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Intravenous Insulin Therapy

  • Author: Guy W Soo Hoo, MD, MPH; Chief Editor: George T Griffing, MD  more...
 
Updated: Nov 09, 2015
 

Overview

Patients with hyperglycemia in the ICU have increased morbidity and mortality. Hyperglycemia is associated with immune dysfunction, increased systemic inflammation, and vascular insufficiency. Elevated blood glucose levels have been shown to worsen outcomes in medical patients who are in the ICU for more than 3 days. Hyperglycemia may result from stress, infection, steroid therapy, decreased physical activity, discontinuation of outpatient regimens, and nutrition.[1]

Improved control of hyperglycemia improves patient outcomes, but clinical confirmation of this thesis has proven elusive. Significant interest was generated by initial single-center results that have not been replicated in multisite studies. In 2001, a randomized controlled study in a surgical ICU demonstrated a decrease in mortality from 8% to 4.6% in patients with intensive continuous intravenous insulin therapy.[2] The author repeated the protocol in a study of 1200 patients in a medical ICU.[3] The conventional treatment group was treated to maintain a blood glucose level between 180-200 mg/dL, whereas the intensive treatment group was treated to maintain a blood glucose level between 80-110 mg/dL. Mortality was not significantly reduced by intensive insulin therapy and was actually higher in patients in the intensive treatment group who were in the ICU for less than 3 days. In patients who were in the ICU for longer than 3 days, the intensive treatment group did demonstrate reduced morbidityfrom decreased kidney injury, earlier weaning from mechanical ventilation, and earlier discharge from the medical ICU and hospital. Hypoglycemia occurred more often in the intensive treatment group than the conventional treatment group. In addition, an experienced physician was actively involved in administration of the protocol, a luxury not uniformly available to many hospitals and a variable that limited the ability to generalize their results to other centers.

However, the results were encouraging and represented a marked improvement in several areas, stimulating great interest in tight glucose control with intravenous insulin, which, in turn, stimulated the development of a multitude of intravenous insulin protocols. However, the protocols widely varied and little uniformity was observed among medical centers. Questions persisted as to the optimal protocol and targets and the need for a unified, uniform approach to control of hyperglycemia.

The NICE SUGAR study published in 2009 was a large, international, randomized trial intended to address the shortcomings of previous studies.[4] The study enrolled 6104 patients who were either assigned to tight glucose control with a target of 81-108 mg/dL or conventional glucose control with a target of 180 mg/dL or less. At the end of the 90-day study period, mortality was 27.5% of patients in the tight glucose control group and 24.9% of patients in the conventional control group, with an odds ratio of 1.14 for death with tight glucose control. No significant difference in the median length of stay in the ICU or hospital was noted. Severe hypoglycemia was significantly more common with tight glucose control. This experience dampened the routine use of intravenous insulin therapy in critically ill patients; however, continuous intravenous insulin therapy still has a role in the management of critically ill patients.

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Key Components of Insulin Protocols

Intravenous insulin titration protocols have been in place for several years and predate the experience outlined by van den Berghe but were not widely considered or adopted until after the 2001 report. Since the NICE-SUGAR report, the pendulum has shifted away from near universal intravenous insulin therapy for the critically ill to utilization in selected patients. It remains an important component of patient management, especially in patient subgroups, such as those undergoing open cardiac surgery. Several tenets of a successful, effective intravenous insulin protocol have been recognized the protocol used is only a minor component. Implementation of an insulin protocol without key nursing, physician, and administrative support is doomed to fail.

Key components to the institution of an intravenous insulin protocol are as follows:

  • Define present management of hyperglycemia.
  • Determine need for improved management of hyperglycemia.
  • Create a multidisciplinary committee for management, including the following:
    • Physician (medical and/or surgical; ICU and endocrinology input ideal)
    • Nurse
    • Nutritionist (dietary service)
    • Pharmacist
  • Identify necessary resources, including the following:
    • Point-of-care glucometers vs laboratory analysis
    • Pharmacy staff (intravenous insulin preparations)
    • Nursing requirements and training
    • Nutritional assessment and monitoring (continuous enteral or parenteral nutrition)
    • Management of hypoglycemia
    • Transition from intravenous to subcutaneous preparations
  • Select the intravenous insulin protocol, which includes the following:
    • Local development vs use of existing protocol (assess need for modification)
    • Nurse-driven vs element of physician oversight
    • Standardization of order sets (paper, computerized, web-based)
    • Computerized order entry programs
    • Training of physician and nursing staff
  • Metrics for evaluation include the following:
    • Percentage of patients above 180 mg/dL
    • Percentage of patients within specific target (ie, 140-180 mg/dL)
    • Hypoglycemia (percentage of patients < 45 mg/dL)
    • Sternal wound infections
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Indications

As noted above, patients with hyperglycemia are at risk for adverse outcomes and infections are a common clinical indicator of the risk associated with hyperglycemia. Patients undergoing cardiac surgery seem to be especially susceptible to deep wound infections, specifically sternal wound infections. This is probably the one group of patients who may still benefit from the routine use of intravenous insulin for glucose control. Experience from several institutions and data that incorporate both observational and randomized investigations indicate improvement in mortality and rate of sternal wound infections with the use of intravenous insulin.[2, 5]

The evidence to support the use of intravenous insulin in this patient subgroup has been designated as a class I recommendation by the Society of Thoracic Surgeons.[6] Routine use of continuous insulin protocols is not endorsed for any other subgroup, but general experience does support its use in those diabetic patients in whom control of hyperglycemia has been demonstrated to be difficult with conventional subcutaneous treatment. In some circumstances, diabetic patients who require therapy that interfere with optimal glucose control such as corticosteroid therapy may also be candidates for intravenous insulin therapy.

