Hypothalamic-Pituitary-Adrenal Axis in Critical Illness

Epinephrine (adrenalin) is released from the medulla of the adrenal glands. Epinephrine increases cerebral blood flow and cerebral oxygen consumption and may be the trigger for recruitment of the hypothalamic-pituitary axis.³

The pituitary gland has two parts (anterior and posterior) that function under control of the hypothalamus, as described in Chapter 31.

The posterior pituitary gland releases antidiuretic hormone (ADH), also known as vasopressin (pitressin), as a component of the physiologic stress response. This hormone is an antidiuretic with a powerful vasoconstrictive effect on blood vessels.³ The combination of epinephrine and vasopressin quickly raises blood pressure; it also decreases gastric motility.³ Epinephrine increases heart rate, causes ventricular dysrhythmias in susceptible patients, and provides some analgesia or lack of pain awareness during acute physical stress.³

The anterior pituitary gland produces several hormones including corticotropin (also called ACTH), which stimulates release of cortisol from the adrenal cortex.⁴ Cortisol release is an important protective response to stress. Increased cortisol levels alter carbohydrate, fat, and protein metabolism so that energy is immediately and selectively available to vital organs such as the brain. However, if critical illness is prolonged, the HPA may not be able to respond adequately to prolonged physiologic stress.

The adrenal gland produces cortisol from the cortex and the epinephrine from the medulla. Diminished adrenal gland function may result from a variety of causes during critical illness:

Serum Cortisol Level

Clinical assessment of adrenal dysfunction is difficult in the critically ill, and a specialized laboratory assay is necessary for an accurate diagnosis. First, a baseline serum cortisol level is obtained. Adrenal failure is likely if the cortisol level is less than 10 mcg/dL.⁵

Cosyntropin Stimulation Test

Further confirmation of adrenal dysfunction may be obtained by performance of a corticotropin stimulation test (cosyntropin test). Cosyntropin is a medication made from the first 24 amino acids of corticotropin. In the test, 250 mcg cosyntropin is administered by the intravenous (IV) route, and serum blood levels are measured 30 minutes later. A serum cortisol rise from baseline of less than 9 mcg/dL after 30 minutes denotes inability of the adrenal gland to respond to a stress stimulus (nonresponder).⁵ If the cortisol rise is greater than 9 mcg/dL in response to corticotropin stimulation, the adrenal glands are functioning normally (responder).⁵ Corticosteroids are given only to nonresponders. The combination of a low baseline cortisol value (less than 10 mcg/dL) with minimal or no rise (less than 9 mcg/dL) after cosyntropin stimulation is evidence of adrenal gland dysfunction with corticosteroid deficiency.⁵

Corticosteroid Replacement

Clinical practice guidelines⁵ recommend short-term provision of low-dose hydrocortisone for patients who have a diagnosis of septic shock with refractory vasopressor-dependent hypotension. Hydrocortisone is the recommended replacement because it is the pharmacologic steroid that most resembles endogenous cortisol.

The guidelines recommend use of the cosyntropin stimulation test as described previously. However, the test is not recommended as a stand-alone method to identify patients who might receive low-dose steroids. This apparent contradiction is explained by the fact that several clinical trials of low-dose steroid replacement in sepsis have demonstrated a faster resolution of the shock symptoms but no difference in overall mortality compared with placebo.⁵ High-dose steroid replacement is never recommended in the management of sepsis. Corticosteroids are never discontinued abruptly and must be tapered gradually over several days.⁵

Liver and Pancreas in Critical Illness

The liver releases the hormone glucagon to stimulate the liver to pour additional glucose into the bloodstream in response to physiologic stress. Glucagon rapidly raises blood glucose levels. Peripheral tissues may become insulin resistant, meaning the tissues are unable to use the available insulin to transport glucose inside the cells. This further raises blood glucose levels, causing persistent stress-induced hyperglycemia.⁶ There is a second metabolic system that enables insulin to enter the cell (see Chapter 31). The insulin-independent glucose transporters (GLUT 1, GLUT 2, and GLUT 3) are active during physiologic stress, but may be unable to keep up with the massive increase in glucose production by the liver. Continuous infusion of insulin to return and maintain blood glucose levels within a safe, near-normal range reduces morbidity and mortality.²

Clinical Practice Guidelines Related to Blood Glucose Management in Critically Ill Patients

As a result of the studies just described, clinical practice guidelines were developed by the American Association of Clinical Endocrinologists (AACE) and the American Diabetes Association (ADA) that recommend the use of continuous insulin infusions to maintain blood glucose in critical care patients between 140 and 180 mg/dL, with frequent monitoring of blood glucose.² The 140 to 180 mg/dL level was selected to minimize the risk of hypoglycemia.

