Site Loader

? Article Title:
The impact of deep versus moderate neuromuscular block on respiratory System mechanics during laparoscopic cholecystectomy a double?blind randomized clinical trial.
Running title: deep block in lap. Chole.

Deep neuromuscular block (NMB) has been suggested to improve surgical conditions during laparoscopy; but, there is little evidence to support that. However, to our knowledge, no published studies have investigated the impact of deep NMB on respiratory mechanics. We tested the hypotheses that deep NMB could improve respiratory mechanics during low-pressure laparoscopic surgery compared with moderate NMB.
In a randomized, prospective, parallel, controlled trial, 76 patients undergoing elective laparoscopic cholecystectomy under general anesthesia were randomized 1:1 to either continuous deep or moderate neuromuscular blockade. The primary outcome was Static respiratory compliance. Secondary outcomes included peak airway pressure, mean airway pressure, surgeon satisfaction, the proportion of procedures completed at Pneumoperitoneum 8 mm Hg, visual analogue scale (VAS) and postoperative nausea and vomiting.
After insufflation static compliance was significantly lower in moderate blockade group than that in deep blockade group (p=0. 001). Also, after insufflation, both Peak airway pressure and mean airway pressure in deep blockade group were significantly lower. Optimal surgical space conditions were found in 15 of 38 (39.5%) patients allocated to deep blockade and in 5 of 38 (13.6%) patients allocated to moderate blockade (P = 0.009). the procedure was completed at Pneumoperitoneum 8 mm Hg in 35 (92%) patients in the deep group compared with 29 (76.3%) patients in the moderate group (P = 0.059). No differences in postoperative pain, nausea or vomiting between groups.
Deep neuromuscular blockade was associated with better respiratory mechanics than with moderate muscle relaxation during low-pressure laparoscopic cholecystectomy.

Keywords: Neuromuscular Blockade, Neuromuscular Monitoring, Respiratory Mechanics.


Laparoscopic surgery has become more efficient and safer over the years due to reductions in intraabdominal pressure (IAP), modifications in surgical technique, selection of the type of insufflation gas, and improvements in anaesthetic management. Despite this, laparoscopic surgery continues to cause specific pathophysiological effects, such as cardiovascular, pulmonary, and splanchnic perfusion changes, where IAP appears to be the primary determinant.(1-3) Lowering insufflations pressures may also result in a reduction in postoperative pain (including shoulder tip pain)(4) and a better quality of life 5 days after surgery.(5, 6) IAP is commonly maintained at around 12 mmHg for most laparoscopic procedures. In order to keep intraperitoneal pressures low, neuromuscular blocking agents (NMBA) are frequently used.
There is some evidence that NMB improves surgical space and operating conditions during laparoscopic surgery (7-9). However, to our knowledge, no published studies have investigated the impact of muscle relaxation on respiratory mechanics during low-pressure laparoscopic surgery.
We designed this study to evaluate the effect of deep, continuous neuromuscular blockade on respiratory mechanics during low-pressure laparoscopic cholecystectomy. We hypothesized that deep, continuous neuromuscular blockade compared to moderate blockade was associated with better lung compliance and airway pressures.
Study Design
This randomized, double-blinded study was approved by the local Ethical Committee of Assiut University. The study was carried out between October 2014 and January 2016 at Al Rajhy liver hospital in Assiut University and registered at (NCT02469831) before patient enrollment. Written informed consent was signed by all patients.
Eligible patients were older than 18 years of age, American Society of Anesthesiology (ASA) classification class I and II scheduled for elective laparoscopic cholecystectomy. Exclusion criteria were Patients over 60 years of age with pulmonary or cardiac disease, previous surgeries, a history of venous or arterial diseases, allergy to Rocuronium, those indicated for rapid sequence induction, known neuromuscular disorders that might impair neuromuscular blockade, pregnancy, breastfeeding, BMI (?30 kg/m2), and significant renal or liver dysfunction. All patients, who were in the childbearing period, had to provide a negative urine pregnancy test within 24 hours prior to surgery.

