BLISS: Effect of Deep BLock on Intraoperative Surgical Conditions
Study Details
Study Description
Brief Summary
Rationale: A deep neuromuscular block is often associated with improved surgical conditions especially in laparoscopic surgery. However, a deep block comes at the expense of a variety of items that may conflict with the use of a deep surgical muscle blockade including a long recovery phase, the need for muscle reversal, postoperative ventilation, impaired postoperative breathing. With the introduction of Sugammadex there is now the possibility to reverse an even deep surgical block. This may overcome most if not all of the issues mentioned.
Objective: To assess whether a deep neuromuscular block provides better surgical conditions than a moderately deep block as derived from a surgical rating score.
Study design: Single center, double-blind randomized controlled trial. Study population: 24 ASA I-III patients scheduled for laparoscopic renal (n=12, GROUP 1) or prostatic surgery (n=12, GROUP 2).
Intervention: In both GROUP 1 and GROUP 2, 6 six patients will receive neuromuscular blockade according to current practice (atracurium (bolus) plus mivacurium (cont. infusion)) aimed at a moderately deep neuromuscular block (1-2 twitches in the Train of Four (TOF) monitor). The other six will receive a bolus plus continuous infusion with rocuronium aimed at a deep neuromuscular block (1-2 twitches post tetanic count (PTC)). All surgical procedures will be performed by one surgeon.
Main study parameters/endpoints: To study the surgical conditions in patients undergoing laparoscopic renal or prostate surgery during deep versus less deep neuromuscular block as assessed by the surgical rating score.
Nature and extent of the burden and risks associated with participation, benefit and group relatedness: Compared to current practice there will be no additional risk.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 4 |
Detailed Description
Surgical conditions in laparoscopic surgery are largely determined by the degree of neuromuscular relaxation during surgery. Especially in procedures which are confined to a narrow working field such as renal and prostatic laparoscopic surgery, deep neuromuscular relaxation may be beneficial. Until recently however, deep neuromuscular block (1-2 twitches post tetanic count) came at the expense of a variety of items that conflicted with its use. Occurrence of postoperative residual neuromuscular blockade after deep neuromuscular block was a common adverse event. Residual neuromuscular block is a risk factor for developing airway obstruction and pulmonary complications such pneumonia and atelectasis. The use of acetylcholinesterase inhibitors, like neostigmine, as a traditional neuromuscular blocking reversal agent, have a slow onset of action. Side effects due to muscarine receptor stimulation are bradycardia, hypersalivation, nausea and vomiting. Coadministration of a muscarine agonist like atropine is often necessary to address the heart rate-related side effects of neostigmine. Atropine, however, in itself may induce other side effects.
Rapid, safe and complete reversal of neuromuscular blockade was not possible until the discovery of Sugammadex. Sugammadex is a modified y-cyclodextrin. It was developed to selectively bind free plasma rocuronium, a non-depolarizing steroidal neuromuscular blocking agent. By binding free rocuronium, less rocuronium becomes available at the neuromuscular junction to bind to the muscarine receptor. Non-depolarizing neuromuscular blocking agents (NMBA's) block the muscarine receptor at the neuromuscular junction, making them unavailable to acetylcholine based signal transmission. Sugammadex has proven to rapidly and safely reverse rocuronium and vecuronium. Even high dose rocuronium (1.2 mg/kg and continuous rocuronium infusion used to achieve deep neuromuscular blockade can safely be reversed by Sugammadex.
Theoretically, the availability of Sugammadex makes it possible to use deep neuromuscular block (DNB) during surgery to improve surgical conditions without the occurrence of the above-mentioned adverse events. The use of DNB to improve surgical conditions, however, has not yet been evaluated. The investigators therefore aim to investigate the use of rocuronium induced-DNB in renal and prostatic laparoscopic surgery. Current anesthesiologic practice during these procedures in the LUMC consists of an intravenous (propofol) or volatile (sevoflurane) anesthetic combined with mivacurium and atracurium to achieve a moderately deep neuromuscular block (0-2 twitches TOF). Reversal of NMB is by the neostigmine atropine combination. In the current study the investigators will assess the effect of a DNB (1-2 twitches post tetanic count) using a continuous rocuronium infusion on surgical conditions. After surgery Sugammadex 4 mg/kg will be used to safely and rapidly reverse the neuromuscular blockade within 5-min.
The main end-point of the study is the effect of the deep block on the surgical conditions. The investigators will study these conditions using two methods. (1) Assessment of the surgical condition by the operating surgeon (all surgeries will be performed by one surgeon), using a 5-point rating surgical rating scale from 1 (= extremely poor surgical condition) to 5 = optimal surgical condition. (2) Video images, used by the surgeon to perform the surgery, will be rated by a team of surgical and non-surgical experts. Apart from the additional scoring data, this approach allows for the validation of the surgical rating scale.
