Jaslok Hospital and Research Centre,
Diabetic Ketoacidosis (DKA) and Hyperglycemic Hyperosmolar Nonketotic state (HONK or HHS) are the two most serious acute hyperglycemic complications of diabetes. They continue to be important causes of morbidity and mortality among patients with diabetes in spite of major advances in the understanding of their pathogenesis and more uniform agreement about their diagnosis and treatment.
Although DKA is usually associated with people with Type 1 DM, it is also often seen in people with Type 2 DM. HONK is more typically seen in the older Type 2 patient.
Although for the purpose of discussion, these are considered separately as two entities, DKA and HONK should be thought of as a continuum of disease. At one extreme is pure DKA without hyperosmolarity of significant amount. As noted above these patients may present with more modest degrees of glucose elevation. At the other extreme is HONK with extreme elevations of glucose, and hyperosmolarity, but without significant ketosis. Finally, there are a range of patients who will have features of both.
It is due to this continuum, that I have dealt with various aspects of HONK along with DKA.
Diabetic Ketoacidosis (DKA) DKA is a metabolic disorder consisting of three major abnormalities: elevated blood glucose level, high ketone bodies, and a metabolic acidosis with an elevated anion gap. Dehydration and hyperosmolarity may be present as well. There is no "typical" presentation and individual patients may present with a range of clinical findings not clearly meeting the above criteria.
When considering the precipitating factors for the development of DKA it is important to remember that DKA develops due to either an absolute or a relative absence of insulin. An absolute insulin deficiency is the major precipitant for those patients presenting in DKA who have new onset type I diabetes. It is estimated that 10-20% of patients with new onset diabetes will present in DKA as their initial presentation. Another major cause of absolute insulin deficiency is omission of normal insulin in a patient with know type I diabetes.
In those patients with known diabetes the precipitating factor for DKA can be identified in greater than 80% of the cases. Except in the case where the patient stops taking their insulin, the usual cause of the DKA is a relative lack of insulin. Relative insulin deficiency occurs when there is an increased requirement for insulin due to an increased physiologic stress such as seen with an infection, trauma, or other process. Infection is the most frequent identifiable cause of DKA with pneumonia and urinary tract infections being two of the most common causes. Myocardial infarction should always be considered in the list of precipitating factors of DKA, particularly in older patients, as the condition is associated with elevations of epinephrine which may stimulate a pathologic process that results in DKA.
Other precipitating causes are noted in the table below.
Absolute lack of insulin
Relative lack of Insulin
The evolution of the acute DKA episode in type 1 Diabetes or even in type 2 diabetes tends to have a much shorter time span as compared to HHS. Although the symptoms of poorly controlled diabetes may be present for several days, the metabolic alterations typical of ketoacidosis usually evolve within a short time frame (typically <24 h). Occasionally, the entire symptomatic presentation may evolve or develop more acutely, and the patient may present in DKA with no prior clues or symptoms.
The classical clinical picture includes a history of polyuria, polydipsia, polyphagia, weight loss, vomiting, abdominal pain, dehydration, weakness, clouding of sensorium, and finally coma. Patients with DKA usually present with complaint of fatigue, malaise, thirst, and polyuria. Depending on the length of symptoms the patient may be able to report weight loss. As the patient becomes increasingly ill they may begin to vomit and complain of abdominal pain.
Physical findings may include poor skin turgor, Kussmaul respirations , tachycardia, hypotension, alteration in mental status, shock, and ultimately coma. Up to 25% of DKA patients have emesis, which may be coffee-ground in appearance and guaiac positive. Endoscopy has related this finding to the presence of hemorrhagic gastritis. Mental status can vary from full alertness to profound lethargy or coma, with the latter more frequent in HHS. Although infection is a common precipitating factor for both DKA and HHS, patients can be normothermic or even hypothermic primarily because of peripheral vasodilation. Hypothermia, if present, is a poor prognostic sign.
