A Prospective Randomized Controlled Trial Comparing a Multitarget Opioid Free Anaesthesia (OFA) and a 3-Liter Volume Calculated Airseal Carbon Dioxide Insufflator with a Balanced Anaesthesia Using Sufentanil-Sevoflurane and a Standard 15 MmHg Carbon Dioxide Pressure Pneumoperitoneum Insufflator in a 2x2 Factorial Design

Abstract

OFA reduces peritoneal inflammation during laparoscopy

Full text

Journal of Clinical Anesthesia and
Pain Medicine
www.scientonline.org J Clin Anesth Pain MedVolume 2 • Issue 2 • 023
Research Article
A Prospective Randomized Controlled Trial Comparing a Multitarget Opioid
Free Anaesthesia (OFA) and a 3-Liter Volume Calculated Airseal Carbon
Dioxide Insufflator with a Balanced Anaesthesia Using Sufentanil-Sevoflurane
and a Standard 15 MmHg Carbon Dioxide Pressure Pneumoperitoneum
Insufflator in a 2x2 Factorial Design
Jan P. Mulier1* and Bruno Dillemans2
1Department of Anaesthesiology, AZ Sint Jan
Brugge-Oostende, B-8000 Brugge, Belgium
2Department of General Surgery, AZ Sint Jan
Brugge-Oostende, B-8000 Brugge, Belgium
Introduction
During a pneumoperitoneum the elevated intra-abdominal pressure decreases

reaction [3]. The mesothelial cells of the peritoneum have a low metabolism consuming
little oxygen. The mesothelial cell membranes therefore allow only a limited amount
of gas diffusion and probably have no active gates to increase passive gas absorption
              
pneumoperitoneum through the peritoneum. However, after some period of ischemia

         
further. Mulier introduced a multitarget opioid free anaesthesia in 2011 to
reduce post-operative opioid consumption and all their side effects [5]. A reduction of
surgical        
         

*Corresponding Author: Jan P. Mulier, Department
of Anaesthesiology, AZ Sint Jan Brugge-Oostende,
Ruddershove 10 B-8000 Bruges, Belgium, Email:
jan.mulier@azsintjan.be
This article was published in the following Scient Open Access Journal:
Journal of Clinical Anesthesia and Pain Medicine
Received October 09, 2018; Accepted October 26, 2018; Published November 02, 2018
Abstract
During a pneumoperitoneum the elevated intra abdominal pressure decreases
splanchnic perfusion and induces peritoneal ischemia followed by an inammation reaction.
After around 30 minutes pneumoperitoneum the peritoneum loses its integrity and CO2
absorption increases.
Use of a multitarget opioid free anaesthesia versus a standard balanced anesthesia with
opioids and use of a Volume Calculated constant 3 liter volume with an Airseal insufator
versus a standard insufator with constant pressure and the combinations of both are
compared in a 2x2 factorial design having 4 parallel-groups. The intra abdominal pressure
(IAP) was set at 15 mmHg in the standard insufation groups while the IAP was adapted to
achieve 3 liter workspace using the abdominal compliance model in the airseal insufation
groups. The effect of peritoneal ischemia and inammatory reactions is measured by the
amount of CO2 absorption in ml/min at the end of the pneumoperitoneum and by the next
day CRP levels. The secondary endpoints are the VAS score and the rst 24 hours opioid
consumption after extubation.
A linear regression analysis of the post operative CRP and the amount of absorbed
CO2 per minute was found to be signicant lower in the patients treated with OFA and
treated with an airseal insufation. Total morphine equivalents consumption 24 hours post
operative dropped only after opioid free anesthesia with no difference in VAS score in any
group.
Conclusion: A multitarget Opioid Free Anaesthesia and a 3-liter Volume Calculated
AirSeal insufflation are both reducing the amount of CO2 absorption and the next day
CRP levels. Post-operative morphine consumption dropped only after opioid free
anesthesia.
Keywords: Anti-inflammatory anaesthesia, Opioid-free anaesthesia, Laparoscopy,
Bariatric surgery, Pneumoperitoneum, Peritoneal ischemia.

