Complete Nurse's Guide to Diabetes Care, 3rd Edition

Chapter 9:

Acute Complications of Diabetes

Irl B. Hirsch, MD,1 and Belinda P. Childs, APRN, BC-ADM, CDE2

1Hirsch is a professor of medicine at the University of Washington School of Medicine in Seattle, WA. 2Childs is executive director and diabetes clinical nurse specialist at Great Plains Diabetes in Wichita, KS.

Diabetic ketoacidosis (DKA), hyperosmolar hyperglycemic syndrome (HHS), and hypoglycemia are the most common acute complications of diabetes. To prevent significant mortality and morbidity, it is important for the health-care provider and the individual with diabetes to identify the symptoms and institute appropriate treatment promptly.

DKA AND HHS

Epidemiology

Despite the fact that insulin was first used clinically >90 years ago, hyperglycemic crisis continues to be a major public health problem. DKA accounts for 14% of all hospital admissions of patients with diabetes and 16% of all diabetes-related fatalities. By 2009, DKA had a crude and age-adjusted rate of 7.1/1,000 and 22.0/1,000 patients with diabetes, respectively.1 Hospitalizations for DKA are increasing in the U.S.2 Hospital discharges for DKA increased from 80,000 in 1988 to 140,000 in 2009.3 The length of stay (LOS) for DKA continues to drop, and by 2009, the mean LOS was 3.4 days.4 HHS, which is more difficult to quantify, is thought to account for <1% of all hospitalizations of people with diabetes.2 According to the U.S. National Hospital Discharge Survey funded by the National Center for Health Statistics, from 1989 to 1991, 10,800 people were discharged annually for HHS in the U.S. As the prevalence of type 2 diabetes (T2D) increases, the incidence of HHS likely will increase as well.2

The cost of treating DKA is staggering, with a current estimated cost of $2.4 billion annually.5 Even more alarming is that DKA is responsible for $1 out of every $4 spent on direct medical care for adult patients with type 1 diabetes (T1D) in the U.S. The mortality rates in experienced centers are <5% for DKA and ~11% for HHS, and the rates increase with age and comorbidities.5 Death from DKA is the most common cause of death in children with T1D. In adults, it is alarming that DKA was the etiology of death in 7.5% of subjects in the Epidemiology of Diabetes Interventions and Complications (EDIC) study.6 Deaths associated with either DKA or HHS more often are due to the underlying precipitating factor than to the metabolic crisis itself.

Pathophysiology

DKA consists of the triad of hyperglycemia, ketonemia, and acidemia. The American Diabetes Association (the Association) classifies DKA by level of acidemia and level of stupor. Although infection usually is thought of as the most likely precipitating factor, omission of insulin is actually the most common etiology in both the U.S. and Europe. This omission may occur from the inability to obtain the insulin for financial reasons, as part of an eating disorder, or as part of some other type of psychological disease process, Significant family dysfunction for the majority of families has been observed in clinical studies of adolescents with recurrent DKA.7

Up to 20% of cases of DKA or HHS may present without a previous diagnosis of diabetes. HHS, more often a disease of the elderly, can be caused by acute illness or drug therapy. DKA most commonly would include an infection, such as pneumonia or sepsis; a vascular event, such as a myocardial infarction or cerebrovascular accident; or acute pancreatitis. Agents that can increase glucose significantly and perhaps lead to HHS include agents such as glucocorticoids, diazoxide, diuretics, and β-blockers. The new class of medication for T2D, sodium-glucose co-transporter 2 (SGLT-2) inhibitors, recently has been reported to be associated with DKA. The glycosuria enhanced by these agents results in glucose levels generally <300 mg/dL (16.6 mM) if not much lower. Despite the mild hyperglycemia, hepatic lipolysis and ketogenesis can proceed unchecked if insulin availability is not sufficient, and a condition called “euglycemic DKA” can ensue. In both DKA and HHS, the fundamental defect is a decrease in the net effective concentration of insulin coupled with a massive elevation of the counterregulatory hormones (glucagon, cortisol, growth hormone, and epinephrine). In DKA, the insulin deficiency is either absolute or relative in relation to the counterregulatory hormones that overwhelm the body’s ability to suppress lipolysis. In HHS, a residual amount of insulin suppresses ketosis but cannot control hyperglycemia. This leads to severe dehydration and impaired renal function that eventually leads to even more severe hyperglycemia. For this reason, hyperglycemia is more profound in HHS than in DKA.

