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Effect of Deep BLock on Intraoperative Surgical Conditions (BLISS)

L

Leiden University Medical Center (LUMC)

Status and phase

Completed
Phase 4

Conditions

Prostate Hypertrophy
Renal Disease

Treatments

Drug: Surgical block (rocuronium; atracurium/mivacurium)

Study type

Interventional

Funder types

Other

Identifiers

NCT01631149
bliss s

Details and patient eligibility

About

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.

Full 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.

Enrollment

24 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

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

Trial design

Primary purpose

Prevention

Allocation

Randomized

Interventional model

Parallel Assignment

Masking

Double Blind

24 participants in 2 patient groups

Deep surgical block
Experimental group
Description:
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.
Treatment:
Drug: Surgical block (rocuronium; atracurium/mivacurium)
Drug: Surgical block (rocuronium; atracurium/mivacurium)
Moderate/normal surgical block
Active Comparator 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.
Treatment:
Drug: Surgical block (rocuronium; atracurium/mivacurium)
Drug: Surgical block (rocuronium; atracurium/mivacurium)

Trial contacts and locations

1

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Data sourced from clinicaltrials.gov

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