Minor end-points of the study are (1) measurement of hemodynamics during surgery using a non-invasive cardiac output and blood pressure device. Assuming that intra-abdominal pressure will affect the venous return and hence cardiac output during surgery, a deep neuromuscular block might affect the hemodynamic parameters positively; (2) measurement of respiration, pain, and alertness in the recovery room to assess whether reversal with Sugammadex influences these parameters positively compared to neostigmine/atropine reversal.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Deep surgical block Continuous rocuronium infusion will be used to induce a deep surgical block with post tetanic twitch count of max 2. Rocuronium loading dose = 1.0 mg/kg, followed by 0.6-1.0 mg/kg per hour. |
Drug: Surgical block (rocuronium; atracurium/mivacurium)
The surgical block will be varied by either induction of a deep block (via rocuronium infusion) or a moderate/normal block (using atracurium/mivacurium infusion)
Other Names:
|
| Active Comparator: Moderate/normal surgical block A normal block will be induced by an atracurium bolus dose followed by a mivacurium infusion to induce a train of four count of 1-2. |
Drug: Surgical block (rocuronium; atracurium/mivacurium)
A surgical block will be induced by infusion of either rocuronium (deep block) or atracurium/mivacurium (normal/moderate block)
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Surgical Rating Scale [Measurements will be made during the stay in the operating room for an average period of 3 hours]
During the procedure, the surgical condition will be scored by the surgeon using a 5-point surgical rating scale. In order to reduce variability in the surgical rating all surgeries will be performed by one single surgeon. The rating scale will be a 5-point ordinal scale ranging from 1 = poor condition to 5 = optimal surgical conditions. The surgeon will score the condition at 15 minute intervals. In case of a sudden change in surgical conditions additional scores will be added to the case record form. If conditions are poor (score 1 or 2), muscle relaxation will be increased, a score of 1 will be used. In each subject the scores over time were averaged and a comparison between treatments was performed using a t-test
Secondary Outcome Measures
- Breathing [Measurements will be made during the stay in the recovery room for an average period of 3 hours]
In the recovery room the respiratory rate will be measured continuously using the Respir8 respiratory rate monitor. The data will be recorded on the CRF at 15 min intervals. Breathing rate units are "number of breaths" as measured in 1 min. Comparison by t-test: NS between treatments
- Post-operative Pain [measurements are made in the recovery room following surgery for an average prior of 1 hour]
Using a 10 cm visual analogue score pain relief score will be measured. 0 = no pain 10 = most severe pain No statistical analysis was performed!
- Postoperative Sedation Score [Measurements will be made during the stay in the operating room for an average period of 3 hours]
Using a 5-point sedation scale, sedation levels will be obtained throughout the postoperative period. 0 = wide awake 5= severely sedated, The sedation data were averaged over time.
- Nausea and Vomiting [Measurements will be made during the stay in the operating room for an average period of 3 hours]
Using a yes - no questionnaire, the patients will be asked whether they are nauseated or not or whether they vomited. In fact yes indicates the nr of participants. No statistical analysis was performed.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Patients diagnosed with renal or prostatic disease who are will undergo an elective laparoscopic renal surgical procedure or laparoscopic prostatectomy;
-
ASA class I-III
-
18 years of age;
-
Ability to give oral and written informed consent
Exclusion Criteria:
-
Known or suspected neuromuscular disorders impairing neuromuscular function;
-
Allergies to muscle relaxants, anesthetics or narcotics;
-
A (family) history of malignant hyperthermia;
-
Patients who have a contraindication for neostigmine administration;
-
Women who are or may be pregnant or are currently breast feeding;
-
Renal insufficiency, as defined by serum creatinine x 2 of normal, or urine output < 0.5 ml/kg/h for at least 6 h. When available, other indices will be taken into account as well such as glomerular filtration rate < 60 ml/h and proteinuria (a ratio of 30 mg albumin to 1 g of creatinine).
-
Previous retroperitoneal surgery at the site of the current surgery.
