Clinical trial NCT03371953: Evaluation of Atracurium-vecuronium Combination in Laparosocpic Surgery
Official title: Efficacy of Atracurium-vecuronium Combination in Patients Undergoing Laparoscopic Surgery:a Randomised Controlled Study
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Patients Undergoing Laparoscopic Surgery
Keywords: vecuronium
atracurium
combination
Lead sponsor: Sir Ganga Ram Hospital
Sponsor class: OTHER
First posted: 2017-12-13
Enrollment: 48
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
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
Primary purpose: OTHER

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.

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.

Eligibility 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

Primary outcomes:
measure: Duration-of-action of the intubating dose
timeFrame: From the time of administration of (0-hours, baseline) till 60-minutes intraoperatively
Secondary outcomes:
measure: Onset-of-action of muscle relaxation following intubating dose
timeFrame: From the time of administration of (0-hours, baseline) till 5-minutes intraoperatively
measure: Qualitative intubating conditions.
timeFrame: From the time of administration of (0-hours, baseline) till 5-minutes intraoperatively
measure: Reversibility of muscle relaxant effect
timeFrame: From the time of administration of (0-hours, baseline) till 5-minutes post administration
Other outcomes:
Locations:
city: New Delhi
country: India
facility: Sir Ganga Ram Hospital
state: Delhi
Study officials:
affiliation: Sir Ganga Ram Hospital
name: Amitabh Dutta, MD,PGDHR
role: STUDY_CHAIR
affiliation: Sir Ganga Ram Hospital
name: Subhash Gupta, MD
role: STUDY_DIRECTOR
affiliation: Sir Ganga Ram Hospital
name: Savitar Malhotra, MD
role: PRINCIPAL_INVESTIGATOR
References: