Sugammadex vs. Neostigmine for Neuromuscular Blockade Reversal in Thoracic Surgical Patients
| Status: | Recruiting |
|---|---|
| Healthy: | No |
| Age Range: | 18 - 80 |
| Updated: | 10/12/2018 |
| Start Date: | September 26, 2017 |
| End Date: | June 30, 2019 |
| Contact: | Tiffany Moon, MD |
| Email: | tiffany.moon@utsouthwestern.edu |
| Phone: | 469-419-5790 |
Sugammadex Versus Neostigmine for Reversal of Rocuronium-induced Neuromuscular Blockade: A Study of Thoracic Surgical Patients
This prospective, randomized, double blinded study is intended to enroll a total of 92
patients undergoing thoracic surgery with general endotracheal anesthesia at Parkland
Hospital. Patients will be randomized to receive either neostigmine or sugammadex for
reversal of neuromuscular blockade. Merck, Inc. will supply the sugammadex through an
agreement with Parkland Investigational Drug Services. Neostigmine is readily available for
anesthesiologists to use and is the current standard of care for reversal of neuromuscular
blockade. A standardized anesthetic protocol that is usual and customary for the type of
operation the patient is having will be provided to the anesthesia teams of enrolled
subjects. The remainder of the anesthetic care of the subject will not deviate from the
standard of care. The surgeon, anesthesia team, PACU nurse, and research assistant will be
blinded as to which reversal drug the patient receives. The only individual that will know to
which drug the patient has been randomized will be the pharmacist who draws up the
medication(s). A blinded research assistant will record postoperative outcomes and the
patient will be followed until postoperative day (POD) 3.
patients undergoing thoracic surgery with general endotracheal anesthesia at Parkland
Hospital. Patients will be randomized to receive either neostigmine or sugammadex for
reversal of neuromuscular blockade. Merck, Inc. will supply the sugammadex through an
agreement with Parkland Investigational Drug Services. Neostigmine is readily available for
anesthesiologists to use and is the current standard of care for reversal of neuromuscular
blockade. A standardized anesthetic protocol that is usual and customary for the type of
operation the patient is having will be provided to the anesthesia teams of enrolled
subjects. The remainder of the anesthetic care of the subject will not deviate from the
standard of care. The surgeon, anesthesia team, PACU nurse, and research assistant will be
blinded as to which reversal drug the patient receives. The only individual that will know to
which drug the patient has been randomized will be the pharmacist who draws up the
medication(s). A blinded research assistant will record postoperative outcomes and the
patient will be followed until postoperative day (POD) 3.
Screening and Informed Consent
A member of the research team will use a screening form to look for surgical patients that
meet all of the inclusion and exclusion criteria. He/she will approach potential subjects
during pre-anesthesia evaluation clinic (PAEC). Patients who are unable to be consented in
PAEC will be approached in the preoperative area and the study will be explained in detail in
a private room. Patients will be informed that they will receive no compensation for
participating in the study and there will be no adverse consequences if they choose not to
participate. If the subjects agree to participate, informed written consent will be obtained
prior to any study procedures and this document will be sent to
pmhresearchparticipants@phhs.org, for inclusion in the patient's medical record, per Parkland
regulations. The study duration is approximately 72 hours, from the start of anesthesia to
postoperative day 3.
Baseline Subjective Measures
In the preoperative area, patients will be asked to complete a baseline assessment in 3
domains:
1. Physiological factors
2. Nociceptive factors
3. Emotional factors
Anesthesia Protocol
The anesthesia team that will be caring for the subject during surgery will be given the
protocol for the study, which standardizes the general anesthetic technique. All patients
will receive 0.6 mg/kg of rocuronium for neuromuscular paralysis during induction. Additional
rocuronium will be given in 0.15 mg/kg increments to keep the patient at a neuromuscular
depth of 1 twitch throughout the surgery. All patients will have the depth of neuromuscular
block monitored at the non-dominant ulnar nerve at 60 mA with a TOF Watch accelerometer
device, which provides real time feedback of the strength of contraction and graphically
displays the relevant ratios.