Other glucose-control guidelines relevant to critical illness have also been published. The Society of Critical Care Medicine (SCCM) recommends initiating glycemic control when the blood glucose rises above 150 mg/dL.1,10 Insulin management must be initiated if the blood glucose level is above 180 mg/dL.^2,10 More liberal glucose control represents the current trend of targeted values.

Frequent Blood Glucose Monitoring

Monitoring the blood glucose with a point-of-care glucometer is the basis of targeted glucose control. As part of the comprehensive initial assessment, the blood sugar is measured by a standard laboratory sample or by a finger-stick capillary blood sample. In many institutions, if the blood sugar is greater than 180 mg/dL, the patient is started on a continuous IV insulin infusion. While the glucose is elevated, blood sample measurements are usually obtained hourly, to allow titration of the insulin drip to lower blood glucose.¹¹ After the patient is stable, blood glucose measurements can be spaced approximately every 2 hours, based on individual hospital protocols.

Several different blood-sampling methods are available. A capillary finger-stick is perhaps the easiest initial option, although the fingers can become noticeably marked if there are numerous sticks over several days. Trauma to the fingers is also exacerbated if peripheral perfusion is diminished. If a central venous catheter (CVC) or an arterial line with a blood conservation system attached is in place, this can be a highly efficient system for sampling, because there is no blood wastage. If a blood conservation setup is not attached, use of the venous or arterial catheter for access is unacceptable because of the quantity of “waste” blood that would be discarded.

Continuous Insulin Infusion

Many hospitals use insulin infusion protocols for management of stress-induced hyperglycemia that are implemented by the critical care nurse.2,11 Effective glucose protocols gauge the insulin infusion rate based on two parameters: 1) the immediate blood glucose result and 2) the rate of change in the blood glucose level since the last hourly measurement. The following three examples illustrate this concept:

The important point to emphasize is that the rate of change of the blood glucose is as important as the most recent blood glucose measurement.¹¹ Each of the patients described in the examples may have the same insulin infusion rate, depending on their catabolic state, but individualization among patients with different diagnoses can be safely achieved as long as the rate of change is also considered.

A person’s insulin requirement often fluctuates over the course of an illness. This occurs in response to changes in the clinical condition, such as development of an infection, caloric alterations caused by stopping or starting enteral or parenteral nutrition, administration of therapeutic steroids, or because the person is less catabolic. A method to allow for corrective incremental changes (up or down) to adapt to the reality of clinical developments and maintain the glucose within the target range is essential. Some protocols alter only the infusion rate, whereas others incorporate bolus insulin doses if the glucose concentration is greater than a pre-established threshold (e.g., 180 mg/dL). Typically, after the blood glucose has remained within the target range for a number of hours (varies according to the hospital protocol), the time interval between measurements for blood glucose monitoring may be extended to every 2 hours.

Transition from Continuous to Intermittent Insulin Coverage

The transition from a continuous insulin infusion to intermittent insulin coverage must be handled with care to avoid large fluctuations in blood glucose levels. Before the conversion, the regular insulin infusion should be at a stable and preferably low rate, and the patient’s blood glucose level should be maintained consistently within the target range. The transition from IV to subcutaneous administration depends on numerous factors, including whether the patient is able to eat a consistent amount of dietary carbohydrate.¹²

Clinicians use various methods to calculate the quantity of insulin to prescribe during the transition from IV to subcutaneous insulin to maintain stable blood glucose levels. Figure 33-1 depicts hypothetical examples of how a combination of basal and bolus insulin regimens (prandial insulin) can work in clinical practice. The following paragraphs describe the application of one calculation method for a 67-year-old patient, Alice Smith, who is recovering from critical illness and has recently been weaned from the ventilator and extubated.

