CURES: The Effect of Deep Curarisation and Reversal With Sugammadex on Surgical Conditions and Perioperative Morbidity

NCT01748643 | Completed Phase 4 Results

• 3 other identifiers: PVRA-012012-005533-378616-085MISP
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to investigate if a deep neuromuscular block with a continuous infusion of rocuronium titrated to a post-tetanic count (PTC) of 1-2 responses combined with reversal of neuromuscular blockade with sugammadex results in improved surgical conditions for the surgeon and/or improved post-operative respiratory function for the patients as compared to a standard technique with an intubation dose of rocuronium and top-ups as needed to maintain a neuromuscular blockade with a train of four (TOF) count of 1-2 and reversal of neuromuscular blockade with neostigmine/glycopyrrolate. Furthermore, we want to investigate the effect of pneumoperitoneum, and NMB with rocuronium and reversal with sugammadex or neostigmine/glycopyrrolate on cerebral tissue oxygenation.

Conditions

Obesity; Laparoscopic Gastric Bypass Surgery; Surgical Conditions; Respiratory Function; Cerebral Tissue Oxygenation

Outcome Measures

Primary Outcomes (3)

• Subjective Evaluation of the View on the Operating Field by the Surgeon

  At the end of surgery, the view on the operating field will be graded by the surgeon using a 5-point rating scale: 1. Extremely poor 2. Poor 3. Acceptable 4. Good 5. Optimal

  Participants will be followed for the duration of the laparoscopic gastric bypass surgery, an expected average of 1.5h

• Number of Intra-abdominal Pressure Rises > 18cmH2O

  The number of intra-abdominal pressure rises \> 18cmH2O detected by the intra-abdominal CO2 insufflator.

  Participants will be followed for the duration of the laparoscopic gastric bypass surgery, an expected average of 1.5h

• Duration of Surgery

  Measured from the time of first skin incision to completion of skin closure.

  Participants will be followed for the duration of the laparoscopic gastric bypass surgery, an expected average of 1.5h

Secondary Outcomes (3)

• Peak Expiratory Flow

  Measured the day before surgery and 30min after completion of surgery (when the modified observer's assessment of alertness/sedation scale is 5 (Patient responds readily to name spoken in normal tone))

• Forced Expiratory Volume in 1 Second

  Measured the day before surgery and 30min after completion of surgery (when the modified observer's assessment of alertness/sedation scale is 5 (Patient responds readily to name spoken in normal tone))

• Forced Vital Capacity

  Measured the day before surgery and 30min after completion of surgery (when the modified observer's assessment of alertness/sedation scale is 5 (Patient responds readily to name spoken in normal tone))

Study Arms (2)

Deep neuromuscular blockade, reversal with sugammadex

EXPERIMENTAL

a continuous rocuronium infusion (0.6mg/kg (lean body mass)/h,) is started and titrated to a post tetanic count of 1-2 twitches. At the end of surgery neuromuscular blockade will be reversed with Sugammadex 4mg/kg. Patients are extubated when the train of four ratio is \> 0.9.

Drug: deep neuromuscular blockade with rocuronium, reversal with sugammadex

normal neuromuscular blockade, reversal with neostigmine

ACTIVE COMPARATOR

After induction of anesthesia, top-ups of rocuronium (10mg) are given as needed to maintain a train of four count of 1-2. At the end of surgery neuromuscular blockade will be reversed with neostigmine 50μg/kg and glycopyrrolate 10μg/kg (lean body mass). Patients are extubated when TOF ratio \> 0.9.

Drug: normal neuromuscular blockade reversal with rocuronium, reversal with neostigmine

Interventions

deep neuromuscular blockade with rocuronium, reversal with sugammadex DRUG

after induction of anesthesia, a rocuronium infusion (0.6mg/kg (lean body mass)/h,) is started and titrated to a post tetanic count of 1-2 twitches. At the end of surgery neuromuscular blockade will be reversed with sugammadex 4mg/kg. Patients are extubated when TOF ratio \> 0.9.

Also known as: rocuronium: Esmeron, sugammadex: Bridion

Deep neuromuscular blockade, reversal with sugammadex

normal neuromuscular blockade reversal with rocuronium, reversal with neostigmine DRUG

After induction of anesthesia, top-ups of rocuronium (10mg) are given as needed to maintain a train of four count of 1-2. At the end of surgery neuromuscular blockade will be reversed with neostigmine 50μg/kg and glycopyrrolate 10μg/kg (lean body mass). Patients are extubated when the train of four ratio is \> 0.9.