This is markedly different from previous practice and is a reflection of the results of the multicenter NICE-SUGAR trial. Intravenous insulin therapy can no longer be recommended as routine treatment in the ICU but should be reserved for patients who undergo open cardiac surgery and diabetic patients with suboptimal glucose control as a result of their underlying diabetes, infection or treatment that fails to be controlled with conventional subcutaneous insulin regimens.

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Optimal Range of Glucose Control

The results of the experience with intravenous insulin and tight glucose control had led to a re-examination of the optimal range of glucose control. Although control of hyperglycemia did reduce infection rates, especially after cardiothoracic surgery, a net benefit was tempered by higher rates of hypoglycemia and mortality. The ideal target blood glucose level in the intensive care setting has yet to be established but seems to be less than 180 mg/dL (< 10 mmol/L).

The lowest acceptable threshold for serum glucose has not been established. However, given the increased risk of hypoglycemia associated with insulin protocols that sought to control blood glucose levels between 80-110 mg/dL, a goal of less than 110 mg/dL cannot be endorsed. This was also the sentiment of a consensus statement that suggested a glucose target of 140-180 mg/dL in critically ill patients; however, certain subgroups, such as patients undergoing cardiothoracic surgery, may benefit from a lower target range.[7] Therefore, a glucose target of 110-140 mg/dL may eventually be a more appropriate range for this subgroup and other critically ill patients; however, this level of control has not been subjected to rigorous investigation and determined with evidence-based support.

The Society of Thoracic Surgeons examined the evidence for intravenous insulin; although they endorsed the use of intravenous insulin therapy in patients undergoing cardiac surgery, they did not endorse a strict glucose target range. They cite evidence that supports a target glucose of less than 180 mg/dL using intravenous insulin for at least the first 24 hours postoperatively, with a target of less than 150 mg/dL if their ICU stay exceeds 3 days because of comorbidities requiring mechanical ventilation, inotropes, ventricular-assist devices, intra-aortic balloon pumps, antiarrhythmics, or renal replacement therapy.[6]

In summary, the optimal range of glucose control in critically ill patients remains to be determined. A glucose control target between 140-180 mg/dL is recommended in most critically ill patients. Those with a higher severity of disease may benefit from control that aims for the upper threshold to be less than 150 mg/dL. The burden of experience and risk of hypoglycemic complications no longer supports to further reduce glucose levels below 110 mg/dL.

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Pitfalls in Bedside Glucose Measurement

Accurate serum glucose levels are crucial to for the successful implementation of any intravenous insulin protocol. Timely and accurate glucose levels guide the dosing of insulin throughout the use of intravenous insulin impacting decisions on implementation, adjustment, and discontinuation. Hypoglycemia is the most feared adverse effect of intravenous insulin therapy, not only for its impact on neurologic function but also because of the association of hypoglycemia with increased mortality; warning signs of hypoglycemia are often difficult to appreciate in the critically ill patient.

The need for rapid testing in critically ill patients has spawned multiple bedside, point-of-care devices, and none is more pervasive in the ICU than the bedside glucometer.[8] Accuracy is reduced, with standards requiring only an agreement of ±20% with laboratory analysis. The glucometers are most accurate in hemodynamically stable patients with glucose readings in the normal range, but disagreement with laboratory readings are more pronounced with glucose readings at the high and low end of the spectrum (hyperglycemia and hypoglycemia) and in conditions of poor tissue perfusion (eg, critically ill patient subject to shock, peripheral edema, vasoconstriction).

In addition, fingerstick glucose measurements tend to be overestimated by the point-of-care devices, and the difference in glucose between capillary blood and venous blood can be as high as 70 mg/dL. Adjusting insulin infusions based on inaccurate glucose measurements may lead to errors in insulin dose on both ends of the spectrum, as well as a failure to detect hypoglycemia.[9, 10]

Factors affecting point-of-care blood glucose measurements include the following:[9]

  • Source of blood (serum, plasma, whole blood)
  • Sampling site (capillary blood, venous blood, arterial blood)
  • Amount of blood on glucometer strip
    • Excess blood (spurious high readings)
    • Insufficient blood (spurious low readings)
  • Anemia (spuriously high levels in whole blood assays)
  • Peripheral hypoperfusion (shock, vasoconstriction, vasospastic disorders, dehydration)
  • Delay in sample processing
  • Substances that interfere with glucose measurements
    • Levodopa
    • Dopamine
    • Mannitol
    • Acetaminophen
    • High unconjugated bilirubin
    • Severe lipemia
    • High uric acid
    • Maltose (found in immunoglobulin solutions)
    • Icodextrin (found in peritoneal dialysis fluid)
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Intravenous Insulin Protocol Selection

Multiple intensive insulin protocols have been developed to manage hyperglycemia; however, no singular protocol has been universally accepted. Significant similarities in strategy exist among the various protocols, and the differences relate to bolus amounts, infusion rates, and target glucose goals.[11] The complexity of these differences can be better appreciated in the summary of variations of protocols outlined below.

