Neuromuscular Block, Renal Transplant Donor of Left Kidney, Renal Transplant Donor of Right Kidney, Surgery
Conditions
Keywords
Laparoscopic donor nephrectomy, Early quality of recovery
Brief summary
Postoperative recovery after live donor nephrectomy (LDN) is largely determined by the consequences of postoperative pain and analgesia consumptions. The investigators' goal is to establish the relationship between the use of deep neuromuscular blockade (NMB) during laparoscopic donor nephrectomy (LDN) and the early quality of recovery. Therefore, the investigators designed a trial in which patients scheduled for living donor nephrectomy are randomized into a group with deep NMB or moderate NMB. The primary outcome measurement will be the Quality of Recovery-40 questionnaire (overall score) at 48 hours after extubation.
Detailed description
Rationale: Postoperative recovery after live donor nephrectomy (LDN) is largely determined by the consequences of postoperative pain and analgesia consumptions. The use of deep neuromuscular blockade (NMB) has shown to reduce postoperative pain scores after laparoscopic surgery. With this study the investigators will investigate if deep NMB also improves the early quality of recovery after LDN. Objective: To establish the relationship between the use of deep neuromuscular blockade (NMB) during laparoscopic donor nephrectomy (LDN) - with standard pressure pneumoperitoneum - and the early quality of recovery. Study design: A multicenter, blinded, randomized controlled trial Study population: 96 adult patients (18 years or older), scheduled for living donor nephrectomy, will be randomized into a group with deep or moderate neuromuscular blockade. Deep neuromuscular blockade is defined as post tetanic count 1-2. Main study parameters/endpoints: The primary outcome measurement will be the Quality of Recovery-40 questionnaire (overall score) at 48 hours after extubation. Secondary outcomes measured are: intra-operative parameters (e.g. surgical conditions, operation time, length of pneumoperitoneum, first warm ischemia time, estimated blood loss, conversion to open or hand-assisted donor nephrectomy, intra-operative complications, cumulative use of rocuronium and sugammadex), the total score of the quality of Recovery-40 questionnaire at 48 hours after extubation, post-operative pain (components of pain scores); postoperative nausea and vomiting (NRS), the cumulative use of analgesics and anti-emetics, time to reach discharge criteria and postoperative complications.
Interventions
OTHERRocuronium
A bolus of 0.7 mg/kg rocuronium is administered just after tracheal intubation and then an infusion of rocuronium (0.3 to 0.4 mg/kg) is started when post-tetanic count (PTC) is more than 0 and titrated towards PTC 1-2.
OTHERNo additional Rocuronium
No additional rocuronium is administered after tracheal intubation.
Sponsors
Merck Sharp & Dohme LLC
Radboud University Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
All adult individuals, who are scheduled for living kidney donation. Inclusion Criteria: * obtained informed consent * age over 18 years
Exclusion criteria
* insufficient control of the Dutch language to read the patient information and to fill out the questionnaires * chronic use of analgesics or psychotropic drugs * use of NSAIDs shorter than 5 days before surgery * known or suspect allergy to rocuronium of sugammadex * neuromuscular disease * indication for rapid sequence induction * deficiency of vitamin K-dependent clotting factors, coagulopathy or active use of coumarin derivates. * Peri-operative use of fusidic acid or flucloxacillin * Severe renal impairment (creatinine clearance \<30ml/min) * Morbid obesity (BMI\>35 kg/m2)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Total Score of the Quality of Recovery-40 Questionnaire (QoR-40) | Day 1: 24 hours after detubation | The QoR-40 is a validated assessment tool for measuring a patient's self-assessed quality of recovery after surgery. It consists of 40 questions measuring 5 dimensions: patient support, comfort, emotions, physical independence and pain. Each item is rated on a scale of 1 to 5, giving a minimal score of 40 and a maximum score of 200. Higher values represent a better outcome |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Surgical Conditions | Day 0: Intraoperative, average of scores up to 240 minutes (assessed each 15 minutes) | Surgical rating score, concerning the quality of the surgical field, scored with the surgical rating scale (SRS) A likert scale from 1 to 5. Higher scores represent better outcomes. 1. = extremely poor conditions 2. = poor conditions 3. = acceptable conditions 4. =good conditions 5. = optimal conditions |
| Length of Pneumoperitoneum | Day 0: once, up to 240 minutes | Intraoperative parameter of duration of pneumoperitoneum |
| Warm Ischemia Time | Day 0: once, up to 240 minutes | Intraoperative parameter measuring the time (in minutes) between dissection of the renal artery and flushing of the kidney after retrieval |
| Estimated Blood Loss | Day 0: once, up to 240 minutes | Intraoperative parameter |
| Intra-operative Complications | Day 0: once, up to 240 minutes | Number of Participants with Complications which occurred during surgery |
| Conversion | Day 0: once, up to 240 minutes | Number of Participants with conversion to open or hand-assisted donor nephrectomy |
| Total Score of the Quality of Recovery-40 Questionnaire | Day 2: 48 hours after detubation | The QoR-40 is a validated assessment tool for measuring a patient's self-assessed quality of recovery after surgery. It consists of 40 questions measuring 5 dimensions: patient support, comfort, emotions, physical independence and pain. Each item is rated on a scale of 1 to 5, giving a minimal score of 40 and a maximum score of 200. Higher values represent a better outcome. |