After the transition to subcutaneous insulin, the dosage is adjusted based upon the patient’s insulin sensitivity, or stated another way, according to how much insulin is needed for each 15 grams of carbohydrate intake. Patients who are insulin resistant require more insulin than those who are insulin sensitive.

Table 33-2 describes the various types of insulin available for use. These include ultra–short-acting, short-acting, intermediate-acting, long-acting, and combination insulin replacement options.¹³ Even after the transition to subcutaneous insulin is completed, blood glucose is monitored frequently to maintain blood glucose within the target range and detect hyperglycemia or hypoglycemia.¹⁴

Corrective Insulin Coverage

A patient may be prescribed supplemental or corrective doses of insulin in addition to the basal/prandial insulin combination. The use of the trio of basal, prandial, and corrective insulin is designed to eliminate the use of the traditional sliding scale. Criticisms of the sliding scale method are that the dosages are rarely re-evaluated or adjusted once established and that the scales treat hyperglycemia only after it has occurred; they are not proactive in the manner of the basal/bolus/corrective insulin method.¹¹

Monitor Hyperglycemic Side Effects of Vasopressor Therapy

Two vasopressors frequently used as continuous infusions to counteract hypotension also raise blood glucose. Epinephrine and norepinephrine stimulate gluconeogenesis (creation of new glucose), increase liver glycogenolysis (glucose production), increase lipolysis (fat breakdown), suppress insulin secretion, and increase peripheral insulin resistance. All of these actions increase blood glucose.

Administer Prescribed Corticosteroids

Critically ill patients with below-normal cortisol levels may be prescribed IV hydrocortisone.¹ Therapeutic steroids raise blood glucose levels and can make glycemic control more difficult. Frequent monitoring of the blood glucose concentration is necessary to guide treatment of hyperglycemia in the patient receiving IV corticosteroids. Ongoing monitoring for the presence of new infection is mandatory.

Monitor Blood Glucose, Insulin Effectiveness, Avoid Hypoglycemia

The critical care nurse is responsible for the hourly monitoring of blood glucose and titration of the insulin infusion according to the hospital’s protocol while the patient is hyperglycemic. The use of standardized protocols makes possible a systematic approach to the control of blood glucose. It is essential and recommended that nurses receive effective and ongoing education about the anabolic impact of insulin therapy in critical illness.² Hospital protocols to minimize development of hypoglycemia, such as using the 140-180 mg/dL target range,² and rapid reversal of any occurrence of severe hypoglycemia (below 40 mg/dL) by provision of IV dextrose (D₅₀W) are essential.¹⁰

Provide Nutrition

Whenever an insulin infusion is started to lower blood glucose, enteral nutritional support should be considered. In the absence of nutrition, a 10% dextrose solution may temporarily be infused. The 10% dextrose offers the advantage of carbohydrate calories for metabolism, limits fluctuations in the blood sugar, and reduces the risk of hypoglycemia. After the patient’s metabolic condition is stable, introduction of non-glucose nutrition (protein and fat) is recommended.¹⁵

Patient Education

While the patient is acutely ill, most of the educational interventions are directed to the family at the bedside. Numerous explications are required to describe the IV medications, the nutritional needs, the purpose of insulin, the role of steroids (if applicable), the ongoing nursing care, prevention of complications, and management of the underlying disease process. Educational issues that may be discussed are listed in the Box 33-2.

Types of Diabetes

Two distinct types of diabetes are discussed in this chapter¹⁷:

The two diseases are different in nature, cause, treatment, and prognosis. A further category of prediabetes describes patients with impaired fasting glucose (FPG between 100 and 125 mg/dL) who are likely to develop diabetes in the future and who are at increased risk for coronary artery disease and stroke.¹⁶ Other conditions, such as gestational diabetes, are not discussed in this chapter.

Glycated Hemoglobin

For individuals with diabetes, maintenance of blood glucose within a tight normal range is fundamental to avoid the development of microvascular and neuropathic secondary conditions. Although the plasma glucose produces a snapshot of the blood glucose concentration at a single point in time, the glycated hemoglobin (HbA_1C), also known as a glycosylated hemoglobin, measures the percentage of glucose the red cells have absorbed from the plasma over the previous 3-month period. The optimal target for patients with diabetes is an A_1C value below 6.5%.¹⁶

Management of Type 1 Diabetes

Patients with type 1 diabetes must receive IV or subcutaneous insulin therapy. Treatment with exogenous insulin replacement restores normal entry of glucose into the cells. The range of insulin replacements available is expanding, and it is essential that critical care nurses be knowledgeable about this class of medications (see Table 33-2). Without insulin, the rapid breakdown of noncarbohydrate substrate, particularly fat, leads to ketonemia, ketonuria, and diabetic ketoacidosis (DKA), a life-threatening complication associated with type 1 diabetes (see later discussion).