Maintenance of anesthesia will be with sevoflurane in 70% oxygen, titrated to keep the
bispectral index (BIS) between 40-60. All patients will have a forced air warming device
(e.g., Bair Hugger, 3M, Maplewood, MN) used to maintain normothermia throughout the surgery.
Subjects will be randomized to receive blinded study drug: either neostigmine or sugammadex
for reversal of neuromuscular blockade, which will be administered intravenously at the
beginning of skin closure. The anesthesia team will be blinded. The blinded study drug
(reversal agent(s)) will be prepared into a 10 mL syringe by a pharmacist in Investigational
Drug Service (IDS) Pharmacy and labeled in a blinded fashion as "sugammadex or
neostigmine/glycopyrrolate." Any volume of blinded study drug (reversal agent(s)) that is
less than 10 mL will be supplemented with 0.9% normal saline solution, preservation-free so
that all syringes contain a volume of 10 mL and appear identical in order to preserve
blinding. The remaining aspects of the anesthetic will be standardized and not differ from
the standard of care and will be similar for all patients.
Randomization & Dosing:
Patients will be randomized to one of two groups for reversal of neuromuscular paralysis:
1. Group 1- neostigmine (NEO group)
1. Neostigmine 50 mcg/kg, maximum 5 mg
2. Glycopyrrolate, 8 mcg/kg, maximum 1 mg
2. Group 2- sugammadex (SUG group).
1. Sugammadex 2 mg/kg
The research coordinator will make randomization envelopes by using a random number
generator. These envelopes will be provided to IDS Pharmacy before any subjects are screened
and later only as needed to replenish supply. The words 'neostigmine/glycopyrrolate' or
'sugammadex' will be printed on a piece of paper and placed in an opaque manila envelope that
bears a unique subject number (#). Upon receiving the physician order for the subject, the
IDS Pharmacist will randomize the subject to a treatment group by opening the randomization
envelope bearing the subject # corresponding to the subject # written on the physician order.
The Investigator or Co-Investigator will write the patient's total body weight (TBW) on the
physician order so that the pharmacist can perform necessary dose calculations and draw up
the appropriate intravenous dose of the blinded study drug (reversal agent(s)): sugammadex OR
neostigmine/glycopyrrolate. After the blinded study drug syringe is prepared, a pharmacist or
pharmacy technician will deliver the syringe to the operating room to the anesthesia
provider, who will sign for receipt of the study drug syringe.
Blinding/Un-blinding:
The patient, all medical providers (surgeons, anesthesia faculty, anesthesia residents,
certified registered nurse anesthetists, nurses), and the postoperative evaluator will be
blinded as to what reversal agent (sugammadex versus neostigmine/glycopyrrolate) the patient
receives. A member of the research team that is not involved in the direct care or assessment
of the patient will provide the randomization envelopes to IDS Pharmacy. IDS Pharmacy staff
will be the only un-blinded personnel.
In emergency scenarios where un-blinding becomes necessary (e.g., anaphylaxis), the Principal
Investigator or Co-Investigators may call the IDS Pharmacy to ascertain which specific
medication(s) was dispensed. A detailed log of patient enrollments, randomization assignments
and drug accountability will be kept in Investigational Drug Service (IDS) Pharmacy, which
has controlled security access.
Calculation of Key Times
The time that the reversal agent (sugammadex versus neostigmine) is given will be marked as
'Reversal Time', and times to last stitch, extubation, and out of OR will be ascertained from
the electronic medical record (EMR) (i.e., Epic Systems, Verona, WI). Once the patient
arrives in the PACU, a trained research assistant will assess the degree of neuromuscular
function the patient has. Adequate reversal will be defined as a train of four ratio (TOFR) ≥