Areas of variation in insulin protocols are as follows:

  • Presence or absence of preexisting diabetes
  • Initial hyperglycemic threshold (>150-200 mg/dL)
  • Initial bolus insulin dose (calculated [formula] versus fixed [predetermined])
  • Subsequent bolus insulin
  • Change in insulin dose (calculated vs fixed dose)
    • Based on direction of change in glucose (decrease, no change, increase)
    • Velocity of change (30-50 mg/dL/h)
    • Dose adjustment for insulin resistance
    • Basis of change in insulin dose (rate, infusion)
    • Unit of change in insulin dose (fixed dose or calculated using a multiplier)
    • Number of steps required (1-3); some requiring calculations to change the dose (8 of 12)
  • Target glucose (80-180 mg/dL; with a wide range of acceptable values

Logistics of implementation are as follows:

  • Paper vs computerized vs web based protocols
  • Nurse-driven, with varying physician input
  • Adherence to protocol or allowance for changes in protocol ("protocol violations")
  • Differences in frequency of glucose monitoring
  • Differences in requirement of a constant glucose source (parenteral or enteral infusions)
  • Adjustments for hypoglycemia (variable levels of adjustment after hypoglycemia)
  • Average time to goal (variable; from 2-24 h)

Despite these differences, most protocols agree that hypoglycemia is associated with worse outcomes. The danger of both hyperglycemia and hypoglycemia is relate to the level and duration of the glucose abnormality. An ideal protocol would aim to reduce such glucose variability. Important considerations in the development of a protocol include allowing 6-8 hours to safely lower glucose to target, reducing the risk of hypoglycemia, and accounting for patient insulin sensitivity and resistance.

In 2006, the American College of Endocrinology and American Diabetes Association released a consensus statement on inpatient glycemic control.[7] They reiterated the impact of tight glycemic control on improved clinical outcomes. Although implementation of new protocols at institutions would create an increase in cost upfront, such an investment would reap long-term financial benefits by potentially reducing morbidity and patients’ length of stay. Quality and safety issues were addressed in light of the dangers of hypoglycemia; common errors include a lack of coordination between feeding and the administration of medications, insufficient blood glucose monitoring, unclear and unstandardized orders, and a failure to recognize changes in the underlying medical conditions that may alter changes in insulin requirements. Insulin protocols are expected to increase the incidence of hypoglycemia; however, the harm of hypoglycemia can be minimized if mild, transient, and rapidly diagnosed.

The success of an insulin protocol depends on many different variables. Various protocols have been developed and modified by different institutions, with the choice often based on elements that are especially suited to the institution. A specific protocol cannot be endorsed as implementation and the success of the protocol will depend on several factors including patient population, ease of use, expertise and experience of staff, infrastructure and medical resources. Each protocol has a learning curve, especially if staff members are not accustomed to the use of intravenous insulin infusions for glucose control. The protocols are labor intensive and require extra nursing time for implementation. Hourly glucose determinations are required initially; if only 5 minutes are devoted to each check, 12 adjustments to the infusion in a day translates into an extra hour of nursing time. Although experience with insulin infusions used to treat diabetic ketoacidosis will help the transition to these intravenousinsulin protocols, the need for close oversight cannot be overestimated. It is acknowledged that the need for bedside calculation of insulin dose adds to the potential for errors in dosing, especially when paper based protocols are used. Preprinted dosing charts and computerized protocols that eliminate the need for calcuation are available and may minimize this problem.

Two archetypal approaches are presented in more detail: the Georgia Hospital Association Protocol[12] , also referred to as the Davidson or Glucommander Protocol, and the Portland Protocol©.[13]

The Georgia Hospital Association Research and Education Foundation developed their own guidelines in 2002 for inpatient diabetes care throughout the state’s hospitals; this standardized approach to manage hyperglycemia has also been referred to as the Davidson or Glucommander Protocol, and authors of this protocol are also involved in the construct of the latest protocol. Although calculations are involved in determining insulin dose, the protocol has also been published in a columnar dosing form to eliminate the need for these calculations.

In 1992, the Providence Heart and Vascular Institute developed the Portland Protocol© from data extrapolated from diabetic patients who underwent cardiac surgery. It has undergone multiple modifications since its inception and takes into account many of the nuances previously identified. Both protocols are available from the respective websites and have been modified with glucose targets than are less stringent the previous 80-110 mg/dL and closer to the 140-180 mg/dL range. These changes should also reduce the incidence of hypoglycemia that was associated with earlier protocols.

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Georgia Hospital Association Intravenous Insulin Protocol

This has also been referred to as the Davidson or Glucommander Protocol. The intravenous infusion protocol is for a target of 140-180 mg/dL.

Initial orders are as follows:

  • Discontinue previous diabetes medications.
  • Obtain basic metabolic profile (repeat in 6 h and then daily)
  • Record intravenous fluid (ie, normal saline, dextrose 5% in 1/2 normal saline, dextrose 5% in 1/2 normal saline/20 meq K+). If the patient is NPO and is not receiving total parenteral nutrition or continuous enteral feedings and has a blood glucose level of less than 250 mg/dL, the intravenous fluid selected and the rate of infusion should have a glucose source of 5 g/h or more.

Intravenous insulin administration is as follows:

  • Mix 250 units of regular human insulin in 250 mL of normal saline (1 U/mL).
  • Flush approximately 30 mL through the line prior to administration.
  • Do not use a filter or filtered set with insulin.
  • Piggyback the insulin drip into intravenous fluid using an intravenous infusion pump with a capability of 0.1 mL/h.

Initiate the intravenous insulin flow sheet.

Blood glucose testing is as follows:

  • Check blood glucose levels initially and then every hour using a finger stick (hospital-certified meter).
  • Do not alternate sites without physician approval.
  • After hourly readings remain in the desired range for 4 consecutive readings, testing can be reduced to every 2 hours.
  • The laboratory must verify as soon as possible all blood glucose readings less than 40 or more than 500.

Determination of intravenous infusion rate is as follows (units of insulin per hour = blood glucose – 60 X multiplier):

  • Initiate drip by applying the current blood glucose and the multiplier 0.02 to the above formula.
  • When blood glucose is more than 110 mg/dL but has not dropped by at least 15%, increase the multiplier by 0.01.
  • When hourly blood glucose rates are 80-110 mg/dL, do not change the multiplier and adjust the rate according to the formula.
  • When the rate is less than 80 mg/dL, decrease multiplier by 0.01 to calculate new drip rate.