-
Body mass index > 35 kg/m2
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Leiden University Medical Center | Leiden | ZH | Netherlands | 2333 ZA |
Sponsors and Collaborators
- Leiden University Medical Center
Investigators
- Principal Investigator: Albert Dahan, MD {hD, LUMC
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
None provided.- bliss s
Study Results
Participant Flow
| Recruitment Details | A total of 30 patients were recruited. In 4 one or more exclusion criteria were met, the others were randomized; 2 patients withdrew consent; two others replaced them. |
|---|---|
| Pre-assignment Detail | No significant events occurred that delayed or interfered with the enrollment |
| Arm/Group Title | Moderate/Normal Surgical Block | Deep Surgical Block |
|---|---|---|
| Arm/Group Description | A normal block will be induced by an atracurium bolus dose followed by a mivacurium infusion to induce a train of four count of 1-2. | Continuous rocuronium infusion will be used to induce a deep surgical block with post tetanic twitch count of max 2. Rocuronium loading dose = 1.0 mg/kg, followed by 0.6-1.0 mg/kg per hour. |
| Period Title: Overall Study | ||
| STARTED | 12 | 12 |
| COMPLETED | 12 | 12 |
| NOT COMPLETED | 0 | 0 |
Baseline Characteristics
| Arm/Group Title | Moderate/Normal Surgical Block | Deep Surgical Block | Total |
|---|---|---|---|
| Arm/Group Description | A normal block will be induced by an atracurium bolus dose followed by a mivacurium infusion to induce a train of four count of 1-2. | Continuous rocuronium infusion will be used to induce a deep surgical block with post tetanic twitch count of max 2. Rocuronium loading dose = 1.0 mg/kg, followed by 0.6-1.0 mg/kg per hour. | Total of all reporting groups |
| Overall Participants | 12 | 12 | 24 |
| Age (Count of Participants) | |||
| <=18 years |
0
0%
|
0
0%
|
0
0%
|
| Between 18 and 65 years |
8
66.7%
|
8
66.7%
|
16
66.7%
|
| >=65 years |
4
33.3%
|
4
33.3%
|
8
33.3%
|
| Age (years) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [years] |
59
(12)
|
60
(12)
|
60
(6)
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
2
16.7%
|
2
16.7%
|
4
16.7%
|
| Male |
10
83.3%
|
10
83.3%
|
20
83.3%
|
| Region of Enrollment (participants) [Number] | |||
| Netherlands |
12
100%
|
12
100%
|
24
100%
|
Outcome Measures
| Title | Surgical Rating Scale |
|---|---|
| Description | During the procedure, the surgical condition will be scored by the surgeon using a 5-point surgical rating scale. In order to reduce variability in the surgical rating all surgeries will be performed by one single surgeon. The rating scale will be a 5-point ordinal scale ranging from 1 = poor condition to 5 = optimal surgical conditions. The surgeon will score the condition at 15 minute intervals. In case of a sudden change in surgical conditions additional scores will be added to the case record form. If conditions are poor (score 1 or 2), muscle relaxation will be increased, a score of 1 will be used. In each subject the scores over time were averaged and a comparison between treatments was performed using a t-test |
| Time Frame | Measurements will be made during the stay in the operating room for an average period of 3 hours |
Outcome Measure Data
| Analysis Population Description |
|---|
| Each participant that was dosed was analyzed |
| Arm/Group Title | Moderate/Normal Surgical Block | Deep Surgical Block |
|---|---|---|
| Arm/Group Description | A normal block will be induced by an atracurium bolus dose followed by a mivacurium infusion to induce a train of four count of 1-2. | Continuous rocuronium infusion will be used to induce a deep surgical block with post tetanic twitch count of max 2. Rocuronium loading dose = 1.0 mg/kg, followed by 0.6-1.0 mg/kg per hour. |
| Measure Participants | 12 | 12 |
| Mean (Standard Deviation) [units on a scale (1-5)] |
4
(0.4)
|
4.7
(0.4)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Moderate/Normal Surgical Block, Deep Surgical Block |
|---|---|---|
| Comments | The individual scores obtained during surgery were averaged. The average values were compared using a t-test between treatments. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | t-test, 2 sided | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Net) |
| Estimated Value | 0.7 | |
| Confidence Interval |
() % to |
|
| Parameter Dispersion |
Type: Standard Deviation Value: 0.4 |
|
| Estimation Comments | ||
| Title | Breathing |
|---|---|
| Description | In the recovery room the respiratory rate will be measured continuously using the Respir8 respiratory rate monitor. The data will be recorded on the CRF at 15 min intervals. Breathing rate units are "number of breaths" as measured in 1 min. Comparison by t-test: NS between treatments |
| Time Frame | Measurements will be made during the stay in the recovery room for an average period of 3 hours |
Outcome Measure Data
