Effect of Neuromuscular Block and Arterial PCO2 on Surgical Rating Scale (SRS), Following Reversal With Sugammadex (BLISSS2)

Effect of Deep Neuromuscular Block and Variations in Arterial PCO2 on the Surgical Rating Scale (SRS), Extubation Conditions and Postoperative Conditions Following Reversal With Sugammadex

The purpose of this study is to study the effect of variations in the arterial CO2 concentration during deep neuromuscular block on the surgical conditions as assessed by the surgical rating scale

Study Overview

• Status: Completed
• Conditions: Prostate Cancer; Renal Cancer
• Intervention / Treatment: Other: hypocapnia; Other: normocapnia

Detailed Description

Surgical conditions in laparoscopic surgery are largely determined by the depth of neuromuscular relaxation during surgery. This is especially true in procedures which are confined to a narrow working field such as retroperitoneal laparoscopic surgery (eg. renal and prostatic surgery). In the previous study (BLISS study) deep neuromuscular block (NMB) has shown to provide superior surgical conditions compared to moderate NMB. Moreover, rapid reversal of a deep NMB at the end of surgery was possible with Sugammadex (4mg/kg). The deep NMB did not lead to any delay in extubation time and did not cause any prolongation of stay in the recovery room when the block was reversed with Sugammadex

Rapid, safe and complete reversal of profound NMB blockade was not possible until the discovery of Sugammadex. Sugammadex is a modified γ-cyclodextrin. It was developed to selectively bind free plasma rocuronium, a non-depolarizing steroidal neuromuscular blocking agent. The BLISS study was the first study in which the effect of deep NMB on surgical conditions was assessed. Surgical conditions in this study were scored by one surgeon on a newly applied surgical rating scale which ranges from one to five.

Although the BLISS study showed that a deep NMB provided better surgical conditions than a moderately deep NMB overall, there was a high variability in surgical rating scores. More over, even at the deep NMB, SRS scores of 3 (moderate, but acceptable conditions) were noted. This indicates that surgical conditions are influenced by other factors as well. Involuntary movement of the diaphragm is possibly such a major disturbant of the surgical field. Previous studies have shown a relative resistance to neuromuscular blocking agents of the diaphragm compared to the musclus adductor pollicis on which neuromuscular block is generally monitored. Hence contractions of the diaphragm may occure despite a deep NMB. This may be due to (high) arterial carbon dioxide (CO2) concentrations, which stimulate the respiratory neuronal pool in the brainstem and consequently activate the phrenic nerve. In normal circumstances, the respiratory centers try to maintain an arterial CO2 pressure of 40 mmHg. With intentional hyperventilation, the arterial CO2 pressure may be lowered to 10-20 mmHg. A low arterial CO2 pressure diminishes the respiratory drive and consequently phrenic nerve activity. This is supported by previous observations which showed increased abdominal muscle relaxation produced by hyperventilation. We therefore designed this study to evaluate the effect of arterial CO2 variation with concurrent deep NMB on the surgical conditions. Arterial CO2 tensions may be altered by adjusting the ventilator settings. Eg. by increasing minute ventilation volume, arterial CO2 concentration will lower. Regular arterial blood samples will be drawn to monitor arterial CO2 concentration.

We hypothesize that a Deep NMB combined with hypocapnia will result in a significant improvement of surgical conditions as rated on the surgical rating scale by one surgeon compared to deep NMB and normocapnia

Additional secondary end-points of the study include the effect of arterial CO2 variation on:

• economic parameters (time to spontaneous breathing, time to extubation, duration of surgery, and time in the post-anesthesia care unit)
• perioperative hemodynamics, abdominal pressure
• postoperative conditions (respiratory conditions, hemodynamics, arterial oxygen saturation, pain, sedation, nausea and vomiting)
• To assess the ability of anesthesiologists and surgeons to rate the surgical field using video snippets of the surgical field.

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Netherlands
  • Zuid-Holland
    • Leiden, Zuid-Holland, Netherlands
      • Leiden University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• (i) Patients diagnosed with renal or prostatic disease who are will undergo an elective laparoscopic renal surgical procedure or laparoscopic prostatectomy;
• (ii) ASA class I-III
• (iii) > 18 years of age;
• (iv) Ability to give oral and written informed consent.