| Postoperative Pain | Day 0: 1h, 6h, day 1: 24h and day 2: 48 hours (and if still admitted 72h) after detubation | components of pain scores after 1 hour, 6 hours, on postoperative day 1 (POD1) and postoperative day 2 (POD2). Likert scale from 0 to 10. Higher scores represent more pain. |
| Postoperative Complications | 24 and 48 hours (and if still admitted 72h) after detubation and 4 and 8 weeks after surgery | Number of participants with postoperative complications that occurred up to 8 weeks after surgery |
| Discharge Criteria | 24 and 48 hours after detubation | Scoring the following criteria: adequate pain control with oral medication, passage of flatus or defecation, intake of solid food tolerated, patient is mobilized and independent and patient accepts discharge. |
| Pain Scores | once, 4 weeks after surgery | Total amount of pain 4 weeks after surgery Likert scale from 0 to 10. Higher scores represent more pain (worse outcome). |
| Cumulative Use of Rocuronium | Day 0: once, up to 240 minutes | Total amount of rocuronium administered during surgery |
Countries
Netherlands
Participant flow
Pre-assignment details
26 patients were assessed for eligibility but excluded, 8 patients did not meet the inclusion criteria 18 patients declined to participate
Participants by arm
| Arm | Count |
|---|---|
| Group A: Deep Neuromuscular Blockade An extra bolus of rocuronium after intubation followed by infusion
Rocuronium: A bolus of 0.7 mg/kg rocuronium is administered just after tracheal intubation and then an infusion of rocuronium (0.3 to 0.4 mg/kg) is started when PTC is more than 0 and titrated towards PTC 1-2. | 48 |
| Group B: Moderate Neuromuscular Blockade Moderate neuromuscular Blockade No additional rocuronium after intubation.
No additional Rocuronium: No additional rocuronium is administered after tracheal intubation. | 48 |
| Total | 96 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | logistic problems | 1 | 1 |
| Overall Study | Lost to Follow-up | 1 | 2 |
Baseline characteristics
| Characteristic | Group B: Moderate Neuromuscular Blockade | Total | Group A: Deep Neuromuscular Blockade |
|---|---|---|---|
| Age, Continuous | 56.6 years STANDARD_DEVIATION 9.7 | 56.1 years STANDARD_DEVIATION 9.9 | 55.7 years STANDARD_DEVIATION 10.2 |
| BMI | 26.5 kg/m2 STANDARD_DEVIATION 3 | 26.6 kg/m2 STANDARD_DEVIATION 3 | 26.7 kg/m2 STANDARD_DEVIATION 2.9 |
| Centre LUMC | 10 Participants | 23 Participants | 13 Participants |
| Centre Radboud | 38 Participants | 73 Participants | 35 Participants |
| Previous abdominal surgery | 10 Participants | 23 Participants | 13 Participants |
| Previous pregnancies | 21 Participants | 42 Participants | 21 Participants |
| Race and Ethnicity Not Collected | — | 0 Participants | — |
| Sex: Female, Male Female | 24 Participants | 51 Participants | 27 Participants |
| Sex: Female, Male Male | 24 Participants | 45 Participants | 21 Participants |
| Side of nephrectomy Left | 42 Participants | 84 Participants | 42 Participants |
| Side of nephrectomy Right | 6 Participants | 12 Participants | 6 Participants |
| Vascular anatomy (more than one renel artery or renal vein) | 17 Participants | 30 Participants | 13 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 48 | 0 / 48 |
| other Total, other adverse events | 9 / 48 | 5 / 48 |
| serious Total, serious adverse events | 0 / 48 | 1 / 48 |
Outcome results
Primary
Total Score of the Quality of Recovery-40 Questionnaire (QoR-40)
The QoR-40 is a validated assessment tool for measuring a patient's self-assessed quality of recovery after surgery. It consists of 40 questions measuring 5 dimensions: patient support, comfort, emotions, physical independence and pain. Each item is rated on a scale of 1 to 5, giving a minimal score of 40 and a maximum score of 200. Higher values represent a better outcome
Time frame: Day 1: 24 hours after detubation
Population: Explanation of missing data:~One patient from group A missed one page of the QOR-40 questionnaire on postoperative day 1.~One patient from group B did not complete the questionnaires on postoperative days 1 and 2 because of personal circumstances
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Group A: Deep Neuromuscular Blockade | Total Score of the Quality of Recovery-40 Questionnaire (QoR-40) | 169.3 score on a scale | Standard Deviation 18.3 |
| Group B: Moderate Neuromuscular Blockade | Total Score of the Quality of Recovery-40 Questionnaire (QoR-40) | 169.5 score on a scale | Standard Deviation 15.5 |
Secondary
Conversion
Number of Participants with conversion to open or hand-assisted donor nephrectomy
Time frame: Day 0: once, up to 240 minutes
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Group A: Deep Neuromuscular Blockade | Conversion | 0 Participants |
| Group B: Moderate Neuromuscular Blockade | Conversion | 2 Participants |
Secondary
Cumulative Use of Rocuronium
Total amount of rocuronium administered during surgery
Time frame: Day 0: once, up to 240 minutes
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Group A: Deep Neuromuscular Blockade | Cumulative Use of Rocuronium | 184.6 mg | Standard Deviation 83.1 |
| Group B: Moderate Neuromuscular Blockade | Cumulative Use of Rocuronium | 67.0 mg | Standard Deviation 41.2 |
Secondary
Discharge Criteria
Scoring the following criteria: adequate pain control with oral medication, passage of flatus or defecation, intake of solid food tolerated, patient is mobilized and independent and patient accepts discharge.