0.9. Anything less than 0.9 will be defined as residual paralysis or inadequate reversal.
PACU Assessment
A blinded, trained research assistant will observe and record all parameters from the time
the patient arrives in the PACU until they are discharged. All episodes of hypoxia will be
recorded and any use of supplemental oxygen will be recorded. All vital signs will be
extracted from the EMR. Any drugs given in the PACU will be recorded. At 15 minutes, 40
minutes and 80 minutes after arrival to the PACU, the patient will be assessed for the
postoperative quality recovery scale (PQRS) in 3 domains:
1. Physiological factors
2. Nociceptive factors
3. Emotional factors
Postoperative Day (POD) 1 and 3 Assessments
On POD 1 and 3 the patient will be assessed for the postoperative quality recovery scale
(PQRS) in 4-5 domains. Patients who have been discharged home will not be evaluated in the
physiological domain. The patient will also be assessed for any major adverse events
(reintubation, pneumonia, myocardial infarction, stroke, unplanned admission.
1. Physiological factors
2. Nociceptive factors
3. Emotional factors
4. Activities of daily living
5. Overall patient satisfaction
A member of the research team will use a screening form to look for surgical patients that
meet all of the inclusion and exclusion criteria. He/she will approach potential subjects
during pre-anesthesia evaluation clinic (PAEC). Patients who are unable to be consented in
PAEC will be approached in the preoperative area and the study will be explained in detail in
a private room. Patients will be informed that they will receive no compensation for
participating in the study and there will be no adverse consequences if they choose not to
participate. If the subjects agree to participate, informed written consent will be obtained
prior to any study procedures and this document will be sent to
pmhresearchparticipants@phhs.org, for inclusion in the patient's medical record, per Parkland
regulations. The study duration is approximately 72 hours, from the start of anesthesia to
postoperative day 3.
Baseline Subjective Measures
In the preoperative area, patients will be asked to complete a baseline assessment in 3
domains:
1. Physiological factors
2. Nociceptive factors
3. Emotional factors
Anesthesia Protocol
The anesthesia team that will be caring for the subject during surgery will be given the
protocol for the study, which standardizes the general anesthetic technique. All patients
will receive 0.6 mg/kg of rocuronium for neuromuscular paralysis during induction. Additional
rocuronium will be given in 0.15 mg/kg increments to keep the patient at a neuromuscular
depth of 1 twitch throughout the surgery. All patients will have the depth of neuromuscular
block monitored at the non-dominant ulnar nerve at 60 mA with a TOF Watch accelerometer
device, which provides real time feedback of the strength of contraction and graphically
displays the relevant ratios.
Maintenance of anesthesia will be with sevoflurane in 70% oxygen, titrated to keep the
bispectral index (BIS) between 40-60. All patients will have a forced air warming device
(e.g., Bair Hugger, 3M, Maplewood, MN) used to maintain normothermia throughout the surgery.
Subjects will be randomized to receive blinded study drug: either neostigmine or sugammadex
for reversal of neuromuscular blockade, which will be administered intravenously at the
beginning of skin closure. The anesthesia team will be blinded. The blinded study drug
(reversal agent(s)) will be prepared into a 10 mL syringe by a pharmacist in Investigational
Drug Service (IDS) Pharmacy and labeled in a blinded fashion as "sugammadex or
neostigmine/glycopyrrolate." Any volume of blinded study drug (reversal agent(s)) that is
less than 10 mL will be supplemented with 0.9% normal saline solution, preservation-free so
that all syringes contain a volume of 10 mL and appear identical in order to preserve
blinding. The remaining aspects of the anesthetic will be standardized and not differ from
the standard of care and will be similar for all patients.
Randomization & Dosing:
Patients will be randomized to one of two groups for reversal of neuromuscular paralysis:
1. Group 1- neostigmine (NEO group)
1. Neostigmine 50 mcg/kg, maximum 5 mg
2. Glycopyrrolate, 8 mcg/kg, maximum 1 mg
2. Group 2- sugammadex (SUG group).
1. Sugammadex 2 mg/kg
The research coordinator will make randomization envelopes by using a random number
generator. These envelopes will be provided to IDS Pharmacy before any subjects are screened
and later only as needed to replenish supply. The words 'neostigmine/glycopyrrolate' or
'sugammadex' will be printed on a piece of paper and placed in an opaque manila envelope that
bears a unique subject number (#). Upon receiving the physician order for the subject, the
IDS Pharmacist will randomize the subject to a treatment group by opening the randomization
envelope bearing the subject # corresponding to the subject # written on the physician order.
