Neuromuscular Blockade and Surgical Conditions

Morbid Obesity Clinical Trial

— Sugamadex  

Official title:

The Influence of the Magnitude of Neuromuscular Blockade on the Surgical Conditions During Laparoscopic Sleeve Gastrectomy

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT01564576
• Other study ID #: SHEBA-12-9237-HB-CTIL
• Status: Not yet recruiting
• Phase: N/A
• First received: March 15, 2012
• Last updated: March 27, 2012
• Start date: April 2012
• Est. completion date: August 2012

Study information

• Verified date: March 2012
• Source: Sheba Medical Center
• Contact: Haim Berkenstadt, MD
• Phone: 97235302966
• Email: haim.berkenstadt[@]sheba.health.gov.il
• Is FDA regulated: No
• Health authority: Israel: Israeli Health Ministry Pharmaceutical Administration
• Study type: Interventional

Clinical Trial Summary

The aim of the present study is to prospectively assess whether deep neuromuscular blockade (NMB) (zero response to train of four and a post tetanic count of no more than 10 responses using a nerve stimulator monitoring) until the end of surgery, followed by sugammadex (bridion®) reversal is superior to the present practice of gradual NMB reduction at the end of surgery followed by neostigmine (Prostigmin®, Vagostigmin®) reversal, in patients undergoing laparoscopic sleeve gastrectomy. The investigators hypothesize that providing deep NMB throughout the procedure creates better conditions for surgery, while reversal of deep NMBwith sugammadex (bridion®) will enable quick and full reversal of relaxation and fewer postoperative respiratory events as compared to neostigmine (Prostigmin®, Vagostigmin®)reversal. Participants will be followed for the duration of hospital stay, an expected average of 7 days.

Description:

In laparoscopic bariatric procedures, CO2 is used to insufflate the peritoneal cavity and increase the intra-abdominal pressure for optimal exposure and a suitable operating field. However, the increased intra-abdominal pressure during pneumoperitoneum has profound physiological effects including a reduction in urine output,portal venous flow,respiratory compliance,and cardiac output.

Abdominal muscle relaxation and changes in abdominal wall compliance, produced by the use of anesthetics and muscle relaxants, are important contributors for the achievement of optimal surgical field using minimal abdominal pressure. A practical dilemma is how to maintain good surgical conditions till the end of the operative procedure by deep anesthesia and muscle relaxation on one hand, and to have an awake and spontaneously breathing patient at the end of surgery on the other.

Reversal agents are often used to ensure the reversal of nondepolarizing neuromuscular blockade (NMB). The most widely used is the acetylcholinesterase inhibitor neostigmine (Prostigmin®, Vagostigmin®). However, neostigmine is only partially effective when NMB is deep (less then 1 response using train of four monitoring) and may also be associated with adverse effects, such as cholinergic cardiovascular and gastrointestinal events.Sugammadex (bridion®) is a modified gamma cyclodextrin specifically designed for the reversal of NMB induced by the aminosteroid muscle relaxants including rocuronium bromide (Zemuron®, Esmeron®). Sugammadex (bridion®) acts by encapsulating unbound rocuronium bromide (Zemuron®, Esmeron®)molecules and reducing their concentration at the neuromuscular junction.Studies in surgical patients have shown that sugammadex (bridion®) rapidly and safely reverses rocuronium bromide (Zemuron®, Esmeron®)induced NMB. Unlike acetylcholinesterase inhibitors, sugammadex (bridion®) is also effective in the reversal of deep NMB (no response in train of four monitoring or even no response in post tetanic count monitoring).

Laparoscopic weight reduction surgery requires the appropriate use of muscle relaxation; however, uncertainty remains including indeterminate dosing and unpredictable effect. Additionally, the time to the recovery to a train of four (TOF) ratio of 0.9 in the obese [25.9 (6.7, 13.5-41.0) min] and the overweight groups [14.6 (7.7, 3.3-28.5) min] were significantly longer than that in the normal weight group [6.9 (2.0, 3.0-10.7) min]. Therefore, obese patients are at increased risk for residual muscle relaxation following surgery. Sugammadex (bridion®) has recently been found to reach a peak effect faster than neostigmine(Prostigmin®, Vagostigmin®), in obese patients. In this study, the time to a TOFR ≥ 0.9 was 13 min with 50 μg/kg neostigmine (Prostigmin®, Vagostigmin®)and only 1.7 min with 2 mg/kg sugammadex. Therefore, it appears that sugammadex (bridion®) may more predictably prevent the occurrence of residual muscle relaxation compared to neostigmine (Prostigmin®, Vagostigmin®).