Time frame: 24 and 48 hours after detubation
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Group A: Deep Neuromuscular Blockade | Discharge Criteria | reached all criteria after 24hours | 13 Participants |
| Group A: Deep Neuromuscular Blockade | Discharge Criteria | reached all criteria after 48 hours | 24 Participants |
| Group B: Moderate Neuromuscular Blockade | Discharge Criteria | reached all criteria after 24hours | 15 Participants |
| Group B: Moderate Neuromuscular Blockade | Discharge Criteria | reached all criteria after 48 hours | 29 Participants |
Secondary
Estimated Blood Loss
Intraoperative parameter
Time frame: Day 0: once, up to 240 minutes
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Group A: Deep Neuromuscular Blockade | Estimated Blood Loss | 60.2 ml | Standard Deviation 68.5 |
| Group B: Moderate Neuromuscular Blockade | Estimated Blood Loss | 69.1 ml | Standard Deviation 72.3 |
Secondary
Intra-operative Complications
Number of Participants with Complications which occurred during surgery
Time frame: Day 0: once, up to 240 minutes
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Group A: Deep Neuromuscular Blockade | Intra-operative Complications | 1 Participants |
| Group B: Moderate Neuromuscular Blockade | Intra-operative Complications | 6 Participants |
Secondary
Length of Pneumoperitoneum
Intraoperative parameter of duration of pneumoperitoneum
Time frame: Day 0: once, up to 240 minutes
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Group A: Deep Neuromuscular Blockade | Length of Pneumoperitoneum | 122.8 minutes | Standard Deviation 44.5 |
| Group B: Moderate Neuromuscular Blockade | Length of Pneumoperitoneum | 113.8 minutes | Standard Deviation 39.2 |
Secondary
Pain Scores
Total amount of pain 4 weeks after surgery Likert scale from 0 to 10. Higher scores represent more pain (worse outcome).
Time frame: once, 4 weeks after surgery
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Group A: Deep Neuromuscular Blockade | Pain Scores | 1.88 score on a scale | Standard Deviation 1.91 |
| Group B: Moderate Neuromuscular Blockade | Pain Scores | 1.85 score on a scale | Standard Deviation 1.92 |
Secondary
Postoperative Complications
Number of participants with postoperative complications that occurred up to 8 weeks after surgery
Time frame: 24 and 48 hours (and if still admitted 72h) after detubation and 4 and 8 weeks after surgery
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Group A: Deep Neuromuscular Blockade | Postoperative Complications | during hospital stay | 2 Participants |
| Group A: Deep Neuromuscular Blockade | Postoperative Complications | 30 days after surgery | 7 Participants |
| Group A: Deep Neuromuscular Blockade | Postoperative Complications | 60 days after surgery | 9 Participants |
| Group B: Moderate Neuromuscular Blockade | Postoperative Complications | during hospital stay | 4 Participants |
| Group B: Moderate Neuromuscular Blockade | Postoperative Complications | 30 days after surgery | 5 Participants |
| Group B: Moderate Neuromuscular Blockade | Postoperative Complications | 60 days after surgery | 5 Participants |
Secondary
Postoperative Pain
components of pain scores after 1 hour, 6 hours, on postoperative day 1 (POD1) and postoperative day 2 (POD2). Likert scale from 0 to 10. Higher scores represent more pain.
