Propofol is the most used intravenous agent for induction and maintenance of anaesthesia
as part of total intravenous anaesthesia (TIVA) regimen.
In the morbidly obese, various factors, such as, increased body fat content, lean body
weight, cardiac output, total blood volume, and alterations in regional blood flow; which
adversely/unpredictably affect the volume of distribution, clearance and elimination of
intravenous anesthetic drugs, thereby making administration of TIVA difficult to control.
A major concern with propofol dosing based on total body weight (TBW) in the obese
patients is disproportionate drug administration leading to undue drug accumulation in
body with potential overdosing, delayed recovery from anaesthesia, and adverse
hemodynamic outcome. Studies on propofol dose regimen for TIVA recommended that LBW
should be used for calculating bolus dose during induction of anaesthesia and TBW or ABW
for arriving at a infusion dose required for maintenance of anaesthesia.
Propofol requirement for induction of anaesthesia is based on LBW is especially relevant
for the morbidly obese patients as because their surplus fat mass increases volume of
distribution of propofol, which, in the face of decreased blood flow to adipose tissue;
imposes the burden of potential drug accumulation. This may result in increased drug
delivery to non-adipose tissue during induction of anaesthesia and possibly leading to
undesirable rarefaction of depth-of-anaesthesia and attendant adverse haemodynamic
effects.
Conversely, during the maintenance phase of propofol TIVA, the volume of distribution and
clearance of propofol increases and correlates linearly with TBW. In this respect,
controlling propofol delivery in the morbidly obese with Eleveld allometric PK model,
which utilizes TBW as weight parameter; has been found to be superior to other models
that employs other weight dosing scalars.
The use of ABW in Schnider and Marsh model takes into consideration drug distribution to
lean tissues as well as a proportion to the body fat weight, thus accounting for lipid
solubility dynamics of propofol. ABW is calculated by adding 40% excess fat weight (FW)
to IBW.
In obese patients propofol delivery using the Eleveld allometric PK model by
incorporating TBW has been found to be superior to other models using other dosing
scalars.
Target-controlled infusion (TCI) forms the core of standard-of-care method used for
administration of propofol TIVA. TCI system typically includes a
microprocessor-controlled syringe pump that is designed to achieve a defined plasma
concentration of the drug based on patient response and multi-compartment pharmacokinetic
(PK) model.
While TCI systems are designed to deliver propofol at a rate based on a predetermined
plasma concentration, they do not take into consideration patient's pharmacodynamic
profile. Hence, it is difficult to determine whether the target plasma concentration
achieved has produced adequate anaesthesia depth. In the absence of reliable depth of
anaesthesia monitors, during the maintenance phase of propofol TIVA, the desired plasma
concentration achieved may either result in intraoperative awareness due to under-dosing
or delayed recovery from anaesthesia because of over-dosing.
Currently, an array of research on automated propofol delivery using computer-controlled
closed loop anaesthesia delivery systems which deliver propofol based on patient's
frontal cortex electrical activity as determined by bispectral index (BIS); have amply
exhibited that these systems deliver propofol and maintain depth of anaesthesia with far
more precision as compared to manual administration.
Liu et al used a BIS-guided dual loop anaesthesia delivery system to determine
requirement of propofol and remifenatnil in the obese versus lean patients. The propofol
delivery was controlled by a closed loop set through TCI pump. Propofol was delivered
with dose calculation by TBW and based on the Schnider model. The propofol dosage
delivered as per TBW in real-time was analyzed post hoc on a IBW scale. The propofol
requirements for induction and maintenance based on TBW was equivalent both in obese and
lean patients.
CLADS is a BIS-guided automated closed-loop anaesthesia delivery system developed by
Puri, which delivers propofol using a non-TCI infusion pump. This system uses a control
algorithm that is based on the relationship between diverse rates of propofol infusion
and BIS variable. CLADS regulates the propofol infusion rate to maintain a predetermined
BIS target (BIS=50) and is independent of plasma propofol concentration status. CLADS is
uniquely versatile in that it can calculate propofol dosage delivered both on basis of
TBW or IBW.
Whereas, in a study comparing CLADS administered propofol versus desflurane-GA in morbid
obese patients undergoing bariatric surgery (unpublished data) the propofol maintenance
dosage based on ABW was 5.5 + 1.3 mg kg-1 h-1; Liu et al reported a median propofol
consumption of 5.2 [4.1, 6] mg kg-1 h-1 with their dual-loop closed loop anaesthesia
delivery system that also utilized TBW based administration of propofol and remifentanil.
In both the study, BIS was used as an input control actuator to close the feedback loop
joining the patient, the delivery system, and the infusion flow system.
Although maintenance of propofol TIVA based on TBW is well established, the dosing
schedule based on ABW is not well explored. Since the ABW takes into consideration a
certain percentage of FW in addition to IBW and not the complete FW as in TBW, we
hypothesize that propofol dosing using ABW will result in lower propofol requirement as
compared to TBW for maintaining equivalent anesthetic depth. Since CLADS gives an
objective assessment of propofol dose delivered and anaesthesia depth consistency, this
randomized study aim to compare the maintenance requirements of propofol in obese
patients given propofol dosing based on TBW versus ABW