The Effect of Propofol and Remifentanil Sequence on ED50 and ED95 of Rocuronium in Rapid Sequence Induction Anesthesia

Anesthesia Clinical Trial

Official title:

Does the Choice of Administration Sequence of Propofol and Remifentanil Affect the ED50 and ED95 of Rocuronium for Rapid Sequence Induction of Anesthesia?

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02709473
• Other study ID #: 31-31412
• Status: Completed
• Phase: Phase 4
• First received: February 23, 2016
• Last updated: July 11, 2016
• Start date: March 2016
• Est. completion date: April 2016

Study information

• Verified date: July 2016
• Source: Ankara University
• Contact: n/a
• Is FDA regulated: No
• Health authority: Turkey: Ethics Committee
• Study type: Interventional

Clinical Trial Summary

Rapid sequence induction (RSI) is a well-known procedure to maintain a safe and rapid airway in patients especially at risk of aspiration. Propofol and rocuronium are generally used agents for RSI. However, the difficult airway scenarios are always valid for these patients, even without predictive signs of difficult airway. Therefore, it is important to decrease the rocuronium dose used in RSI to achieve a rapid recovery of a neuromuscular conduction with the aid of a reversal agent in case of difficult airway. The short acting opioids such as remifentanil may be helpful to reduce the dose of rocuronium in RSI.

Description:

Rapid sequence induction is a widely used anesthesia technique to achieve a safe airway control. However, the difficult airway may be expected in these patients as in the others. In the difficult airway situation, cholinesterase inhibitors and sugammadex may be used for the reversal. However, sugammadex is not always available due to its cost in every hospital. In addition to this, it is well-known that cholinesterase inhibitors do not work well in case of deep neuromuscular block. In consideration of these informations, the recovery of the neuromuscular block gain an importance in patients undergoing RSI with difficult airway. Therefore, decreasing the dosage of non-depolarizing neuromuscular agent may be helpful in case of the difficult airway situations. With the aim of decreasing the neuromuscular blocker dosage, opioid analgesics especially remifentanil is preferred combined with propofol to decrease the hemodynamic response to laryngoscopy and intubation. A recent study demonstrated that after induction of anesthesia with remifentanil and propofol, ED50 of rocuronium for acceptable intubation conditions was 0.20 mg/kg. In another study, the authors showed that the administration sequence of propofol and remifentanil for target controlled anesthesia affect the onset time of rocuronium due to change in cardiac output. The authors concluded that the prior administration of remifentanil decreased the cardiac output and delayed the onset time of rocuronium.

The investigators hypothesized that prior administration of remifentanil compared to propofol may increase the ED50 and ED95 of rocuronium for acceptable intubation conditions in RSI.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 84
• Est. completion date: April 2016
• Est. primary completion date: March 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

• American Society of Anesthesiologists (ASA) physical status I-II patients

• patients scheduled for elective surgery

Exclusion Criteria:

• suspected or known difficult airway

• a significant renal or hepatic dysfunction

• a known neuromuscular disease

• hypertension

• a known allergy to one of the drugs used in general anesthesia

• a body mass index lower than 18.5 kg/m2 or higher than 30 kg/m2

• intake of any medication that might interact with rocuronium

• patient refusal

Study Design

Allocation: Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Screening

Related Conditions & MeSH terms

• Anesthesia
• Neuromuscular Blockade

Intervention

Drug:
• Propofol
Propofol will be used in either two arms. The injection sequence will be changed. In propofol arm of the study, general anesthesia will be started with 2 mg/kg propofol administered within 15 seconds. And, then remifentanil will be given. In remifentanil arm of the study, 2 mg/kg propofol will be applied within 15 seconds following remifentanil injection.
• Remifentanil
Remifentanil will be used in either two arms. The injection sequence will be changed. In remifentanil arm, general anesthesia will be started with 2 µg/kg remifentanil administered within 30 seconds. And then propofol will be given. In propofol arm of the study the same dose will be applied within 30 seconds following propofol administration.
• Rocuronium
Rocuronium will be used for either two study arms. Rocuronium will be given in a 0.8 mg/kg dosage in the first study subject. And then, if the intubation condition is acceptable, the dose of the rocuronium will be decreased by 0.1 mg/kg for the next patient. Otherwise, if the intubation condition is not acceptable, the rocuronium dosage will be increased by 0.1 mg/kg for the next patient. This will be continue for ten crossover points (the point that turn from unsuccessful intubation to successful intubation).

Locations

Country	Name	City	State
Turkey	Ankara University	Ankara
Turkey	Harran University	Sanliurfa

Sponsors (1)

Lead Sponsor	Collaborator
Ankara University

Country where clinical trial is conducted

Turkey, 

References & Publications (3)

Dewhirst E, Tobias JD, Martin DP. Propofol and remifentanil for rapid sequence intubation in a pediatric patient at risk for aspiration with elevated intracranial pressure. Pediatr Emerg Care. 2013 Nov;29(11):1201-3. doi: 10.1097/PEC.0b013e3182aa136d. Review. — View Citation

Na HS, Hwang JW, Park SH, Oh AY, Park HP, Jeon YT, Do SH. Drug-administration sequence of target-controlled propofol and remifentanil influences the onset of rocuronium. A double-blind, randomized trial. Acta Anaesthesiol Scand. 2012 May;56(5):558-64. doi: 10.1111/j.1399-6576.2012.02648.x. Epub 2012 Feb 7. — View Citation

Oh AY, Cho SJ, Seo KS, Ryu JH, Han SH, Hwang JW. Dose of rocuronium for rapid tracheal intubation following remifentanil 2 µg kg-1 and propofol 2 mg kg-1. Eur J Anaesthesiol. 2013 Sep;30(9):550-5. doi: 10.1097/EJA.0b013e3283622ba0. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	ED50 of rocuronium	ED50 of rocuronium means the dose of rocuronium that is required for providing acceptable intubation conditions in the 50% of patients undergoing intubation. Each individual dose that allow or not allow an acceptable intubation condition will determine the next patient rocuronium dose. At the end, ED50 of rocuronium will be calculated as means of drug dosage that providing acceptable intubation condition.	One minute after rocuronium injection	No
Primary	ED95 of rocuronium	ED595 of rocuronium means the dose of rocuronium that is required for providing acceptable intubation conditions in the 95% of patients undergoing intubation. Each individual dose that allow or not allow an acceptable intubation condition will determine the next patient rocuronium dose. At the end, ED95 of rocuronium will be estimated by using statistical tools such as pava estimator or R code.	One minute after rocuronium injection	No
Secondary	mean arterial blood pressure	the effect of propofol and remifentanil administration sequence on mean arterial blood pressure will be evaluated.	before and after 10 minutes of induction of anesthesia	Yes