Treatment for hypoglycemia is as follows:

  • Decrease multiplier by 0.01 as stated above.
  • Administer D50W by intravenous push.
  • Recheck blood glucose levels in 15 minutes.
  • Resume hourly blood glucose monitoring and insulin drip adjustments.

Notify a physician if the following is observed:

  • Blood glucose level is less than 60 mg/dL for 2 consecutive measurements.
  • Blood glucose level reverts back to more than 200 mg/dL for 2 consecutive measurements.
  • Insulin requirements exceed 24 U/h.
  • The patient’s K+ level drops to less than 4.
  • Continuous enteral feedings, total parenteral nutrition, or intravenous insulin infusion is stopped or interrupted.

Transition to subcutaneous insulin is as follows:

  • Blood glucose levels should be within target range for at least 4 hours before intravenous insulin is discontinued.
  • Calculate total daily insulin (TDI). The formula is: Units of insulin for the last 2 hours of intravenous drip x 12 for patients on D5W.
  • Begin glargine is equal to 50% TDI (for pregnant patients, use neutral protamine Hagedorn twice daily).
  • Begin fast acting analog is equal to 50% of TDI divided by 3 (give 3 times a day immediately after meals).
  • Continue intravenous insulin infusion for 2 hours after initiation of subcutaneous therapy.
  • Refer to subcutaneous transition orders for administration times and dosage adjustments.
  • Refer the patient for diabetes education, nutritional services, and discharge planning to ensure the patient can afford the medications and supplies and has follow-up disease state management after discharge.
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The Portland Protocol

The latest protocol can be viewed on their Web site. The Portland Protocol©, which targets a blood glucose level of 125-175 mg/dL is summarized below.

The protocol is initiated on all ICU patients follows (place these orders on all ICU admission and postoperative order sets):

  • Initial blood glucose check upon admission and every 2 hours.
  • HbA1c measurement should be obtained if not obtained upon admission.
  • Start the Portland Protocol© for any blood glucose level of more than 150 mg/dl (including "nondiabetic" patients).

Mix 1 unit of regular human insulin per 1 ml of 0.9% normal saline and start IV infusion via pump as follows:

  • Blood glucose level 110-150 mg/dL
    • Intravenous regular insulin syringe bolus - 0 U/h
    • Noninsulin-dependent diabetes mellitus or no diabetes mellitus – None
    • Insulin-dependent diabetes mellitus – None
  • Blood glucose level 125-150 mg/dL
    • Intravenous regular insulin syringe bolus - 2 U/h (for patients with diabetes mellitus only)
    • Noninsulin-dependent diabetes mellitus or no diabetes mellitus – 1 U/h
    • Insulin-dependent diabetes mellitus – 2 U/h
    • Blood glucose level 151-180 mg/dL
    • Intravenous regular insulin syringe bolus - 4 U/h
    • Noninsulin-dependent diabetes mellitus or no diabetes mellitus – 2 U/h
    • Insulin-dependent diabetes mellitus – 3.5 U/h
  • Blood glucose level 181-240 mg/dL
    • Intravenous regular insulin syringe bolus - 6 U/h
    • Noninsulin-dependent diabetes mellitus or no diabetes mellitus – 3.5 U/h
    • Insulin-dependent diabetes mellitus – 5 U/h
  • Blood glucose level 241-300 mg/dL
    • Intravenous regular insulin syringe bolus - 8 U/h
    • Noninsulin-dependent diabetes mellitus or no diabetes mellitus – 5 U/h
    • Insulin-dependent diabetes mellitus – 6.5 U/h
  • Blood glucose level 301-360 mg/dL
    • Intravenous regular insulin syringe bolus - 12 U/h
    • Noninsulin-dependent diabetes mellitus or no diabetes mellitus – 6.5 U/h
    • Insulin-dependent diabetes mellitus – 8 U/h
  • Blood glucose level >360 mg/dL
    • Intravenous regular insulin syringe bolus - 16 U/h
    • Noninsulin-dependent diabetes mellitus or no diabetes mellitus – 8 U/h
    • Insulin-dependent diabetes mellitus – 10 U/h

General orders are as follows:

  • All intermittent (noncontinuous) intravenous medications should be mixed in normal saline.
  • Do not administer intermittent (noncontinuous) intravenous medications mixed in dextrose-containing solutions.
  • Do not use any dextrose-containing intravenous solutions for maintenance or daily fluids except when total parenteral nutrition is required.
  • If daily steroids are required administer as a continuous infusion over a 24 hours. Do not administer bolus intravenous steroids or oral steroids while on intravenous insulin protocol.

Protocol duration is as follows:

  • All diabetic patients and nondiabetic patients who remain hyperglycemic should continue on the protocol throughout their ICU stay.
  • Nondiabetic, euglycemic patients may stop protocol when the target range is maintained with less than 0.5 U/h. Check blood glucose levels every 2 hours (6 times) and then before meals, 2 hours after meals, and at bedtime for 24 hours. If all blood glucose levels remain less than 150 mg/dL, monitoring can be stopped; if any blood glucose levels are more than 150 mg/dL, resume the protocol.
  • If the need for insulin continues in patients without diabetes after transfer 3 days after surgery and admission HgbA1c level is greater than 6%, ask the physician to consult with an endocrinologist for diabetes workup and further follow-up orders.