At both the molecular and cellular levels, our understanding of both of these conditions has improved substantially during the past 40 years. As is the case with chronic vascular complications of diabetes, we now appreciate that these two conditions are proinflammatory states generating oxidative stress. Despite this understanding, what has not changed is that many of these hyperglycemic crises are preventable and that prevention is the fundamental goal.

Assessment and Clinical Presentation

DKA and HHS are both medical emergencies that require a brief but directed assessment. Key issues that require special assessment include 1) airway patency, 2) mental status, 3) cardiovascular and renal status, 4) possible source of infection, and 5) state of hydration. The presentation of DKA and HHS has many similarities as well as some subtle differences. Table 9.1 presents the similarities and differences. DKA usually presents quickly, often over the span of 24 h, whereas HHS usually presents over several days because the level of consciousness often decreases in a less acute manner. DKA also is associated more often with nausea, vomiting, and abdominal pain. The classic rapid deep breaths observed with acidosis (Kussmaul breathing) generally are not seen with HHS. The fruity breath associated with DKA is a result of acetone loss through the lungs. Patients with HHS are more often hyperosmolar than those with DKA; thus, obtundation and coma are more common in this group. Another important diagnostic detail for those with HHS is that even though infection is a common precipitating event, fever is rare.

Table 9.1—Comparison of DKA and HHS

 

DKA

HHS

Features

Age of patient

Usually <40 years

Usually >60 years

Duration of symptoms

Usually <2 days

Usually >5 days

Glucose level

Usually <600 mg/dL (<33 mmol/L)

Usually >800 mg/dl (>44 mmol/L)

Sodium concentration

Likely normal or low

Likely normal or high

Potassium concentration

High, normal, or low

High, normal, or low

Bicarbonate concentration

Low

Normal

Ketone bodies

Present

Usually absent

pH

Low, <7.3

Normal

Serum osmolality

Usually <350 mOsm/kg

Usually >350 mOsm/kg

Cerebral edema

Often subclinical

Rare

Assessment

Skin

Flushed: dry, warm

Pallor: moist, cool

Breath

Fruity, acetone

Normal

Vital signs

Blood pressure decreased, pulse increased

Blood pressure decreased, pulse increased, afebrile

Gastrointestinal

Severe abdominal pain, nausea, vomiting

Mild abdominal pain, nausea, vomiting

Mental status

Lethargic

Lethargic

Prognosis

<5% mortality

~11% mortality

In a patient with known diabetes, a presumptive diagnosis usually can be made quickly by a capillary glucose measurement and a urine dipstick. Because patients with DKA may present to the outpatient clinic, these tests are relatively easy to obtain, but for the obtunded individual in an emergency room, a urinary catheter often is required. Nevertheless, for definitive diagnosis, laboratory studies are needed.

Practical Point

Euglycemic DKA can be seen in surgical patients with T1D when adequate intravenous fluids are given to prevent dehydration but insulin is either withheld or administered in doses too low to prevent ketosis. It also has been reported in patients with T1D and T2D receiving SGLT-2 inhibitors.

Labs and Tests

For either of the hyperglycemic emergencies, it is necessary to send stat labs for plasma glucose, electrolytes, urea nitrogen, creatinine, complete blood count (with differential), serum β-hydroxybutyrate, and arterial blood gas. The severity of the DKA is determined by the degree of acidemia and mental status: pH <7.24 and a stuporous level of consciousness is considered “moderate” DKA, whereas pH <7.00 with coma is considered “severe.” Many mild cases of DKA, especially in the absence of abnormalities in mental status, can be managed in an outpatient setting or after volume repletion in an emergency room.

The initial urinalysis may need to be interpreted with caution. Urine (and for that matter, serum) ketones may be evaluated by the nitroprusside reaction, which is a semiquantitative test for acetoacetate and acetone but not for β-hydroxybutyrate, the main keto acid of DKA.5 Capillary β-hydroxybutyrate assay now can be used at home and in the emergency room, and plasma levels are measured routinely for assessment. Normal levels are <0.5 mmol/L and levels >1.0 mmol/L are clearly elevated. On average, patients presenting with DKA have levels of 9.1 mmol/L.5

With the initial blood draw, if there is no obvious etiology, it is reasonable to draw blood for blood cultures. Obviously, if another etiology becomes apparent, the cultures can be canceled. Similarly, a urine culture should be obtained with the initial laboratory assessment.

