Hospital Medicine

Glycemic control of the hospitalized patient

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I. What every physician needs to know.

A growing number of hospitalized patients have issues with glucose regulation. Though a significant portion have been diagnosed with diabetes, patients without a diagnosis of diabetes and increasingly the undiagnosed or 'new onset' diabetics, are frequently encountered in today's hospitalized patient.

The epidemic of obesity has contributed significantly to the rising population of diabetic patients, and lack of access to primary care increases the likelihood of long-term complications of this disease. Often referred to as "Type 2 Diabetes", "Type 1 Diabetes", "adult-onset diabetes", "glucose intolerance", "pre-diabetes", "impaired fasting glucose", or "stress induced hyperglycemia", abnormalities in glucose homeostasis represent a significant challenge for management in both the inpatient and outpatient settings, and transitions in between.

This chapter will attempt to explain the common glucose management strategies for management of the hospitalized patient.

II. Diagnostic Confirmation: Are you sure your patient has diabetes?

The diagnosis of abnormal glucose regulation is not difficult in the outpatient setting, however, exact clinical criteria are lacking for acutely ill inpatients. A body under stress is subjected to intense hormonal and counterregulatory pressures (glucagon, catecholamines, cytokines) which alter glucose homeostasis. A glycosylated hemoglobin (hemoglobin A1C) is more often being used as a marker for diagnosis of diabetes as an outpatient and may indicate if a hospitalized patient will have problems with glucose regulation.

A hemoglobin A1C greater than, or equal to, 6.5% is a good indication that the patient has diabetes; some patients can have impaired glucose tolerance before reaching this level.

The patient who demonstrates a fasting blood glucose level of 126 millgrams/deciliter (mg/dL) or above and a glucose level over 200 mg/dL two hours after a 75 gram (g) glucose challenge would, in the outpatient setting, be considered to have diabetes. A medically ill patient, on the other hand, will likely have a significantly impaired glucose tolerance that may change or revert to normal once no longer ill, thus follow-up monitoring and testing would be appropriate before the label of diabetes is given to a hospitalized inpatient.

For practical purposes, any patient with a blood glucose of over 200 mg/dL during their hospitalization but without overt diabetes (hemoglobin A1C ≥ 6.5%) would be labeled as impaired glucose tolerance.

A. History Part I: Pattern Recognition:

A typical patient with impaired glucose tolerance or a new diabetic may not have any particular abnormalities on history that would lead to the diagnosis. Uncontrolled or undiagnosed diabetics, however, often present with a variety of abnormal findings including dehydration, polyuria, multiple infections, neuropathy and visual changes, abdominal pain, and possibly ketosis in the case of diabetic ketoacidosis or hyperosmolar hyperglycemic state.

Those patients who may have inflammatory bowel disease history or a history of chronic obstructive pulmonary disease (COPD) may have cushingoid features (moon facies, abdominal striae) that may indicate prolonged exposure to high dose steroids. History may reveal polyuria, polydipsia, polyphagia, visual changes. The patient may have had a history of diabetes with pregnancy or may be currently pregnant. Any patient who is thought to have had a seizure or stroke should be evaluated for abnormal blood glucose levels.

A young thin person who is disoriented, stuporous, dehydrated, and breathing with a deep, gasping character ("Kussmaul respirations") may be in extreme diabetic ketoacidosis. An older person with high blood glucose and no acidosis may have hyperosmolar hyperglycemic state.

B. History Part 2: Prevalence:

Diabetes affects persons of all ages and races and arises from abnormalities of either decreased insulin production (Type 1) or decreased insulin sensitivity (Type 2). Type 1 diabetes is usually diagnosed in children to young adults, and Type 2 is usually later onset, though persons of any age can develop Type 2 diabetes. There may exist an overlap type of diabetes (Diabetes 1.5) which has features of both Type 1 and Type 2.

D. Physical Examination Findings.

Below are exam findings that can be seen in diabetics, though many patients may have none of these findings. When present, however, the clinician should have increased suspicion for diabetes:

  • Profound dehydration

  • Kussmaul respiration

  • Necrobiosis Lipoidica Diabeticorum

  • Acanthosis nigricans

  • Diabetic dermopathy

  • Related ulcers

  • Eruptive xanthomas

  • Vitiligo

  • Psoriasis

  • Abdominal striae and moon facies

  • Obesity

E. What diagnostic tests should be performed?

For the previously controlled diabetic:

  • A basic chemistry evaluation including sodium, potassium, bicarbonate level, blood urea nitrogen (BUN) and creatinine.

  • An A1C if a prolonged hospital stay is expected and not done in the past 3-6 months.

  • Routine blood glucose evaluation:

    • at least every 6 hours for floor patients who are nil per os (NPO/nothing by mouth) or on continuous infusion of glucose substrate with difficult to control blood sugars

    • before meals and bedtime if those who are eating and relatively well controlled

    • twice daily to intermittent for those patients who have few excursions from target range or who are receiving little to no treatment for their glucose levels

In uncontrolled or new onset diabetes:

  • Routine blood glucose evaluation (at least every 1 hour for patients on intravenous (IV insulin), less frequent for subcutaneous insulins).

  • Urinalysis (UA) (to evaluate for infection, glycosuria, ketones, protein).

  • Serum ketones if suspicion for diabetic ketoacidosis.

  • Serum osmolarity (usually exceeding 350 milliosmoles/kilogram [mosm/kg]) for hyperosmolar hyperglycemic state.

  • Arterial blood gas.

  • Infectious Work-up (UA, chest x-ray, etc) if the patient is newly diagnosed, difficult to control, or in ketoacidosis to exclude infection.

  • Pregnancy test for females of childbearing status.

  • Hemoglobin A1C.

  • Cardiac enzymes and electrocardiogram (EKG) if chest pain is present or if nonspecific complaints of nausea/vomiting are present in uncontrolled or undiagnosed diabetic patients.

1. What laboratory studies (if any) should be ordered to help establish the diagnosis? How should the results be interpreted?

Initial evaluation

  • Point of care (POC) glucose measurements or a measurement taken as part of routine chemistry evaluation should be used to indicate impaired glucose tolerance.

  • A Hemoglobin A1C should be obtained to determine chronicity of elevation of blood sugar if not done in the past 3 months, and to determine initial level of aggressiveness by which to start/adjust insulin dosing.