Time frame: Day 0: 1h, 6h, day 1: 24h and day 2: 48 hours (and if still admitted 72h) after detubation
Population: 1 patient from the moderate NMB group was not able to complete the questionnaires on day 1 and day 2 because of personal circumstances.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Group A: Deep Neuromuscular Blockade | Postoperative Pain | Overall_1h (PACU) | 4.0 score on a scale | Standard Deviation 2.3 |
| Group A: Deep Neuromuscular Blockade | Postoperative Pain | Referred pain_1h (PACU) | 0.0 score on a scale | Standard Deviation 0.2 |
| Group A: Deep Neuromuscular Blockade | Postoperative Pain | overall_6h | 3.7 score on a scale | Standard Deviation 2.7 |
| Group A: Deep Neuromuscular Blockade | Postoperative Pain | Referred pain_6h | 0.7 score on a scale | Standard Deviation 1.6 |
| Group A: Deep Neuromuscular Blockade | Postoperative Pain | Overall_POD1 | 5.0 score on a scale | Standard Deviation 2.3 |
| Group A: Deep Neuromuscular Blockade | Postoperative Pain | Referred pain+POD1 | 2.5 score on a scale | Standard Deviation 2.7 |
| Group A: Deep Neuromuscular Blockade | Postoperative Pain | Overall_POD2 | 4.6 score on a scale | Standard Deviation 1.9 |
| Group A: Deep Neuromuscular Blockade | Postoperative Pain | Referred pain_POD2 | 2.4 score on a scale | Standard Deviation 2.7 |
| Group B: Moderate Neuromuscular Blockade | Postoperative Pain | Referred pain_POD2 | 3.3 score on a scale | Standard Deviation 2.9 |
| Group B: Moderate Neuromuscular Blockade | Postoperative Pain | Overall_1h (PACU) | 4.31 score on a scale | Standard Deviation 2.4 |
| Group B: Moderate Neuromuscular Blockade | Postoperative Pain | Overall_POD1 | 5.6 score on a scale | Standard Deviation 2.1 |
| Group B: Moderate Neuromuscular Blockade | Postoperative Pain | Referred pain_1h (PACU) | 0.3 score on a scale | Standard Deviation 1.1 |
| Group B: Moderate Neuromuscular Blockade | Postoperative Pain | Overall_POD2 | 4.9 score on a scale | Standard Deviation 2.2 |
| Group B: Moderate Neuromuscular Blockade | Postoperative Pain | overall_6h | 4.5 score on a scale | Standard Deviation 2.2 |
| Group B: Moderate Neuromuscular Blockade | Postoperative Pain | Referred pain+POD1 | 3.2 score on a scale | Standard Deviation 2.8 |
| Group B: Moderate Neuromuscular Blockade | Postoperative Pain | Referred pain_6h | 1.0 score on a scale | Standard Deviation 1.8 |
Secondary
Surgical Conditions
Surgical rating score, concerning the quality of the surgical field, scored with the surgical rating scale (SRS) A likert scale from 1 to 5. Higher scores represent better outcomes. 1. = extremely poor conditions 2. = poor conditions 3. = acceptable conditions 4. =good conditions 5. = optimal conditions
Time frame: Day 0: Intraoperative, average of scores up to 240 minutes (assessed each 15 minutes)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Group A: Deep Neuromuscular Blockade | Surgical Conditions | 4.8 score on a scale | Standard Deviation 0.3 |
| Group B: Moderate Neuromuscular Blockade | Surgical Conditions | 4.7 score on a scale | Standard Deviation 0.5 |
Secondary
Total Score of the Quality of Recovery-40 Questionnaire
The QoR-40 is a validated assessment tool for measuring a patient's self-assessed quality of recovery after surgery. It consists of 40 questions measuring 5 dimensions: patient support, comfort, emotions, physical independence and pain. Each item is rated on a scale of 1 to 5, giving a minimal score of 40 and a maximum score of 200. Higher values represent a better outcome.
Time frame: Day 2: 48 hours after detubation
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Group A: Deep Neuromuscular Blockade | Total Score of the Quality of Recovery-40 Questionnaire | 175.6 score on a scale | Standard Deviation 17.8 |
| Group B: Moderate Neuromuscular Blockade | Total Score of the Quality of Recovery-40 Questionnaire | 175.3 score on a scale | Standard Deviation 16.5 |
Secondary
Warm Ischemia Time
Intraoperative parameter measuring the time (in minutes) between dissection of the renal artery and flushing of the kidney after retrieval
Time frame: Day 0: once, up to 240 minutes
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Group A: Deep Neuromuscular Blockade | Warm Ischemia Time | 3.6 minutes | Standard Deviation 1.3 |
| Group B: Moderate Neuromuscular Blockade | Warm Ischemia Time | 3.9 minutes | Standard Deviation 1.6 |