Although the electrolytes are being analyzed, an electrocardiogram should be obtained, especially for adults. First, a myocardial infarction can precipitate DKA or HHS. In children, an electrocardiogram can give important clues to hypokalemia or hyperkalemia. Second, if abnormalities are detected with the T-waves, suggesting abnormalities in potassium homeostasis, a telemetry device needs to be placed immediately. Hypokalemia from the treatment of these emergencies was formerly a common cause of mortality; however with adherence to guidelines about preemptive initiation of potassium before overt hypokalemia has developed (A low-dose insulin regimen has the advantage of not inducing the severe hypoglycemia or hypokalemia that may be observed with a high-dose insulin regimen).8

When evaluating laboratory data, it is important to understand two key formulas. Perhaps the most important is the anion gap, defined as the serum sodium − (chloride + bicarbonate). Usually, the anion gap is calculated as part of the electrolyte measurement; if not, the clinician needs to perform the calculation. In modern assays, the normal anion gap is 7–9 mEq/L. An elevated anion gap confirms an unmeasured anion. Although this may include β-hydroxybutyrate (and acetoacetate), the differential diagnosis for an anion gap acidosis includes lactic acidosis, uremic acidosis, salicylate intoxication, ethanol intoxication, rhabdomyolysis, and ethylene glycol intoxication. Numerous different acid–base disturbances need to be diagnosed because both metabolic alkalosis and primary respiratory diseases causing hypoventilation or hyperventilation may be complications and also may present with DKA. Furthermore, a non–anion gap acidosis can be seen in DKA, as can a mixed–anion gap and hyperchloremic acidosis.

The other important formula that needs to be calculated is the total serum osmolality. This is calculated as follows:

2 × [serum sodium (mEq/L)] + [glucose (mg/dL)/18] + [blood urea nitrogen (mg/dL)/2.8]

The normal range for this measurement is 290 ± 5 mOsm/kg. The diagnosis of HHS can be made with a serum osmolality >330 mOsm/kg, usually with a blood glucose level >600 mg/dl and the absence of significant ketonemia.

Several other issues related to laboratory assessment should be considered. The first is that serum creatinine may be elevated falsely because of acetoacetate interfering with the assay. After treatment, the creatinine level usually will return to normal or at least to the baseline level. Next, high amylase levels need to be interpreted cautiously in the initial evaluation of DKA because these may be the result of extrapancreatic secretion. A leukocytosis with very high white blood cell counts is common and does not necessarily reflect an infectious process. Again, with therapy for DKA, the white blood cell count will normalize, but if it remains high after successful treatment, investigation for an occult infection should be considered.

Hyperglycemia will result in a falsely low sodium level because of the movement of water from the intracellular to the extracellular space in the presence of hyperglycemia. To calculate the corrected serum sodium level in the context of hyperglycemia, add 1.6 mEq/L to the measured serus sodium level for every 100 mg/dL glucose above 180 mg/dL.9 If severe hyponatremia is still present after this calculation, other etiologies of hyponatremia need to be considered. Most patients with HHS present with profound hypernatremia, which is indicative of a severe free-water deficit. When the serum sodium is corrected for the hyperglycemia in these patients, the corrected sodium level is often >170 mEq/L.

Special attention needs to be paid to serum potassium levels. First, despite massive kaliuresis from hyperglycemia and often further potassium losses from vomiting, serum potassium levels are usually normal or even high. The reason for this level is that insulin deficiency, acidemia, and hyperosmolarity all result in potassium moving from the cell into the blood. Clinicians should not be misled; potassium levels can drop quickly, leading to life-threatening arrhythmias as fluids and insulin are replaced. For this reason, potassium replacement is a key component of the therapy of DKA and HHS and is the reason many of these patients, especially older patients with possible coronary artery disease at risk for arrhythmias, need to be monitored with telemetry. However, treatment must be initiated before overt hypokalemia has occurred as indicated by monitoring protocols for response of glucose and potassium to initial therapy.10

Treatments

Nursing plays a vital role in the therapy for acute hyperglycemic episodes. Appropriate monitoring is the first important component of therapy. This monitoring is best addressed with a complete flowsheet that includes both physical examination findings (e.g., blood pressure, heart rate) and laboratory results (e.g., glucose, bicarbonate, potassium, phosphate). The flowsheet also should include aspects of therapy (e.g., rate and type of fluid, insulin and potassium rates, bicarbonate and phosphate rates). Table 9.2 presents an example of a flowsheet for tracking DKA therapy. Table 9.3 presents key treatment tips and precautions.