Transition to floor (ward) from ICU is as follows:

  • All hyperglycemic patients - Within 3 days of operation or ICU admission or those eating less than 50% of a regular diet
  • Nondiabetic patients - Need for insulin after transfer 3 days postoperative and admission HgbA1c is greater than 6% (diabetes workup)

Protocol cessation permissible only on transfer is indicated in the following:

  • Diabetic patients more than 3 days since last operation or ICU admission and eating more than 50% of a regular diet.
    • If admission HgbA1c is less than 6.5%: Restart preadmission glycemic control meds at 7 am on day of transfer and stop intravenous insulin infusion at 9 am prior to transfer
    • If admission HgbA1c is more than 6.5%: Consider additional basal-prandial subcutaneous insulin therapy. Initiate Portland Basal-Prandial SQ Insulin Transition Protocol©.
  • Continue to monitor blood glucose before meals, 2 hours after meals, and at bedtime throughout rest of hospital stay.
  • Nondiabetic euglycemic patients may stop the protocol if they meet criteria outlined above.
  • Nondiabetic patients who remain hyperglycemic beyond the postoperative day 3 have no need to continue protocol upon transfer. However, endocrinology consultation should be requested by a physician.

Test blood glucose by finger stick, arterial, or venous line drop samples. Frequency of testing is as follows:

  • Check blood glucose every 30 minutes when blood glucose is more than 200 mg/dL or less than 100 mg/dL; after drip is stopped or decreased more than 50%; after bolus intravenous insulin dose is given; or when rapidly titrating vasopressors (eg, epinephrine, norepinephrine).
  • Check blood glucose every hour when levels are 100-200 mg/dL.
  • Check blood glucose every two hours when levels are 125-175 mg/dL and blood glucose varies less than 15 mg/dL over 4 hours and the insulin rate remains unchanged for 4 hours. Note: If any change in blood glucose more than 15mg/dL occurs or any change in insulin rate more than 0.5 units occurs, return to checking blood glucose every hour.
  • During initiation of, rate change of, or cessation of any nutritional support or renal correction therapy, check blood glucose every 30 minutes (4 times).
    • Nutritional support (enteral or parenteral) includes tube feedings, total parenteral nutrition, and partial parenteral nutrition.
    • Renal correction therapy includes renal dialysis, continuous venovenous hemofiltration, continuous venovenous hemodialysis, and peritoneal dialysis.

The Portland Protocol Titration Guidelines© are listed below. Insulin infusion may be titrated between 0-30 U/H using these guidelines to rapidly (within 3 h) achieve and maintain blood glucose in the target range (125-175 mg/dL). Round insulin infusion to the nearest tenth of a unit (0.1 U) when necessary.

If blood glucose level is less than 40 mg/dL or more than 450 mg/dL, obtain confirmatory laboratory blood glucose level.

  • Blood glucose level - 70 mg/dL
    • If not alert or nothing by mouth, administer 15 mL of D50W intravenously; if blood glucose is less than 40 mg/dL, administer 25 mL of D50W intravenously.
    • If alert and able to take by mouth, give 8 oz of juice or 6 glucose tablets orally.
    • Recheck blood glucose levels every 30 minutes until more than 100 mg/dL.
    • If the next blood glucose level is less than 60 mg/dL, double the amount of the previous treatment.
    • If the next blood glucose level is 60-70 mg/dL, repeat the treatment.
    • When blood glucose is more than 125 mg/dL, restart insulin rate at 50% of previous rate and recheck blood glucose in 30 minutes.
  • Blood glucose level - 70-100 mg/dL
    • If previous blood glucose level is more than 120 mg/dL or if symptomatic from hypoglycemia and the patient is not receiving anything orally, give 15 mL of D50W intravenously; if the patient is able, administer 4-6 oz of juice or 3 glucose tablets orally.
    • Recheck blood glucose levels ever 30 minutes until it is more than 100 mg/dL.
    • If the next blood glucose measurement is 70-99 mg/dL, repeat previous treatment.
    • When the blood glucose level is more than 125 mg/dL, restart the insulin rate at 50% of the previous rate and recheck the blood glucose level in 30 minutes.
  • Blood glucose level - 101-124 mg/dL
    • If greater than the last test result, decrease rate by 0.3 U/h.
    • If lower than the last test result, stop drip and recheck blood glucose in 30 minutes. If the infusion is turned off, recheck blood glucose in 30 minutes. When blood glucose is more than 125 mg/dL, restart at 50% of previous rate and recheck the blood glucose level in 30 minutes.
    • If lower than last result by 15-30 mg/dL, decrease the rate by half (50%) and recheck blood glucose in 30 minutes.

o If equal to the last result or lower than the last result by less than 7 mg/dL, decrease the rate by 0.3 U/h.