Lifestyle Management for Type 2 Diabetes

For most patients with type 2 diabetes, a program of weight reduction, increased physical exercise, and a change in diet pattern is the first step.¹⁸ The diet should contain less than 30% of calories from fat, with an increased quantity of whole grains, vegetables, and fruits. Crash diets are discouraged, and a gradual program of weight loss, if needed, is recommended. The exercise program is tailored to the individual but might start with 30 minutes of brisk walking each day if the person was previously sedentary.

Patients who have type 2 diabetes are prone to a wide range of other complications that increase morbidity and mortality. In addition to medications to control blood glucose, patients often require medications to lower their blood pressure, lower their cholesterol and triglyceride levels, treat ischemic heart disease, and manage symptoms of heart failure.16,19

Pharmacologic Management of Type 2 Diabetes

If lifestyle changes are unsuccessful in reversing the pattern of type 2 diabetes, oral noninsulin antihyperglycemic medications are prescribed (Table 33-3).¹⁶ These medications are not oral forms of insulin, because insulin would be destroyed by gastric juices. There are several types of oral agents: sulfonylureas, glinides, biguanides, thiazolidinediones, alpha-glucosidase inhibitors, incretin mimetics, and incretin enhancers. These oral antidiabetic medications work to lower plasma glucose levels by a variety of mechanisms: increasing insulin secretion, increasing sensitivity to insulin, and delaying carbohydrate absorption (Box 33-4). The pharmacologic management of type 2 diabetes is increasingly complex. Current guidelines recommend a patient-focused, individualized approach that includes pharmacologic management and risk factor modification to reduce early mortality from cardiovascular disease.¹⁹

Insulin secretagogues stimulate the secretion of insulin from the pancreatic beta cells. Two medication classes have this action: the second generation sulfonylureas (glyburide, glipizide, glimepiride, and gliclazide), and the meglitinides (repaglinide and nateglinide).¹⁶ The sulfonylureas reduce the A_1C by 1 to 2 percentage points and have a long duration of action. Side effects include hypoglycemia and weight gain.¹⁸

Insulin sensitizers work at two locations in the body. They increase insulin sensitivity in the liver, thereby increasing the ability of insulin to suppress endogenous glucose production, and they increase insulin sensitivity at the peripheral cellular level (fat and muscle), to increase glucose uptake. Two separate classes of medications work in different ways to increase insulin sensitivity.

The biguanides (metformin) increase insulin sensitivity in the liver and have only a minor effect on skeletal muscle. Metformin is considered first-line therapy for patients with type 2 diabetes.18,20 Metformin may be used as monotherapy or be combined with basal insulin or with other oral medications that lower blood glucose.¹⁸ Metformin is associated with a rare risk of metabolic acidosis; gastrointestinal side effects are common.

The thiazolidinediones (TZDs), also known as glitazones (pioglitazone and rosiglitazone), belong to a class of medications called peroxisome proliferator–activated receptor gamma modulators, which increase the sensitivity of muscle, fat, and liver cells to endogenous and exogenous insulin (insulin sensitizers).²¹ Caution is recommended when using these medications with patients who have risk factors for heart failure (pioglitazone and rosiglitazone), or risk factors for myocardial infarction (rosiglitazone).¹⁸

The alpha-glucosidase inhibitors slow digestion of ingested carbohydrates in the proximal small intestine.¹⁸ These medications delay glucose absorption and reduce postprandial hyperglycemia following meals.²² The medications in this class are acarbose and miglitol.¹⁹ A review of the physiology of carbohydrate digestion is helpful to understand how these agents work. Carbohydrates are broken down to absorbable components in the duodenum and upper jejunum. The carbohydrates are digested to oligosaccharides in the small intestine by pancreatic lipase, after which the oligosaccharides are cleaved to monosaccharides by alpha-glucosidase enzymes. The monosaccharides are then available to be absorbed from the intestine into the bloodstream. The alpha-glucosidase inhibitor medications work by decreasing the conversion of carbohydrates from oligosaccharides to monosaccharides, thus limiting the rise in blood glucose that occurs after eating. The most frequently prescribed medication in this class is acarbose, which is nonabsorbable.

