Optimal Dose of Combination of Rocuronium and Cisatracurium

NCT02495038 | Completed Results DMC

• 1 other identifier: combination P-1
• Study Type: interventional
• Target: 81
• Locations: 0 countries
• Sites: N/A

Brief Summary

BACKGROUND: The combinations of rocuronium and cisatracurium have a synergic effect. The investigators studied whether the prediction is possible to have a sufficient effect of reducing the dose when combining the two neuromuscular blocking agents through monitoring neuromuscular relaxation during surgery. METHODS: Each group were intubating dose group (Group I, n=27) combined Effective Dose (ED)95 rocuronium and ED95 cisatracurium, small amount reducing group (Group S, n=27) reduced 10% of each ED95 and large amount reducing group (Group L, n=27) reduced 20% of each ED95. Before patients arrived in the operating room, rocuronium and cisatracurium were prepared by a nurse who was not involved in this study. Each study drug was administrated to the patient and timer was started with TOF-Watch® monitoring. Train-of-four (TOF) of the ulnar nerve was used as setting of 2 Hz per 12 sec. The investigators checked time to TOF ratio=0 (Onset), time to 1st TOF ratio\>25% (Duration 25%) and TOF 25-75% (recovery index) under total i.v. anesthesia (TIVA). One way ANOVA was used for statistical analysis (α=0.05, β=0.2).

Conditions

Chronic Otitis Media; Anesthesia

Keywords

combination; rocuronium; cisatracurium; neuromuscular blockade monitoring; drug synergism

Outcome Measures

Primary Outcomes (3)

• Onset of Neuromuscular Blocking Agents(NMBAs)

  Time from administration of initial NMBAs to Train-of-four (TOF) ratio=0, assessed up to 15 minutes during general anesthesia.

  Intraoperative, an average of 5 minutes

• Duration 25% of Neuromuscular Blocking Agents(NMBAs)

  Time from administration of initial NMBAs to Train-of-four (TOF) ratio \>25%, assessed up to 2 hours during general anesthesia.

  Intraoperative, an average of 1 hours

• Recovery Index of Neuromuscular Blocking Agents(NMBAs)

  Time from TOF ratio 25% to 75%, assessed up to 1 hour during general anesthesia.

  Intraoperative, an average of 20 minutes

Secondary Outcomes (3)

• Operation Time

  Intraoperative, an average of 3 hours.

• Anesthetic Time

  Intraoperative, an average 4 hours.

• Additional Rescue Doses Per Hour Ratio.

  Intraoperative, an average of 3 hours.

Other Outcomes (4)

• Non Invasive Blood Pressure,

  Before and after induction of anesthesia, an average 10 min.

• Peripheral Oxygen Saturation

  Before and after induction of anesthesia, an average 10 min.

• Body Temperature

  Before and after induction of anesthesia, an average 10 min.

Study Arms (3)

Intubating dose, Group I

NO INTERVENTION

combined ED95 rocuronium and ED95 cisatracurium ED95, dose causing on average 95% suppression of neuromuscular response.

10% reduction of combination of Esmeron® and Nimbex®, Group S

EXPERIMENTAL

This arm reduced 10% of combined ED95 rocuronium and ED95 cisatracurium

Drug: 10% reduction of combination of Esmeron® and Nimbex®

20% reduction of combination of Esmeron® and Nimbex®, Group L

EXPERIMENTAL

This arm reduced 20% of combined ED95 rocuronium and ED95 cisatracurium

Drug: 20% reduction of combination of Esmeron® and Nimbex®

Interventions

10% reduction of combination of Esmeron® and Nimbex® DRUG

Patients were randomly assigned to each group by opening of sealed allocation envelope. After collection of data, allocation number was matched with each group. The participants matched at Group S were administered with NMBAs reduced 10% of each ED95. Before patients arrived in the operating room, rocuronium and cisatracurium were prepared by a nurse who was not involved in this study. Each drug dosage was determined by allocation number. The syringe containing each study drug was conveyed to the performer of this study as the status of shielding the scale. The syringes of rocuronium and cisatracurium used each other syringe.

Also known as: Esmeron®, 74119419, ATC code:M03AC09, Nimbex®, 74500213, ATC code:M03AC11

10% reduction of combination of Esmeron® and Nimbex®, Group S

20% reduction of combination of Esmeron® and Nimbex® DRUG

The participants matched at Group L were administered with NMBAs reduced 20% of each ED95.