The physical signs of DKA can be variable. Most patients will have some degree of tachycardia, but the blood pressure is often normal. Evidence of dehydration, such as loss of skin turgor, and dry mucus membranes may be present. The patient may be febrile, and extreme elevations of temperature should not be assumed to be the result of dehydration. Hypothermia may also be seen. The respiratory rate may be normal or somewhat rapid, but if the patient is examined closely the deep breathing typical of "Kussmaul" respirations may be noted. Caution needs to be taken with patients who complain of abdominal pain on presentation. The exact cause of abdominal pain that is associated with DKA is not known. The abdominal pain is disturbing since it may be secondary to the DKA, or be from the pathologic process that initiated the crisis, such as pyelonephritis, pancreatitis, etc. Usually, abdominal pain secondary to DKA will begin to resolve with treatment. Further evaluation is necessary if this complaint does not resolve with resolution of dehydration and metabolic acidosis.
Physical examination reveals other findings, such as a fruity breath odor (similar to the odor of nail polish remover) as the result of volatile acetone and signs of dehydration, including loss of skin turgor, dry mucous membranes, tachycardia, and hypotension. Mental status can vary from full alertness to profound lethargy; however, <20% of patients with DKA or HHS are hospitalized with loss of consciousness. In HHS, mental obtundation and coma are more frequent because the majority of patients, by definition, are hyperosmolar. In some patients with HHS, focal neurological signs (hemiparesis or hemianopsia) and seizures may be the dominant clinical features. Although the most common precipitating event is infection, most patients are normothermic or even hypothermic at presentation, because of either skin vasodilation or low fuel-substrate availability.
Although usually straightforward, the diagnosis of diabetic ketoacidosis is occasionally missed in unusual situations, such as when it is the initial presentation of diabetes in infants or elderly patients or when patients present with sepsis or infarction of the brain, bowel or myocardium. These presentations can distract the physician from the underlying diagnosis of diabetic ketoacidosis.
In general, the laboratory diagnosis of DKA is based on an elevated blood glucose (usually above 250mg/dl), a low serum bicarbonate level (usually below 15 mEq/L), and elevated anion gap, and demonstrable ketonemia. Individually, all of these values may vary considerably, but taken together they help make the diagnosis of DKA. In addition to the above there are several calculations that are important in the evaluation and therapy of the patient with DKA.
Mental status changes can occur in DKA and may be the result of DKA, or some underlying process that may have caused the patient to develop DKA. Obviously, it is critical to determine the cause of the patient's altered mental status. It has been well documented that mental status changes in DKA correlate with the effective serum osmolality. Thus, a patient with mental status changes can only have this decompensation explained by the elevated glucose level if the serum osmolality is significantly elevated.
The effective serum osmolality is calculated as follows:
Serum Osmolality = 2(Na+K) + glu/18 + BUN/2.8
Calculated total osmolalities of greater than 340 mOsm/kg H2O are associated with stupor and coma. Calculated values below this level would not explain a patient with coma and an additional cause such as meningitis, or stroke should be considered.
Despite volume depletion, serum sodium may be low, normal, or elevated. This variation has several causes. First, dehydration from an osmotic diuresis may result in excess loss of water compared to sodium, this may give increased values of serum sodium despite total body sodium depletion. On the other hand, serum sodium level frequently "appears" low. Insulin deficiency results in reduced clearance of triglycerides. The presence of triglycerides displaces plasma water and cause a low reading for the sodium concentration (this is pseudohyponatremia). It is possible to recognize this clinically by noting that the plasma is milky or cloudy appearing. Finally, Sodium levels often appear artificially low due to the osmotic pull of the elevated serum glucose levels. The presence of the increased glucose causes water to shift into the extracellular space resulting in a dilutional reduction on the serum sodium. When trying to determine the degree of dehydration in a patient it is best to use corrected serum sodium level.
To assess the severity of sodium and water deficits, serum sodium may be corrected by adding 1.6 mEq to the measured serum sodium for each 100 mg/dl of glucose above 100 mg/dl
This can be calculated using the following formula:
Corrected Na = [Na+] + 1.6 x [glu in mg/dl] - 100/100
Often, the initial serum sodium appears low, but when the above calculation in performed, the final value is elevated. This indicates a marked intracellular dehydration.
The ketoacids produced during DKA are buffered by the serum bicarbonate and then excreted in the urine. This causes a loss of bicarbonate which is a measured anion. As the bicarbonate is lost the anion gap increases.