Exclusion Criteria:

• (i) Known or suspected neuromuscular disorders impairing neuromuscular function;
• (ii) Allergies to muscle relaxants, anesthetics or narcotics;
• (iii) A (family) history of malignant hyperthermia;
• (iv) Women who are or may be pregnant or are currently breast feeding;
• (v) Renal insufficiency, as defined by serum creatinine x 2 of normal, or urine output < 0.5 ml/kg/h for at least 6 h. When available, other indices will be taken into account as well such as glomerular filtration rate < 60 ml/h and proteinuria (a ratio of 30 mg albumin to 1 g of creatinine).
• (vi) Previous retroperitoneal surgery at the site of the current surgery.
• (vii) Body mass index > 35 kg/m2
• (viii) Chronic obstructive pulmonary disease GOLD 2-4 or a FEV1 less than 70% predicted or VC less than 70% predicted
• (ix) chronic pulmonary disease with altered lung physiology (eg. sarcoidosis, cycstic fibrosis, obstructing pulmonary tumors, previous lung surgery)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: TRIPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: hypocapnia; arterial pCO2 of 3.5 kPa	Other: hypocapnia; Hyperventilation to the level of hypocapnia; Other Names: Low CO2
Active Comparator: normocapnia; arterial PCO2 of 6.5-7.0 kPa	Other: normocapnia; Normal ventilation to the level of nromocapnia; Other Names: normal CO2

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Surgical Rating Scale	During a procedure, the surgical condition will be scored by one surgeon using a 5-point surgical rating scale. The rating scale is a 5-point ordinal scale ranging from 1 = poor condition to 5 = optimal surgical conditions. The surgeon will score the condition at 15 minute intervals.The values given on the surgical rating scale are averaged and the average value is used in the data analysis.	Peroperative

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hemodynamics	Hemodynamic conditions are studied during low arterial CO2 concentration and normal arterial CO2 concentration. The average of the measured mean arterial pressures at 15 minute intervals during anesthesia are presented	peroperative
Respiratory Function	The effect of low versus normal pCO2 concentrations on the postoperative respiratory function will be studied. Postoperative saturations are obtained at 15 minutes intervals. The data are averaged over time.	from the end of surgery untill 2 hours postoperative
Pain Intensity on an 11-point Scale in the Postoperative Period	The effect of low versus normal pCO2 concentrations on postoperative pain will be studied. Painscores are obtained at 15 minutes intervals and are expressed as a number on a 10 point scale (numeric rating scale; 1 (low)-10(maximum)). The data is avaraged over time	from the end of surgery untill 2 hours postoperative
Sedation	The effect of low versus normal pCO2 concentrations on postoperative sedation will be studied using the using the validated Leiden Observer's Assessment of Alertness/Sedation (0 (awake) - 6 (unarousable)) scale at 15 min intervals. The data are averaged over time.	from the end of surgery untill 2 hours postoperative
Nausea	The effect of low versus normal pCO2 concentrations on the incidence of postoperative nausea will be studied. The incidence is expressed as the percentage of people experiencing nausea per arm.	from the end of surgery untill 2 hours postoperative
Vomiting	The effect of low versus normal pCO2 concentrations on the incidence of postoperative vomiting will be studied. The incidence of vomiting is expressed as a precentage of the patients per arm.	from the end of surgery untill 2 hours postoperative

Collaborators and Investigators

• Sponsor: Leiden University Medical Center
• Collaborators: Merck Sharp & Dohme LLC
• Investigators: Principal Investigator: Albert Dahan, MD, LUMC

Publications and helpful links

General Publications

• Boon M, Martini C, Hellinga M, Bevers R, Aarts L, Dahan A. Influence of variations in arterial PCO2 on surgical conditions during laparoscopic retroperitoneal surgery. Br J Anaesth. 2016 Jul;117(1):59-65. doi: 10.1093/bja/aew114. Epub 2016 May 6.

Study record dates

Study Major Dates

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

Study Registration Dates

• First Submitted: October 7, 2013
• First Submitted That Met QC Criteria: October 19, 2013
• First Posted (Estimate): October 24, 2013

Study Record Updates

• Last Update Posted (Actual): March 16, 2020
• Last Update Submitted That Met QC Criteria: February 29, 2020
• Last Verified: February 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Kidney Diseases; Urologic Diseases; Kidney Neoplasms
• Other Study ID Numbers: NL45461.058.13

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED