Propofol: A Risk Factor for Caloric Overfeeding and Inadequate Protein Delivery

Propofol is a commonly used intravenous sedative for ventilator-dependent, critically ill patients due to its rapid onset and short half-life which allows for daily awakening and spontaneous breathing trials. Since propofol is poorly soluble in water, it is formulated in a 10% soybean lipid emulsion which provides 1.1 kcal/mL. As a result, propofol can significantly contribute to the overall energy intake for a patient who receives parenteral nutrition (PN) or enteral nutrition (EN). Prolonged continuous high-dose propofol therapy, such as that employed for patients with severe traumatic brain injury to lower intracranial pressure,¹ poses as a significant risk factor for development of hypertriglyceridemia and caloric overfeeding complications² even in the absence of propofol infusion syndrome.³ Serum triglyceride concentrations in excess of 400 mg/dL associated with intravenous soybean oil emulsion infusion can result in reticuloendothelial system clogging, compromised immune function, and pancreatitis.⁴ Caloric overfeeding predisposes the patient to hypercapnia with impaired ventilator weaning, hyperglycemia, and hepatic dysfunction which can worsen morbidity and possibly mortality.⁵

For patients who receive PN, caloric overfeeding and hypertriglyceridemia can often be avoided by reducing or omitting lipid emulsion from the patient’s PN prescription. However, with high doses of lipid emulsion from propofol, it might be necessary to also reduce the glucose content in the PN prescription in addition to omitting the lipid emulsion from the PN to lessen caloric intake. Under the conditions of lowering the glucose content of the PN regimen, it is recommended that a minimum glucose intake of 130 g/d be given to medical patients and 200 to 300 g/d for surgical patients (to account for obligatory glucose requirements and additional glucose needs of the healing surgical/burn wound, respectively)⁶ as long as the patient is not experiencing hyperglycemia. These caloric manipulations in the PN prescription can be easily accomplished without compromising protein (amino acid) intake for those institutions that have the ability to compound individual PN prescriptions or by use of low glucose-containing standardized solutions for those institutions that cannot compound individualized PN solutions.

Adjustment of EN regimens is more problematic than PN prescriptions as the EN formulation components are fixed without the ability to alter individual macronutrients within the EN formulation. As a result, some clinicians have empirically decreased the rate of EN to avoid caloric overfeeding during propofol therapy, but this approach may result in inadequate protein intakes for critically ill patients. Some studies indicated that many patients received <1 g/kg/d of protein when reducing EN rate because of propofol.^7,8 It is recommended by the Society of Critical Care Medicine–American Society for Parenteral and Enteral Nutrition guidelines that critically ill patients receive 1.2 to 2 g/kg/d of protein with the exception of certain subpopulations (e.g., trauma, continuous renal replacement therapy) that require higher protein intakes (e.g., 2-2.5 g/kg/d).⁴ It is common practice in the United States to target a protein intake of 1.5 to 2 g/kg/d for the majority of critically ill patients. The clinical judgment error of avoiding caloric overfeeding by a simple reduction in EN rate during propofol therapy is poignant in light of a growing body of evidence that indicates improved clinical outcomes for critically ill patients who receive an adequate protein intake when compared to those who received lower protein intakes.^9-12

To deliver an adequate protein intake with a restricted caloric intake via EN, we have employed the use of “high protein” and “very high protein” enteral formulas (e.g., 1 kcal/mL, 64 g protein/L and 1 kcal/mL, 92 g protein/L, respectively) at a reduced infusion rate and are often combined with liquid protein supplements given as boluses via the feeding tube. We will use two case scenarios to illustrate this technique. Both case studies involve an intensive care unit (ICU) patient who weighs 80 kg, is 72 inches tall, has a body mass index of 23.9 kg/m², and is receiving an intravenous propofol infusion at 20 mL/hr. This propofol infusion rate would provide a caloric intake of about 7 kcal/kg/d. In these cases, we will be using enteral formulas and a liquid protein supplement available from the hospital’s formulary. It is important to ascertain the exact caloric and protein contents of all EN products at your institution as the calculations in these case studies will need to be adjusted depending on what products are available at the reader’s institution. Of particular note is that the liquid protein supplement on our formulary contains non-protein calories (flavoring agents, etc.) so that the total caloric content is in excess of that contributed by protein calories alone. The liquid protein formulation used at Regional One Health in Memphis, TN provides 6.67 kcal/g of protein (whereas protein without any other ingredients contributes 4 kcal/g).

• Case 1: Medical ICU patient. Typical caloric and protein goals would be 25 to 30 kcal/kg/d and 1.5 to 2 g/kg/d, respectively.⁴ A “high protein” enteral formula (e.g., 1 kcal/mL, 64 g protein/L) at 90 mL/hr would provide 27 kcal/kg/d and 1.7 g/kg/d of protein. If the enteral regimen was not adjusted for propofol, the patient would receive 34 kcal/kg (from the combined calories of EN and propofol) which would put the patient at risk for overfeeding complications. One solution to this caloric overfeeding issue would be to reduce the rate of the “high protein” enteral formula to 55 mL/hr and add 45 g of liquid protein per day (as a bolus) which would provide 20 kcal/kg (27 kcal/kg/d when including propofol calories) and 1.6 g/kg/d of protein. Another solution would be to change the EN to a “very high protein” enteral formula (1 kcal/mL, 92 g protein/L) at 65 mL/hr which would provide 20 kcal/kg/d (27 kcal/kg/d when including propofol kcals) and 1.8 g/kg/d of protein.

• Case 2: Trauma ICU patient. Typical caloric and protein goals are higher for this patient population (e.g., 30-32 kcal/kg/d and 2-2.5 g/kg/d, respectively) than the medical ICU patient.⁴ Without propofol, use of a “high protein” enteral formula (e.g., 1 kcal/mL, 64 g protein/L) at 95 mL/hr plus 30 g of liquid protein per day would provide 31 kcal/kg/d and 2.2 g/kg/d of protein. But with propofol (providing 7 kcal/kg/d), this would amount to an excessive caloric intake of 38 kcal/kg/d. By reducing the rate of the “high protein” formula to 55 mL/hr and providing 45 g of liquid protein twice daily, caloric intake would be reduced to 24 kcal/kg/d (31 kcal/kg/d when including propofol calories) and 2.2 g/kg/d of protein. The second option would be to use the “very high protein” enteral formula (1 kcal/mL, 92 g protein/L) at a rate of 80 mL/hr which would provide 24 kcal/kg/d (31 kcal/kg/d when including propofol calories) and 2.2 g/kg/d of protein.

Manipulation of EN and PN regimens is necessary when a significant amount of calories from propofol are provided. Care must be taken to avoid an inadequate protein intake. We recommend that whenever propofol is used in conjunction with enteral or parenteral nutrition therapy, serial serum triglyceride concentrations should be obtained to minimize the adverse effects of excessive soybean lipid emulsion and hypertriglyceridemia. Although the presented EN strategy is simple in concept, it may also be considered somewhat labor-intensive in practice. Yet this approach can potentially resolve poor protein delivery associated with EN rate reduction to avoid caloric overfeeding during propofol therapy. It is important that the critical care pharmacist be well versed in the use and components of propofol and know how to modify PN and EN regimens to circumvent serious complications and optimize nutritional therapy.