Ongoing evaluation

  • Eating or bolus feeding: preprandial, fasting, and 2 hour post prandial blood sugars can be performed on patients who are eating or receiving scheduled bolus of carbohydrates. Routinely however, only preprandial and night time blood sugars are evaluated. For safety, a blood sugar check should occur right before any insulin is given.

  • NPO: For patients who are NPO or are on tube feeding on a continuous basis, every 6 hours is routine for POC blood sugar checks.

  • Post op: To meet early morning goals of blood sugar control, a 2AM POC glucose check is often performed. It is the opinion of this author that these evaluations should only be done if there is concern for nighttime hypoglycemia, as otherwise careful titration of insulin dosing should eliminate any AM hyperglycemia that would otherwise occur. If done, it should not be relied upon as a means to simply obtain a goal, but more to recognize that further refinement of the insulin regimen is needed. Any intervention at 2AM to lower the AM blood glucose warrants re-evaluation of the patient's overall insulin regimen.

  • Insulin drips: Most protocols for insulin drips (IV insulin) require close monitoring of blood sugars for safety, at intervals usually no less than every 1 hour for patients in diabetic ketoacidosis or requiring intensive lowering of blood sugars.

2. What imaging studies (if any) should be ordered to help establish the diagnosis? How should the results be interpreted?

An infectious work-up is recommended for any patient who is newly diagnosed, difficult to control, or in ketoacidosis to exclude infection. Imaging should be guided by symptoms, history and physical and may include chest x-rays, computed tomography (CT) scans, or other imaging depending on the clinical scenario.

F. Over-utilized or “wasted” diagnostic tests associated with this diagnosis.

Hemoglobin A1c measurements for those patients who have this information otherwise readily available (outpatient labs, etc) or those who have had one performed within the last 3 months without significant alteration of therapy likely do not need repeated testing.

III. Default Management.

  • Check and record the patients' weight (in kg) and body mass index (BMI.)

  • Review outpatient regimen, prior control and on which agents (oral, subcutaneous [SC], diet only, etc).

  • If patient is transferring from another unit, estimate based on total insulin administered over the past 24 hours, or extrapolate from the last 6 hours of IV insulin (if stable on that regimen).

    • Typically, when converting from IV to a SC regimen, the average infusion rate for the past 6 hours is used to determine a patient's approximate 24-hour needs. This number is then adjusted down 20% for safety to determine an equivalent SC regimen.

  • Review outpatient labs (if applicable) for renal function, prior A1C readings, outside lab reports.

  • Discontinue use of all oral agents for all inpatients. Many patients who may not have any particular contraindication to oral agents may develop these contraindications while hospitalized.

  • Engage hypoglycemic protocols (per institutional policies), for all diabetics, regardless of whether insulin administration is planned.

  • Establish treatment goals and target range desired (American Diabetic Association [ADA] 2016):

    • Critically ill patients: 140-180 mg/dl

    • Non-critically ill patients: Pre-meal < 140 mg/dl, random < 180 mg/dl

  • Determine the patients level of illness and stress based on clinical acumen (low, medium, high).

  • Review, then anticipate the nutritional needs of patients (were they NPO and now beginning to eat regularly [>50% of their carbs] or will they continue to be NPO).

  • Establishing a diet of consistent carbohydrates is helpful (for patients who are eating) so that there is predictable and consistent intake regimen that can be matched to an insulin regimen.

  • Determine if, and how much, insulin will be used to control glucose excursions while hospitalized:

    • Small patients with low BMI with little stress may need no additional insulin, especially if not eating, if they have low BMI, if they are failing to thrive or if they have never been exposed to insulin.

      • New diagnosed Type 2 diabetics or those who are well controlled on oral medications as outpatients with little confounding metabolic issues can be initially monitored on correction insulin alone. Once their insulin needs are known and if they require over 20 units/day, however, conversion to a fixed+correction regimen is recommended. Often, oral medications have a period of washout so an initial aggressive strategy may not be warranted.

      • All Type 1 diabetics and Type 2 diabetics who have been on insulin for over 5 years need a basal insulin at all times.

      • NPO patients will not need prandial doses but all other needs will need to be calculated.

    • Patients presenting with hypoglycemia symptoms on an outpatient regimen likely should not be started on basal insulins until the cause of hypoglycemia is known and corrected.

    • If the patient has ongoing or expected periods of extremely uncontrolled blood glucose, consider initiation or continuation of IV insulin therapy until stable, particularly if the patient has diabetic ketoacidosis or hyperglycemia hyperosmolar state.

A patient's total insulin needs are usually expressed as a TDD (Total Daily Dose), which includes the following components:

Total Daily Dose (TDD) = Basal + Prandial + Stress + Infusions + Correction

If a patient has never been hospitalized or is not on an outpatient insulin regimen for which inpatient estimations can be made, it is possible to estimate, based on weight, a initial strategy for insulin administration.

Most patients can be classified into a low start, medium start, or high start category to determine the initial insulin strategy that will be utilized:

  • Those with low stress, low weight, good prior control and no prior insulin exposure will start in a low range, if any supplemental insulin is used at all. Again, determine targets as set above and if the patient is already within this goal, they may be managed INITIALLY with correction alone.

  • Those patients with medium to high stress, high BMI, large dose insulin needs and/or exposure to insulin in the past will start medium to high.

  • Those patients for which there is no record or availability of the prior insulin use, a total daily dose can be calculated as follows:

    • For a low start category, TDD can be calculated as: TDD = 0.3 units/kg/day (u/kg/day)

    • For a medium start category, TDD can be calculated as: TDD = 0.5 u/kg/day

    • For a high start category, TDD can be calculated as: TDD = 0.7 u/kg/day

The above equation will result in a number that should establish an approximate total amount of insulin to be given to a patient in a 24 hour period.

This calculated TDD should subsequently be divided in half, with one half becoming the basal infusion need and the remainder distributed equally between 3 prandial doses if the patient is expected to eat. Stress and infusion management will be covered separately.

(For example: a 100 kg patient, medium start, will require approximately 100 kg x 0.5 u/kg/day = 50 units total daily dose. The basal will be 25 u, and with each meal 8 u will be given.)

This should roughly estimate the starting needs of a patient admitted to the hospital. A correctional dose (often called a sliding scale though this term is falling out of favor) should be used to add or remove insulin units to the prandial dose in order to correct for excursions outside of the previously discussed treatment goals.

