The American Journal of Medicine (2007) 120, 563-567

REVIEW

AJM Theme Issue: Diabetes/Metabolism

Sliding Scale Insulin Use: Myth or Insanity? Guillermo E. Umpierrez, MD, Andres Palacio, MD, Dawn Smiley, MD Department of Medicine/Division of Endocrinology, Emory University School of Medicine, Atlanta, Ga. ABSTRACT Inpatient hyperglycemia in people with or without diabetes is associated with an increased risk of complications and mortality, a longer hospital stay, a higher admission rate to the intensive care unit, and higher hospitalization costs. Despite increasing evidence that supports intensive glycemic control in hospitalized patients, blood glucose control continues to be challenging, and sliding scale insulin coverage, a practice associated with limited therapeutic success, continues to be the most frequent insulin regimen in hospitalized patients. Sliding scale insulin has been in use for more than 80 years without much evidence to support its use as the standard of care. Several studies have revealed evidence of poor glycemic control and deleterious effects in sliding scale insulin use. To understand its wide use and acceptance, we reviewed the origin, advantages, and disadvantages of sliding scale insulin in the inpatient setting. © 2007 Elsevier Inc. All rights reserved. KEYWORDS: Diabetes; Hypoglycemia; Inpatient hyperglycemia; Mortality; Sliding scale insulin

Diabetes mellitus represents a significant public health burden because of increased morbidity, mortality, and economic cost. A large body of observational studies have indicated that hyperglycemia is associated with an increased risk of complications and mortality, a longer hospital stay, and a higher admission rate to the intensive care unit, and is more likely to require transitional or nursing home care after hospital discharge.1-7 In addition, prospective randomized studies indicate that aggressive glycemic control reduces the length of hospitalization, the rate of multiorgan failure and systemic infections, and short- and long-term mortality.4,8-10 In view of this evidence, a recent position statement by the American Association of Clinical Endocrinologists11 recommended glycemic targets for hospitalized patients in the intensive care unit between 80 and 110 mg/dL, and in noncritical care settings a preprandial glucose goal less than 110 mg/dL and a random glucose less than 180 mg/dL. The Joint Commission on Accreditation of Healthcare Organization recently proposed tight glucose control for the critically ill as a core Requests for reprints should be addressed to Dawn Smiley, MD, Emory University School of Medicine, Division of Endocrinology and Metabolism, 49 Jesse Hill Jr Drive, Atlanta, GA 30303. E-mail address: [email protected]

0002-9343/$ -see front matter © 2007 Elsevier Inc. All rights reserved. doi:10.1016/j.amjmed.2006.05.070

quality of care measure for all US hospitals that participate in the Medicare program (www.jcaho.org). Despite the increasing evidence in support of intensive glycemic control in hospitalized patients, blood glucose control continues to be deficient and is frequently overlooked in general medicine and surgery services.3,12,13 Many factors could explain the physician’s inactivity in addressing in-hospital hyperglycemia. First, hyperglycemia is rarely the focus of care during the hospital stay, because the overwhelming majority of hospitalizations in patients with hyperglycemia occur for comorbid conditions.3,14 Second, fear of hypoglycemia constitutes a major barrier to efforts to improve glycemic control in hospitalized subjects, especially in patients with poor caloric intake.13,15 Third, practitioners frequently do not administer insulin until blood glucose levels exceed 180 to 200 mg/mL because of the misconception that mild elevations are not deleterious.13 Finally, and perhaps more important, in the presence of altered nutrition and associated medical illness, physicians frequently discontinue their patients’ previous outpatient antidiabetic regimen and initiate sliding scale coverage with regular insulin, a practice associated with limited therapeutic success.3,12,13 Several studies have provided evidence of poor glycemic control and deleterious effects in those using sliding scale

