal Agents Participants administered any other agent (other than sugammadex) for NMB reversal | 327 |
| Total | 659 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 | 0 |
| Overall Study | Lost to Follow-up | 1 | 2 | 6 |
Baseline characteristics
| Characteristic | Spontaneous Reversal | Sugammadex | Other Reversal Agents | Total |
|---|---|---|---|---|
| Age, Continuous | 41.7 years STANDARD_DEVIATION 13.7 | 45.3 years STANDARD_DEVIATION 13.6 | 42.7 years STANDARD_DEVIATION 12.7 | 43.2 years STANDARD_DEVIATION 13.2 |
| Sex: Female, Male Female | 109 Participants | 106 Participants | 210 Participants | 425 Participants |
| Sex: Female, Male Male | 46 Participants | 71 Participants | 117 Participants | 234 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 21 / 155 | 23 / 177 | 40 / 327 |
| serious Total, serious adverse events | 2 / 155 | 3 / 177 | 2 / 327 |
Outcome results
Primary
Number of Participants With a Train-Of-Four (TOF)-Ratio <0.9 at Extubation
Neuromuscular function assessment was performed according to routine anesthesiology practice. This typically involves application of repetitive Train-Of-Four (TOF) electrical stimulations to the ulnar nerve and assessment of twitch response at the adductor pollicis muscle. The TOF-ratio, expressed as a decimal from 0.0 up to 1.0, is the ratio of the magnitude of the fourth twitch (T4) to that of the first twitch (T1). The greater the T4/T1 ratio the greater the recovery from neuromuscular blockade. The TOF-ratio was measured at the time of post-surgical extubation. TOF-ratio at time of extubation was to be recorded for each participant, if available, irrespective of the criteria used to make the decision to extubate the participant. TOF-ratio \<0.9 at extubation is considered to indicate a high risk for development of postoperative residual curarization (i.e, residual neuromuscular blockade), which can result in respiratory complications.
Time frame: At extubation (approximately <1 to 125 minutes after end of surgery)
Population: Evaluable participants with TOF-ratio measurement at time of extubation
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Spontaneous Reversal | Number of Participants With a Train-Of-Four (TOF)-Ratio <0.9 at Extubation | 55 participants |
| Sugammadex | Number of Participants With a Train-Of-Four (TOF)-Ratio <0.9 at Extubation | 17 participants |
| Other Reversal Agents | Number of Participants With a Train-Of-Four (TOF)-Ratio <0.9 at Extubation | 95 participants |
Primary
Time From End of Surgery (End of Last Stitch) to Extubation
This measure is the duration from the last surgical wound stitch to the post-surgical extubation of the participant. The time of extubation was to be recorded for each participant, irrespective of the criteria used to make the decision to extubate the participant. Data are presented by TOF-ratio \<0.9 and ≥0.9 at extubation. The TOF-ratio is a measure of neuromuscular function ranging from 0.0 to 1.0. The greater the T4/T1 ratio the greater the recovery from neuromuscular blockade. TOF-ratio \<0.9 at extubation is considered to indicate a high risk for development of postoperative residual curarization (i.e, residual neuromuscular blockade), which can result in respiratory complications.
Time frame: From end of surgery (end of last stitch) to extubation (duration of approximately <1 to 62 minutes)
Population: Evaluable participants with TOF-ratio measurement at time of extubation and available procedure duration data. Three sugammadex participants with duration from end of surgery to extubation \>1 hour were excluded from analysis; delay of extubation was considered due to factors unrelated to administration of sugammadex.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Spontaneous Reversal | Time From End of Surgery (End of Last Stitch) to Extubation | TOF-ratio <0.9 at extubation (N=55, 17, 95) | 12.80 minutes | Standard Deviation 11.54 |
| Spontaneous Reversal | Time From End of Surgery (End of Last Stitch) to Extubation | TOF-ratio ≥0.9 at extubation (N=82, 155, 223) | 9.73 minutes | Standard Deviation 7.96 |
| Sugammadex | Time From End of Surgery (End of Last Stitch) to Extubation | TOF-ratio <0.9 at extubation (N=55, 17, 95) | 8.82 minutes | Standard Deviation 5.16 |
| Sugammadex | Time From End of Surgery (End of Last Stitch) to Extubation | TOF-ratio ≥0.9 at extubation (N=82, 155, 223) | 10.01 minutes | Standard Deviation 7.28 |
| Other Reversal Agents | Time From End of Surgery (End of Last Stitch) to Extubation | TOF-ratio <0.9 at extubation (N=55, 17, 95) | 11.76 minutes | Standard Deviation 7.14 |
| Other Reversal Agents | Time From End of Surgery (End of Last Stitch) to Extubation | TOF-ratio ≥0.9 at extubation (N=82, 155, 223) | 12.20 minutes | Standard Deviation 6.97 |
Primary
Type of NMB-reversal Agent Administered to Study Participants
For all participants who received an NMB-reversal agent, the specific agent administered was recorded.