Use of sliding scale alone as a method to control a diabetic patient, especially one who is known to be uncontrolled or have significant daily insulin needs as an outpatient, is strongly discouraged and usually results in wide swings in glucose levels. Type 1 diabetics treated with this method alone will become ketotic rapidly so this practice should be avoided.

After initiating a starting regimen, frequent and careful review of the patient's trends are necessary to make subsequent adjustments in the patients insulin needs. Any utilization of the correction scale should indicate that insulin needs were not accurately predicted and those extra insulin doses should be used to adjust subsequent insulin needs.

For the purposes of the above illustration, a basal insulin would be one that does not peak (glargine, etc), whereas correction and prandial insulins will be one of short action and onset (glulisine, aspart, lispro, etc).

B. Step 1: Adjusting the Basal

The patient will receive the initial doses of basal and bolus insulins according to the above equation. Because each patient will have different levels of insulin resistance, stress and infusional needs, continual and ongoing adjustment is essential to maintaining glucose control.

Basal insulin is used primarily to control the intrinsic production of glucose. This amount is usually in a ratio relative to weight. A good rule of thumb is that the basal need approximates 10% of the patient's body weight in pounds. This calculation also closely approximates, though in less steps, the calculated equivalent in the TDD calculation method, for example:

  • a 100 kg patient, at 0.5 u/kg/day TDD = 0.25 u/kg/day Basal = 25 units basal

  • a 100 kg patient weighs 220 pounds, 10% of the body weight in pounds = 22 units basal

Once the patient is on a basal insulin, the correct way to determine if the amount of BASAL insulin is appropriate is to monitor the patient's blood glucose through any fasting states. A fasting state, when the basal is set correctly, should produce little to no change in the patient's blood glucose over time (+/- 50 mg/dl). Examples of fasting states include the time between 9pm and 7am when most patients are not eating and are not receiving other insulins (corrections or slides).

It is imperative that the patient not be under the influence of other insulins during the assessment of basal dosing. In other words, if the patient is on a short acting correction insulin given at the 5pm meal, this should "wash out" by 9pm, and therefore not influence the fasting state glucose though the night. This also requires the patient not receive correction insulin at bedtime in order to make the initial basal calculation.

  • Example 1 (basal set too high): At 9pm, the glucose level is 250 mg/dl, the patient receives only a basal insulin, and the morning glucose level is 180 mg/dl. The basal insulin administered is too high for the rate of basal production, and the basal insulin should be lowered.

  • Example 2 (basal set correctly): If the glucose level at 9pm is 300 mg/dl, the patient receives only a basal insulin, and the morning glucose level is 300 mg/dl, then the basal insulin administered matches the rate of production, and no change in the basal rate is needed. Though the patient is definitely out of range, the next step, as will be done later, is that the patient needs to go into the fasting state at a controlled level, rather than using the basal insulin only to bring a high blood glucose down.

  • Example 3 (basal set too low): If the glucose level at 9pm is 280 mg/dl, the patient receives only a basal insulin, and the morning glucose level is 340 mg/dl, then the basal insulin is set too low and the dose should be raised.

If blood sugars are consistently variable (some mornings unexpectedly high or some mornings unexpectedly low), make sure that the patient is not getting extra unexpected carbohydrate sources (snacking, candies, etc). Any adjustments in insulins should be with full knowledge of any outside/unplanned source of carbohydrates to avoid unsafe glucose excursions. A typical scenario is that a patient is requesting a snack on some nights to "prevent hypoglycemia" and the physician escalates the insulin doses to accommodate the resulting high blood glucose levels. Subsequently, if the patient is placed NPO or skips the snack, the glucose drops precipitously.

To anticipate the adjustment level for the basal insulin, I use the equivalent correction scale that would produce the change needed if this were a prandial adjustment. In other words, if the patient is on 20 u of basal, and their BG dropped by 100 points during a fasting state, I would decrease the amount of basal by approximately 5-10 units, making more dramatic changes customized for each patient's prior needs and response to insulin.

The KEY POINT is that the purpose of the basal is to lock-in a fasting glucose level, not necessarily to "treat" hyperglycemia. Once a glucose level is locked-in, the short acting insulins are used to move the lock point to the target range. Basal should never be used as a sole method to lower blood glucose levels. If the use of correctional insulin exceeds 20 units, however, an increase of basal may be beneficial to help lower blood sugars, as long as there is no evidence of rapid lowering of blood sugar in the fasting state.

C. Step 2: Adjusting the Prandial Doses

Prandial doses are derived from the initial weight-based calculation, as they are for the basal. The prandial doses are short acting (<4 hour) insulins given to treat the glucose surge associated with meals or bolus feeds. The insulin is usually given in close approximation to the anticipated meal or bolus so that the effect, duration and strength of the insulin surge most closely matches the glucose response of the infusion or meal.

Before a meal or bolus, the patient's blood glucose is checked. This value represents the results of the previous glucose/infusion interaction and in the best case scenario, is expected to remain stable over time, as long as the basal is set appropriately as above.

If the basal is too high, or if shorter acting insulins are still in the system (especially in renal patients, or if insulin is administered too close together (<3 hours apart), then the patient may experience a low blood sugar event, secondary to glucose stacking, or an imbalance in the carbohydrate to insulin ratio. This is why SC insulins should never be given too frequently (<3 hours) as the effects of stacking and incomplete clearance are difficult to predict and can result in dangerously low blood sugars.

As long as the patient is scheduled to receive a fixed amount of carbohydrate (either through carbohydrate counting or calculated glucose infusion rate), then the ability to predict a fixed amount of insulin required to prevent glucose excursion should be straightforward. Usually, approximated by the TDD calculation above, the prandial doses are 1/2 of the TDD, divided into 3 meals or bolus amounts.

For example, for a 100 kg patient, the TDD is 0.5 u/kg/day = 50 u TDD per day. 25 units would be the basal and 8 units for each of three meals (for a total of approximately 24 units).

A correction factor should be added to each of these doses to "correct" for failing to predict the glucose excursion from the previous glucose/insulin interaction. Any correction factor used should indicate a failure to anticipate insulin needs and these total correction needs have to be placed into the fixed schedule for upcoming doses.

The amount of strength for the correction factor is usually set by an institution or pharmacy, can be customized, and basically gives additional units of insulin according to a pre-arranged algorithm or scale. These are set at low, medium and high levels, the choice usually made based on patient factors, insulin needs, insulin sensitivity and stress.