A newer class of medications lowers blood glucose by acting on gastric incretin hormones. The main therapeutic target is the incretin hormone glucagon-like peptide-1 (GLP-1), which is secreted from the gastric mucosa in response to food ingestion. GLP-1 stimulates the pancreatic beta cells to produce insulin. See Table 31-3 in Chapter 31 for a description of the incretin hormones’ physiologic effects.²³

Pharmacologic incretin therapies have two different mechanisms of action¹⁶:

A serious complication of type 2 diabetes that, when present, mandates admission to a critical care unit, is hyperglycemic hyperosmolar state (HHS). This severe, sustained elevation of glucose levels leads to a serum hyperosmolality, and if left untreated, it progresses toward cellular dehydration, coma, and death (discussed later).

Hyperglycemia

Hyperglycemia increases the plasma osmolality, and the blood becomes hyperosmolar. Cellular dehydration occurs as the hyperosmolar extracellular fluid draws the more dilute intracellular and interstitial fluid into the vascular space in an attempt to return the plasma osmolality to normal. Dehydration stimulates catecholamine production in an effort to provide emergency support. Catecholamine output stimulates further glycogenolysis, lipolysis, and gluconeogenesis, pouring glucose into the bloodstream.

Fluid Volume Deficit

Polyuria (excessive urination) and glycosuria (sugar in the urine) occur as a result of the osmotic particle load that occurs with DKA. The excess glucose, filtered at the glomeruli, cannot be resorbed at the renal tubule and spills into the urine. The unresorbed solute exerts its own osmotic pull in the renal tubules, and less water is returned to circulation through the collecting ducts. As a result, large volumes of water, along with sodium, potassium, and phosphorus, are excreted in the urine, causing a fluid volume deficit. The serum sodium concentration may be decreased because of the movement of water from the intracellular to the extracellular (vascular) space.²⁴

Ketoacidosis

In the healthy individual, the presence of insulin in the bloodstream suppresses the manufacture of ketones. In insulin deficiency states, fat is rapidly converted into glucose (gluconeogenesis). Ketoacidosis occurs when free fatty acids are metabolized into ketones: acetoacetate, β-hydroxybutyrate, and acetone are the three ketone bodies that are produced. During normal metabolism, the ratio of β-hydroxybutyrate to acetoacetate is 1 : 1, with acetone present in only small amounts. In insulin deficiency, the quantities of all three ketone bodies increase substantially, and the ratio of β-hydroxybutyrate to acetoacetate increases to as much as 10 : 1. β-Hydroxybutyrate and acetoacetate are the ketones responsible for acidosis in DKA. Acetone does not cause acidosis and is safely excreted in the lungs, causing the characteristic fruity odor.

Ketones are measurable in the bloodstream (ketonemia). Blood tests that measure the quantity of β-hydroxybutyric acid, the predominant ketone body in the blood, are the most useful.²⁴ Because ketones are excreted by the kidney, they are also measurable in the urine (ketonuria). Ketone blood tests are preferred over urine tests for diagnosis and monitoring of DKA in critical care. When the blood and urine become clear of ketones, the DKA is resolved.

Acid–Base Balance

The acid–base balance varies depending on the severity of the DKA. The patient with mild DKA typically has a pH between 7.25 and 7.30. In severe DKA, the pH can drop below 7.00 (see Table 33-4).²⁴ Acid ketones dissociate and yield hydrogen ions (H⁺), which accumulate and precipitate a fall in serum pH. The level of serum bicarbonate also decreases, consistent with a diagnosis of metabolic acidosis. Breathing becomes deep and rapid (Kussmaul respirations) to release carbonic acid in the form of carbon dioxide. Acetone is exhaled, giving the breath its characteristic fruity odor.

Gluconeogenesis

Gluconeogenesis is the process of breaking down fat or protein to make new glucose. Fat is metabolized to ketones, as described earlier. Protein used for gluconeogenesis leaves no reserve protein available for synthesis and repair of vital body tissues. Nitrogen accumulates as protein is metabolized to urea. Urea, added to the bloodstream, increases the osmotic diuresis and accentuates the dehydration.