Also known as: Esmeron®, 74119419, ATC code:M03AC09, Nimbex®, 74500213, ATC code:M03AC11

20% reduction of combination of Esmeron® and Nimbex®, Group L

Eligibility Criteria

• Age: 20 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• the American Society of Anesthesiologists (ASA) physical status I-II
• BMI 20-30 kg/m2
• Patients scheduled for mastoidectomy and tympanoplasty.

You may not qualify if:

• a history of allergy to the study drugs,
• neuromuscular disease,
• pregnancy
• breast-feeding,
• preoperative medication of antipsychotics or neuroleptics known to interact with NMBAs
• serum creatinine level\>1.2 mg/dL,
• liver transaminase\>40 U/L.

Sponsors & Collaborators

• Yonsei University: lead

Related Publications (23)

• Naguib M, Samarkandi AH, Ammar A, Elfaqih SR, Al-Zahrani S, Turkistani A. Comparative clinical pharmacology of rocuronium, cisatracurium, and their combination. Anesthesiology. 1998 Nov;89(5):1116-24. doi: 10.1097/00000542-199811000-00011.

  PMID: 9821999 BACKGROUND

• Donati F, Plaud B. Rocuronium-cisatracurium combinations. Anesthesiology. 1999 Aug;91(2):587-8. doi: 10.1097/00000542-199908000-00054. No abstract available.

  PMID: 10443637 BACKGROUND

• Miller DR, Wherrett C, Hull K, Watson J, Legault S. Cumulation characteristics of cisatracurium and rocuronium during continuous infusion. Can J Anaesth. 2000 Oct;47(10):943-9. doi: 10.1007/BF03024863.

  PMID: 11032267 BACKGROUND

• Cammu G, de Baerdemaeker L, den Blauwen N, de Mey JC, Struys M, Mortier E. Postoperative residual curarization with cisatracurium and rocuronium infusions. Eur J Anaesthesiol. 2002 Feb;19(2):129-34. doi: 10.1017/s0265021502000236.

  PMID: 11999596 BACKGROUND

• Hans P, Welter P, Dewandre PY, Brichant JF, Bonhomme V. Recovery from neuromuscular block after an intubation dose of cisatracurium and rocuronium in lumbar disc surgery. Acta Anaesthesiol Belg. 2004;55(2):129-33.

  PMID: 15264506 BACKGROUND

• Mak PH, Irwin MG. The effect of cisatracurium and rocuronium on cisatracurium precurarization and the priming principle. J Clin Anesth. 2004 Mar;16(2):83-7. doi: 10.1016/j.jclinane.2003.05.004.

  PMID: 15110367 BACKGROUND

• Kopman AF, Zank LM, Ng J, Neuman GG. Antagonism of cisatracurium and rocuronium block at a tactile train-of-four count of 2: should quantitative assessment of neuromuscular function be mandatory? Anesth Analg. 2004 Jan;98(1):102-106. doi: 10.1213/01.ANE.0000094985.19305.E9.

  PMID: 14693596 BACKGROUND

• de Morais BS, de Castro CH, Teixeira VC, Pinto AS. Residual neuromuscular block after rocuronium or cisatracurium. Rev Bras Anestesiol. 2005 Dec;55(6):622-30. doi: 10.1590/s0034-70942005000600005. English, Portuguese.

  PMID: 19468536 BACKGROUND

• Kopman AF, Kopman DJ, Ng J, Zank LM. Antagonism of profound cisatracurium and rocuronium block: the role of objective assessment of neuromuscular function. J Clin Anesth. 2005 Feb;17(1):30-5. doi: 10.1016/j.jclinane.2004.03.009.

  PMID: 15721727 BACKGROUND

• Flockton EA, Mastronardi P, Hunter JM, Gomar C, Mirakhur RK, Aguilera L, Giunta FG, Meistelman C, Prins ME. Reversal of rocuronium-induced neuromuscular block with sugammadex is faster than reversal of cisatracurium-induced block with neostigmine. Br J Anaesth. 2008 May;100(5):622-30. doi: 10.1093/bja/aen037. Epub 2008 Apr 2.

  PMID: 18385265 BACKGROUND

• Adamus M, Gabrhelik T, Marek O. Influence of gender on the course of neuromuscular block following a single bolus dose of cisatracurium or rocuronium. Eur J Anaesthesiol. 2008 Jul;25(7):589-95. doi: 10.1017/S026502150800402X. Epub 2008 Apr 11.

  PMID: 18405411 BACKGROUND

• Lin SP, Chang KY, Chen YJ, Lin SM, Chang WK, Chan KH, Ting CK. Priming with rocuronium to accelerate the onset time of cisatracurium during intubation. J Chin Med Assoc. 2009 Jan;72(1):15-9. doi: 10.1016/S1726-4901(09)70014-0.