A sample fixed plus correction factor scale regimen is given below (again using our example 100 kg patient):

  • 8 units + 3 units subcutaneously for fingerstick blood glucose 120-160 mg/dl

  • 8 units + 5 units subcutaneously for fingerstick blood glucose 161-200 mg/dl

  • 8 units + 8 units subcutaneously for fingerstick blood glucose 201-240 mg/dl

  • 8 units + 12 units subcutaneously for fingerstick blood glucose 241-280 mg/dl

  • 8 units + 16 units subcutaneously for fingerstick blood glucose 281-320 mg/dl

  • 8 units + 20 units subcutaneously for fingerstick blood glucose > 321 mg/dl

Upon review of the patient's insulin needs, and preferably once the basal is set as described above, the next step is to review all the prandial and correction insulins given, and find the lowest common denominator administered to make subsequent adjustment to the fixed doses.

Alternatively, one could sum all the units and divide the number into 3 equal parts, presuming the patient consumes or is administered similar carbohydrates for each meal or bolus.

For example, our example patient yesterday received 14 units in the morning for breakfast, 10 units for lunch, and 14 units for dinner. This is a sum of 38 total units, divided into 3 meals equals approximately 13 units for each meal. Alternatively, you could find simply the lowest common denominator and use this as the fixed dose. In the above example, the lowest common denominator would be 10 units. All new fixed doses should be adjusted now for at least this amount.

Customization for meal sizes or patient preference should allow for tailoring of the distribution of insulin across the day, as necessary.

Contrary to a more popular method of simply adding all the doses together and putting it back into the TDD calculation, this method will allow for optimization of more complex patient types such as those that receive steroids.

It is very common for patients on steroids to require prandial doses that far exceed their basal needs, often in ratios of 3-5 times the basal daily requirement. If you were to simply add all the insulins needed back into the TDD calculation, for patients on steroids especially, their basal dose becomes set inappropriately high, resulting in lows, especially during fasting states. See "brittle diabetes" below.

D. Stress and Infusion Calculations

Total Daily Dose (TDD) = Basal + Prandial + Stress + Infusions + Correction

As above, the calculation for total insulin needs should include not only the basal and prandial doses, but also needs related to infusions and stress.

The best way to manage these needs is to realize that most types of meals, carbohydrates and drips/infusional carbohydrate sources can be matched to an insulin that has a similar absorption and peak profile. In other words, one could "draw" a particular patient's daily glucose response on a time scale and find an appropriate insulin regimen to match.

For example, a patient who is NPO and on no oral antihyperglycemics, nor dextrose containing intravenous fluids, will essentially have a flat glucose profile over time, barring minor variances for dawn phenomenon and stress factors. In this example, the patient could be managed with a once daily long acting insulin alone.

A patient who is NPO on 5% dextrose at 100 ml/hour, however, will need accommodation for the additional carbohydrate infusion, but again, in a flat profile if administered continuously. In this example, 100 mlf/hr times 5% times 24 hours equals 120 g of extra carbohydrates. Carbohydrates are usually covered with approximately 1u for every 10g carbohydrate for a resistant person, to 1 u for every 15 g carbohydrate for a sensitive person. So, for our example 100 kg patient, they will need approximately:

  • (TDD = Basal + Prandial + Stress + Infusions + Correction) 50u (0.5u/kg/day) = 25u + 0 Prandial + 0 + 12u Infusions + Corrections = 37 units of basal to cover this need + correction factor.

Only basal insulins would be used as it would cover for the dextrose infusion which is being infused at a constant rate over time, rather than what would be seen with bolus infusions.

If the patient above starts to eat, and IV fluids are continued, then the patients calculated needs are added to the equation:

  • (TDD = Basal + Prandial + Stress + Infusions + Correction) 50u (0.5u/kg/day) = 25u + 8u Prandial (x3 meals) + 0u Stress + 12u Infusions + Correction = 61 units TDD cover this need + correction factor.

In this instance, the patient would receive 37 units of a basal insulin (25 is the patients basal and 12 is the infusion need), 8 u of a rapid onset short acting insulin three times a day to cover each meal (for a total of 24 units with meals) for a sum total of 61 units per day.

Infusional carbohydrates can be quite complex, as they are often either given in bolus forms or constant infusions. Most carbohydrate ingredients are printed on the tube feeding formula or can be obtained through your nutritionist, however, the calculations remain the same for the amount of insulin that would be needed to cover these infusions, as long as the method to give them is matched to an appropriate insulin (short acting for bolus infusions and long acting for continuous infusions).

Constant infusion tube feeds or total parenteral nutrition, since their glucose infusion rate would be expected to be a flat, can be managed with additional basal insulins, provided the patient is monitored for loss of carbohydrate infusion, as their insulin:carb ratio will favor hypoglycemia rapidly once their source of carbohydrates is lost.

"Stress" needs are slightly more empiric, rather than calculable or accurately estimated. However, a patient who presents with sepsis or severe illness may need adjustments (10% to 30% of their TDD) to accommodate for stress factors. This can usually be accounted for by close following of the patient's insulin needs and making adjustments several times a day, especially for critically ill patients. However, one should anticipate that the patient's insulin needs may decrease as the patient's medical illness resolves.

Alternatively, a patient who is previously well controlled, requiring no correction factor for several days, who suddenly has increasing needs may have a burgeoning infection or other illness that may shortly present itself in a clinically detectable manner.

Correction Doses

The use of a correction dose scale is to cover unanticipated excursions in blood sugars, such that one could determine where to make adjustments for the next day's fixed and basal doses. Correction doses are always rapid acting insulins (RAA), such as lispro, aspart, etc.

If the patient is noted to consistently need correction factor insulin, this should be an indication that there is room for improvement in the estimated patient's fixed prandial and/or basal needs. For example, a patient who is on 10 units of prandial insulin but receiving 4-5 additional units per meal needs adjustment of their prandial doses to at least 14 units so that there is diminishing need to utilize correction factor insulin.

The purpose of correction factor insulin, therefore, is to not only treat excursions, but also to capture errors in predicting insulin needs.

Institutional protocols may already have a correction factor scale, sometimes known as a sliding scale protocol usually graded into low, medium, or high level adjustment scales. Though your protocol may vary, one that could be used is based on basal needs:

If basal needs are:

  • Under 40 units, use 1 unit of RAA for every 50 mg/dl over 150

  • Between 40-80 units, use 2 units of RAA for every 50 mg/dl over 150.