  • Recheck the blood glucose every 30 minutes until more than 100 mg/dL.
    • Blood glucose level - 125-175 mg/dL
    • If higher than the last blood glucose level by more than 10 mg/dL, increase rate by 0.5 U/h
    • If lower than the last blood glucose level by more than 40 mg/dL, stop drip and recheck the blood glucose level again in 30 minutes. If the infusion is turned off, recheck the blood glucose in 30 minutes; when the blood glucose is more than 150 mg/dL, restart at 50% of previous rate.
    • If lower than the last blood glucose level by 21-40 mg/dL, decrease rate by half (50%) and recheck blood glucose levels in 30 minutes.
    • If lower than the last blood glucose level by 10-20 mg/dL, decrease rate by 0.5 U/h.
    • If within 10 mg/dL of last blood glucose level, remain at the same rate the blood glucose has consistently decreased each of last 4 measurements. Then, decrease rate by 0.3 U/h.
    • If the blood glucose has consistently increased each of last 4 measurements, increase rate by 0.2 U/h.
  • Blood glucose level - 176-200 mg/dL
    • If higher than the last blood glucose level by more than 50 mg/dL, increase rate by 2 U/h.
    • If higher than the last blood glucose level by 20-50 mg/dL, increase rate by 1 U/h.
    • If higher than the last blood glucose level by 0-20 mg/dL, increase rate by 0.5 U/h.
    • If lower than the last blood glucose level by 1-20 mg/dL, remain at the same rate.
    • If lower than the last blood glucose level by 21-40 mg/dL, decrease rate by 1 U/h.
    • If lower than the last blood glucose level by 41-60 mg/dL, decrease rate by half and recheck in 30 minutes
    • If lower than the last blood glucose level by more than 60 mg/dL, stop drip and recheck blood glucose in 30 minutes. If the infusion is turned off, recheck the blood glucose in 30 min. When the blood glucose is more than 175 mg/dL, restart at 50% of previous rate.
  • Blood glucose level – 201-225 mg/dL
    • If lower than the last blood glucose level by more than 30 mg/dL, increase rate by 2 U/h and bolus with 4 U intravenously.
    • If higher than the last blood glucose level by 0-30 mg/dL, increase rate by 1 U/h and bolus with 3 U intravenously.
    • If lower than the last blood glucose level by 1-20, increase rate by 1 U/h and bolus with 2 U intravenously.
    • If lower than the last blood glucose level by 21-50 mg/dL, remain at the same rate.
    • If lower than the last blood glucose level by 51-80 mg/dL, decrease rate by half (50%) and recheck blood glucose levels in 30 minutes.
    • If lower than the last blood glucose level by more than 80 mg/dL: Stop drip and recheck blood glucose level in 30 minutes . If the infusion is turned off, recheck the blood glucose level in 30 minutes; when BG is more than 175 mg/dL, restart at 50% of previous rate.
    • Recheck blood glucose levels in 30 minutes. Repeat every 30 minutes until less than 200 mg/dL.
  • Blood glucose level – 226-250 mg/dL
    • If lower than the last blood glucose level by more than 80 mg/dL, decrease rate by half (50%).
    • If lower than the last blood glucose level by 30 –80 mg/dL, continue same rate.
    • If lower than the last blood glucose level by 0-30 mg/dL, increase the insulin rate by 1 U/h and bolus with 2 intravenous units.
    • If higher than the last blood glucose level by 1-20 mg/dL, increase the insulin rate by 2 U/h and bolus with 4 intravenous units.
    • If higher than the last blood glucose level by more than 20 mg/dL, increase the insulin rate by 3 U/h and bolus 6 intravenous units; recheck blood glucose level in 30 minutes.
    • Repeat blood glucose testing every 30 minutes until less than 200 mg/dL.
  • Blood glucose level – 250-300 mg/dL
    • If lower than the last blood glucose level by more than 100 mg/dL, decrease rate by half (50%).
    • If lower than the last blood glucose level by 50-100 mg/dL, continue same rate.
    • If lower than the last blood glucose level by less than 50 mg/dL or higher than the last blood glucose level, bolus with 6 U of regular insulin intravenously and increase the insulin rate by 2 U/h.
    • If the blood glucose remains higher than 250 mg/dL and has not decreased after 3 consecutive increases in insulin, administer double the previous intravenous bolus dose up to a maximum of 24 U double the insulin drip rate up to a maximum of 20 U/h. If on 20 U/h and no response is seen after 4 maximum boluses, call physician for further orders
    • Recheck blood glucose level in 30 minutes and repeat every 30 minutes until less than 200 mg/dL.
  • Blood glucose level >300 mg/dL
    • If lower than the last blood glucose level by more than 150 mg/dL, decrease the rate by half (50%)
    • If lower than the last blood glucose level by 101-150 mg/dl, keep the same rate.
    • If lower than the last blood glucose level by 0-100 mg/dL or higher than the last blood glucose level, with 10 Units of regular insulin intravenously and double the insulin rate up to a maximum of 30 U/h.
    • If the blood glucose level remains greater than 300 mg/dL and has not decreased after 3 consecutive increases in insulin administer double the previous intravenous bolus dose up to a maximum of 40 U and double the insulin drip rate up to a maximum of 30 U/h.
    • If on 30 units/hour and no response after 4 maximum boluses, call physician for further orders.

o Recheck the blood glucose level in 30 minutes. Repeat blood glucose monitoring every 30 minutes until it is less than 200 mg/dL.

o If the level is more than 300 mg/dL for more than 4 consecutive readings, call the physician for additional intravenous bolus orders.

The Portland Meal Orders and Adjunctive Periprandial Subcutaneous Dosing Schedules are listed below. The ICU target blood glucose level is 125-175 mg/dL. The 1800 American Diabetes Association Diabetic Diet starts with any oral intake. When the diet is advanced, begin with full liquids or sugar-free clear liquids and advance as tolerated. Patient may take oral or enternal nutrition at any time in conjunction with this protocol. Prandial subcutaneous rapid-acting insulin analogue (Humalog/Novolog/Apidra) is administered in addition to insulin infusion at meal times. For the patient’s first meal, administer subcutaneous rapid-acting insulin analogue immediately after the meal, according to the dosing schedule in the table below.

Table 1. Subcutaneous Rapid-acting Insulin Analogue Dosing. (Open Table in a new window)

Insulin Infusion Drip Rate at First Meal Eats >50% of Meal Eats 25-50% of Meal Snacks or Eats < 25% of meal Row
0-1.9 U/h 4 U 2 U 1 U 1
2-3.9 U/h 6 U 3 U 2 U 2
4-5.9 U/h 8 U 4 U 3 U 3
6-7.9 U/h 10 U 5 U 4 U 4
8-10 U/h 12 U 6 U 5 U 5
More than 10 U/h 14 U 7 U 6 U  

Chart the row number used from the above dosing schedule from the initial meal. Continue protocol blood glucose level frequency monitoring and treatment as noted in the intravenous portion of this protocol. For all subsequent meals and periprandial subcutaneous rapid-acting insulin analogue doses and titration, use the table below. Note: Ignore the insulin intravenous insulin infusion rate after the first periprandial dose calculation and adjust all further doses using row number references. If the patient is consistently eating entire meal tray, administer subcutaneous rapid-acting insulin analogue when the tray arrives at bedside. If uncertain of oral intake, then administer subcutaneous rapid-acting insulin analogue immediately after the meal.