Also known as: rocuronium: Esmeron, neostigmine, glycopyrrolate

normal neuromuscular blockade, reversal with neostigmine

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Able to give written informed consent
• American Society of Anaesthesiologists class I, II or III
• Obese or morbid obese as defined by BMI \> 30 and \>40 kg/m2 respectively

You may not qualify if:

• Neuromuscular disorders
• Allergies to, or contraindication for muscle relaxants, neuromuscular reversing agents, anaesthetics, narcotics
• Malignant hyperthermia
• Pregnancy or lactation
• Renal insufficiency defined as serum creatinine of 2x the upper normal limit, glomerular filtration rate \< 60ml/min, urine output of \< 0.5ml/kg/h for at least 6h
• Chronic obstructive pulmonary disease GOLD classification 2 or higher.
• Clinical, radiographic or laboratory findings suggesting upper or lower airway infection
• Congestive heart failure.
• Pickwick syndrome
• Psychiatric illness inhibiting cooperation with study protocol or possibly obscuring results

Sponsors & Collaborators

• Ziekenhuis Oost-Limburg: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (1)

Ziekenhuis Oost-Limburg

Genk, Limburg, 3600, Belgium

Location

Related Publications (15)

• Ali HH, Wilson RS, Savarese JJ, Kitz RJ. The effect of tubocurarine on indirectly elicited train-of-four muscle response and respiratory measurements in humans. Br J Anaesth. 1975 May;47(5):570-4. doi: 10.1093/bja/47.5.570.

  PMID: 1138775 BACKGROUND

• Eikermann M, Groeben H, Husing J, Peters J. Accelerometry of adductor pollicis muscle predicts recovery of respiratory function from neuromuscular blockade. Anesthesiology. 2003 Jun;98(6):1333-7. doi: 10.1097/00000542-200306000-00006.

  PMID: 12766640 BACKGROUND

• Berg H, Roed J, Viby-Mogensen J, Mortensen CR, Engbaek J, Skovgaard LT, Krintel JJ. Residual neuromuscular block is a risk factor for postoperative pulmonary complications. A prospective, randomised, and blinded study of postoperative pulmonary complications after atracurium, vecuronium and pancuronium. Acta Anaesthesiol Scand. 1997 Oct;41(9):1095-1103. doi: 10.1111/j.1399-6576.1997.tb04851.x.

  PMID: 9366929 BACKGROUND

• Sundman E, Witt H, Olsson R, Ekberg O, Kuylenstierna R, Eriksson LI. The incidence and mechanisms of pharyngeal and upper esophageal dysfunction in partially paralyzed humans: pharyngeal videoradiography and simultaneous manometry after atracurium. Anesthesiology. 2000 Apr;92(4):977-84. doi: 10.1097/00000542-200004000-00014.

  PMID: 10754616 BACKGROUND

• Murphy GS, Szokol JW, Marymont JH, Greenberg SB, Avram MJ, Vender JS. Residual neuromuscular blockade and critical respiratory events in the postanesthesia care unit. Anesth Analg. 2008 Jul;107(1):130-7. doi: 10.1213/ane.0b013e31816d1268.

  PMID: 18635478 BACKGROUND

• Eriksson LI. Reduced hypoxic chemosensitivity in partially paralysed man. A new property of muscle relaxants? Acta Anaesthesiol Scand. 1996 May;40(5):520-3. doi: 10.1111/j.1399-6576.1996.tb04482.x.

  PMID: 8792879 BACKGROUND

• Wyon N, Joensen H, Yamamoto Y, Lindahl SG, Eriksson LI. Carotid body chemoreceptor function is impaired by vecuronium during hypoxia. Anesthesiology. 1998 Dec;89(6):1471-9. doi: 10.1097/00000542-199812000-00025.

  PMID: 9856722 BACKGROUND

• Pratt CI. Bronchospasm after neostigmine. Anaesthesia. 1988 Mar;43(3):248. doi: 10.1111/j.1365-2044.1988.tb05560.x. No abstract available.

  PMID: 3364648 BACKGROUND

• Payne JP, Hughes R, Al Azawi S. Neuromuscular blockade by neostigmine in anaesthetized man. Br J Anaesth. 1980 Jan;52(1):69-76. doi: 10.1093/bja/52.1.69.