  • Between 80 units, use 3 units of RAA for every 50 mg/dl over 150.

E. Diabetic Ketoacidosis (DKA) and Hyperosmolar Hyperglycemic States (HHS)

Patients with extremely high blood sugars can have diabetic ketoacidosis (DKA) or Hyperosmolar Hyperglycemic State (HHS). Some patients may have overlap of both states.

In HHS, patients do not produce ketones as much as seen in DKA, however, they have increase in the plasma osmolality to very high levels, up to 350-380 mosmol/kg. Neurologic complications are typically present and can be severe (including coma). Despite extremely high blood sugars (>800 mg/dl) most patients with HHS have a normal appearing blood gas with negative to low ketones in serum and urine.

DKA, however, is associated with lower blood sugars than HHS (<800 mg/dl), a high anion gap metabolic acidosis, and large amounts of ketone production. Given the spectrum of illness that hyperglycemia can produce, one should presume that these are not absolutes and that patients may have overlap of both DKA and HHS, for which the treatment may need to be modified.

Patients who meet criteria for diabetic ketoacidosis can present with a range of illnesses, but can present with severe dehydration, electrolyte abnormalities, and altered mental status. Extremely ill patients with altered mentation, a high anion gap acidosis or multiple electrolyte abnormalities are often managed in an intensive care unit setting.

A patient diagnosed with DKA and HHS often is treated with IV insulin therapy. This allows for rapid titration and adjustment of insulin based on blood sugars and anion gap measurements. Your institution may utilize commercially available protocols or decision support systems that will make recommendations for adjustments of insulin based on patient variables.

The management of DKA and HHS is complex and requires not only careful attention to blood sugar, but also acid:base status, electrolyte shifts, dehydration and volume depletion, mental status changes, and other complications which may arise from severe uncontrolled diabetes. Also, it would be imperative to evaluate the patient for a precipitating factor for severe DKA/HHS such as non-compliance, infection, steroid use, or simply the initial presentation of new onset Type 1 diabetes.

This section will not attempt to address the management of all the associated conditions of DKA, but rather focuses on management of the blood sugar and anion gap.

Diabetic ketoacidosis

A patient who is diagnosed with DKA (high blood sugars and acidosis from ketogenesis) is in a state of severe insulin deficiency. Cell metabolism without adequate entry of glucose into the cell causes an inefficient metabolism that results in the formation of ketone bodies. The ketone bodies of beta-hydroxybutyric acid and acetoacetic acid are the primary drivers of the acidosis.

Despite the fact these patients will require insulin to halt ketogenesis, it is absolutely critical to hydrate them (they are often profoundly dehydrated due to osmotic diuresis from glucosuria) and check their electrolyte levels. Patients with low normal or low serum potassium levels actually have severe total-body potassium deficiency and require aggressive potassium repletion as well as cardiac monitoring, as insulin therapy can significantly lower serum potassium levels and drive dysrhythmias. If potassium levels are <3.3 milliequivalents/liter (mEq/L) prior to initiation of treatment, fluid hydration and potassium supplementation should occur BEFORE starting insulin; goal range for potassium should be 4-5 mEq/L, and this can generally be maintained by adding potassium to hydration fluids once any initial deficiencies are corrected.

Given the inherent risks of infusion of IV insulin and the electrolyte shifts that occur with aggressive fluid hydration, it is imperative that frequent assessment of labs be performed, usually in a staged fashion so that the patient will have a blood sugar check of some sort every one hour and appropriate electrolyte evaluation every 2-4 hours.

The initial infusion of insulin for a patient confirmed to be in DKA by laboratory evaluation of acid:base status, ketone formation and hyperglycemia can be calculated based on weight. There are two strategies generally used; one utilizes an initial insulin bolus followed by a low continuous rate, while the other uses only a continuous rate calculated at a slightly higher dose.

If a bolus is used, it should be approximately 0.1 u per kg of body weight given as a one time dose, followed by a continuous infusion of 0.1 u/kg/hour. Alternatively, a continuous hourly infusion of 0.14 u/kg body weight can be given without the bolus, as long as the overall dose is >0.1 u/kg/hour.

Though several protocols exist for management of diabetic ketoacidosis and HHS, each of them have the goal of lowering of blood sugar to approximately 250 mg/dl (150-200 mg/dl for DKA and 250-300 mg/dl for HHS). The patient is usually kept at this level until ketone production is suppressed, as manifested by a correction of the anion gap to normal levels. The rate of insulin that is required to keep the patient in the desired range may decrease over time as the patient becomes less glucose toxic, but should stabilize over the course of treatment.

It is a fundamental error to stop insulin in a patient who has not yet corrected their acidosis in DKA (their anion gap has not yet "closed"). If the blood sugar is at or approaches low levels (<200 mg/dl) while the anion gap is still "open" (the acidemia persists), the patient should have supplemental dextrose given in their IV fluids so that insulin can continue to suppress ketone formation.

Criteria for resolution of ketoacidosis, or the point at which transition to a subcutaneous regimen can be considered, include a blood glucose <200 and two of the following: a serum bicarbonate greater than or equal to 15 mEq/l, a venous pH >7.3, and a calculated anion gap <12 mEq/l. To calculate an appropriate subcutaneous regimen, the average glucose rate over the past 6 hours should be used to estimate a 24 hour need, or TDD, for the patient as described previously. Once the TDD is calculated, it is a common strategy to decrease this dose by 20% when starting the initial subcutaneous regimen. It is important to overlap the IV insulin with the subcutaneous insulin for 1-2 hours after administration of the subcutaneous dose to prevent recurrence of hyperglycemia and ketoacidosis.

As an example, a patient who is in DKA on presentation begins treatment with insulin at a rate of 10 u/hr. By the time the blood sugars are stable, their insulin needs are only about 2 u/hr averaged over the past 6 hours. In this example, we will estimate that the patient will need 2 u/hr to maintain stable glucose levels. Over 24 hours, this would be approximately 48 units total daily dose (2 u/hr x 24h). 48 u TDD x 80% = ~38 units TDD.

The reason that the total amount of insulin needed over the past 24 hours is not used to calculate the TDD is that patients in DKA are usually quite glucose toxic and have a lower insulin sensitivity early in treatment than they do near the end point of treatment.