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lation of insulin dosage based on urinary glucose conceninsulin; however, it continues to be the most prescribed tration per “sliding scale” was the standard of care. insulin regimen, especially in those without a history of The use of the “sliding scale” insulin regimen was first diabetes. Strong terms have been used in its condemnation, introduced by Elliot Joslin in 1934.22 He recommended including “mindless medicine,” “paralysis of thought,” “action without benefit,” “a recipe for diabetic instability,” giving regular insulin according to the amount of glycos“action without benefits,” and “a uria: 5 units for “green urine,” 10 relic from the past.”16-20 What exunits for “yellow urine,” and 15 plains physicians’ entrenchment units for “orange urine.” Table 1 CLINICAL SIGNIFICANCE with the use of sliding scale insushows an example of sliding scale lin in the management of in-hospital insulin for patients with acute ill● Hyperglycemia, in hospitalized pahyperglycemia? To understand its ness recommended in the 11th tients with or without diabetes, is aswide use and acceptance, we reedition of Joslin’s Diabetes Mellisociated with increased length of hosviewed the history and available littus Textbook in 1971.30 Similarly, pital stay and increased morbidity and erature on the use of the sliding in hospitalized patients with decommortality. scale in the treatment of diabetic pensated diabetes or diabetic ketosubjects. acidosis, the use of regular insulin ● Aggressive glycemic control reduces the per sliding scale according to urilength of hospital stay and the rate of nary glucose excretion was the premultiorgan failure, systemic infection, THE ORIGIN OF SLIDING ferred method of insulin administraand mortality. SCALE INSULIN tion until the late 1970s.31,32 In the Following the discovery of insulin ● Sliding scale insulin, the most commonly landmark trial by Kitabchi et al33 on by Banting and Best in 1921, regthe efficacy of high-dose versus prescribed inpatient insulin regimen, is ular insulin was the only insulin low-dose insulin for treatment of diassociated with poorer glycemic control formulation available, and it was abetic ketoacidosis, when the and increased risks of hypoglycemia. not until 1937 that the first modiplasma glucose reached 250 mg/dL, fied insulin was introduced. Mul● Implementing basal/bolus therapy to sliding scale insulin was administiple injections given 2 to 4 times manage inpatient hyperglycemia in nontered every second hour according daily was the insulin regimen reccritically ill patients will result in subto the amount of urinary glucose ommended for most patients.21 (Table 2).33 Following the introstantial improvement in glycemic control Since the early days it became duction of capillary blood glucose and fewer hyperglycemic and hypoglyceevident that the administration monitoring, Skyler et al34,35 and mic episodes. of pancreatic extracts decreased others36 modified the urine glublood glucose levels in a dosecose algorithms to use blood gludependent fashion, but insulin cose targets. These algorithms overtreatment could result in significant “toxicity” and conbecame widely accepted by general practitioners, and vulsions.22 Because the “toxicity” of pancreatic extracts was their use was encouraged by endocrinologists, medical rapidly recognized as the result of severe hypoglycemia institutions, and manufacturers of blood glucose rather than toxic contaminants, it became an obvious need to meters.35 Although these algorithms were not intended to measure blood glucose levels in all diabetic patients receivbe used as the sole method of insulin administration, they ing treatment with insulin. Blood glucose measurement in subsequently underwent additions35 and modifications hospitalized patients was available in the 1920s; however, early methods for measuring blood glucose were cumbersome and required large volumes of blood.23 The glucose oxidase technique for measuring glucose in biological fluids Table 1 Early Algorithm for the Use of Additional Regular was first published in 1948,24 and it was not until the 1970s Insulin during Acute Illness 25-27 when home monitoring became available. Therefore, If Benedict’s Urine Red, Orange, Yellow or Green or for the first 50 years of insulin therapy, researchers and Test Shows: or Brown YellowBlue clinicians had to rely on indirect estimates of glycemia by green measuring urinary glucose. Urine testing for glucose was Give regular insulin, 10 6 0 introduced by using the reducing properties of glucose to units produce a color change with Fehling’s solution (copper sulphate).24 This required boiling urine with the solution. The numeric scale must be adjusted to the requirements of the patient and might range from 6-4-0 to 12-8-0 or greater. If significant Despite its inconvenience, measurement of urinary glucose glycosuria persists, additional insulin may be given at bedtime. was welcomed by patients and physicians, and provided Adapted from Joslin EP. Insulin requirement during acute illness. guidance in estimating the amount of insulin necessary to In: Marble A, White D, Bradley RF, Krall LP, eds. Joslin’s Diabetes 28,29 correct hyperglycemia. The primary goal of insulin Mellitus Textbook. Philadelphia: Lea and Febiger; 1971:295. therapy at that time was to eliminate glycosuria, and calcu-

Umpierrez et al Table 2 Therapy

Sliding Scale Insulin Use

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High-Dose versus Low-Dose Insulin for Treatment of Diabetic Ketoacidosis: Schedule for Crystalline (U-100) Insulin High-Dose Insulin* Insulin (units)

Plasma glucose (mg/dL)

Intravenous

Subcutaneous

Low-Dose Insulin† Intramuscular insulin (units)

(a) ⬎1000 (b) 600-1000 (c) 400-599 (d) 300-399

50 25 15 10

⫹ 100 ⫹ 75 ⫹ 50 ⫹ 30

0.1 U/lb body weight given intramuscularly with 1.5-inch needle in deltoid area

Repeat initial dose of insulin in the first hour if glucose is not decreased by 10%. Thereafter, give crystalline insulin hourly until blood glucose is ⬍ 250 mg/dL as follows: For groups a, b, and c, give 50 units subcutaneously Give 5 units intramuscularly per hour with 1.5-inch needle. per hour. For group d, give 15 units subcutaneously per hour. As soon as serum glucose reaches 250 mg/dL, replace saline with D5 saline infusion and monitor blood and urine glucose every 2 hours. Give crystalline insulin subcutaneously every 2 hours according to the following urine sliding scale: 4⫹ ⫽ 20 units; 3⫹ ⫽ 15 units; 2⫹ ⫽ 10 units; 1⫹ ⫽ 5 units until ketoacidosis is resolved and the patient can be maintained with oral intake. Adapted from Kitabchi AE, Ayyagari V, Guerra SM. The efficacy of low-dose versus conventional therapy of insulin for treatment of diabetic ketoacidosis. Ann Intern Med. 1976;84:633-638. *Based on initial plasma glucose. †Based on body weight.

made by practitioners and resulted in the sliding scale algorithms currently available.

