Effect of Deep BLock on Intraoperative Surgical Conditions (BLISS)

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2012 by Leiden University Medical Center
Sponsor:
Collaborator:
MSD Nederland BV
Information provided by (Responsible Party):
Albert Dahan, Leiden University Medical Center
ClinicalTrials.gov Identifier:
NCT01631149
First received: June 19, 2012
Last updated: June 27, 2012
Last verified: June 2012
  Purpose

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 Intervention Phase
Prostate Hypertrophy
Renal Disease
Drug: Surgical block (rocuronium; atracurium/mivacurium)
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacodynamics Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Prevention
Official Title: Effect of Deep BLock on Intraoperative Surgical Conditions, Perioperative Hemodynamic Status and Respiratory Parameters Following Reversal With Sugammadex in Patients Undergoing Laparoscopic Renal and Prostate Surgery.

Resource links provided by NLM:


Further study details as provided by Leiden University Medical Center:

Primary Outcome Measures:
  • Surgical rating scale [ Time Frame: Measurements will be made during the stay in the operating room for an average period of 3 hours ] [ Designated as safety issue: No ]
    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 CRF. If conditions are poor (score 1 or 2), muscle relaxation will be increased, a score of 1 will be used.


Secondary Outcome Measures:
  • Breathing [ Time Frame: Measurements will be made during the stay in the operating room for an average period of 3 hours ] [ Designated as safety issue: Yes ]
    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.

  • Postoperative pain [ Time Frame: measurements are made in the recovery room following surgery for an average prior of 1 hour ] [ Designated as safety issue: No ]
    Using a 10 cm visual analogue score pain relief score will be measured.

  • Postoperative sedation score [ Time Frame: Measurements will be made during the stay in the operating room for an average period of 3 hours ] [ Designated as safety issue: Yes ]
    Using a 5-point sedation scale, sedation levels will be obtained throughout the postopertive period.

  • nausea and vomiting [ Time Frame: Measurements will be made during the stay in the operating room for an average period of 3 hours ] [ Designated as safety issue: No ]
    Using a yes - no questionnaire, the patients will be asked whether they are nauseated or not or whether they vomited.


Estimated Enrollment: 24
Study Start Date: June 2012
Estimated Study Completion Date: December 2014
Estimated Primary Completion Date: July 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: deep muscle blockade
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 Name: moderate muscle blockade

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01631149

Contacts
Contact: Albert Dahan, MD PhD +31715262301 a.dahan@lumc.nl
Contact: Roals Schaad, MD +31715262301 r.r.schaad@lumc.nl

Locations
Netherlands
Leiden University Medical Center Recruiting
Leiden, ZH, Netherlands, 2333 ZA
Contact: Albert Dahan, MD PhD    +31715262301    a.dahan@lumc.nl   
Contact: Roald Schaad, MD    +31715262301    R.R.schaad@lumc.nl   
Principal Investigator: Albert Dahan, MD PhD         
Sponsors and Collaborators
Leiden University Medical Center
MSD Nederland BV
Investigators
Principal Investigator: Albert Dahan, MD {hD LUMC
  More Information

Additional Information:
No publications provided by Leiden University Medical Center

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Albert Dahan, Professor, Leiden University Medical Center
ClinicalTrials.gov Identifier: NCT01631149     History of Changes
Other Study ID Numbers: bliss s
Study First Received: June 19, 2012
Last Updated: June 27, 2012
Health Authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)

Keywords provided by Leiden University Medical Center:
urology
muscle relaxation
laparoscopy
anesthesia
rocuronium

Additional relevant MeSH terms:
Kidney Diseases
Hypertrophy
Prostatic Hyperplasia
Urologic Diseases
Pathological Conditions, Anatomical
Prostatic Diseases
Genital Diseases, Male
Rocuronium
Atracurium
Mivacurium
Neuromuscular Nondepolarizing Agents
Neuromuscular Blocking Agents
Neuromuscular Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Nicotinic Antagonists
Cholinergic Antagonists
Cholinergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on September 22, 2014