Hemodynamic and Respiratory Variations During Laparoscopic Surgery With and Without Deep Neuromuscular Blockade.

A Prospective, Double-blind, Randomized, Crossover Design Study to Compare the Hemodynamic and Respiratory Variations During Laparoscopic Surgery in Patients With and Without Deep Neuromuscular Blockade.

The goal of this study is to investigate the effect of depth of neuromuscular block (NMB) on global and regional (dependent versus nondependent) respiratory mechanics during laparoscopic surgery. Furthermore, we will investigate if the level of NMB influences intraoperative hemodynamic and cerebral oxygenation.

Study Overview

• Status: Completed
• Conditions: Postoperative Complications; Ventilator-Induced Lung Injury; Intraoperative Complications; Laparoscopy; Surgical Complications From General Anesthesia
• Intervention / Treatment: Drug: Rocuronium

• Study Type: Interventional
• Enrollment (Actual): 37
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age 18 years or older
• Elective patients scheduled to undergo laparoscopic surgery with expected duration > 2h
• Physical status ASA I - III

Exclusion Criteria:

• Pregnancy
• Severe cardiac disease (NYHA class III or IV, acute coronary syndrome, or persistent ventricular tachyarrhythmia)
• Previous lung surgery
• History of severe chronic obstructive pulmonary disease
• Gastro-esophageal pathology (including but not limited to recent gastric or esophageal surgery including bypass/banding, history of esophageal varices, known anatomical gastric or esophageal defects such as strictures, hernias or fistulas)
• Mechanical ventilation within the last 30 days
• Neuromuscular disease
• Consented for another interventional study or refusal to participate in the present study
• Hypersensitivity (e.g., anaphylaxis) to rocuronium bromide or other neuromuscular blocking agents

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Deep Neuromuscular Block (NMB); Muscle paralysis with rocuronium 0.6 - 1.2 mg/kg with the dose adjusted to achieve 1-2 post-tetanic counts (neuromuscular function monitor).	Drug: Rocuronium; Rocuronium 0.6 - 1.2 mg/kg with the dose adjusted to achieve 1-2 post-tetanic counts (Deep NMB) or 1-2 twitches in the train-on-four (Moderate NMB).; Other Names: Zemuron
Active Comparator: Moderate Neuromuscular block (NMB); Muscle paralysis with rocuronium 0.6 - 1.2 mg/kg with the dose adjusted to achieve 1-2 twitches in the train-on-four (neuromuscular function monitor).	Drug: Rocuronium; Rocuronium 0.6 - 1.2 mg/kg with the dose adjusted to achieve 1-2 post-tetanic counts (Deep NMB) or 1-2 twitches in the train-on-four (Moderate NMB).; Other Names: Zemuron

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Regional Change in Air Content (Delta Z, %)	We will measure continuous respiratory flows and pressures in the intraoperative period to assess continuously the compliance and resistance of the respiratory system (T1 to T5). In addition, we will use an esophageal balloon to assess esophageal pressures and partition the global mechanical properties of the respiratory system, into their lung and chest wall components (T1 to T5). Regional lung aeration will be assessed for quantification of intraoperative lung recruitment using Electrical Impedance Tomography (EIT) (T0 to T6). Percent change was calculated using electrical impedance measurements obtained at time T0 as reference.	BL; During pneumoperitoneum; Stage w/2 depths neuromuscular blockade targeted - TOF1 and Deep: 1-2 twitches in post-tetanic count (50-Hz tetanus followed by three-second pause and 15 1-Hz stimuli); and immediately after release of pneumoperitoneum
Ejection Fraction (%)	To assess cardiac performance, transthoracic echocardiography will be used. Ejection fraction was measured as fractional shortening (FS). FS is the fraction of any diastolic dimension that is lost in systole. FS = 100*(LVEDD - LVESD) / LVEDD, LVEDD = LV end-diastolic dimension (mm); LVESD = LV end-systolic dimension (mm).	BL; During pneumoperitoneum; Stage w/2 depths neuromuscular blockade targeted - TOF1 and Deep: 1-2 twitches in post-tetanic count (50-Hz tetanus followed by three-second pause and 15 1-Hz stimuli); and immediately after release of pneumoperitoneum
Cerebral Oximetry (%)	Regional cerebral oxygenation will be assessed continuously during the intraoperative period using NIRS technology.	BL; During pneumoperitoneum; Stage w/2 depths neuromuscular blockade targeted - TOF1 and Deep: 1-2 twitches in post-tetanic count (50-Hz tetanus followed by three-second pause and 15 1-Hz stimuli); and immediately after release of pneumoperitoneum

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Postoperative Pain	The patient will be inquired about pain with a visual analogue scale (VAS). Pain will be evaluated as incisional pain using VAS (0 = no pain; 100 = worst possible pain).	Postoperative Day 1

Collaborators and Investigators

• Sponsor: Massachusetts General Hospital
• Collaborators: Merck Sharp & Dohme LLC
• Investigators: Principal Investigator: Marcos Vidal Melo, MD, PhD, Massachusetts General Hospital

Publications and helpful links

General Publications

• Joris J, Cigarini I, Legrand M, Jacquet N, De Groote D, Franchimont P, Lamy M. Metabolic and respiratory changes after cholecystectomy performed via laparotomy or laparoscopy. Br J Anaesth. 1992 Oct;69(4):341-5. doi: 10.1093/bja/69.4.341.
• Ivankovich AD, Miletich DJ, Albrecht RF, Heyman HJ, Bonnet RF. Cardiovascular effects of intraperitoneal insufflation with carbon dioxide and nitrous oxide in the dog. Anesthesiology. 1975 Mar;42(3):281-7. doi: 10.1097/00000542-197503000-00008.
• Dexter SP, Vucevic M, Gibson J, McMahon MJ. Hemodynamic consequences of high- and low-pressure capnoperitoneum during laparoscopic cholecystectomy. Surg Endosc. 1999 Apr;13(4):376-81. doi: 10.1007/s004649900993.
• Karsten J, Heinze H, Meier T. Impact of PEEP during laparoscopic surgery on early postoperative ventilation distribution visualized by electrical impedance tomography. Minerva Anestesiol. 2014 Feb;80(2):158-66. Epub 2013 Jul 23.

Study record dates

Study Major Dates

• Study Start: January 1, 2014
• Primary Completion (Actual): October 1, 2015
• Study Completion (Actual): October 1, 2015

Study Registration Dates

• First Submitted: December 19, 2013
• First Submitted That Met QC Criteria: December 27, 2013
• First Posted (Estimate): December 31, 2013

Study Record Updates

• Last Update Posted (Actual): May 30, 2017
• Last Update Submitted That Met QC Criteria: April 25, 2017
• Last Verified: April 1, 2017

More Information

Terms related to this study

• Keywords: Echocardiography; Tomography; Oximetry
• Additional Relevant MeSH Terms: Pathologic Processes; Respiratory Tract Diseases; Lung Diseases; Wounds and Injuries; Thoracic Injuries; Postoperative Complications; Lung Injury; Intraoperative Complications; Ventilator-Induced Lung Injury; Physiological Effects of Drugs; Peripheral Nervous System Agents; Neuromuscular Agents; Neuromuscular Nondepolarizing Agents; Neuromuscular Blocking Agents; Rocuronium
• Other Study ID Numbers: Merck-50706