Mimicking the Eleveld propofol target-controlled infusion model using the Marsh model with weight adjustment in a super-obese patient

Target-controlled infusion (TCI) of propofol using traditional pharmacokinetic models such as the Marsh and Schnider models for super-obese patients, defined as body mass index (BMI) greater than 55 kg/m², poses significant challenges. ¹ Using the Marsh model with total body weight can result in excessively large induction boluses and potential haemodynamic instability, whereas the Schnider model can lead to excessively high maintenance infusion rates at high BMIs. ² While the Society for Intravenous Anaesthesia has made general recommendations regarding TCI use in the obese surgical patient, including the use of processed EEG monitoring and titration to clinical effect, there is currently no widely agreed standard practice. ²

The Eleveld model, a newer general purpose TCI model, has demonstrated improved precision in the obese population. ³ However, it is currently not widely available on commercial infusion pumps in many countries, including Australia and New Zealand. Recently, we have demonstrated through in silico simulation that the Eleveld model’s infusion behaviour could be accurately replicated using the Marsh model together with a simple weight scalar, namely the ‘EleMarsh’ adjusted body weight (ABW), derived from a least squares fitting algorithm. ⁴ Here we report a case, with written informed consent from the patient, in which our EleMarsh method was successfully used to anaesthetise a super-obese patient.

A 60-year-old woman with World Health Organization class 3 obesity (120 kg, 145 cm, BMI 57.1 kg/m²) presented with necrotising fasciitis of the perineum requiring emergency debridement. Her medical history included coronary artery disease, type 2 diabetes mellitus requiring insulin, and obstructive sleep apnoea. As the Eleveld model was unavailable at our institution and her BMI exceeded the upper limit allowable for the Schnider model, we used the Marsh model with EleMarsh ABW of 85 kg to mimic the Eleveld model for propofol TCI. Using the Eleveld pharmacodynamic model, ⁵ an initial effect site concentration target (CeT) of 2.5 µg/mL was chosen for this patient given her critical illness, which corresponded to a predicted bispectral index of 49. To replicate the infusion behaviour of an effect site targeting model using a plasma targeting model, a manual plasma overshoot is necessarily required. Using the EleMarsh algorithm, we found that an induction CeT of 2.5 µg/mL with the Eleveld model corresponded to a Marsh induction plasma concentration target (CpT) of 6.7 µg/mL. Given the critical illness and reduced cardiovascular reserve of our patient, we decided to use the reduced Marsh CpT of 4 µg/mL on induction, accepting a slower rise towards the maintenance CeT as trade-off to minimise haemodynamic instability. The Minto model with weight input of 73 kg, the largest allowable for her height, was used for remifentanil TCI. ²

Following pre-oxygenation, general anaesthesia was induced using propofol TCI with slow up-titration to the predetermined induction CpT of 4 µg/mL. Immediately after the bolus was delivered by the infusion pump and loss of consciousness was achieved, CpT was reduced to the planned maintenance value of 2.5 µg/mL, and rocuronium 150 mg was administered. The trachea was intubated and mechanical ventilation commenced. After initial surgical incision, remifentanil TCI was commenced at CeT of 1 ng/mL, and propofol CpT was reduced to 2 µg/mL, which was maintained for the remainder of surgery. Depth of anaesthesia was monitored using frontal entropy electrodes. The state entropy (SE) remained stable throughout and the EEG waveform did not show features of burst suppression or arousal. At the conclusion of surgery, neuromuscular blockade was reversed using sugammadex and propofol TCI was weaned. The trachea was extubated 14 min after TCI cessation. The surgical procedure lasted 153 min and a total of 999 mg propofol was infused. At the time of extubation, the patient was fully alert, obeying commands and had normal vital signs. She was transferred to our intensive care unit for further management.

This case highlights the use of the Marsh model with EleMarsh ABW for propofol TCI in a critically unwell patient with super-obesity, which produced an infusion profile that closely replicated the Eleveld CeT model (Figure 1). This resulted in a stable maintenance phase, which facilitated smooth and timely emergence.

Figure 1.

Plasma concentration (Cp) profile from the Marsh target-controlled infusion (TCI) model using the EleMarsh input weight adjustment algorithm shows excellent agreement with the corresponding effect site concentration (Ce) profile derived from the Eleveld model using the propofol infusion regime in the present case.^4,5 The patient’s state entropy (SE) during the case was averaged in 10-min epochs.

The EleMarsh ABW has several key advantages over traditional weight scalars for the Marsh model such as the ideal body weight (IBW) or adj40BW (IBW + 0.4 (total body weight – IBW)). First, the EleMarsh ABW corrects for the influence of age on propofol clearance, thereby reducing potential drift during the maintenance phase for elderly patients. Second, as the resulting infusion profile closely mimics the Eleveld model, this enables the use of the Eleveld pharmacodynamic model to guide initial CeT (and thus Marsh CpT) selection. The EleMarsh ABW can be easily calculated using our freely available App, Propofol Dreams, ⁶ or using our spreadsheet, which is provided as online supplementary material.

The implementation of the EleMarsh algorithm in clinical practice necessitates consideration of several important limitations. First, despite in silico demonstrations of the EleMarsh method's close approximation to the Eleveld model's infusion behaviour for durations up to 4 h across diverse patient populations, ⁴ and anecdotal evidence of its successful use by the authors for a wide range of clinical scenarios beyond the single case reported here, robust clinical validation studies are currently pending. Furthermore, inherently as a plasma targeting model, the EleMarsh Cp displayed on the infusion pump will only mirror the Eleveld Ce at steady state, inevitably exhibiting hysteresis during CpT titration. Finally, it must be noted that the EleMarsh ABW, like all weight scalars for the Marsh model, has not received regulatory approval from the Therapeutic Goods Administration (TGA). Nonetheless, the EleMarsh ABW is currently the only weight scalar for the Marsh model that generates an infusion regimen mirroring a TGA-approved model for obese patients weighing up to 160 kg.

The EleMarsh ABW is a simple yet robust approximation method for clinicians to access the general purpose Eleveld model until it becomes more widely available in commercial infusion pumps. As with all pharmacokinetic models, inherent inter-individual pharmacodynamic variations mean that anaesthetists must always remain vigilant to the clinical picture, closely monitor the EEG waveform and titrate infusion targets accordingly.

Supplemental Material

sj-xlsx-1-aic-10.1177_0310057X241275122 - Supplemental material for Mimicking the Eleveld propofol target-controlled infusion model using the Marsh model with weight adjustment in a super-obese patient

Supplemental material, sj-xlsx-1-aic-10.1177_0310057X241275122 for Mimicking the Eleveld propofol target-controlled infusion model using the Marsh model with weight adjustment in a super-obese patient by George Zhong and Sarah J Wong in Anaesthesia and Intensive Care