Table 9.2—Suggested DKA/HHS Flowsheet

Table 9.2—Suggested DKA/HHS Flowsheet

Table 9.2—Suggested DKA/HHS Flowsheet, continued

Table 9.3—Acute Complication Treatment Tips and Precautions

• Establish diagnosis; if known to have diabetes and unable to test glucose, assume hypoglycemia and give intravenous glucose or glucagon.

• If triage call, vomiting present, or hyperglycemia, request urine ketone measurement.

• Treat the volume depletion first.

• Insulin should not be replaced until the potassium level is known.

• HHS/DKA usually requires intensive care monitoring for at least 12 h.

• Monitor and replace potassium to prevent life-threatening arrhythmias.

• Cerebral edema is a risk with too rapid correction of blood glucose.

• Consider a major vascular incident in the elderly as etiology for hyperglycemic crisis.

One of the most controversial areas in the treatment of hyperglycemic crisis has been the rate and type of fluids that should be infused. Initially, this should be determined by the volume status of the patient. Supine hypotension signifies an ~20% decrease in extracellular fluid, whereas orthostatic hypotension confirms a 15–20% reduction in extracellular volume. An orthostatic increase in pulse without a change in blood pressure suggests a 10% reduction in extracellular volume. For all of these situations, the first fluid infused should be 0.9% normal saline, administered as quickly as possible over the first hour, followed by 500–1,000 mL/h for the next 2 h of either 0.9% normal saline or 0.45% normal saline, depending on the degree of hydration and the serum sodium level. Even with severe dehydration and hypernatremia, 0.9% normal saline is hypotonic compared with the extracellular fluid. Some authors prefer the initial use of 0.9% saline for the first hour, followed by 0.45% saline unless volume losses are severe and hypotension is not corrected after the first liter of fluid. While others advocate hypotonic saline (0.45% normal saline) from the outset if the effective serum osmolality [calculated as 2 × measured sodium (mEq/L) + glucose (mg/dL)/18] is >320.

Dextrose (5%) should be added to the solution when blood glucose reaches 250 mg/dL (13.9 mmol/L) in DKA or 300 mg/dL (16.6 mmol/L) in HHS. Two main reasons support this approach. First, it allows continued insulin administration to control the ketogenesis in DKA. Furthermore, particularly in children, too rapid a decrease in blood glucose can result in cerebral edema.

Second, once blood pressure is stabilized and glucose levels decrease to the point at which osmotic diuresis is not leading to further water and electrolyte losses, urine volumes also will decrease, allowing a decrease in intravenous fluids. This is critical in young children and older adults, who are at a greater risk of overhydration. The excess of free water from overhydration also can result in cerebral edema. The exact fluid rate will vary depending on the clinical situation, but it generally will range from 4 to 14 mL/kg/h. Although variations are large, the average duration of time that intravenous hydration will be required is ~48 h.

Perhaps the most important point about the use of insulin therapy in either DKA or HHS is that electrolyte levels need to be confirmed before starting an intravenous insulin infusion. In the rare patient who presents with hypokalemia, insulin therapy needs to be postponed until the potassium levels are corrected. Although controversial, most authorities begin the insulin infusion (all human regular insulin) with an intravenous bolus of 0.1–0.15 units/kg, followed by 0.1 units/kg/h. Some endocrinologists will use intramuscular insulin at 7–10 units, except when hypotension is present, in which case only the intravenous route can ensure appropriate absorption. Occasionally, insulin resistance will require much larger doses of insulin than the starting rates previously noted. Even very low doses of insulin will inhibit lipolysis and ketogenesis. When the blood glucose level reaches 250–300 mg/dL (13.3–16.3 mmol/L), the insulin infusion rate can be decreased and the intravenous dextrose added. In general, it is appropriate to measure blood glucose every hour in these patients. The electrolytes can be measured less frequently. The blood glucose should decrease at a rate of 50–70 mg/dL/h (if initial rehydration rate is optimal). If blood glucose is not improving, other etiologies should be investigated, such as patient’s volume status not being corrected or an error in the insulin infusion mixture.