The three ketone bodies are beta- hydroxybutyrate, acetoacetate, and acetone. Only acetoacetate and acetone are measured in the nitroprusside reaction, but the formation of these ketone bodies favors the development of beta-hydroxybutyrate. Thus, the test for ketone bodies may be only weakly positive even when large amounts of total ketones are present. Acetone does not contribute to the anion gap, but it is measured in the nitroprusside reaction and is a precursor for the regeneration of bicarbonate. It is not uncommon for the patient to be improving clinically, but to have the nitroprusside test become more strongly positive since acetone is being produced. At this point, the anion gap should be narrowing, even as the nitroprusside test is getting stronger.
Other tests should be varied out initially. Many of these common tests will give the data needed to do the above important calculations. A tube should be sent for exact glucose determination, but a bedside test can me used to determine gross blood sugar levels. To determine the degree of acidosis and bicarbonate loss, an ABG should be sent early in the evaluation of a patient considered to have DKA.
The complete blood count often shows an elevation of the white blood cells. This may be, in part, due to hemoconcentration secondary to dehydration. Thus, WBC's of 20,000 occur commonly. Those patients with WBC's greater than 30,000 who have a bandemia on peripheral smear should be assumed to have an infectious process.
Additional evaluation should take into consideration the best tests to help determine the potential cause of the patient's decompensation into DKA. Urinalysis, chest radiograph, and electrocardiogram should be done on most patients.
In assessment of blood glucose and electrolytes in DKA, certain precautions need to be taken in interpreting results. Severe hyperlipidemia, which is occasionally seen in DKA, could reduce serum glucose and sodium levels, factitiously leading to pseudohypo- or normoglycemia and pseudohyponatremia, respectively, in laboratories still using volumetric testing or dilution of samples with ion-specific electrodes. This should be rectified by clearing lipemic blood before measuring glucose or sodium or by using undiluted samples with ion-specific electrodes. Creatinine, which is measured by a colormetric method, may be falsely elevated as a result of acetoacetate interference with the method. Hyperamylasemia, which is frequently seen in DKA, may be the result of extrapancreatic secretion and should be interpreted cautiously as a sign of pancreatitis. The usefulness of urinalysis is only in the initial diagnosis for glycosuria and ketonuria and detection of urinary tract infection. For quantitative assessment of glucose or ketones, the urine test is unreliable, because urine glucose concentration has poor correlation with blood glucose levels and the major urine ketone, -hydroxybutyrate, cannot be measured by the standard nitroprusside method.
The therapeutic goals for treatment of hyperglycemic crises in diabetes consist of 1) improving circulatory volume and tissue perfusion, 2) decreasing serum glucose and plasma osmolality toward normal levels, 3) clearing the serum and urine of ketones at a steady rate, 4) correcting electrolyte imbalances, and 5) identifying and treating precipitating events.
The severity of fluid and sodium deficits is determined primarily by the duration of hyperglycemia, the level of renal function and the patient's fluid intake. Dehydration can be estimated by clinical examination and by calculating total serum osmolality and the corrected serum sodium concentration.
The severity of dehydration and volume depletion can be estimated by clinical examination using the following guidelines, with the caveat that these criteria are less reliable in patients with neuropathy and impaired cardiovascular reflexes:
1. An orthostatic increase in pulse without change in blood pressure indicates ~10% decrease in extracellular volume (i.e., ~2 liters isotonic saline).
2. An orthostatic drop in blood pressure (>15/10 mmHg) indicates a 15-20% decrease in extracellular volume (i.e., 3-4 liters).
3. Supine hypotension indicates a decrease of >20% in extracellular fluid volume (i.e., >4 liters).
The measured serum sodium concentration must be corrected for the changes related to hyperglycemia. Corrected serum sodium concentrations of greater than 140 mEq per L (140 mmol per L) and calculated total osmolalities of greater than 330 mOsm per kg of water are associated with large fluid deficits. Calculated total osmolalities are correlated with mental status, in that stupor and coma typically occur with an osmolality of greater than 330 mOsm per kg of water.