Citation: Jan P. Mulier, Bruno Dillemans (2018). A Prospective Randomized Controlled Trial Comparing a Multitarget Opioid Free Anaesthesia
(OFA) and a 3-Liter Volume Calculated Airseal Carbon Dioxide Insufator with a Balanced Anaesthesia Using Sufentanil-Sevourane
and a Standard 15 Mmhg Carbon Dioxide Pressure Pneumoperitoneum Insufator in A 2x2 Factorial Design.
Page 2 of 6
www.scientonline.org J Clin Anesth Pain MedVolume 2 • Issue 2 • 023
        
       
       

        
       


        

           
        
and
dexamethasone are used for the multitarget opioid free

Methods
       
      
          

      
a laparoscopic bariatric surgery are included. Diabetic patients
are excluded to avoid use of glucose and insulin intra operative.
This is an open randomized, controlled study. Use of a standard

         

in a 2x2 factorial design having 4 parallel-groups.
        
      
         
       
 

      
     
     
     
            
          
 

          
given until return of normovolemia.
        

        
          
            
         
and manual regulated according to the anesthesia requests. Extra
boli of sufentanil were added at the discretion of the attending
anesthesiologist.
           


extubation in both groups at the same dose if not contra indicated.

    

      
pain free and calculated as an equal dose of morphine.

 


          
of the surgeons to improve the stapling compression in order to

         

the bleeding spots to clip during the second phase of surgery. This
prevents post-operative bleedings and revisions.
Patients are Randomized into 4 Groups
   
set at a pressure of 15 mmHg and a standard balanced anaesthesia
       

administration needed to achieve hemodynamic stability is given.
   
         

       
 
needed to achieve hemodynamic stability is given.
   
        
    

 ,dexmedetomidine and Magnesium at
induction and Sevoflurane inhalation and clonidine for
maintenance combined with procaine.
  
         


         
      
inhalation and clonidine for maintenance combined with
procaine.



   
       
         
           



      
         


Citation: Jan P. Mulier, Bruno Dillemans (2018). A Prospective Randomized Controlled Trial Comparing a Multitarget Opioid Free Anaesthesia
(OFA) and a 3-Liter Volume Calculated Airseal Carbon Dioxide Insufator with a Balanced Anaesthesia Using Sufentanil-Sevourane
and a Standard 15 Mmhg Carbon Dioxide Pressure Pneumoperitoneum Insufator in A 2x2 Factorial Design.
Page 3 of 6
www.scientonline.org J Clin Anesth Pain MedVolume 2 • Issue 2 • 023
free during induction phase and each time patient is hypotensive
in the opioid groups. The total amount given is measured at end
of anaesthesia by measuring the number of 0.5 or 1.0 liter bags
           
total dose of nicardipine and metoprolol is measured.
The primary endpoint is peritoneal damage through ischemia.
 

       
production before and during pneumoperitoneum with the
ventilator having a metabolic computer allows to calculate
         
absorption during pneumoperitoneum as proposed by J Mulier.
Assuming that respiratory quotient does not change intra
       
   
 



       
        
       
         
protein metabolism and 1,0 for carbohydrate metabolism. To
      
for diabetic patients who are excluded therefore from the study
as they require insulin therapy combined with glucose.
Due to changes in ventilation and circulation, transient changes


reached value at end of pneumoperitoneum. Ventilation parameters
         
            

   
         
    
use the value at the end of the laparoscopy during a comparable
stable ventilation period.
       
  



The secondary endpoint is the post-operative opioid

All major surgical and anesthetic complictions per and post-
operative are noted and compared.
Data is analyzed using analysis of variance, t test and linear

Results
There are no demographic differences between the four
groups for sex, age,    
(Table 1).

was different between the opioid and opioid free anesthesia
        

as requested during stapling (Table 1).
      
         
         
   
almost the longest laparoscopic duration time and reached a high


        
hours post-operative between the four groups (Table 2).
      