In general, these patients may have a 500–700 mEq/L potassium deficit when they present. Intravenous fluids will increase renal plasma flow, whereas intravenous insulin will result in a movement of potassium from extracellular to intracellular areas. These two events will lead to a profound decrease in serum potassium levels shortly after the treatment of a hyperglycemic emergency. When hypokalemia is present at the onset, potassium levels should be replaced at least to a level of 3.3 mEq/L before insulin is started. These patients also should be monitored with telemetry. In general, potassium replacement should not exceed 40 mEq the first hour and then should be replaced at a level of 20–30 mEq/h after that. Because potassium chloride in addition to the saline used usually will result in hyperchloremia, many authors recommend replacing some of the potassium as either potassium phosphate or potassium acetate. No studies, however, have examined a change of outcomes with these alternative potassium solutions.

Bicarbonate use is also a controversial topic in the treatment of DKA. We have little reason to consider adding bicarbonate for most of those with DKA because acidemia will improve as bicarbonate is generated by the liver, and the ketogenesis is reversed by insulin therapy. In children, it is suggested that therapy with bicarbonate will result in more profound altered consciousness and headache.11 Clearly, the addition of bicarbonate will lead to more profound hypokalemia. For this reason, some authors feel the only indication for the use of bicarbonate therapy is life-threatening hyperkalemia. Controlled trials, however, now are examining the use of bicarbonate therapy in severe acidemia (pH 6.9–7.1).12 The results of these small trials showed no beneficial or adverse effects from the bicarbonate therapy. The Association suggests bicarbonate therapy for those patients who present with severe acidemia (pH <6.9) because of the potential for severe vascular effects.5 The solution never should be given as a bolus, but rather it should be infused as 1 ampoule (50 mmol) into another solution, such as 1 L of 0.45% normal saline.

As with potassium, initial levels of serum phosphate are often normal or increased despite a total-body deficit. Insulin therapy will result in a shift of phosphate into the cell, often resulting in hypophosphatemia during the treatment of DKA and HHS. Other than in the rare situation of the serum phosphate dropping <1 mg/dL, complications from hypophosphatemia are unusual. Furthermore, controlled trials have not demonstrated a benefit from the routine use of phosphate therapy in the treatment of DKA. Current recommendations are to replace phosphate if levels drop <1.0 mg/dL.5 This can be accomplished by adding 20–30 mEq/L of potassium phosphate to the intravenous solution over 2–3 h. The most important complication of phosphate replacement is hypocalcemia, so serum calcium levels need to be monitored during the time period.

Protocols for the management of DKA and HHS are presented in Figure 9.1. These protocols are taken from the Association’s review of hyperglycemic crisis in patients with diabetes.5

Figure 9.1—Mangement for adult patients with DKA or HHS.

Figure 9.1—Management for adult patients with DKA or HHS. DKA diagnostic criteria: blood glucose 250 mg/dL, arterial pH 7.3, bicarbonate 15 mEq/L, and moderate ketonuria or ketonemia. HHS diagnostic criteria: serum glucose >600 mg/dL, arterial pH >7.3, bicarbonate >15 mEq/L, and minimal ketonuria and ketonemia. †15–20 mL/kg/h; ‡ serum Na should be corrected for hyperglycemia (for each 100 mg/dL glucose >180 mg/dL add 1.6 mEq to sodium value for corrected serum value).

Unlike HHS, mild DKA can be managed on an outpatient basis. Patients are encouraged to call their providers when moderate or high urine ketones (or capillary β-hydroxybutyrate) or unmanageable high blood glucose levels are noted. Early replacement of insulin using frequent doses of insulin lispro, insulin aspart, or intramuscular regular insulin (0.1 units/kg) every 2–3 h plus good hydration will allow the individual to decrease the blood glucose levels and restore hydration. Using sports drinks will assist in correcting the electrolyte imbalance. Sugared liquids will be required to prevent a rapid glucose drop from the supplemental insulin. Management principles follow the guidelines for hospital care. If the blood glucose does not decrease within 3–5 h or if vomiting occurs, then the individual needs to be treated at the hospital. Antiemetics are not recommended because vomiting may be the symptom that guides whether the metabolic acidosis is being corrected.

Educational and Behavioral Considerations

The most important area for educational consideration is determining how DKA and HHS can be prevented. Because a large percentage of these patients develop these life-threatening emergencies as a result of insulin omission, factors leading to this need to be explored and attempts need to be made to correct the situation. The patient who returns with a hyperglycemic crisis on a frequent basis must be assessed for underlying causes. These patients (previously termed brittle) often return in crisis because of some other major problem that could be related to a severe psychological stress, an eating disorder, or even major financial troubles that make obtaining insulin difficult. Alternatively, some patients with frequent hospitalizations have waited too long to ask for assistance during a pump malfunction or systemic infection. If the etiology is related to a psychological problem, the patient will require special attention. A referral to a mental health specialist would be appropriate for the vast majority of these patients.

