Evaluation of Atracurium-vecuronium Combination in Laparosocpic Surgery

• ClinicalTrials.gov Identifier: NCT03371953
• Recruitment Status: Unknown
• First Posted: December 13, 2017
• Last Update Posted: December 14, 2017
• Sponsor: Sir Ganga Ram Hospital
• Information provided by (Responsible Party): Amitabh Dutta, Sir Ganga Ram Hospital

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Patients Undergoing Laparoscopic Surgery	Drug: Vecuronium; Drug: Atracurium; Drug: Vecuronium + Atracurium	Phase 4

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 Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 48 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment

Intervention Model Description

Patients will be randomly divided into three groups in a 1:1:1 distribution undertaken by a computer-generated random number system.

Vecuronium group - 0.08mg/kg vecuronium alone

Atracurium group- 0.6mg/kg atracurium alone

Vecuronium-atracurium group- 0.04mg/kg vecuronium and 0.3 mg/kg atracurium combination

• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Masking Description: The patient, the attending anaesthesiologist, and the personnel recording the assessment parameters will be blinded to the randomisation sequence and the drug inside the 5-ml solution is supplied in a 5-ml syringe. The study drug for the three group allocation will be contained in a similar 5-ml solution (drug+0.9% saline solution).
• Primary Purpose: Other
• Official Title: Efficacy of Atracurium-vecuronium Combination in Patients Undergoing Laparoscopic Surgery:a Randomised Controlled Study
• Estimated Study Start Date: December 20, 2017
• Estimated Primary Completion Date: October 25, 2018
• Estimated Study Completion Date: October 25, 2018

Arms and Interventions

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.

Outcome Measures

Primary Outcome Measures :

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

Secondary Outcome Measures :

1. Onset-of-action of muscle relaxation following intubating dose [ Time Frame: From the time of administration of (0-hours, baseline) till 5-minutes intraoperatively ]
   Onset-of-action will be calculated from the time the drug is administered till theTOF count is 0 on the accelerometer.
2. Qualitative intubating conditions. [ Time Frame: From the time of administration of (0-hours, baseline) till 5-minutes intraoperatively ]

   Quality of intubating condition will be assessed using 3-point modified Cooper's scale. The intubating conditions will be graded as excellent, good & poor.

   1. 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)
   2. 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.
   3. Each of the five subscale range, i. e. 0-2, are added up to gain a 'total scale range score' of 0-10.
3. Reversibility of muscle relaxant effect [ Time Frame: From the time of administration of (0-hours, baseline) till 5-minutes post administration ]
   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.

Eligibility Criteria

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

Criteria

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

Contacts and Locations

Contacts

Contact: Amitabh Dutta, MD,PGDHR; 00919810848064; duttaamiatbh@yahoo.co.in

Contact: Palem Reshmika; 00919773587847; reshmika.palem@gmail.com

Locations

India

Sir Ganga Ram Hospital

New Delhi, Delhi, India, 110060

Contact: Amitabh Dutta, MD, PGDHR 00919810848064 duttaamiatbh@yahoo.co.in

Contact: Palem Reshmika, MBBS 00919773587847 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

Sub-Investigator: Jayashree Sood, MD, FFARCS

Sponsors and Collaborators

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

More Information

• Responsible Party: Amitabh Dutta, Senior Consultant & Professor, Sir Ganga Ram Hospital
• ClinicalTrials.gov Identifier: NCT03371953
• Other Study ID Numbers: EC/10/17/1280
• First Posted: December 13, 2017
• Last Update Posted: December 14, 2017
• Last Verified: December 2017

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• 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

Keywords provided by Amitabh Dutta, Sir Ganga Ram Hospital:

vecuronium; atracurium; combination

Additional relevant MeSH terms:

Atracurium; Vecuronium Bromide; Neuromuscular Nondepolarizing Agents; Neuromuscular Blocking Agents; Neuromuscular Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Nicotinic Antagonists; Cholinergic Antagonists; Cholinergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action