       
           
          
        
standard insufator-OA standard insufator-OFA airseal insufator-OA airseal insuator-OFA p test
Sex (male/woman) 3/9 6/13 3/6 4/9 0.97 chi-square
Age (years) (mean±SD) 35.2 ± 4.6 37.7 ± 2.8 41.1 ± 5.5 39.8 ± 4.9 0.92 anova
BMI (kg/m2) (mean±SD) 37.3 ± 7.9 38.9 ± 3.5 37.6 ± 3.2 37.8 ± 2.5 0.92 anova
PP duration (minutes) (mean±SD) 78 ± 13 79 ± 10 82 ± 13 74 ± 17 0.89 anova
Fluids (ml) (mean±SD) 650 ± 201 202 ± 43 800 ± 282 192 ± 58 <0.001 anova
Sufentanil (mcg) (mean±SD) 35 ± 10 0 39 ± 10 0 <0.001 anova
Metoprolol (mg) (mean±SD) 0.17 ± 0.37 0.47 ± 0.40 0.33 ± 0.54 0.46 ± 0.84 0.82 anova
Nicardipine (mg) (mean±SD) 1.25 ± 0.98 0.63 ± 0.65 1.22 ± 1.37 0.54 ± 0.63 0.45 anova
Table 1: Demographic data of four study groups
PP: pneumoperitoneum; OA: opioid anaesthesia; OFA: opioid free anaesthesia
Graph 1:

Citation: Jan P. Mulier, Bruno Dillemans (2018). A Prospective Randomized Controlled Trial Comparing a Multitarget Opioid Free Anaesthesia
(OFA) and a 3-Liter Volume Calculated Airseal Carbon Dioxide Insufator with a Balanced Anaesthesia Using Sufentanil-Sevourane
and a Standard 15 Mmhg Carbon Dioxide Pressure Pneumoperitoneum Insufator in A 2x2 Factorial Design.
Page 4 of 6
www.scientonline.org J Clin Anesth Pain MedVolume 2 • Issue 2 • 023
pneumoperitoneum pressures up and down in order to achieve
       
multiplied with the duration of the pneumoperitoneum in

(Graph 3)
         
   
consumption 24 hours post-operative (Graph 4)

  
  

      
multiplied with the intra-abdominal pressure for all patients
together had no impact (Table 3). The linear regression for this
  
A linear regression analysis of the total morphine equivalents


 
     between the four
groups (Table 2) and a linear regression analysis of the post-
       

more vasodilators needed during the hypotension phase in the
Table 2: CO2 absorption, CRP and Morphine consumption
standard insufator-OA standard insufator-OFA airseal insufator-OA airseal insuator-OFA ptest
CO2 absorption (mean±SD) 162 ± 53 60 ± 21 81 ± 21 32 ± 16 <0.001 anova
CRP post op (mean±SD) 117 ± 48 48 ± 33 42 ± 9 45 ± 23 0.003 anova
total morphine post op (mean±SD) 18.2 ± 5.0 3.1 ± 1.1 13.3 ± 6.3 3.7 ± 1.5 <0.001 anova
max VAS score post operative 3.11 ± 2.65 1.4 ± 3.89 5.57 ± 2.44 1.40 ± 3.89 0.192 anova
p<0.05
CRP: C-reactive protein; OA: opioid anaesthesia; OFA: opioid free anaesthesia
*
*
Graph 2: End laparoscopic CO2 absorption, CRP levels next day and total
morphine equivalents consumption 24 hours post operative in the standard
groups versus the airseal group
Graph 3: End laparoscopic CO2 absorption versus IAP x PPduration for
groups treated with a variable IAP.
Pearson correlation p=0.037
Multi regression for CO2 absorption found that IAP x PP duration was
signicant (p = 0.045) in this subgroup.
*
*
*
*
Graph 4: End laparoscopy CO2 absorption, CRP levels next day and total
morphine consumption post operative in the opioid anesthesia versus the
opioid free anesthesia group