Education of the individual with diabetes and family is essential. See Table 9.4 for educational tips. Patients should be referred to appropriate resources to prevent the next episode.

Table 9.4—Patient Education Tips

Problem

Key Education Points

Insulin omission

Access to care, including insulin supply

Poor storage of insulin, old insulin

Intentional insulin omission or missed insulin in those at risk, e.g., those with disabilities, children, teens, older adults.

Access to ketone monitoring supplies management

Recognition of symptoms of DKA, HHS, and hypoglycemia

Understanding of action needed if ketones present

Access to glucose-containing fluids

Understanding of when to treat

Importance of continuing insulin, even with illness

Guidelines for when to call the health-care provider or emergency medical services

Guidelines, if appropriate, for insulin supplementation during illness

 

Frequent DKA

Referral to mental health professional

Practical Point

Education is the key to the prevention of the acute complications of diabetes: hypoglycemia and hyperglycemia. Nurses should review with patients their strategies for treating high and low blood glucose levels and potential precipitating causes. Reinforce good practices.

HYPOGLYCEMIA

Epidemiology

The classification of hypoglycemia is shown in Table 9.5.13,14 Most patients with T1D have daily if not weekly hypoglycemia. Severe hypoglycemia (requiring the assistance of another person) increases with the duration of diabetes in both T1D and T2D. In those with >40 years duration of T1D seizure or coma from hypoglycemia (a subgroup of severe hypoglycemia) occurs at 19% per year.15 Of individuals with T1D, 30–40% will experience one to three episodes of severe hypoglycemia per year, whereas those with insulin-treated T2D will experience about one-third that number.16 It is estimated that 2–4% of deaths in patients with T1D occur because of hypoglycemia,17 although other studies, including EDIC, show levels as high as 8.4%.6 Iatrogenic (as a result of treatment) hypoglycemia is much less common in T2D. Although hypoglycemia may not be as common in those with T2D, the risk from mortality increases significantly for those who do experience severe hypoglycemia. Hypoglycemic death from sulfonylureas has been documented.

Table 9.5—Classification of Hypoglycemia

Level

Glycemic criteria

Description

Glucose alert value (level 1)

≤70 mg/dL (3.9 mmol/L)

Sufficiently low for treatment with fast-acting carbohydrate and dose adjustment of glucose-lowering therapy

Clinically significant hypoglycemia (level 2)

<54 mg/dL (3.0 mmol/L)

Sufficiently low to indicate serious, clinically important hypoglycemia

Severe hypoglycemia (level 3)

No specific glucose threshold

Hypoglycemia associated with severe cognitive impairment requiring external assistance for recovery

Pathophysiology

Normally, as glucose levels decline, both glucagon and epinephrine levels respond as a protective mechanism against hypoglycemia. In nondiabetic individuals, the glycemic threshold for this counterregulatory response is between 65 and 70 mg/dL (3.6 and 3.9 mmol/L), but this shifts to higher levels in individuals with suboptimally controlled diabetes and to lower levels in diabetic individuals with near-normal A1C levels. The glucagon and epinephrine response will result in an increase of hepatic glucose output in addition to a suppression of glycogenesis. Furthermore, the elevated epinephrine levels will result in the autonomic symptoms frequently seen with hypoglycemia: tremor, palpitations, and anxiety. Common signs include elevated heart rate, pallor, and elevated systolic blood pressure. A cold sweat and hunger appear to be cholinergic (not related to epinephrine). Eventually, if oral or parenteral glucose is not provided, neuroglycopenic symptoms will occur (e.g., nausea, diplopia, confusion, seizures, and even coma may result from profound hypoglycemia). These neuroglycopenic symptoms occur after the autonomic symptoms. Symptoms of hypoglycemia, however, may present differently in the elderly and children. Parents fail to recognize 40–-50% of hypoglycemic episodes in their children with T1D. Some parents and caregivers are able to observe behavior changes or pallor as hypoglycemia.16

The mechanisms for hypoglycemia and hypoglycemia unawareness are better understood in T1D than in T2D. In the former, as endogenous insulin secretion declines, the normal glucagon response to hypoglycemia diminishes to the point that the patient’s only initial response is epinephrine secretion. Furthermore, the brain adapts to antecedent hypoglycemia so that the epinephrine response to hypoglycemia is shifted to a lower plasma glucose level. A severely reduced epinephrine response can be seen in the absence of classic autonomic dysfunction, leading to hypoglycemia unawareness. The presence of autonomic neuropathy, however, typically diminishes the epinephrine response, leading to an even higher risk of severe hypoglycemia.