Based on a postprandial blood glucose level reading obtained approximately 2 hours after subcutaneous rapid-acting insulin analogue was given, and using the initial row number as the first baseline row, titrate (adjust) the subcutaneous dosing schedule row number for the next meal as follows:

  • If the 2 hour postprandial blood glucose level is more than 200 mg/dL, increase insulin schedule for the next meal by 2 rows.
  • If the 2 hour postprandial blood glucose level is 176-200 mg/dl, increase insulin schedule for the next meal by one row.
  • If the 2 hour postprandial blood glucose level is 125-175 mg/dl, then repeat this dosing schedule with the next meal .
  • If the 2 hour postprandial blood glucose level is 100-124 mg/dL, then decrease the insulin schedule for the next meal by one row.
  • If the 2 hour postprandial blood glucose level is less than 100 mg/dl, then decrease the insulin schedule for the next meal by two rows.

Table 2. Subsequent Meals and Periprandial Subcutaneous Rapid-Acting Insulin Analogue Doses and Titration. (Open Table in a new window)

Row Eats >50% of Meal Eats 25-50% of Meal Snacks or Eats < 25% of meal
1 4 U 2 U 1 U
2 6 U 3 U 2 U
3 8 U 4 U 2 U
4 10 U 5 U 3 U
5 12 U 6 U 3 U
6 14 U 7 U 4 U
7 16 U 8 U 4 U
8 18 U 9 U 5 U
9 20 U 10 U 5 U
10 22 U 11 U 6 U
11 24 U 12 U 6 U
12 26 U 13 U 7 U

With each meal chart, the actual row number is used for subcutaneous periprandial dosing. This previous meal row number becomes the new baseline row number from which the next meal-related periprandial dose of subcutaneous analogue will again be adjusted according to the titration schedule. Continue to titrate each subsequent meal-related subcutaneous dose of insulin analogue according to the titration schedule, using the row number actually used from the previous (immediately preceding) meal as the baseline row number.

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Other Insulin Protocols

Numerous other intravenous insulin protocols have been successfully implemented and are in use. More than 20 different protocols are known, representing variations of that core group.[14] As may be expected, they vary in complexity and instructions. A repository of many of these protocols are available for review as part of the Society of Hospital Medicine Web site which includes both published (peer-reviewed) and unpublished protocols. In addition, the reader should also be aware that their are computerized intravenous insulin progams available for purchase. These can be integrated into the electronic health record system and/or order entry menu, therefore eliminating the need for paper or printed protocols. Experience with this approach has been favorable, but limited. Available programs include The Glucommander PlusTM program[15] , GlucoStabilizerTM program,[16] and the EndoTool® program.[17]

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Summary

Hyperglycemia often complicates the management of critically ill patients. Control of hyperglycemia leads to improve outcomes in many conditions. Hyperglycemia may be difficult to control with intermittent subcutaneous insulin and intravenous insulin infusions can provide more efficient control of hyperglycemia and may be the preferred management method is certain conditions, such as postcardiac surgery. The institution of continuous intravenous insulin infusions for control of hyperglycemia must be carefully assessed because it represents a large institutional committment by multiple disciplines, especially nursing. Likewise, patient demographics and goals of hyperglycemia may also influence the choice of an intravenous insulin protocol.

Nursing input and acceptance are especially important in the success of an insulin protocol. The need for and complexity of bedside calculation of insulin doses may sway the choice between printed protocols to those with columnar schedules (no calculation required) or to computerized protocols where calculations are performed automatically as part of the program. No one protocol fits all patients, and some institutions are better served with more than one protocol.

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Contributor Information and Disclosures
Author

Guy W Soo Hoo, MD, MPH Clinical Professor of Medicine, University of California, Los Angeles, David Geffen School of Medicine; Director, Medical Intensive Care Unit, Pulmonary and Critical Care Section, West Los Angeles Healthcare Center, Veteran Affairs Greater Los Angeles Healthcare System

Guy W Soo Hoo, MD, MPH is a member of the following medical societies: American College of Chest Physicians, American College of Physicians, American Thoracic Society, Society of Critical Care Medicine, California Thoracic Society, American Association for Respiratory Care

Disclosure: Nothing to disclose.

Coauthor(s)

Jasper Ip, MD, MPH, MS Fellow in Pulmonary and Critical Care Medicine, Cedars Sinai Medical Center

Jasper Ip, MD, MPH, MS is a member of the following medical societies: American College of Physicians, American Medical Association, American Thoracic Society

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Chief Editor

George T Griffing, MD Professor Emeritus of Medicine, St Louis University School of Medicine

George T Griffing, MD is a member of the following medical societies: American Association for the Advancement of Science, International Society for Clinical Densitometry, Southern Society for Clinical Investigation, American College of Medical Practice Executives, American Association for Physician Leadership, American College of Physicians, American Diabetes Association, American Federation for Medical Research, American Heart Association, Central Society for Clinical and Translational Research, Endocrine Society

Disclosure: Nothing to disclose.

References
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  2. van den Berghe G, Wouters P, Weekers F, Verwaest C, Bruyninckx F, Schetz M, et al. Intensive insulin therapy in the critically ill patients. N Engl J Med. 2001 Nov 8. 345(19):1359-67. [Medline].

  3. Van den Berghe G, Wilmer A, Hermans G, Meersseman W, Wouters PJ, Milants I, et al. Intensive insulin therapy in the medical ICU. N Engl J Med. 2006 Feb 2. 354(5):449-61. [Medline].