A standardized protocol including ventilatory strategy, fluid therapy, antibiotics, temperature control as well as administration of analgesics and antiemetics was carried out. Standard hemostatic and respiratory monitoring (3-lead ECG, noninvasive blood pressure manometer, and pulse oximeter) was used. Anesthesia was induced with Fentanyl 1 ?g/kg and propofol 2 mg/kg and maintained with Sevoflurane. Volume controlled ventilation was performed in all patients and the ventilator was set to deliver 8 mL/kg tidal volume, 12/ min frequency, I/E 1:2, inspiratory pause 20 % of inspiration, and a constant inspiratory flow rate.
Acceleromyography with the TOF-watch-SX monitor (MSD BV, Haarlem, The Netherlands) was used for neuromuscular function monitoring. The left arm and hand were secured to the arm board. Electrodes were placed over the course of the ulnar nerve at the wrist, we have placed the ipsilateral thumb in a flexible adaptor to generate preload and placed a sensor on the tip of the thumb to detect adduction of the thumb through contractions of the adductor pollicis brevis muscle. After induction of anesthesia but prior to administration of rocuronium, the device was calibrated according to the following steps to standardize the neuromuscular monitoring: (i) application of a tetanic ulnar nerve stimulation (50 Hz for 5 s); (ii) calibration of the TOF watch; and (iii) performing a series of TOF measurements to ensure that the TOF ratio differs by 5%. The TOF ratio was normalized to the values obtained during calibration. After these procedures, the neuromuscular blocking agent was administered according to protocol. Upon electrical stimulation, the number of thumb twitches of the ulnar nerve was measured and recorded. At 10 min intervals, the TOF was measured and in the case of TOF = 0, PTC was done.
After calibration, a dose of rocuronium of 0.6 mg/kg was administered for Intubation. Assessment of NMB was performed every 5 minutes.
For the depth of NMB, we used the definitions by Kopman and Naguib(10) (deep NMB: no response to a TOF stimulation and PTC >1 ; moderate NMB: TOF count of 1–3). In the deep NMB group, a continuous rocuronium infusion of 0.6 mg/kg/h was used and titrated to a PTC of 1 to 2 twitches. In the deep NMB group, sugammadex 4 mg/kg was used for reversal of NMB at the end of surgery.
In the moderate NMB group, top-up doses of rocuronium (10 mg) were given to maintain a TOF count of 1 to 2. NMB was reversed with a combination of neostigmine 50 ?g/kg and atropine 0.01 mg/kg at the end of surgery. In both groups, patients were extubated when the TOF ratio was >0.9.
After the introduction of the 4 Trocars, Pneumoperitoneum was reduced from 12 into 8 mm Hg. Patients were positioned in 30° reverse Trendelenburg after insufflation.
All laparoscopies were performed by 1 of 2 experienced surgeons, In case of inadequate surgical space conditions, the following interventions were used in both groups:
1.? Increase intraabdominal pressure from 8 to 12 mm Hg.
2.? If still inadequate, the surgeon would decide according to usual practice.

Outcome Measures
As a primary outcome The Avance® Carestation – GE Healthcare patient spirometry was used to record respiratory mechanics. Static respiratory compliance, peak airway pressure (PAWP) and mean airway pressure (MAWP) were measured at three-time points: 10 min after anesthesia induction (T1: induction), 10 min after pneumoperitoneum (T2: pneumoperitoneum), and 10 min after the end-pneumoperitoneum (T3: end-pneumoperitoneum).
The secondary outcomes were surgeon satisfaction (Optimal surgical space conditions), assessed by a single surgeon using a 5-point rating scale (1 = extremely poor, 2 = poor, 3 = acceptable, 4 = good, 5 = optimal)(11) proportion of procedures completed at Pneumoperitoneum 8 mm Hg, visual analog scale (VAS) at arrival in the postoperative care unit and postoperative nausea and vomiting up to 24 hours after surgery.
Systolic arterial pressure (SAP), diastolic arterial pressure (DAP), mean arterial pressure (MAP) and heart rate (HR) were recorded at the same 3-time points as respiratory mechanics.

Before surgery, all included patients were carefully instructed by the same investigator in the use of a visual analogue scale (VAS) (VAS 0 = no pain, 10 = worst possible pain).
Blinding and Randomization
Before arrival in the operating room included patients were randomized immediately by a computer randomization system to ensure adequate allocation concealment. Patients allocated to either continuous deep or moderate neuromuscular blockade.
The surgeons, surgical staff, patients, personnel in the postoperative care unit as well as the investigator collecting postoperative data were blinded to group allocation. In a separate room, syringes containing Rocuronium, and NaCl were prepared. To blind the surgeon, each patient had a syringe marked “Rocuronium” in a syringe pump attached to the intravenous line. In the moderate NMB group, the syringe contained normal saline 0.9%. Whereas, in the deep NMB group, the syringe contained actual rocuronium. During surgery, the “Rocuronium” syringe pumps in both groups were operated by the anesthesiologist as if they contained the active drug. The patient’s hand with the neuromuscular monitoring equipment and the connecting neuromuscular monitor were covered from the surgeon to keep him blinded to group allocation. However, the investigator who gave Rocuronium could follow the level of neuromuscular blockade. Information about group allocation, administered doses of Rocuronium, and neuromuscular data were recorded on a separate form and placed in a sealed opaque envelope when the patient left the operating room.
Statistical Analysis:
All outcomes were reported with the mean ± (standard deviation) or number (%) and compared with the Mann-Whitney U test, student t-test, or the ?2 test. A P value of

Post Author: admin