Laboratory Studies

Considering the complexity and potential seriousness of DKA, the laboratory diagnosis is straightforward. With a known type 1 diabetic patient, the presence of hyperglycemia and ketones provides rapid diagnostic confirmation of DKA. A blood gas sample can confirm the acid–base imbalance. Other clues may be gleaned from the venous blood chemistry panel. CO₂, if measured, is low in the presence of uncompensated metabolic acidosis, and the anion gap is elevated. Serum sodium may be low as a result of the movement of water from the intracellular space into the extracellular (vascular) space.²⁴ The serum potassium level is often normal; a low serum potassium level in DKA suggests a significant potassium deficiency may be present.²⁴

Reversing Dehydration

The patient with DKA is dehydrated and may have lost 5% to 10% of body weight in fluids. Aggressive IV fluid replacement is provided to rehydrate the intracellular and extracellular compartments and prevent circulatory collapse (Fig. 33-3).²⁴ Assessment of hydration is an important first step in the treatment of DKA.

Intravenous isotonic normal saline (0.9% NaCl) is infused to replenish the vascular deficit and to reverse hypotension. For the severely dehydrated patient, 1 L of normal saline is infused immediately. Laboratory assessment of serum osmolality and the serum sodium concentration can help guide the subsequent interventions. If the serum osmolality is elevated and serum sodium is high (hypernatremia), infusions of hypotonic sodium chloride (0.45) follow the initial saline replacement. The replacement infusion typically includes 20 to 30 mEq of potassium per liter to restore the intracellular potassium debt, provided kidney function is normal (see Fig. 33-3).²⁴ In patients without normally functioning kidneys and in those with cardiopulmonary disease, careful attention must be paid to the volume of fluid replacement to avoid fluid overload.

After the serum glucose level decreases to 200 mg/dL, the infusing solution is changed to a 50/50 mix of hypotonic saline and 5% dextrose. Dextrose is added to replenish depleted cellular glucose as the circulating serum glucose decreases to 200 mg/dL.²⁴ Dextrose infusion also prevents unexpected hypoglycemia when the insulin infusion is continued but the patient cannot take in sufficient carbohydrate from an oral diet.

Replacing Insulin

In moderate to severe DKA, an initial IV bolus of regular insulin at 0.1 unit for each kilogram of body weight may be administered. Subsequently, a continuous infusion of regular insulin at 0.1 unit/kg/hr is infused simultaneously with IV fluid replacement (see Fig. 33-3).²⁴ In a 70-kg adult, the infusion would be 7 units of insulin per hour. If the plasma glucose concentration does not fall by 50 to 70 mg/dL during the first hour of treatment, the glucose measurement should be rechecked. When the plasma glucose level is decreasing as expected, the insulin infusion will be increased each hour until a steady glucose decline of between 50 and 70 mg/dL per hour is achieved.²⁴

Frequent assessment of the patient’s blood glucose concentration is mandatory in moderate to severe DKA. Initially, blood glucose tests are performed hourly. The frequency then decreases to every 2 to 4 hours as the patient’s blood glucose level stabilizes and approaches normal. After the level has decreased to 200 mg/dL, the acidosis has been corrected, and rehydration has been achieved, the insulin infusion rate may be decreased to 0.05 to 0.1 unit/kg/hr. This usually represents 3 to 6 units per hour in an adult receiving a continuous IV insulin infusion. It is important to verify that the serum potassium concentration is not lower than 3.3 mEq/L and to replace potassium if necessary, before administering the initial insulin bolus.²⁴

Reversing Ketoacidosis

Replacement of fluid volume and insulin interrupts the ketotic cycle and reverses the metabolic acidosis. In the presence of insulin, glucose enters the cells, and the body ceases to convert fats into glucose.

Adequate hydration and insulin replacement usually correct the acidosis, and this treatment is sufficient for many patients with DKA. As shown in Figure 33-3, replacement of bicarbonate is no longer routine except for the severely acidotic patient with a serum pH value lower than 7.0.²⁴ An indwelling arterial line provides access for hourly sampling of arterial blood gases (ABGs) to evaluate pH, bicarbonate, and other laboratory values in the patient with severe DKA.