  4. Finfer S, Chittock DR, Su SY, Blair D, Foster D, Dhingra V, et al. Intensive versus conventional glucose control in critically ill patients. N Engl J Med. 2009 Mar 26. 360(13):1283-97. [Medline].

  5. Furnary AP, Gao G, Grunkemeier GL, Wu Y, Zerr KJ, Bookin SO. Continuous insulin infusion reduces mortality in patients with diabetes undergoing coronary artery bypass grafting. J Thorac Cardiovasc Surg. 2003 May. 125(5):1007-21. [Medline].

  6. Lazar HL, McDonnell M, Chipkin SR, Furnary AP, Engelman RM, Sadhu AR. The Society of Thoracic Surgeons practice guideline series: Blood glucose management during adult cardiac surgery. Ann Thorac Surg. 2009 Feb. 87(2):663-9. [Medline].

  7. American College of Endocrinology and American Diabetes Association Consensus statement on inpatient diabetes and glycemic control. Diabetes Care. 2006 Aug. 29(8):1955-62. [Medline].

  8. Louie RF, Tang Z, Sutton DV, Lee JH, Kost GJ. Point-of-care glucose testing: effects of critical care variables, influence of reference instruments, and a modular glucose meter design. Arch Pathol Lab Med. 2000 Feb. 124(2):257-66. [Medline].

  9. Fahy BG, Coursin DB. Critical glucose control: the devil is in the details. Mayo Clin Proc. 2008 Apr. 83(4):394-7. [Medline].

  10. Fahy BG, Sheehy AM, Coursin DB. Glucose control in the intensive care unit. Crit Care Med. 2009 May. 37(5):1769-76. [Medline].

  11. Wilson M, Weinreb J, Hoo GW. Intensive insulin therapy in critical care: a review of 12 protocols. Diabetes Care. 2007 Apr. 30(4):1005-11. [Medline].

  12. Osburne RC, Cook CB, Stockton L, Baird M, Harmon V, Keddo A. Improving hyperglycemia management in the intensive care unit: preliminary report of a nurse-driven quality improvement project using a redesigned insulin infusion algorithm. Diabetes Educ. 2006 May-Jun. 32(3):394-403. [Medline].

  13. Furnary AP, Wu Y. Clinical effects of hyperglycemia in the cardiac surgery population: the Portland Diabetic Project. Endocr Pract. 2006 Jul-Aug. 12 Suppl 3:22-6. [Medline].

  14. Krikorian A, Ismail-Beigi F, Moghissi ES. Comparisons of different insulin infusion protocols: a review of recent literature. Curr Opin Clin Nutr Metab Care. 2010 Mar. 13(2):198-204. [Medline].

  15. Davidson PC, Steed RD, Bode BW. Glucommander: a computer-directed intravenous insulin system shown to be safe, simple, and effective in 120,618 h of operation. Diabetes Care. 2005 Oct. 28(10):2418-23. [Medline].

  16. Juneja R, Roudebush CP, Nasraway SA, Golas AA, Jacobi J, Carroll J. Computerized intensive insulin dosing can mitigate hypoglycemia and achieve tight glycemic control when glucose measurement is performed frequently and on time. Crit Care. 2009. 13(5):R163. [Medline].

  17. Saager L, Collins GL, Burnside B, Tymkew H, Zhang L, Jacobsohn E. A randomized study in diabetic patients undergoing cardiac surgery comparing computer-guided glucose management with a standard sliding scale protocol. J Cardiothorac Vasc Anesth. 2008 Jun. 22(3):377-82. [Medline].

  18. Wernerman J, Desaive T, Finfer S, Foubert L, Furnary A, Holzinger U, et al. Continuous glucose control in the ICU: report of a 2013 round table meeting. Crit Care. 2014 Jun 13. 18 (3):226. [Medline]. [Full Text].

  19. Gomez AM, Umpierrez GE. Continuous glucose monitoring in insulin-treated patients in non-ICU settings. J Diabetes Sci Technol. 2014 Sep. 8 (5):930-6. [Medline]. [Full Text].

  20. Boom DT, Sechterberger MK, Rijkenberg S, Kreder S, Bosman RJ, Wester JP, et al. Insulin treatment guided by subcutaneous continuous glucose monitoring compared to frequent point-of-care measurement in critically ill patients: a randomized controlled trial. Crit Care. 2014 Aug 20. 18 (4):453. [Medline]. [Full Text].

 
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Table 1. Subcutaneous Rapid-acting Insulin Analogue Dosing.
Insulin Infusion Drip Rate at First Meal Eats >50% of Meal Eats 25-50% of Meal Snacks or Eats < 25% of meal Row
0-1.9 U/h 4 U 2 U 1 U 1
2-3.9 U/h 6 U 3 U 2 U 2
4-5.9 U/h 8 U 4 U 3 U 3
6-7.9 U/h 10 U 5 U 4 U 4
8-10 U/h 12 U 6 U 5 U 5
More than 10 U/h 14 U 7 U 6 U  
Table 2. Subsequent Meals and Periprandial Subcutaneous Rapid-Acting Insulin Analogue Doses and Titration.
Row Eats >50% of Meal Eats 25-50% of Meal Snacks or Eats < 25% of meal
1 4 U 2 U 1 U
2 6 U 3 U 2 U
3 8 U 4 U 2 U
4 10 U 5 U 3 U
5 12 U 6 U 3 U
6 14 U 7 U 4 U
7 16 U 8 U 4 U
8 18 U 9 U 5 U
9 20 U 10 U 5 U
10 22 U 11 U 6 U
11 24 U 12 U 6 U
12 26 U 13 U 7 U
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