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The Pros and Cons of Adding Insulin to Total Parenteral Nutrition

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Dr Paul Chidester, MD, FACP

Chief Medical Officer

Executive Summary:

Patients receiving total parenteral nutrition (TPN) often require insulin to manage hyperglycemia, particularly in cases of underlying diabetes or acute illness. TPN can lead to hyperglycemia due to factors such as increased hepatic glucose production, insulin resistance, and stress-related hormone elevations. Effective glycemic control is crucial for improving patient outcomes and reducing complications like infections and organ failure.

Three primary methods for administering insulin to TPN patients are considered:

  1. Placing Insulin in TPN Solution
    • Pros: Simplifies administration, reduces hypoglycemia risk, and decreases nursing workload.
    • Cons: Limits dose adjustability, risks insulin degradation, and requires TPN formulation changes for dose adjustments.
  1. Continuous Insulin Infusion (CII)
    • Pros: Offers precise control with rapid adjustments, ideal for critically ill patients.
    • Cons: Increases nursing workload, poses higher hypoglycemia risk, and requires complex setup.
  1. Subcutaneous Injections
    • Pros: Allows independent adjustment from TPN, widespread clinical use, and flexibility in dosing.
    • Cons: Requires multiple injections, risks variable absorption, and increases nursing workload.

Considerations and Recommendations:

Choice of insulin administration depends on physician preference, organizational policy, patient acuity, and available resources such as computerized dosing algorithms like EndoTool.

Selecting the appropriate insulin administration method in TPN-associated hyperglycemia management involves balancing simplicity, precision, and patient-specific needs.

Insulin Dosing with Total Parenteral Nutrition

For patients receiving total parenteral nutrition (TPN) there is usually a need for the administration of insulin to maintain glycemic control. This need is especially prevalent in patients with diabetes.

The development of hyperglycemia in conjunction with specialized nutritional support may occur because of a variety of factors which are predominantly related to the stress of an acute illness or surgery.

These factors may include:

  • increased hepatic glucose production with poor peripheral glucose uptake
  • insulin resistance
  • bed rest
  • increased levels of cortisol, catecholamines and glucagon
Along with the increased delivery of glucose and gluconeogenic substrates in TPN, hyperglycemia development is expected when treating critically ill patients with TPN.

The management of this hyperglycemia is essential to improving patient outcomes.

Several studies have demonstrated an increased incidence of death, renal failure and infections when euglycemia was not achieved in patients treated with TPN.

Treatment of hyperglycemia in patients on TPN can be managed in many ways.

For critically ill patients, insulin can be administered via a continuous insulin infusion (CII) with hourly titration or insulin can be placed in the TPN solution.

For more stable patients, there is also the option for administration of subcutaneous insulin with frequent blood glucose monitoring. However, there have been no randomized controlled trials comparing various approaches to insulin therapy.

There is one retrospective analysis suggesting that adding insulin in the TPN bag provides better control with less hypoglycemia than using intravenous or subcutaneous insulin alone.

However, this may not be the case if the insulin is administered with a computerized dosing protocol such as EndoTool. The use of EndoTool intravenous dosing application consistently demonstrates extremely low rates of hypoglycemia less than 70mg/dl (0.26%) and less than 40mg/dl (0.01%).

As there is not an established gold standard for how insulin should be administered to treat TPN associated hyperglycemia, let’s review the potential pros and cons with each modality.

Pros and Cons of Placing Insulin in TPN vs. Continuous Insulin Infusion

Placing Insulin in TPN

Pros:

  1. Convenience: Combining insulin with TPN can simplify the administration process, reducing the need for multiple injections or infusions.
  2. Reduced Nursing Workload: It can decrease the nursing workload since it involves fewer steps and monitoring compared to CII.
  3. Stable Blood Glucose Control: For many patients, adding insulin to TPN provides stable glycemic control, as the insulin is released in tandem with nutrient delivery​.
  4. Fewer Hypoglycemic Episodes: Some studies indicate that this method can result in fewer hypoglycemic episodes compared to separate insulin infusions​.

Cons:

  1. Adjustability: It is less flexible in adjusting insulin doses rapidly in response to changing blood glucose levels since the insulin is pre-mixed in the TPN bag.​
  2. Risk of Insulin Degradation: There is a potential risk of insulin degradation when mixed with TPN solutions, which could affect its potency and effectiveness.​
  3. Delayed Response: Any necessary adjustments to insulin dosing require changes to the TPN formulation, which can delay response times.

Continuous Insulin Infusion

Pros:

  1. Precise Control: CII allows for precise and rapid adjustments to insulin dosing based on real-time blood glucose monitoring​
  2. Rapid Response: This method can quickly correct hyperglycemia, which is particularly beneficial in critically ill patients or those with highly variable blood glucose levels​
  3. Flexibility: It offers the flexibility to adjust insulin doses as needed, providing more tailored glycemic control for individual patients​
  4. Consistent Insulin Delivery: CII ensures a steady and consistent delivery of insulin, which can help maintain blood glucose within target ranges more effectively.

