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

Condition(s) targeted: Obesity; Laparoscopic Gastric Bypass Surgery; Surgical Conditions; Respiratory Function; Cerebral Tissue Oxygenation

Intervention: deep neuromuscular blockade with rocuronium, reversal with sugammadex (Drug); normal neuromuscular blockade reversal with rocuronium, reversal with neostigmine (Drug)

Phase: Phase 4

Status: Completed

Sponsored by: Ziekenhuis Oost-Limburg

Official(s) and/or principal investigator(s):
Pieter De Vooght, M.D., Study Chair, Affiliation: Ziekenhuis Oost-Limburg
Jeroen Van Melkebeek, M.D., Study Chair, Affiliation: Ziekenhuis Oost-Limburg
Dimitri Dylst, M.D., Study Chair, Affiliation: Ziekenhuis Oost-Limburg
Maud Beran, M.D., Study Chair, Affiliation: Ziekenhuis Oost-Limburg
Margot Vander Laenen, M.D., Study Chair, Affiliation: Ziekenhuis Oost-Limburg
Jan Van Zundert, M.D., PhD., Study Chair, Affiliation: Ziekenhuis Oost-Limburg
René Heylen, M.D., PhD., Study Chair, Affiliation: Ziekenhuis Oost-Limburg
Hans Verhelst, M.D., Study Chair, Affiliation: Ziekenhuis Oost-Limburg

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 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/glycopyrolate on cerebral tissue oxygenation.

Official title: Effect of Deep Curarisation and Reversal With Sugammadex on Surgical Conditions and Perioperative Morbidity in Patients Undergoing Laparoscopic Gastric Bypass Surgery

Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator, Outcomes Assessor), Primary Purpose: Supportive Care

Primary outcome:

Subjective evaluation of the view on the operating field by the surgeon

Number of intra-abdominal pressure rises > 15cmH2O

Secondary outcome:

Respiratory function

Oxygen saturation

Effect of pneumoperitoneum on cerebral tissue oxygenation.

Effect of neuromuscular blockade on cerebral tissue oxygenation

The effect of reversal of neuromuscular blockade (with sugammadex or neostigmine) on cerebral tissue oxygenation

Detailed description: 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.

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

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

Ziekenhuis Oost-Limburg, Genk, Limburg 3600, Belgium

Related publications:

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.

Eikermann M, Groeben H, Hüsing J, Peters J. Accelerometry of adductor pollicis muscle predicts recovery of respiratory function from neuromuscular blockade. Anesthesiology. 2003 Jun;98(6):1333-7.

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.

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.

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.

Eriksson LI. Reduced hypoxic chemosensitivity in partially paralysed man. A new property of muscle relaxants? Acta Anaesthesiol Scand. 1996 May;40(5):520-3.

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.

Pratt CI. Bronchospasm after neostigmine. Anaesthesia. 1988 Mar;43(3):248.

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

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.

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.

Pühringer FK, Rex C, Sielenkämper 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.

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.

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. Review.

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

Starting date: April 2013
Last updated: January 24, 2015