Hypoglycemia has other major cardiovascular effects and all-cause mortality, many of which have not been appreciated until recently.18 Activation of inflammation, endothelial dysfunction, and coagulopathies all have been noted with hypoglycemia.12 The biggest concern, however, potentially affecting both the young and the elderly, are the proarrhythmic abnormalities initially noted with an increase in the QT interval, potentially leading to life-threatening conduction disturbances.19

For individuals with T2D, the frequency of severe hypoglycemia is similar to that in individuals with T1D when matched for duration of insulin therapy. Given the progressive nature of insulin deficiency in T2D, clinical hypoglycemia becomes a greater problem as endogenous insulin secretion declines. Table 9.6 lists risk factors for the development of hypoglycemia.

Alcohol consumption is a common etiology of hypoglycemia. Alcohol can inhibit gluconeogenesis, especially in a starved state, placing an insulin-requiring patient at high risk for iatrogenic hypoglycemia. Indeed, even individuals without diabetes can develop hypoglycemia from alcohol. In the fed state, alcohol actually may increase hepatic glucose production, thus making alcohol ingestion quite risky because it may be quite difficult to predict the glycemic effects at any given time.20 To further complicate matters, the type of alcohol ingested may alter the glucose. For example, a sweet liqueur may raise the glucose, whereas a dry wine may lower it, depending on the fed state of the individual. Given this wide variability, alcohol can be dangerous and should be ingested in moderation. Furthermore, frequent blood glucose testing should be performed to help guide treatment, especially as it relates to the prevention of hypoglycemia because typical symptoms may be altered.

Labs and Test

Usually, little needs to be done for the diagnosis of insulin- or sulfonylurea-induced hypoglycemia. In a symptomatic patient, a capillary blood glucose level will confirm the diagnosis. Those with hypoglycemia unawareness need to perform more frequent self-monitoring of blood glucose in an attempt to avoid severe hypoglycemia. Often, these patients are found to be hypoglycemic on routine blood checks even though they may not have any symptoms. For many, continuous glucose monitoring has been extremely helpful and use of a sensor-augmented pump with “threshold suspend” has been shown to reduce hypoglycemia exposure.21

Treatment

Most episodes of symptomatic and asymptomatic (found by checking blood glucose) hypoglycemia can be treated with the ingestion of oral carbohydrate. This carbohydrate may be in the form of glucose tablets, juice, milk, or crackers. The vast majority of these cases can be treated with 15–20 g carbohydrate. This step can be repeated in 15–20 min if the symptoms have not improved or if the blood glucose level has not increased. The most common mistake made by patients is to overtreat the hypoglycemic episode because of insatiable hunger, failure of the symptoms to resolve immediately, or fear of a continuing drop in glucose levels. All too often this results in posthypoglycemic hyperglycemia because additional insulin is not injected for the extra food ingested.

Treating Severe Hypoglycemia

Parenteral therapy is required when the patient is unable to take carbohydrate orally. Crushed glucose tablets or gel should not be placed in the mouth or rubbed onto the buccal mucosa of a person who is not able to swallow. Glucagon or intravenous glucose is the only remedy. Family members or caregivers often administer subcutaneous or intramuscular glucagon to patients with T1D. Glucagon is less helpful for individuals with T2D because it stimulates insulin secretion as well as glycogenolysis. After glucagon administration, the patient often will experience nausea, vomiting, and headache.

When possible, intravenous glucose is the preferred treatment for severe hypoglycemia. The usual treatment is 10–25 g of 50% dextrose administered over 1–3 min. Blood glucose level should be checked after completion of the administration. Doses are variable, based on the weight of the individual, the type of diabetes, and the cause of the hypoglycemia. A continuous glucose infusion of 10% dextrose may be needed because the glucose bolus is transient. In patients who are unable to ingest oral carbohydrates or those with sulfonylurea-induced hypoglycemia, the hypoglycemia may be prolonged.

