Evaluation of Atracurium-vecuronium Combination in Laparosocpic Surgery

Efficacy of Atracurium-vecuronium Combination in Patients Undergoing Laparoscopic Surgery:a Randomised Controlled Study

Non-depolarising muscle relaxants are routinely employed to provide skeletal muscle relaxation during general anaesthesia (GA). Generally investigators use one or the other type of relaxant agent for this purpose and they are categorised based on their duration-of-action. Atracurium and vecuronium are two common muscle relaxant used during GA. They have an intermediate duration of action (around 40 minutes). Though they are effective relaxants and easy to reverse with reversal agents after the surgery, in case of the common laparoscopy procedures lasting an hour, they are relatively inefficient. There is evidence that when these agents are combined together (in 1:1 ratio), the duration-of-action, and reversibility improves. To render atracurium and vecuronium more efficient with laparoscopic surgery, the proposed study is aimed to evaluate the effects of combining 1/2 the respective standard doses of atracurium and vecuronium given together, in terms of its effect on the onset of block, duration-of-action, and reversibility of the neuromuscular blockade in adults undergoing laparoscopic surgery under GA. The study will be conducted with objective assessment parameter evaluation by TOF Watch SX (Organon, Teknica BV, Boxtel, The Netherlands), which will be used for facilitating institution, control, and monitoring the neuromuscular blockade during surgery. The objective of this study is to evaluate the additive effect of atracurium-vecuronium combination and profile its impact in patients undergoing laparoscopic surgery, especially in terms of increase in duration-of-action of muscle relaxation with the combination of drugs, when compared to respective individual drugs.

Study Overview

• Status: Unknown
• Conditions: Patients Undergoing Laparoscopic Surgery
• Intervention / Treatment: Drug: Vecuronium; Drug: Atracurium; Drug: Vecuronium + Atracurium

Detailed Description

The principal pharmacological effect of neuromuscular blocking drugs is to interrupt the transmission of nerve impulses at the neuromuscular junction. They are classified into depolarising (mimics the action of acetylcholine) and non-depolarising (interfere with the action of acetylcholine).In general, we use vecuronium (0.08mg/kg) or atracurium (0.5mg/kg), which are intermediate-acting non-depolarising neuromuscular blocking agents for skeletal muscle relaxation.

The main use of neuromuscular blocking drugs is to provide skeletal muscle relaxation for facilitation of intubation of the trachea and to improve surgical working conditions in the anaesthetised patients. A 2×ED95 dose of non-depolarising muscle relaxant is recommended to facilitate tracheal intubation. In practice, 90% suppression of the single twitch response is usually considered clinical evidence of adequate drug-induced skeletal muscle relaxation.

Laparoscopy has become the most preferred means of surgical access for a variety of procedures. There are many laparoscopic surgeries that last about an hour. But the duration-of-action of bolus (intubating) dose of atracurium or vecuronium when used alone is not sufficient to last for an hour. As a result, for surgeries lasting an hour(e.g. laparoscopic cholecystectomy, laparoscopic total extra-peritoneal repair, etc.), one either end up giving a top up (maintenance) dose of vecuronium/atracurium to extend muscle relaxation or withhold the add-on dose and continue with surgery towards completion. While in the former situation, the anaesthesiologist is required to wait for long even though the surgery is completed; in the latter, either the surgery gets disturbed due to patient's movement (e.g. coughing, bucking) or there may be associated hemodynamic activation, which requires deepening of anaesthesia plane; both harbinger for patient-related adversity.

There are studies which have evaluated the effect of combining two non-depolarizing neuromuscular relaxants on the profile of skeletal muscle relaxation pertinent to anaesthetic (tracheal intubation) and surgical conditions.Atracurium and vecuronium are the most common non- depolarizing muscle relaxants we routinely employ during general anaesthesia (GA). Till date, to our knowledge, there are a very few studies that have evaluated combination of atracurium and vecuronium given together.Though, the limited number of studies which analysed effects of combined neuromuscular relaxation with atracurium and vecuronium underlined that there is an additive effect, commented only on onset-of-action and reversibility of muscle relaxation effect. In addition, no study has yet evaluated the duration-of-action of atracurium- vecuronium combination in adults undergoing laparoscopic surgeries. Muscle relaxation is used for optimising laparoscopic operating conditions by preventing diaphragmatic movement due to irritation by the presence of pneumoperitoneum and achieving more intra-abdominal space for a particular intra-abdominal insufflation pressure. In this context, deeper than normally maintained level of neuromuscular blockade appears to be superior. The investigators contend that combining vecuronium and atracurium would not only facilitate increase in duration-of-action of the relaxation but also provide quality muscle relaxation for the duration of surgery.

The proposed study looks forward to analyse the effect of muscle relaxation profile of vecuronium-atracurium combination versus vecuronium-alone or atracurium-alone in patients undergoing laparoscopic surgery.