The Investigator or Co-Investigator will write the patient's total body weight (TBW) on the
physician order so that the pharmacist can perform necessary dose calculations and draw up
the appropriate intravenous dose of the blinded study drug (reversal agent(s)): sugammadex OR
neostigmine/glycopyrrolate. After the blinded study drug syringe is prepared, a pharmacist or
pharmacy technician will deliver the syringe to the operating room to the anesthesia
provider, who will sign for receipt of the study drug syringe.
Blinding/Un-blinding:
The patient, all medical providers (surgeons, anesthesia faculty, anesthesia residents,
certified registered nurse anesthetists, nurses), and the postoperative evaluator will be
blinded as to what reversal agent (sugammadex versus neostigmine/glycopyrrolate) the patient
receives. A member of the research team that is not involved in the direct care or assessment
of the patient will provide the randomization envelopes to IDS Pharmacy. IDS Pharmacy staff
will be the only un-blinded personnel.
In emergency scenarios where un-blinding becomes necessary (e.g., anaphylaxis), the Principal
Investigator or Co-Investigators may call the IDS Pharmacy to ascertain which specific
medication(s) was dispensed. A detailed log of patient enrollments, randomization assignments
and drug accountability will be kept in Investigational Drug Service (IDS) Pharmacy, which
has controlled security access.
Calculation of Key Times
The time that the reversal agent (sugammadex versus neostigmine) is given will be marked as
'Reversal Time', and times to last stitch, extubation, and out of OR will be ascertained from
the electronic medical record (EMR) (i.e., Epic Systems, Verona, WI). Once the patient
arrives in the PACU, a trained research assistant will assess the degree of neuromuscular
function the patient has. Adequate reversal will be defined as a train of four ratio (TOFR) ≥
0.9. Anything less than 0.9 will be defined as residual paralysis or inadequate reversal.
PACU Assessment
A blinded, trained research assistant will observe and record all parameters from the time
the patient arrives in the PACU until they are discharged. All episodes of hypoxia will be
recorded and any use of supplemental oxygen will be recorded. All vital signs will be
extracted from the EMR. Any drugs given in the PACU will be recorded. At 15 minutes, 40
minutes and 80 minutes after arrival to the PACU, the patient will be assessed for the
postoperative quality recovery scale (PQRS) in 3 domains:
1. Physiological factors
2. Nociceptive factors
3. Emotional factors
Postoperative Day (POD) 1 and 3 Assessments
On POD 1 and 3 the patient will be assessed for the postoperative quality recovery scale
(PQRS) in 4-5 domains. Patients who have been discharged home will not be evaluated in the
physiological domain. The patient will also be assessed for any major adverse events
(reintubation, pneumonia, myocardial infarction, stroke, unplanned admission.
1. Physiological factors
2. Nociceptive factors
3. Emotional factors
4. Activities of daily living
5. Overall patient satisfaction
Inclusion Criteria:
- 18-80 years old
- Undergoing non-emergent thoracic surgery
- ASA physical status classification 1 to 4
- Willing and able to consent in English or Spanish
- No personal history of neuromuscular disease
Exclusion Criteria:
- Age less than 18 or older than 80
- Patient does not speak English or Spanish
- Planned postoperative intubation or ICU admission
- Allergy to sugammadex, neostigmine, glycopyrrolate, or rocuronium
- Family or personal history of malignant hyperthermia
- Patient refusal
- Monitored anesthesia care (MAC) or regional anesthesia planned
- Pregnant or nursing women
- "Stat" (emergent) cases
- Estimated creatinine clearance <30 mL/min
- Pre-existing muscle weakness of any etiology
- Patients on toremifene (a selective estrogen receptor modulator)
- Women on oral contraceptives who do not wish to use a non-hormonal method of
contraception for 7 days following surgery
We found this trial at
1
site
Click here to add this to my saved trials