A patient who has been treated for hypoglycemia with glucagon or intravenous glucose should be provided oral carbohydrates as soon as he or she is able to eat.

Hypoglycemia Unawareness

Hypoglycemia unawareness is defined as the loss of the epinephrine-mediated warning symptoms of hypoglycemia. Lack of hypoglycemia awareness is associated with hypoglycemia frequency. The more hypoglycemia a patient experiences, the lower the threshold for symptoms. Fortunately, clinical trials have shown that this type of hypoglycemia unawareness may be reversed by strict avoidance of hypoglycemia. Most clinicians advise individuals with hypoglycemia unawareness to measure their glucose before driving. If the individual is not using a continuous glucose sensor, it would seem prudent for these individuals to measure their blood glucose when driving more frequently if the trip is during a time of suspected glycemic reduction (e.g., after exercise or 1–2 h after injecting a rapid-acting analog; see Table 9.6).

Table 9.6—Risk Factors for Hypoglycemia

Risk Factors

Possible Causes

Insulin excess

Too much insulin, insulin secretagogue, or insulin sensitizer; taken at the wrong time or wrong type

Decreased exogenous glucose

Missed meal or snack; not enough food

Overnight fast

Decrease in endogenous glucose production

Alcohol

Increased glucose utilization

Too much exercise or activity without enough food

Increased insulin sensitivity

Late after exercise

Improved fitness

Weight loss

Use of an insulin sensitizer

Middle of the night

Decreased insulin clearance

Renal failure, newly diagnosed or inadequately treated hypothyroidism

Compromised glucose counterregulation

Insulin deficiency, history of severe hypoglycemia, aggressive therapy and glucose goals, lower A1C

Educational AND Behavioral Considerations

All patients at risk for iatrogenic hypoglycemia need to learn typical symptoms and treatment. Aspects that require review include strategies for prompt oral treatment and avoidance of overtreatment (see Table 9.7). Family members and caregivers of individuals with T1D need training in the use of subcutaneous or intramuscular glucagon. Published education programs have shown improvements of hypoglycemia awareness and severe hypoglycemia, but without adverse impact to A1C levels.22

Table 9.7—Reduction and Treatment of Hypoglycemia Unawareness

Goal

Actions

Decrease symptoms of hypoglycemia

Rigorous avoidance of hypoglycemia

Increased glucose monitoring

Increase glucose targets for at least 3 weeks

Assist patient in identifying nonclassic symptoms

Possible: Blurred vision, numbness in limbs or lips, nausea, many others

Encourage documentation in symptom log

Log should include exercise, food, insulin timing

Use log to identify atypical symptoms and patterns

Secure assistance at work, school, and home medical services

Identification and training of family, friends, and

coworkers to give glucagon and know when to call emergency

For those individuals treated with insulin and insulin secretagogues, clinicians and educators should assess for the risk of hypoglycemia at every visit. A hypoglycemia patient questionnaire should be completed by the individual at each visit (see Table 9.8). The questions provide an opportunity to identify individuals who are at greatest risk for future hypoglycemia and to educate individuals on prevention, and early and appropriate hypoglycemia treatment.

Table 9.8—Hypoglycemia Patient Questionnaire

Table 9.8—Hypoglycemia Patient Questionnaire

Patients who develop a severe fear of hypoglycemia (usually after one or more episodes of severe hypoglycemia) require special attention. Families also can become extremely fearful. The provider needs to appreciate that this fear can be overwhelming and that individuals may intentionally maintain extremely high blood glucose levels because of this fear. Often, they require psychological counseling. Slowly lowering glycemic targets over time can be an effective method to address this fear and return to glycemic goals.

SUMMARY

Prevention is the key to effective management of the acute complications of diabetes. These complications are costly, not only in the expenditure of health-care dollars but also in the decrease in the quality of life for people with diabetes.

Specific protocols, order sets, treatment algorithms, and clinical pathways should be developed and implemented to guide the best practices in the hospital (see Chapter 32, Diabetes and Cancer. Nurses should take a leadership role in developing and implementing these clinical pathways. The nurse’s monitoring of the patient with DKA and HHS will be crucial. Preventing future episodes of DKA or HHS will depend on patient and family or caregiver education. Managing mild DKA and hypoglycemia at home requires patients and families who are well educated. The nurse should take every opportunity to assess the patient’s and the family’s knowledge levels and ability to prevent and treat hyperglycemia and hypoglycemia.

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