Cons:

  1. Increased Nursing Workload: Requires more frequent monitoring and adjustments, increasing the workload for nursing staff​
  2. Risk of Hypoglycemia: There is a higher risk of hypoglycemia due to the continuous presence of insulin in the bloodstream, requiring careful monitoring​, though this is a rare event when utilizing a computerized dosing application such an EndoTool.
  3. Complexity: It involves a more complex setup and maintenance, including the use of infusion pumps and IV lines, which can be a challenge in some clinical settings.

Subcutaneous Injections

Pros:

  1. Flexibility: Allows for more immediate and frequent adjustments to insulin doses based on real-time blood glucose levels.
  2. Independence from TPN: Can be administered independently of the patient’s nutrition plan, making it easier to respond quickly to blood glucose changes. No need to alter TPN formulation to change insulin therapy
  3. Common Practice: Subcutaneous injections are a well-established practice with clear protocols and widespread clinical experience​.

Cons:

  1. Multiple Injections: Requires multiple daily injections, which can be uncomfortable and inconvenient for patients.
  2. Variable Absorption: Absorption rates can vary based on factors such as injection site, leading to potential fluctuations in blood glucose levels.
  3. Increased Nursing Workload: Requires more frequent administration and monitoring, which can increase the workload for healthcare providers.
  4. Risk of Hypoglycemia: Frequent injections and dose adjustments can increase the risk of hypoglycemia if not carefully managed​.

How insulin is administered to control TPN associated hyperglycemia may be dependent upon:

  • Physician or nursing preference
  • Organizational policy
  • Resources available such as a computerized dosing algorithm
  • Acuity of the patient’s illness
  • Difficulty in achieving glycemic control

Our Take on Insulin in TPN

EndoTool’s predictive and patient specific insulin dosing ensures that optimal glycemic control is achieved with consistently low rates of hypoglycemia, even with the increased insulin needs associated with TPN. When utilizing EndoTool on a patient requiring CII, it is recommended not to add insulin to the TPN solution.

For non-critically ill patients receiving TPN managed with EndoTool for subcutaneous insulin dosing, we recommend not adding insulin to the TPN bag. EndoTool generates a personalized dosing plan considering TPN dextrose and other carbohydrates consumed or administered. It also prompts additional blood glucose checks or IV dextrose administration if TPN is paused to prevent hypoglycemia.

The ability of EndoTool to adapt to a patient’s insulin needs while receiving TPN is one of the many unique features of the application that allows for the delivery of safe and effective insulin dosing.

About EndoTool

EndoTool insulin dosing software recommends individual insulin dosing for patients on IV or subcutaneous insulin. The recommended dosing is specific and different for each patient based on multiple clinical characteristics. The FDA-cleared platform is utilized in hundreds of hospitals across the United States and is fully integrated with all major electronic medical records. To see how EndoTool can support your institution, get in touch today.

About the author

Dr Paul Chidester, MD, FACP | Chief Medical Officer

Dr. Paul Chidester is the Chief Medical Officer for Monarch Medical Technologies. After practicing for two decades as a nephrologist, he assumed a senior leadership role at Sentara Healthcare where he led the implementation of computerized insulin dosing software. He is involved with product development and customer engagement at Monarch Medical Technologies where the focus is to provide precision insulin dosing for patients. His key interest is working to further enhance this precision through the use of technologies such as CGM.

References

  1. Gosmanov, A. R., Smiley, D. D., Robalino, G., Siquiera, J., Khan, B., & Le, N. A. (2013). Management of adult diabetic ketoacidosis. Current Diabetes Reports, 13(1), 155-162. https://doi.org/10.1007/s11892-012-0356-5 
  2. Cao, L., Zhang, D., Zhao, Y., Zhou, N., & Zhang, P. (2023). Efficacy and safety of different insulin infusion methods in the treatment of total parenteral nutrition-associated hyperglycemia: A systematic review and network meta-analysis. Frontiers in Nutrition, 10, Article 1181359. https://doi.org/10.3389/fnut.2023.1181359 
  3. Low Wang, C. C., & Draznin, B. (2013). Insulin use in hospitalized patients with diabetes: Navigate with care. Diabetes Spectrum, 26(2), 124–130. https://doi.org/10.2337/diaspect.26.2.124 
  4. Takahashi, Y., Matsuura, H., Domi, H., & Yamamura, H. (2022). A continuous intravenous insulin infusion protocol to manage high-dose methylprednisolone-induced hyperglycemia in patients with severe COVID-19. Clinical Diabetes and Endocrinology, 8(4). https://doi.org/10.1186/s40842-022-00192-3 
  5. EndoTool Customer Outcomes. Data on file. 2023 
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