Hyperglycemia usually resolves before the ketoacidemia does.²⁴ Type 1 diabetes patients with DKA can require 6 L of IV fluid replacement even for mild DKA.²⁵ In one clinical report, patients with previously diagnosed type 1 diabetes in DKA took an average of 21 hours after being started on an IV insulin protocol to clear ketones from the urine. The insulin infusion was continued for 36 hours until the patients could tolerate an oral diet; during this time, the patients received a total of 9.5 L of normal saline for rehydration.²⁶ Patients who are newly diagnosed with type 1 diabetes take longer to clear urine ketones and require more insulin to achieve normal glycemic control, compared with long-term diabetics.²⁶

Replenishing Electrolytes

Low serum potassium (hypokalemia) occurs as insulin promotes the return of potassium into the cell and metabolic acidosis is reversed. Replacement of potassium by administration of potassium chloride (KCl) begins as soon as the serum potassium falls below normal. Frequent verification of the serum potassium concentration is required for the DKA patient receiving fluid resuscitation and insulin therapy.

The serum phosphate level is sometimes low (hypophosphatemia) in DKA. Insulin treatment may make this more obvious as phosphate is returned to the interior of the cell. If the serum phosphate level is less than 1 mg/dL, phosphate replacement is recommended.²⁴

Administering Fluids, Insulin, and Electrolytes

Rapid IV fluid replacement requires the use of a volumetric pump. Insulin is administered intravenously to patients who are severely dehydrated or have poor peripheral perfusion, to ensure effective absorption. Patients with DKA are kept on NPO status (nothing by mouth) until the hyperglycemia is under control. The critical care nurse is responsible for monitoring the rate of plasma glucose decline in response to insulin. The goal is to achieve a fall in glucose levels of approximately 50 to 70 mg/dL each hour.²⁴ The coordination involved in monitoring blood glucose, potassium, and often blood gases on an hourly basis is considerable.

When the blood glucose level falls to 200 mg/dL, a 5% dextrose solution (D₅W) with 0.45% NaCl solution is infused to prevent hypoglycemia.²⁴ At this time, it is likely that the insulin dose per hour will also be decreased. The regular insulin drip is not discontinued until the ketoacidosis subsides, as identified by absence of ketones and a normal pH by arterial blood gas analysis.²⁴

Insulin is given subcutaneously after glucose levels, dehydration, hypotension, and acid–base balance are normalized; the patient is in stable condition and taking an oral diet.

Monitoring Response to Therapy

Accurate intake and output (I&O) measurements must be maintained to monitor reversal of dehydration. Hourly urine output is an indicator of kidney function and provides information to prevent overhydration or insufficient hydration. Vital signs, especially heart rate (HR), hemodynamic values, and blood pressure (BP), are continuously monitored to assess response to the fluid replacement. Evidence that fluid replacement is effective includes normal central venous pressure (CVP), decreased HR, and normal BP. Box 33-6 lists the standard features to be included in an assessment of hydration status. More invasive hemodynamic monitoring, such as a pulmonary artery catheter, is rarely needed. Further evidence of hydration improvement includes a change from a previously weak, thready pulse to a pulse that is strong and full, and a change from hypotension to a gradual elevation of systolic BP. Respirations are assessed frequently for changes in rate, depth, and presence of the fruity acetone odor.

Blood glucose is measured each hour in the initial period. Sometimes potassium is measured just as frequently. The serum osmolality and serum sodium concentration are evaluated, and blood urea nitrogen (BUN) and creatinine levels are assessed for possible kidney impairment related to decreased renal perfusion. The purpose of these frequent assessments is to determine that the patient’s clinical status is improving. After the patient has stable laboratory indicators and is awake and alert, the transition to subcutaneous insulin and an oral diet can be made. Hypoglycemia is a risk during the transition period. For example, in anticipation of discontinuing the insulin and IV dextrose infusion, a patient receives a subcutaneous dose of insulin and is expected to eat a meal. However, if the patient is then unable to eat an adequate amount, hypoglycemia results from the administration of subcutaneous insulin without adequate glucose.

Surveillance for Complications

The patient in DKA can experience a variety of complications, including fluid volume overload, hypoglycemia, hypokalemia or hyperkalemia, hyponatremia, cerebral edema, and infection.