  PMID: 19181592 BACKGROUND

• Amin AM, Mohammad MY, Ibrahim MF. Comparative study of neuromuscular blocking and hemodynamic effects of rocuronium and cisatracurium under sevoflurane or total intravenous anesthesia. Middle East J Anaesthesiol. 2009 Feb;20(1):39-51.

  PMID: 19266825 BACKGROUND

• Fassbender P, Geldner G, Blobner M, Hofmockel R, Rex C, Gautam S, Malhotra A, Eikermann M. Clinical predictors of duration of action of cisatracurium and rocuronium administered long-term. Am J Crit Care. 2009 Sep;18(5):439-45. doi: 10.4037/ajcc2009883.

  PMID: 19723864 BACKGROUND

• Lee H, Jeong S, Choi C, Jeong H, Lee S, Jeong S. Anesthesiologist's satisfaction using between cisatracurium and rocuronium for the intubation in the anesthesia induced by remifentanil and propofol. Korean J Anesthesiol. 2013 Jan;64(1):34-9. doi: 10.4097/kjae.2013.64.1.34. Epub 2013 Jan 21.

  PMID: 23372884 BACKGROUND

• Leykin Y, Pellis T, Lucca M, Lomangino G, Marzano B, Gullo A. The pharmacodynamic effects of rocuronium when dosed according to real body weight or ideal body weight in morbidly obese patients. Anesth Analg. 2004 Oct;99(4):1086-1089. doi: 10.1213/01.ANE.0000120081.99080.C2.

  PMID: 15385355 RESULT

• Breslin DS, Jiao K, Habib AS, Schultz J, Gan TJ. Pharmacodynamic interactions between cisatracurium and rocuronium. Anesth Analg. 2004 Jan;98(1):107-110. doi: 10.1213/01.ANE.0000093387.15263.48.

  PMID: 14693597 RESULT

• Leykin Y, Pellis T, Lucca M, Gullo A. Intubation conditions following rocuronium: influence of induction agent and priming. Anaesth Intensive Care. 2005 Aug;33(4):462-8. doi: 10.1177/0310057X0503300407.

  PMID: 16119487 RESULT

• Kim KS, Chun YS, Chon SU, Suh JK. Neuromuscular interaction between cisatracurium and mivacurium, atracurium, vecuronium or rocuronium administered in combination. Anaesthesia. 1998 Sep;53(9):872-8. doi: 10.1046/j.1365-2044.1998.00492.x.

  PMID: 9849281 RESULT

• Liu M, Dilger JP. Synergy between pairs of competitive antagonists at adult human muscle acetylcholine receptors. Anesth Analg. 2008 Aug;107(2):525-33. doi: 10.1213/ane.0b013e31817b4469.

  PMID: 18633030 RESULT

• Zeidan A, Nahle N, Maaliki H, Baraka A. Cisatracurium or rocuronium versus rocuronium-cisatracurium combination. Middle East J Anaesthesiol. 2006 Jun;18(5):879-86.

  PMID: 17094524 RESULT

• Lighthall GK, Jamieson MA, Katolik J, Brock-Utne JG. A comparison of the onset and clinical duration of high doses of cisatracurium and rocuronium. J Clin Anesth. 1999 May;11(3):220-5. doi: 10.1016/s0952-8180(99)00030-6.

  PMID: 10434218 RESULT

• Park WY, Choi JC, Yun HJ, Jeon YG, Park G, Choi JB. Optimal dose of combined rocuronium and cisatracurium during minor surgery: A randomized trial. Medicine (Baltimore). 2018 Mar;97(10):e9779. doi: 10.1097/MD.0000000000009779.

  PMID: 29517695 DERIVED

MeSH Terms

Interventions

cisatracurium; Rocuronium

Intervention Hierarchy (Ancestors)

Androstanols; Androstanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Results Point of Contact

• Title: Dr. Wooyoung Park
• Organization: Yonsei University Wonju college of medicine

wongulung28@gmail.com

563664250

Study Officials

• Young Gwan Cheon

  Institutional Review Board of Wonju Severance Christian Hospital

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: clinical assistant professor

Study Record Dates

• First Submitted: June 4, 2015
• First Posted: July 13, 2015
• Study Start: March 1, 2014
• Primary Completion: February 1, 2015
• Study Completion: February 1, 2015
• Last Updated: March 2, 2018
• Results First Posted: December 20, 2017

Record last verified: 2018-01