Citation: Jan P. Mulier, Bruno Dillemans (2018). A Prospective Randomized Controlled Trial Comparing a Multitarget Opioid Free Anaesthesia
(OFA) and a 3-Liter Volume Calculated Airseal Carbon Dioxide Insufator with a Balanced Anaesthesia Using Sufentanil-Sevourane
and a Standard 15 Mmhg Carbon Dioxide Pressure Pneumoperitoneum Insufator in A 2x2 Factorial Design.
Page 5 of 6
www.scientonline.org J Clin Anesth Pain MedVolume 2 • Issue 2 • 023
opioid group while there were more vasoconstrictors needed

         
protocol.
Discussion
     
        
        

        
  

effect, there was however a large variation as every patient is
     
abdominal pressure close to the set value while the standard

       


that the average of the real intra-abdominal pressures was equal
between both groups and another mechanism should explain the


during laparoscopy in both groups as requested to improve

  
           
  
        
       
       
that induce peripheral vasodilation on  
  or labetolol given
to reduce systolic arterial pressure below 100 mmHg.
          
stich on the peritoneum. The question is how important these
         
water vapor and not toxic. A third mechanism explaining this

trocars inside the abdomen on moments of instrument changes
   

        
concentration during laparoscopy and found strong variations
           
instrument switches, comparable to what was described to
      
 
      

        
       
during laparoscopy and probably during other types of surgery?
The post operative analgesic effect when given intra operative
        
reduction if no opioids are given intra operative.
 
      
explained by absence in tolerance and hyperalgesia of the opioids,

of the drugs used instead of opioids to achieve sympathetic
         
     
consumption.
     

or morphine used when analyzed with a linear regression for all
patients. Most procedures were less than 2 hours and the impact


        
CO2 absorption end operation CRP 24h post operative total Morphine post operative
variable coefcient p-value coefcient p-value coefcient p-value
age (years) 0.123 0.816 0.101 0.192 0.054 0.3234
BMI (kg/m2) -1.071 0.506 -0.112 0.951 0.009 0.958
sex (male=1) 5.283 0.759 17.877 0.341 -1.042 0.558
OFA vs OA -55.635 0.001 -37.986 0.028 -10.117 0.000
stand vs airseal 35.428 0.014 35.863 0.037 -0.64 0.652
IAP x PP duration in mmHg.min 0.023 0.229 -0.022 0.573 -0.002 0.365
constant 93.07 0.148 93.07 0.148 13.409 0.046
Table 3: Linear regression analysis for CO2 absorption per minute at end laparoscopy, CRP 24h post-operative and total Morphine consumption rst 24 h post-
operative for all groups together
variable coefcient std. error t-statistic p-value
age (years) 0.272 0.524 0.519 0.608
BMI (kg/m2) -4.409 1.952 -2.258 0.032
sex (male=1) 6.765 16.333 0.414 0.682
OFA vs OA -40.531 13,593 -2.981 0.006
IAP x PP duration in mmHg.min 0.04 0,015 2.667 0.013
constant 180.737 69.587 2.597 0.015
Table 4: linear regression analysis for CO2 absorption per minute at end laparoscopy in airseal groups

Citation: Jan P. Mulier, Bruno Dillemans (2018). A Prospective Randomized Controlled Trial Comparing a Multitarget Opioid Free Anaesthesia
(OFA) and a 3-Liter Volume Calculated Airseal Carbon Dioxide Insufator with a Balanced Anaesthesia Using Sufentanil-Sevourane
and a Standard 15 Mmhg Carbon Dioxide Pressure Pneumoperitoneum Insufator in A 2x2 Factorial Design.
Page 6 of 6
www.scientonline.org J Clin Anesth Pain MedVolume 2 • Issue 2 • 023
        
         
       
might have given larger differences.
        
hyper ventilated and certainly at moments that the minute
      

         
absorption. Therefore, the minute volume was gradual adapted
     


     

           
difference.
Conclusion
target      
       
          
    
morphine consumption dropped only after opioid free anesthesia.
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