  PMID: 7378232 BACKGROUND

• Gallagher SF, Haines KL, Osterlund LG, Mullen M, Downs JB. Postoperative hypoxemia: common, undetected, and unsuspected after bariatric surgery. J Surg Res. 2010 Apr;159(2):622-6. doi: 10.1016/j.jss.2009.09.003. Epub 2009 Sep 25.

  PMID: 20006346 BACKGROUND

• Saliman JA, Benditt JO, Flum DR, Oelschlager BK, Dellinger EP, Goss CH. Pulmonary function in the morbidly obese. Surg Obes Relat Dis. 2008 Sep-Oct;4(5):632-9; discussion 639. doi: 10.1016/j.soard.2008.06.010. Epub 2008 Jul 17.

  PMID: 18722823 BACKGROUND

• Puhringer FK, Rex C, Sielenkamper AW, Claudius C, Larsen PB, Prins ME, Eikermann M, Khuenl-Brady KS. Reversal of profound, high-dose rocuronium-induced neuromuscular blockade by sugammadex at two different time points: an international, multicenter, randomized, dose-finding, safety assessor-blinded, phase II trial. Anesthesiology. 2008 Aug;109(2):188-97. doi: 10.1097/ALN.0b013e31817f5bc7.

  PMID: 18648227 BACKGROUND

• Eikermann M, Zaremba S, Malhotra A, Jordan AS, Rosow C, Chamberlin NL. Neostigmine but not sugammadex impairs upper airway dilator muscle activity and breathing. Br J Anaesth. 2008 Sep;101(3):344-9. doi: 10.1093/bja/aen176. Epub 2008 Jun 16.

  PMID: 18559352 BACKGROUND

• Cohen LB, Delegge MH, Aisenberg J, Brill JV, Inadomi JM, Kochman ML, Piorkowski JD Jr; AGA Institute. AGA Institute review of endoscopic sedation. Gastroenterology. 2007 Aug;133(2):675-701. doi: 10.1053/j.gastro.2007.06.002. No abstract available.

  PMID: 17681185 BACKGROUND

• Miller MR, Dickinson SA, Hitchings DJ. The accuracy of portable peak flow meters. Thorax. 1992 Nov;47(11):904-9. doi: 10.1136/thx.47.11.904.

  PMID: 1465746 BACKGROUND

MeSH Terms

Conditions

Obesity; Respiratory Aspiration

Interventions

Rocuronium; Sugammadex; Neostigmine; Glycopyrrolate

Condition Hierarchy (Ancestors)

Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Respiration Disorders; Respiratory Tract Diseases; Pathologic Processes

Intervention Hierarchy (Ancestors)

Androstanols; Androstanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; gamma-Cyclodextrins; Cyclodextrins; Macrocyclic Compounds; Dextrins; Starch; Glucans; Polysaccharides; Carbohydrates; Phenylammonium Compounds; Quaternary Ammonium Compounds; Amines; Organic Chemicals; Onium Compounds; Pyrrolidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Dr. Pascal Vanelderen
• Organization: Ziekenhuis Oost-Limburg

pascal.vanelderen@gmail.com

+3289325298

Study Officials

• Pieter De Vooght, M.D.

  Ziekenhuis Oost-Limburg

  STUDY CHAIR

• Jeroen Van Melkebeek, M.D.

  Ziekenhuis Oost-Limburg

  STUDY CHAIR

• Dimitri Dylst, M.D.

  Ziekenhuis Oost-Limburg

  STUDY CHAIR

• Maud Beran, M.D.

  Ziekenhuis Oost-Limburg

  STUDY CHAIR

• Margot Vander Laenen, M.D.

  Ziekenhuis Oost-Limburg

  STUDY CHAIR

• Jan Van Zundert, M.D., PhD.

  Ziekenhuis Oost-Limburg

  STUDY CHAIR

• René Heylen, M.D., PhD.

  Ziekenhuis Oost-Limburg

  STUDY CHAIR

• Hans Verhelst, M.D.

  Ziekenhuis Oost-Limburg

  STUDY CHAIR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: SUPPORTIVE CARE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: M.D., Principal Investigator

Study Record Dates

• First Submitted: December 6, 2012
• First Posted: December 12, 2012
• Study Start: April 1, 2013
• Primary Completion: January 1, 2015
• Study Completion: January 1, 2015
• Last Updated: August 3, 2017
• Results First Posted: August 3, 2017

Record last verified: 2017-04

Locations

BE (1)