Hyperosmolar hyperglycemic state

Most of the treatment of HHS is similar to the treatment of DKA with regards to correction of hyperglycemia. However, since acidosis is not present and ketogenesis is less of a factor, the correction of HSS focuses more on correction of plasma osmolality.

The 2009 ADA guidelines on hyperglycemic crises in diabetes in adults (both DKA and HHS) suggests that avoidance of rapid correction of hyperosmolar states or hyperglycemia may reduce the risk of cerebral edema in high-risk patients:

  • Gradual replacement of sodium and water deficits in patients who are hyperosmolar. The usual regimen for the first hour should be isotonic saline at a rate of 15 to 20 mL/kg body weight per hour (about 1000 mL/h in an average-sized person), with subsequent rate determined by the patient's hemodynamics, electrolyte levels and urine output.

  • Gradual reduction in serum glucose. This generally requires the addition of dextrose to the saline solution once the serum glucose levels reach 200 mg/dL (11.1 mmol/L) in DKA, or 250 to 300 mg/dL(13.9 to 16.7 mmol/L) in HHS. In HHS, the serum glucose should be maintained at 250 to 300 mg/dL (13.9 to 16.7 mmol/L) until the hyperosmolality and mental status improve.

IV. Management with Co-Morbidities

N/A

A. Renal Insufficiency.

For patients with any degree of renal insufficiency, particular attention needs to be paid to insulin stacking. It is well known that long duration insulins (glargine for example) do not peak, but they can add up gradually over time due to decreased renal clearance in patients with renal insufficiency.

For example, a renal patient who clears glargine in 28 hours will effectively have 4 hours (if administered q24h) where the effective dose in the patient is twice that intended. This effect can be mitigated by having any long acting insulin given in the morning. This way, the dawn phenomenon, as well as patient factors (i.e., they are usually eating breakfast), can counteract the increased insulin action, resulting in less risk of hypoglycemia often seen in these patients.

KEY POINT: Long acting insulin given to a renal patient at night, when they are most likely to be unobserved, not eating, and not having blood sugar checks, is a patient safety issue that can be mitigated by re-timing of long acting insulins to morning so that any stacking effect is counteracted.

Blood sugar checks within the time frame of action of a fast/rapid acting insulin (<4 hours) should not be used to guide management in order to prevent stacking and potentially dangerous hypoglycemia.

IV insulins (usually regular insulin) have immediate action and rapid clearing, thus more frequent blood sugar checks and treatment can be accommodated, as long as no other insulin types are present, or oral agents are not at therapeutic levels.

B. Liver Insufficiency.

Patients with liver insufficiency may have issues with gluconeogenesis and therefore have difficulty with intrinsic glucose production while in a fasting state. These patients need close monitoring of blood glucose and the provider is encouraged to start at lower doses of insulin in these patients, especially the basal dose, to prevent potentially dangerous hypoglycemia.

C. Systolic and Diastolic Heart Failure

No change in standard management, however, patients with decreased perfusion may have different rates of absorption of subcutaneous insulins.

D. Coronary Artery Disease or Peripheral Vascular Disease

No change in standard management, however, patients with decreased perfusion may have different rates of absorption of subcutaneous insulins.

E. Diabetes and other Endocrine issues (BRITTLE DIABETES), including Steroid Use

Steroid use

Patients on high-dose steroids who are newly diagnosed or have had previously diagnosed diabetes are frequently mismanaged in the hospital setting (as a result of altering the basal dose in favor of prandial doses, where they are most needed).

Usually, with steroid administration, the ratio of basal:bolus needs is markedly skewed from the usual 1:1 pattern. Patients begin to develop significant excursions in their post-prandial glucose levels at about 48 hours after start of steroids. This is, in turn, usually noted as more frequent use of the correction factor insulin. With increasing titration, patients often require massive increases in total insulin administered per day.

KEY POINT: Do not add up the total insulin in one day and re-divide this into a new total daily dose calculation. With steroids, there is usually little to no change in basal needs, as most excursions are post-prandial. The amount of correction factor used should be put back into the prandial doses, leaving the basal amount close to that calculated based on the patients weight. Often, moving the basal administration to the morning can help prevent hypoglycemia as well, as the steroid effect usually goes away at night, peaking approximately 2 hours post-prandial.

Patients on steroids who have their insulin adjusted by adding up the total used and re-dividing into the TDD are usually labeled as "brittle," though careful attention to adjustment of the basal and prandial doses based on the methods above usually result in adequate control of often challenging patients.

Since daily oral prednisone once daily usually produces a predictable surge in blood glucose in the morning, some methods use a separate dose of NPH to cover for this shorter excursion of hyperglycemia (in addition to basal and fixed doses previously calculated), without exposing the patient to additional insulin during times of the day when this effect is less prominent.

  • Effective dose can be estimated by taking the amount of supplemental "correctional" insulin needed to suppress hyperglycemia and using 1/2 of that as the initial NPH dose. The dose is titrated to effect. Once this dose is determined, one could estimate the NPH to steroid ratio required to suppress the effect, in anticipation for outpatient control during a taper.

  • For example: A patient with COPD on a prednisone taper is prescribed oral prednisone. It is determined that for this patient, 60 mg of prednisone is found to need 30 u of NPH to suppress the hyperglycemia. Thirty units insulin/60 mg = 0.5 units NPH per mg of prednisone.

  • As the patient is tapered to 40 mg of prednisone, 20 u of NPH should control the hyperglycemia. At 20 mg, 10 u of NPH will be sufficient. At the end of the taper, the patient can stop the NPH. Obviously the complexity of such a regimen requires intensive education and follow-up to be successful. In this situation, given a particular patients needs and for safety, a daily nurse call or home health visit to manage dosing may be required.

Insulin pumps

For those patients who are on an insulin pump and mentating normally, continuance of the pump is acceptable as long as there is clear expectations, reporting, and guidelines for patient use. Administration is always observed by a trained healthcare person and confirmed in the medication record. If the patient is sent to testing where the pump needs to be removed, consideration of the patients metabolic needs is appropriate to make sure they are not off insulin for a prolonged period of time (Type 1 DM especially) as this can lead to unintended ketosis.

F. Malignancy

Any malignancy that produces glucose intolerance or excess cortisol production may produce diabetes or diabetic complications.

