Clinical trial NCT01968447: Effect of Neuromuscular Block and Arterial PCO2 on Surgical Rating Scale (SRS), Following Reversal With Sugammadex
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Prostate Cancer
Renal Cancer
Lead sponsor: Leiden University Medical Center
Sponsor class: OTHER
Collaborators: name: Merck Sharp & Dohme LLC
First posted: 2013-10-24
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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

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.

Eligibility criteria: 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)

Primary outcomes:
measure: Surgical Rating Scale
timeFrame: Peroperative
Secondary outcomes:
measure: Hemodynamics
timeFrame: peroperative
measure: Respiratory Function
timeFrame: from the end of surgery untill 2 hours postoperative
measure: Pain Intensity on an 11-point Scale in the Postoperative Period
timeFrame: from the end of surgery untill 2 hours postoperative
measure: Sedation
timeFrame: from the end of surgery untill 2 hours postoperative
measure: Nausea
timeFrame: from the end of surgery untill 2 hours postoperative
measure: Vomiting
timeFrame: from the end of surgery untill 2 hours postoperative
Other outcomes:
Locations:
city: Leiden
country: Netherlands
facility: Leiden University Medical Center
state: Zuid-Holland
Study officials:
affiliation: LUMC
name: Albert Dahan, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.