• Study Type: Interventional
• Enrollment (Anticipated): 48
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Amitabh Dutta, MD,PGDHR; Phone Number: 00919810848064; Email: duttaamiatbh@yahoo.co.in
• Study Contact Backup: Name: Palem Reshmika; Phone Number: 00919773587847; Email: reshmika.palem@gmail.com

Study Locations

• India
  • Delhi
    • New Delhi, Delhi, India, 110060
      • Sir Ganga Ram Hospital
      • Contact: Amitabh Dutta, MD, PGDHR; Phone Number: 00919810848064; Email: duttaamiatbh@yahoo.co.in
      • Contact: Palem Reshmika, MBBS; Phone Number: 00919773587847; Email: reshmika.palem@gmail.com
      • Principal Investigator: Amitabh Dutta, MD,PGDHR
      • Sub-Investigator: Palem Reshmika, MBBS
      • Principal Investigator: Savitar Malhotra, MD
      • Sub-Investigator: Subhash Gupta, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. ASA physical status I and II
2. Laparoscopic surgeries likely to last for 1 hour duration

Exclusion Criteria:

1. Patient refusal
2. ASA physical status III and IV
3. History of hypersensitivity to atracurium or vecuronium
4. Alcoholism and drug addiction
5. Neuromuscular disorders
6. Neuropsychiatric patients
7. Hepatic and renal disease patients
8. Obese patients
9. Abnormal airway anatomy
10. Risk of oesophageal reflux

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Vecuronium group; Vecuronium 0.08 mg/kg will be administered at induction of anaesthesia for facilitating muscle relaxation	Drug: Vecuronium; A top-up dose of vecuronium will be administered when the TOF count is 1 on the accelerometer. However, if there is a diaphragmatic contraction which interferes with surgical procedure then a dose will be given irrespective of the TOF count.
Active Comparator: Atracurium group; Atracurium 0.6 mg/kg will be administered at induction of anaesthesia for facilitating muscle relaxation	Drug: Atracurium; A top-up dose of vecuronium will be administered when the TOF count is 1 on the accelerometer. However, if there is a diaphragmatic contraction which interferes with surgical procedure then a dose will be given irrespective of the TOF count.
Active Comparator: Vecuronium-Atracurium group; Vecuronium 0.04 mg/kg + atracurium 0.3 mg/kg will be administered at induction of anaesthesia for facilitating muscle relaxation	Drug: Vecuronium + Atracurium; A top-up dose of vecuronium + atracurium will be administered when the TOF count is 1 on the accelerometer. However, if there is a diaphragmatic contraction which interferes with surgical procedure then a dose will be given irrespective of the TOF count.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Duration-of-action of the intubating dose	Duration of action will be calculated from the time the drug is administered till theTOF count is 1 on the accelerometer.	From the time of administration of (0-hours, baseline) till 60-minutes intraoperatively

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Onset-of-action of muscle relaxation following intubating dose	Onset-of-action will be calculated from the time the drug is administered till theTOF count is 0 on the accelerometer.	From the time of administration of (0-hours, baseline) till 5-minutes intraoperatively
Qualitative intubating conditions.	Quality of intubating condition will be assessed using 3-point modified Cooper's scale. The intubating conditions will be graded as excellent, good & poor.; The scale "Intubating conditions following intubating dose of non-depolarizing muscle relaxant" is modified from Cooper's Scale. The scale's name is derived from the name of the investigator (Cooper R) who first used it. (Br J Anaesth 1992; 69: 269-73); The Cooper Scale includes five major variable sets [1. Laryngoscopy (Jaw Relaxation), 2.Vocal-cord position, 3. Vocal cord movement, 4. Reaction to intubation and/or cuff inflation 5. Movement of limbs/ coughing] which are classified as poor, good or excellent. For ease of the study analysis, poor is scored '0', good is scored '1', and excellent is scored '2'. Therefore, each variable has subscale range of 0-2 and, five variables are together ranged as 0-10.; Each of the five subscale range, i. e. 0-2, are added up to gain a 'total scale range score' of 0-10.	From the time of administration of (0-hours, baseline) till 5-minutes intraoperatively
Reversibility of muscle relaxant effect	Time for complete reversal of effect of muscle relaxation will be determined from the time of administration of reversal agent till the the point when TOF ratio is 90-percent.	From the time of administration of (0-hours, baseline) till 5-minutes post administration

Collaborators and Investigators

• Sponsor: Sir Ganga Ram Hospital
• Investigators: Study Chair: Amitabh Dutta, MD,PGDHR, Sir Ganga Ram Hospital; Study Director: Subhash Gupta, MD, Sir Ganga Ram Hospital; Principal Investigator: Savitar Malhotra, MD, Sir Ganga Ram Hospital

Study record dates

Study Major Dates

• Study Start (Anticipated): December 20, 2017
• Primary Completion (Anticipated): October 25, 2018
• Study Completion (Anticipated): October 25, 2018

Study Registration Dates

• First Submitted: December 2, 2017
• First Submitted That Met QC Criteria: December 7, 2017
• First Posted (Actual): December 13, 2017

Study Record Updates

• Last Update Posted (Actual): December 14, 2017
• Last Update Submitted That Met QC Criteria: December 13, 2017
• Last Verified: December 1, 2017

More Information

Terms related to this study

• Keywords: combination; vecuronium; atracurium
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Cholinergic Antagonists; Cholinergic Agents; Neuromuscular Agents; Nicotinic Antagonists; Neuromuscular Nondepolarizing Agents; Neuromuscular Blocking Agents; Atracurium; Vecuronium Bromide
• Other Study ID Numbers: EC/10/17/1280

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No