Time frame: At administration of NMB-reversal agent (up to approximately 395 minutes after start of surgery)
Population: All study participants who received an NMBA or NMB-reversal agent
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Spontaneous Reversal | Type of NMB-reversal Agent Administered to Study Participants | neostigmine | 327 participants |
| Spontaneous Reversal | Type of NMB-reversal Agent Administered to Study Participants | sugammadex | 177 participants |
| Spontaneous Reversal | Type of NMB-reversal Agent Administered to Study Participants | NMB-reversal agent not administered | 155 participants |
Primary
Type of Surgical Procedure Performed in Study Participants
The type of surgical procedure performed in each study participant was recorded.
Time frame: Day of surgery (Day 1)
Population: All study participants who received a neuromuscular blocking agent (NMBA) or NMB-reversal agent
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Spontaneous Reversal | Type of Surgical Procedure Performed in Study Participants | nasal septal operation | 47 participants |
| Spontaneous Reversal | Type of Surgical Procedure Performed in Study Participants | thyroidectomy | 36 participants |
| Spontaneous Reversal | Type of Surgical Procedure Performed in Study Participants | intervertebral disc operation | 34 participants |
| Spontaneous Reversal | Type of Surgical Procedure Performed in Study Participants | hysterectomy | 28 participants |
| Spontaneous Reversal | Type of Surgical Procedure Performed in Study Participants | other surgical procedure | 385 participants |
| Spontaneous Reversal | Type of Surgical Procedure Performed in Study Participants | cholecystectomy | 129 participants |
Secondary
Time From NMB-reversal Agent Administration to Operating Room Dismissal
This measure is the duration from NMB-reversal agent administration to dismissal of the participant from the Operating Room. The time of dismissal from the Operating Room was to be recorded for each participant, irrespective of the criteria used to make the decision to dismiss the participant.
Time frame: Post-surgical period (up to approximately 24 hours post-surgery)
Population: Evaluable participants who received an NMB-reversal agent and had available procedure duration data. Participants in the Spontaneous Reversal group did not receive any NMB-reversal agents and therefore were not included in this analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Spontaneous Reversal | Time From NMB-reversal Agent Administration to Operating Room Dismissal | 15.90 minutes | Standard Deviation 14.96 |
| Sugammadex | Time From NMB-reversal Agent Administration to Operating Room Dismissal | 40.46 minutes | Standard Deviation 109.9 |
Secondary
Time From NMB-reversal Agent Administration to Recovery Room Dismissal
This measure is the duration from NMB-reversal agent administration to dismissal of the participant from the Recovery Room. The time of dismissal from the Recovery Room was to be recorded for each participant, irrespective of the criteria used to make the decision to dismiss the participant.
Time frame: Post-surgical and recovery period (up to approximately 170 hours post-surgery)
Population: Evaluable participants who received an NMB-reversal agent and had available procedure duration data. Participants in the Spontaneous Reversal group did not receive any NMB-reversal agents and therefore were not included in this analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Spontaneous Reversal | Time From NMB-reversal Agent Administration to Recovery Room Dismissal | 630.5 minutes | Standard Deviation 1070 |
| Sugammadex | Time From NMB-reversal Agent Administration to Recovery Room Dismissal | 619.2 minutes | Standard Deviation 1348 |