ADVANTAGES AND DISADVANTAGES OF SLIDING SCALE INSULIN Potential advantages of the sliding scale insulin are convenience, simplicity, and promptness of treatment initiation. The sliding scale ensures that insulin therapy will be given when hyperglycemia is first recognized. The regimen is easily implemented in general surgical and medicine areas, and does not depend on locating the attending physician or housestaff concerning the necessary insulin dosage. The use of regular insulin per sliding scale, however, as a single insulin regimen in hospitalized subjects is not supported by the literature and has never been associated with improved clinical outcome. A search of MEDLINE for the period from 1966 to 2003 with the terms “sliding scale insulin,” “sliding scale,” and “sliding” combined with “insulin” yielded a total of 52 publications, none of which showed a benefit of sliding scale insulin in improving glycemic control or clinical outcome. In fact, these clinical studies and reviews concluded that the use of sliding scale insulin is an inappropriate approach to blood glucose control in diabetic patients,37 and that the hazards of its use exceed the advantages of its convenience. There are several problems associated with the sliding scale insulin regimen.16,19,29,38 The regimen therapy treats hyperglycemia after it has already occurred instead of preventing the occurrence of hyperglycemia. This “reactive” approach can lead to rapid changes in blood glucose levels, exacerbating both hyperglycemia and hypoglycemia.12,13,37 Several studies have evaluated the efficacy of sliding scale insulin therapy. Gearhart et al17 evaluated the out-

comes of patients admitted for the treatment of diabetic ketoacidosis. These authors found that the median blood glucose level was 262 mg/dL and that the length of stay was 6.3 days in sliding scale-treated patients, compared with 200 mg/dL and 4.4 days, respectively, in patients treated with intermediate and short-acting insulin. MacMillan29 also reported similar problems with the use of sliding scale insulin in children admitted with diabetic ketoacidosis. Subjects treated with sliding scale insulin had a longer duration of ketosis and worse glucose control than those who received basal insulin. A prospective cohort study by Queale et al39 looked at the effectiveness of sliding scale insulin among 171 adult diabetic patients admitted to an inpatient medical service. Of these patients, 76% were given a sliding scale regimen on admission, sometimes in addition to their usual antidiabetic therapy but often (37%) as the only therapy. Of these, 37% received neutral protamine Hagedorn insulin, 25% received oral agents, and 76% were placed on sliding scale insulin. They found that suboptimal glycemic control was common: Patients treated solely with sliding scale insulin had blood glucose levels greater than 300 mg/dL 3 times more than patients treated with other glucose-lowering therapy. These investigators also observed that in 80% of patients, the diabetes control orders prescribed on admission were not changed during the inpatient stay, despite poor glucose control.

MYTH OR INSANITY? The use of sliding scale insulin could be considered a medical myth. Medical myths are concepts we are taught that are just plain wrong. Myths are usually easy to remem-

566 ber and thus are passed from generation to generation without evidence to support their use.40 Although it has long been recognized that sliding scale insulin has many drawbacks, its use in the inpatient setting has been a reflex action passed down from attending physicians to residents to medical students despite a lack of scientific evidence. A medical myth is an aggressive defensive device used by orthodox medicine to retain the status quo and impede progress in the introduction of new and valuable therapies. Albert Einstein defined insanity as the process of “doing the same thing over and over again and expecting different results.” Despite the simplicity and convenience of the sliding scale insulin regimen, not a single study has shown improvement in glycemic control or clinical outcome. For more than 50 years several editorials and original articles have discouraged its use, as elegantly indicated in a 1963 editorial entitled “Let’s Get the Sliding Scale Out of Medicine.”41 Implementing a standardized subcutaneous insulin order set promoting the use of scheduled insulin therapy is a key intervention in the inpatient management of diabetes. These order sets should encourage basal replacement insulin therapy (ie, neutral protamine Hagedorn, glargine, and detemir) and scheduled nutritional/prandial, short/rapid-acting insulin (ie, regular, aspart, lispro, and glulisine). Examples of such order sets are widely available.13,42 This simple intervention will result in the subsequent substantial improvement in ward patients’ glycemic control and a significant reduction of hyperglycemic and hypoglycemic event rates, thus transforming the medical myth of inpatient glycemic control into reality.

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11.

12. 13. 14.

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16. 17.

18. 19.

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21. 22. 23. 24.

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