Many malignancy treatment regimens may include high-dose steroids (brain tumors, breast cancer, etc) which may in turn promote glucose intolerance.

G. Immunosuppression (HIV, chronic steroids, etc).

No change in standard management except those patients on steroids, as described above in section E.

H. Primary Lung Disease (COPD, Asthma, ILD)

No change in standard management except that seen in patients on steroids, as described in section E.

I. Gastrointestinal or Nutrition Issues

Patients who are both eating and on supplemental nutrition (tube feeds, TPN, dextrose containing fluids, etc) can represent special challenges to glucose management, however, employment of the basic formula will accommodate for these variables.

  • NPO Patients: can be managed using previous TDD calculations, adjusted as the patients' illness progresses.

  • Starting to eat, but inconsistent: may give the recommended calculated dose of insulin, but immediately after the meal instead of before the meal. The patient can then be given a graded amount of insulin according to their carbohydrate tolerance at that meal.

  • Continuous infusions: calculation of the dextrose infusion over 24 hours can be used to estimate the additional insulin needs of the patient for this infusion. The method of control, given a constant infusion rate, is best accommodated by a basal type insulin added to the patient's calculated intrinsic basal needs. Carbohydrates are usually covered with approximately 1 u for every 10 g carbohydrate for a resistant person, to 1 u for every 15 g carbohydrate for a sensitive person.

For example, a 100 kg patient on a continuous TPN with 300 g of carbohydrate will need approximately 30 additional units (300 g/1u per 10) of insulin per day. This will be in addition to their approximate basal needs of 25 u a day (100 kg x 0.5 u/day x 1/2). In total, the patient will need 45 units of insulin per day plus correction to accommodate for this need. Since they are usually not eating, prandial doses do not require calculation.

Some hospitals allow insulin to be placed within the TPN infusion itself. In this situation, it is favorable to put the nutritional insulin (usually regular) "in the bag" and keep the basal needs as SC, so that if the patient loses access or the infusion is stopped, they will still have basal coverage.

Should insulin "in the bag" not be allowed, one would have to consider that these patients may require large amounts of insulin all at once, especially if using long acting (24h) basal to cover these patients. A hospitalist will frequently encounter patients who lose access, pull tubes, etc and thus may be at increased risk of hypoglycemia from unopposed insulin.

One method that can be used if you have a patient with frequent access issues or who pulls tubes is to take the nutritional insulin calculation and divide its dose into multiple infusions per day. This way, if the patient on TPN loses access 10 minutes into the infusion, you will not have to find a way to keep their glucose up for 24 hours. This author usually accomplishes this through the use of NPH insulin administered every 6 hours.

For example, I have calculated that a 100 kg patient will require 25 units of basal and 30 units for their TPN. They have been known to either pull their line or have difficulty with access. I give the 25 units as a basal subQ, and the 30 units to cover the TPN I give as 7 units q6h. Since NPH has a duration which extends greater than 6 hours, I'm actually using stacking to my advantage.

After a couple of doses, the patient will have stacked the NPH to appear (to the body at least) to be an equivalent dose of approximately 30 units of basal once daily. If the patient loses access, just stop the NPH and the effect will extinguish in a shorter period of time than if given all at once as a 24h basal dose.

The benefits to this method is that there is some protection for patients who lose their lines and tubes, but the cost is that the regimen becomes very complicated for nursing, hand-offs, etc.

J. Hematologic or Coagulation Issues

None

K. Dementia or Psychiatric Illness/Treatment

Significant issues may arise with patients who have psychiatric illness and comorbid diabetes. They may have significant issues with medications used inappropriately, non-compliant, variably compliant, or even as a means of attention getting or factitious disorders. Patients at a high risk of drug use or suicide threats/attempts should have their diabetes management plan corroborated with a psychiatrist.

Patients with dementia usually require no specific changes to their inpatient management, except for more close observation (and sign-out) for behavioral and mood changes. Since these patients are prone to delirium and other alterations of consciousness, blood sugar evaluations should be routine for any change in sensorium as they may have issues with reporting and classic hypoglycemia signs and symptoms may not be present/obvious.

Delirious patients should be taken off their pump, if this is used as a method of outpatient control.

A. Sign-out considerations While Hospitalized.

A cross-covering physician should know if a patient is made NPO and, if so, what dose of insulin they had already received / how their regimen was altered to accommodate their new nutritional status. If the patient is on correct amounts (as estimated by weight, etc) then no particular change, for instance starting supplemental dextrose-containing fluids, may be needed. If a patient is made NPO, however, they will likely need independent assessment with occasional glucose checks for safety.

Cutting the basal in half is a frequent and misguided strategy for adjusting a patients insulin needs in anticipation of being NPO. We often see that halving a patient's basal dose actually gets the patient to what their daily calculated dose of basal insulin should be based on weight, indicating their outpatient basal insulin dose is too high (e.g., they are using basal insulin to control their blood glucose).

These patients are easy to recognize, they are on extreme amounts of insulin for weight, often may not even take a prandial insulin, snack frequently ("to prevent from getting low") and have issues with hypoglycemia when skipping meals. They are hypoglycemia averse and resist changes in their insulin regimen and often have extensive rationale for their blood sugar excursions that makes little physiologic sense.

B. Anticipated Length of Stay.

Patients admitted solely for high blood sugars are usually discharged after the complication that predisposed them to hyperglycemia is corrected (infection, lack of medications, etc) or after the complication resulting from the hyperglycemia (dehydration, electrolyte abnormalities) is corrected and a safe outpatient transition plan has been put into place.

C. When is the Patient Ready for Discharge.

Patients are ready for discharge when they can demonstrate how to measure, adjust and react to blood sugar excursions, high and low. There is little need to get patients to "goal" prior to discharge, and there is good rationale that a patient with tight inpatient control at discharge may have issues with hypoglycemia as an outpatient since their illness is resolving and glucose intolerance is improving with increasing activity.

Therefore, more specific education on low blood sugar recognition and treatment, early follow-up, and leaning towards a less aggressive regimen are recommended at discharge. A patient with a blood sugar of 250 mg/dl at discharge with a good plan is better than a patient at 110 mg/dl at discharge with no plan, follow-up or education.

If the patient has relatively controlled blood sugars as an outpatient on oral medications alone, it is reasonable to restart home medications at discharge, provided no new complications exist (i.e. new renal failure) and no medications would interact in such a way to cause adverse event or complication.

