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

NCT ID: NCT01748643

Last Updated: 2017-08-03

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE4

Total Enrollment

60 participants

Study Classification

INTERVENTIONAL

Study Start Date

2013-04-30

Study Completion Date

2015-01-31

Brief Summary

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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.

Detailed Description

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Laparoscopic bariatric surgery poses special demands on the anaesthesiologist as well as the surgeon. The surgeon requires good visualisation of the operative field while the anaesthesiologist is concerned with adequate postoperative respiratory function in these morbidly obese patients. With the advent of advanced laparoscopic techniques the time span between adequate neuromuscular blockade (NMB) and adequate postoperative recovery of respiratory muscle function is growing ever shorter with an increasing risk of postoperative residual NMB.

Even minimal postoperative residual NMB with a train of four ratio (TOF) of 0.8 is associated with impaired respiratory function as witnessed in reductions of forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC) in healthy volunteers. Moreover, a TOF \< 0.7 correlates with increased postoperative respiratory complications due to the inability to swallow normally leading to aspiration, atelectasis and pneumonia. However, neuromuscular blocking agents not only impair respiratory function due to skeletal muscle relaxation. Also the body's response to hypoxia is impeded due to carotid body chemoreceptor suppression. Worryingly, reversal of NMB with neostigmine can lead to respiratory complications such as bronchospasm and even induce neuromuscular transmission failure in patients who already recovered from NMB.

Obese patients are at even greater risk for postoperative respiratory complications. In a recent study after bariatric surgery, 100% of patients had at least one hypoxic event (oxygen saturation \<90% more then 30seconds). Restrictive ventilatory defects are clearly associated with body mass index (BMI) and obesity hypoventilation syndrome. Since respiratory failure is responsible for 11.8% of mortalities after bariatric surgery, optimal respiratory care for these patients is primordial. Optimal reversal of NMB plays an important role herein. With the advent of Sugammadex, a cyclodextrin molecule that encapsulates and inactivates rocuronium and vecuronium, rapid and dose-dependent reversal of profound NMB by high dose rocuronium is possible without the risk of impaired upper airway dilator muscle activity when given after recovery from NMB.

Furthermore, little is known about the cerebral tissue oxygen saturation (SctO2) in these morbidly obese patients during laparoscopic gastric bypass surgery. Since the unexpected finding that NMB influences hypoxic ventilatory response, more research is needed into the effect of neuromuscular blockers and their reversing agents on cerebral oxygenation. Using near infrared spectroscopy (Fore-sight®) technology absolute brain tissue oxygenation can be quantified to study these effects.

In this study we wish 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 NMB with sugammadex results in:

i. Improved surgical conditions for the surgeon ii. 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 NMB with a TOF count of 1-2 and reversal of NMB with neostigmine/glycopyrrolate.

Furthermore, we wish to investigate the effect of pneumoperitoneum, and NMB with rocuronium and reversal with Sugammadex or neostigmine/glycopyrrolate on cerebral tissue oxygenation.

Conditions

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

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

SUPPORTIVE_CARE

Blinding Strategy

TRIPLE

Participants Investigators Outcome Assessors

Study Groups

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Deep neuromuscular blockade, reversal with sugammadex

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.

Group Type EXPERIMENTAL

deep neuromuscular blockade with rocuronium, reversal with sugammadex

Intervention Type 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.

normal neuromuscular blockade, reversal with neostigmine

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.

Group Type ACTIVE_COMPARATOR

normal neuromuscular blockade reversal with rocuronium, reversal with neostigmine

Intervention Type 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.

Interventions

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deep neuromuscular blockade with rocuronium, reversal with sugammadex

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.

Intervention Type DRUG

normal neuromuscular blockade reversal with rocuronium, reversal with neostigmine

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.

Intervention Type DRUG

Other Intervention Names

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rocuronium: Esmeron sugammadex: Bridion rocuronium: Esmeron neostigmine glycopyrrolate

Eligibility Criteria

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Inclusion Criteria

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

Exclusion Criteria

1. Neuromuscular disorders
2. Allergies to, or contraindication for muscle relaxants, neuromuscular reversing agents, anaesthetics, narcotics
3. Malignant hyperthermia
4. Pregnancy or lactation
5. 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
6. Chronic obstructive pulmonary disease GOLD classification 2 or higher.
7. Clinical, radiographic or laboratory findings suggesting upper or lower airway infection
8. Congestive heart failure.
9. Pickwick syndrome
10. Psychiatric illness inhibiting cooperation with study protocol or possibly obscuring results
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role collaborator

Ziekenhuis Oost-Limburg

OTHER

Sponsor Role lead

Responsible Party

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Pascal Vanelderen

M.D., Principal Investigator

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Pieter De Vooght, M.D.

Role: STUDY_CHAIR

Ziekenhuis Oost-Limburg

Jeroen Van Melkebeek, M.D.

Role: STUDY_CHAIR

Ziekenhuis Oost-Limburg

Dimitri Dylst, M.D.

Role: STUDY_CHAIR

Ziekenhuis Oost-Limburg

Maud Beran, M.D.

Role: STUDY_CHAIR

Ziekenhuis Oost-Limburg

Margot Vander Laenen, M.D.

Role: STUDY_CHAIR

Ziekenhuis Oost-Limburg

Jan Van Zundert, M.D., PhD.

Role: STUDY_CHAIR

Ziekenhuis Oost-Limburg

René Heylen, M.D., PhD.

Role: STUDY_CHAIR

Ziekenhuis Oost-Limburg

Hans Verhelst, M.D.

Role: STUDY_CHAIR

Ziekenhuis Oost-Limburg

Locations

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Ziekenhuis Oost-Limburg

Genk, Limburg, Belgium

Site Status

Countries

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Belgium

References

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Reference Type BACKGROUND
PMID: 1138775 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 12766640 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 9366929 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 10754616 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 18635478 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 8792879 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 9856722 (View on PubMed)

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

Reference Type BACKGROUND
PMID: 3364648 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 7378232 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 20006346 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 18722823 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 18648227 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 18559352 (View on PubMed)

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.

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Reference Type BACKGROUND
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Other Identifiers

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2012-005533-37

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

8616-085MISP

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

PVRA-01

Identifier Type: -

Identifier Source: org_study_id

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