| Analysis Population Description |
|---|
| In each subject the scores over time were averaged and a comparison between treatments was performed using a t-test |
| Arm/Group Title | Moderate/Normal Surgical Block | Deep Surgical Block |
|---|---|---|
| Arm/Group Description | A normal block will be induced by an atracurium bolus dose followed by a mivacurium infusion to induce a train of four count of 1-2. | Continuous rocuronium infusion will be used to induce a deep surgical block with post tetanic twitch count of max 2. Rocuronium loading dose = 1.0 mg/kg, followed by 0.6-1.0 mg/kg per hour. |
| Measure Participants | 12 | 12 |
| Mean (Standard Deviation) [breaths per min] |
14.5
(2.2)
|
14.5
(2.2)
|
| Title | Post-operative Pain |
|---|---|
| Description | Using a 10 cm visual analogue score pain relief score will be measured. 0 = no pain 10 = most severe pain No statistical analysis was performed! |
| Time Frame | measurements are made in the recovery room following surgery for an average prior of 1 hour |
Outcome Measure Data
| Analysis Population Description |
|---|
| The pain data were averaged over time and compared by t-test between groups |
| Arm/Group Title | Moderate/Normal Surgical Block | Deep Surgical Block |
|---|---|---|
| Arm/Group Description | A normal block will be induced by an atracurium bolus dose followed by a mivacurium infusion to induce a train of four count of 1-2. | Continuous rocuronium infusion will be used to induce a deep surgical block with post tetanic twitch count of max 2. Rocuronium loading dose = 1.0 mg/kg, followed by 0.6-1.0 mg/kg per hour. |
| Measure Participants | 12 | 12 |
| Mean (Standard Deviation) [units on a scale (0-10 cm)] |
2.6
(1.6)
|
2.1
(2.2)
|
| Title | Postoperative Sedation Score |
|---|---|
| Description | Using a 5-point sedation scale, sedation levels will be obtained throughout the postoperative period. 0 = wide awake 5= severely sedated, The sedation data were averaged over time. |
| Time Frame | Measurements will be made during the stay in the operating room for an average period of 3 hours |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Moderate/Normal Surgical Block | Deep Surgical Block |
|---|---|---|
| Arm/Group Description | A normal block will be induced by an atracurium bolus dose followed by a mivacurium infusion to induce a train of four count of 1-2. | Continuous rocuronium infusion will be used to induce a deep surgical block with post tetanic twitch count of max 2. Rocuronium loading dose = 1.0 mg/kg, followed by 0.6-1.0 mg/kg per hour. |
| Measure Participants | 12 | 12 |
| Mean (Standard Error) [units on a scale (0-5)] |
2.0
(0.6)
|
1.3
(1.0)
|
| Title | Nausea and Vomiting |
|---|---|
| Description | Using a yes - no questionnaire, the patients will be asked whether they are nauseated or not or whether they vomited. In fact yes indicates the nr of participants. No statistical analysis was performed. |
| Time Frame | Measurements will be made during the stay in the operating room for an average period of 3 hours |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Moderate/Normal Surgical Block | Deep Surgical Block |
|---|---|---|
| Arm/Group Description | A normal block will be induced by an atracurium bolus dose followed by a mivacurium infusion to induce a train of four count of 1-2. | Continuous rocuronium infusion will be used to induce a deep surgical block with post tetanic twitch count of max 2. Rocuronium loading dose = 1.0 mg/kg, followed by 0.6-1.0 mg/kg per hour. |
| Measure Participants | 12 | 12 |
| Number [participants] |
0
0%
|
0
0%
|
Adverse Events
| Time Frame | 4-5 hours | |||
|---|---|---|---|---|
| Adverse Event Reporting Description | ||||
| Arm/Group Title | Moderate/Normal Surgical Block | Deep Surgical Block | ||
| Arm/Group Description | A normal block will be induced by an atracurium bolus dose followed by a mivacurium infusion to induce a train of four count of 1-2. | Continuous rocuronium infusion will be used to induce a deep surgical block with post tetanic twitch count of max 2. Rocuronium loading dose = 1.0 mg/kg, followed by 0.6-1.0 mg/kg per hour. | ||
All Cause Mortality |
||||
| Moderate/Normal Surgical Block | Deep Surgical Block | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | ||
Serious Adverse Events |
||||
| Moderate/Normal Surgical Block | Deep Surgical Block | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/12 (0%) | 0/12 (0%) | ||
Other (Not Including Serious) Adverse Events |
||||
| Moderate/Normal Surgical Block | Deep Surgical Block | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/12 (0%) | 0/12 (0%) | ||
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT 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.
Results Point of Contact
| Name/Title | Dr. Albert Dahan |
|---|---|
| Organization | Leiden University Medical center |
| Phone | 3171 526 2301 |
| a.dahan@lumc.nl |
- bliss s