If a patient has been started on insulin, and it is anticipated that they will need to continue insulin at discharge, the patient will usually benefit from specific diabetic education as well as provision of general supplies prior to discharge.

Patients will need verbal and written instructions, as well as observation that they are able to perform the necessary functions to administer their insulin. Family should be involved as much as possible and teach-back is helpful to confirm understanding of knowledge.

The patient should be instructed on frequency of blood sugar checks and how to chronicle this data for a follow-up physician. Patients who are started on oral medications do not usually need frequent blood sugar checks, however, they should be instructed to have by follow-up a record of several blood sugars taken at various times throughout the day so that a complete daily picture is available.

Should patients be started on insulin, orals, or nothing?

An A1C can used to guide the use of insulin at discharge.

  • Less than 5.7 = no diabetes, no insulin.

  • 5.7-6.5 = pre-diabetes, lifestyle changes, close follow-up.

  • 6.6-6.9 =

    • new diagnosis: lifestyle modification, metformin.

    • established: continuous previous diabetic regimen.

  • 7.0-9.0 =

    • new diagnosis: lifestyle modification, single oral agent.

    • established: lifestyle modification, troubleshoot compliance or social issues, add/adjust orals, add basal insulin.

  • Greater than 9 =

    • new diagnosis: lifestyle modification, insulin therapy pre-meal and basal, consider dual therapy.

    • established: lifestyle modification, troubleshoot compliance or social issues, monitored insulin administration for technique, review/re-educate on outpatient regimen.

Recommendations for oral insulin therapy differ slightly between American Association of Diabetes (ADA) 2016 standards of care and the American Association of Clinical Endocrinologists (AACE) 2015 guidelines. The ADA recommends starting with Metformin, while the AACE does not suggest initiation of one class of oral agents above any other. The AACE does, however, discourage the use of sulfonylureas, especially in combination with insulin. Oral agent classes recommended by both groups include metformin, sulfonylureas, GLP-1 receptor agonists, dipeptidyl peptdtase-4 (DPP-4) inhibitors, sodium/glucose transporter 2 (SGLT2) inhibitors, and thiazolidinedione; the AACE also makes note of other classes, including alpha-glucosidase inhibitors, bile acid sequestrants, and bromocriptine quick release (BCR-QR).

D. Arranging for Clinic Follow-up

Any major alteration in a patient's usual diabetic regimen, or any patient newly started on insulin, requires contact with the patient's primary care physician (PCP) or follow-up clinic. Should any problems occur, the PCP or on-call physician may be the first to respond and have to manage complications or clarify instructions, therefore they should have the opportunity to understand the goals of therapy, regimen, and patient factors which could complicate therapy.

1. When should clinic follow up be arranged and with whom.

General medicine follow-up should be scheduled within 5-7 days for a new diabetic on insulin and within 2 weeks for a new diabetic on oral medications alone.

Ophthalmology, podiatry, nutrition and diabetes education clinics for patients who are either new diagnosis or lapsed in their chronic management, within 6 weeks, unless there are suspected or active issues which would necessitate earlier intervention (diabetic foot ulcer, visual changes, etc.).

2. What tests should be conducted prior to discharge to enable best clinic first visit.

A Hemoglobin A1C should be performed (if one has not been checked within 3 months), as well as lipid panel (fasting), foot check and basic visual screening as more prompt referral to specialities may be expedited by the inpatient physician. A baseline urine albumin/creatinine ratio as well as routine chemistry (for creatinine) should also be performed if not already done.

3. What tests should be ordered as an outpatient prior to, or on the day of, the clinic visit.

None

E. Placement Considerations.

None

F. Prognosis and Patient Counseling.

  • The prognosis for diabetes depends mostly on long-term control. Patients should be counseled that weight loss, dietary modification and regular exercise can often lead to better diabetes control in the long term, including delay of onset of diabetic complications of neuropathy, nephropathy, and renal failure.

  • Patients started on drugs such as metformin should be counseled on its interaction with IV contrast agents and to hold this medication usually 24 hours before and 24 hours after a contrast procedure, or per institutional policy.

  • Patients should be given specific information on sick care and hypoglycemia symptoms. Also, any medications used for diabetes control should include routine information on possible side effects specific to that medication, noting that the most prominent side effect is hypoglycemia.

  • Patients started on insulin and given injectable medications should be counseled on skin care, standard precautions, and needle safety. Patients should be instructed to follow directions carefully for all insulins, noting that some cannot be mixed while others can.

A. Core Indicator Standards and Documentation.

The physician should document whether the patient is controlled or uncontrolled when documenting diabetes care, in addition to whether the patient has type 1 or type 2 diabetes, and any complication resulting directly from their disease (e.g., neuropathy or retinopathy).

B. Appropriate Prophylaxis and Other Measures to Prevent Readmission.

Patients with diabetes should be considered to have a state of chronic immune compromise. Therefore, appropriate validation of immunization status is imperative. Patients should be updated on all immunizations for which they qualify given their age and comorbid status, to include but not limited to influenza, pneumococcus, tetanus, pertussis, etc.

What's the evidence?

Moghissi, ES,, Korytkowski, MT,, Dinardo, M,. "American Association of Clinical Endocrinologists and American Diabetes Association Consensus Statement on Inpatient Glycemic Control.". Diabetes Care. vol. 32. 2009. pp. 1119-1131.

Fonseca, V:. "Nwely diagnosed diabetes/hyperglycemia in hospitals: what should we do?". Endocr Pract.. vol. 12. 2006. pp. 108-111.

Endocr Pract. vol. 13. 2007. pp. 4-68.

Endocr Pract. vol. 12. 2007. pp. 458-468.

"2016 Standards of Medical Care in Diabetes.". Diabetes Care.. vol. 39. 2016. pp. S13-22.

"Summary of Revisions.". Diabetes Care. vol. 39. 2016. pp. S4-S5.

Bloomgarden, ZT,, Handelsman, Y.. "Approaches to treatment 2: Comparison of American Association of Clinical Endocrinologists (AACE) and American Diabetes Association (ADA) type 2 diabetes treatment guidelines.". Journal of diabetes JID. pp. 1753-0407.

Kitabchi, AE,, Umpierrez, GE,, Miles, JM,, Fisher, JN.. "Hyperglycemic Crises in Adult Patients With Diabetes.". Diabetes Care. 2009. pp. 1335-1343.

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