The aim of the present study is to prospectively assess whether deep NMB (zero response to train of four and a post tetanic count of no more than 10 responses using a nerve stimulator monitoring) till the end of surgery, followed by sugammadex (bridion®) reversal is superior to the present practice of gradual NMB reduction at the end of surgery followed by neostigmine (Prostigmin®, Vagostigmin®)reversal, in patients undergoing laparoscopic sleeve gastrectomy. The investigators hypothesize that providing deep NMB throughout the procedure creates better conditions for surgery, while reversal of deep muscle relaxation with sugammadex (bridion®) will enable quick and full reversal of relaxation and fewer postoperative respiratory events as compared to neostigmine (Prostigmin®, Vagostigmin®) reversal. Surgical conditions will be assessed by the surgeons, blinded to the treatment given to the patients, on a 1-4 Likert scale in 5 minutes intervals from abdominal insufflation with gas till the end of surgery (estimated time of 120 minutes). Participants will be followed for respiratory adverse events from admission to the post anesthesia care unit to discharge to the surgical department (continuous measurement of hemoglobin oxygen saturation and respiratory rate for an expected average of 3 hours) and from admission to the surgical department till the time of home discharge (measurement of hemoglobin oxygen saturation and respiratory rate every 6 hours for an expected average of 5 days).

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 40
• Est. completion date: August 2012
• Est. primary completion date: August 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 20 Years to 65 Years

Eligibility

Inclusion Criteria:

• American Society of Anesthesiologists physical status Class I-III, scheduled to undergo elective sleeve gastrectomy

Exclusion Criteria:

• Neuromuscular disorder affecting NMB

• history of malignant hyperthermia

• significant renal dysfunction

• allergy to medications used during general anesthesia

• concurrent use of medications known to interfere with NMBAs or with sugammadex (antibiotics, anticonvulsants, magnesium salts).

Study Design

Allocation: Randomized, Endpoint Classification: Pharmacodynamics Study, Intervention Model: Parallel Assignment, Masking: Single Blind (Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Morbid Obesity
• Obesity, Morbid

Intervention

Drug:
• Profound neuromuscular blockade (Rocuronium, Rocuronium bromide, sugammadex, Bridion)
Rocuronium dose will be adjusted to maintain a depth of NMB of zero response to train of four and a post tetanic count of no more than 10 responses. At the end of surgery patients will receive a single bolus dose of 4 mg/kg sugammadex according to ideal body weight + 40%12. Extubation will be performed when train-of-four ratios = 0.9.

Locations

Country	Name	City	State
Israel	Sheba Medical Center	Tel Hashomer

Sponsors (1)

Lead Sponsor	Collaborator
Sheba Medical Center

Country where clinical trial is conducted

Israel, 

References & Publications (6)

Daskalakis M, Scheffel O, Weiner RA. High flow insufflation for the maintenance of the pneumoperitoneum during bariatric surgery. Obes Facts. 2009;2 Suppl 1:37-40. doi: 10.1159/000198252. Epub 2009 Mar 18. Review. — View Citation

Fahy BG, Barnas GM, Nagle SE, Flowers JL, Njoku MJ, Agarwal M. Changes in lung and chest wall properties with abdominal insufflation of carbon dioxide are immediately reversible. Anesth Analg. 1996 Mar;82(3):501-5. — View Citation

Matot I, Paskaleva R, Eid L, Cohen K, Khalaileh A, Elazary R, Keidar A. Effect of the volume of fluids administered on intraoperative oliguria in laparoscopic bariatric surgery: a randomized controlled trial. Arch Surg. 2012 Mar;147(3):228-34. doi: 10.1001/archsurg.2011.308. Epub 2011 Nov 21. — View Citation

Nsadi B, Gilson N, Pire E, Cheramy JP, Pincemail J, Scagnol I, Meurisse M, Defraigne JO, Detry O. Consequences of pneumoperitoneum on liver ischemia during laparoscopic portal triad clamping in a swine model. J Surg Res. 2011 Mar;166(1):e35-43. doi: 10.1016/j.jss.2010.10.033. Epub 2010 Nov 24. — View Citation

Popescu WM, Bell R, Duffy AJ, Katz KH, Perrino AC Jr. A pilot study of patients with clinically severe obesity undergoing laparoscopic surgery: evidence for impaired cardiac performance. J Cardiothorac Vasc Anesth. 2011 Dec;25(6):943-9. doi: 10.1053/j.jvca.2010.11.012. Epub 2011 Jan 12. — View Citation

Suy K, Morias K, Cammu G, Hans P, van Duijnhoven WG, Heeringa M, Demeyer I. Effective reversal of moderate rocuronium- or vecuronium-induced neuromuscular block with sugammadex, a selective relaxant binding agent. Anesthesiology. 2007 Feb;106(2):283-8. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Subjective surgeon feedback on the exposure and surgical field.	The surgeons blinded to the treatment given to the patients will be asked to assess the quality of the surgical fiels using 1-4 likert scale	From abdominal insufflation with gas till the end of surgery (estimated time of 120 minutes).	No
Secondary	Incidence of respiratory adverse events	The incidence of respiratory events including- hypoxemia (defined as hemoglobin oxygen saturation lower then 92% while breathing room air), pneumonia (elevated body temperature and findings in chest x-ray), and the need for non invasive or invasive mechanical ventilation; will be assessed continuously during the post anesthesia care unit stay and on 6 hours intervals during the surgical department stay.	From admission to the post anesthesia care unit till discharge to the surgical department (expected average of 3 hours) and from admission to the surgical department till the time of home discharge (expected average of 5 days).	No