The initial priority in the treatment of diabetic ketoacidosis is the restoration of extracellular fluid volume through the intravenous administration of a normal saline (0.9 percent sodium chloride) solution. This step will restore intravascular volume, decrease counterregulatory hormones and lower the blood glucose level. As a result, insulin sensitivity may be augmented. The initial treatment is typically with a 0.9 percent saline solution administered at a rate of 7 to 14 mL per kg per hour. In patients with mild to moderate volume depletion, infusion rates of 7 mL per kg per hour have been as efficacious as infusion rates of 14 mL per kg per hour. The subsequent administration of a hypotonic saline (0.45 percent sodium chloride) solution, which is similar in composition to the fluid lost during osmotic diuresis, leads to gradual replacement of deficits in both intracellular and extracellular compartments.
When the blood glucose concentration is approximately 250 mg%, glucose should be added to the hydration fluid (i.e., 5 percent dextrose in hypotonic saline solution). This allows continued insulin administration until ketonemia is controlled and also helps to avoid iatrogenic hypoglycemia. Another important aspect of rehydration therapy in patients with diabetic ketoacidosis is the replacement of ongoing urinary losses.
The use of isotonic versus hypotonic saline in treatment of DKA and HHS is still controversial, but there is uniform agreement that in both DKA and HHS, the first liter of hydrating solution should be normal saline (0.9% NaCl), given as quickly as possible within the 1st hour and followed by 500-1,000 ml/h of 0.45 or 0.9% NaCl (depending on the state of hydration and serum sodium) during the next 2 h. State of hydration can also be estimated by calculating total and effective plasma osmolality and by calculating corrected serum sodium concentration.
Dextrose should be added to replacement fluids when blood glucose concentrations are <250 mg/dl in DKA or <300 mg/dl in HHS. This can usually be accomplished with the administration of 5% dextrose; however, in rare cases, a 10% dextrose solution may be needed to maintain plasma glucose levels and clear ketonemia. This allows continued insulin administration until ketogenesis is controlled in DKA and avoids too rapid correction of hyperglycemia, which may be associated with development of cerebral edema (especially in children).
An additional important aspect of fluid replacement therapy in both DKA and HHS is the replacement of ongoing urinary losses. Failure to adjust fluid replacement for urinary losses leads to a delay in repair of sodium, potassium, and water deficits. Overhydration is a concern when treating children with DKA, adults with compromised renal or cardiac function, and elderly patients with incipient congestive heart failure. Once blood pressure stability is achieved with the use of 10-20 ml · kg-1 · h-1 0.9% NaCl for 1-2 h, one should become more conservative with hydrating fluid.
Reduction in glucose and ketone concentrations should result in concomitant resolution in osmotic diuresis of DKA. The resulting decrease in urine volume should lead to a reduction in the rate of intravenous fluid replacement. This reduces the risk of retention of excess free water, which contributes to brain swelling and cerebral edema, particularly in children. The duration of intravenous fluid replacement in adults and children is ~48 h depending on the clinical response to therapy. However, in a child, once cardiovascular stability is achieved and vomiting has stopped, it is safer and as effective to pursue oral rehydration.
Modern management of diabetic ketoacidosis has emphasized the use of lower doses of insulin. This has been shown to be the most efficacious treatment in both children and adults with diabetic ketoacidosis. The current recommendation is to give low-dose (short-acting regular) insulin after the diagnosis of diabetic ketoacidosis has been confirmed by laboratory tests and fluid replacement has been initiated.
It is prudent to withhold insulin therapy until the serum potassium concentration has been determined. In the rare patient who presents with hypokalemia, insulin therapy may worsen the hypokalemia and precipitate life-threatening cardiac arrhythmias. Standard low-dose insulin therapy consists of an initial intravenous bolus of 0.15 unit of regular insulin per kg followed by the continuous intravenous infusion of regular insulin prepared in normal saline or hypotonic saline solution at a rate of 0.1 unit per kg per hour.
In clinical situations in which continuous intravenous insulin cannot be administered, the recommended initial insulin dose is 0.3 unit per kg, with one half of the dose given as an intravenous bolus and the remainder given subcutaneously or intramuscularly. Subsequently, regular insulin should be given in a dosage of 0.1 unit per kg per hour until the blood glucose level is approximately 250 mg per dL.
If the blood glucose concentration does not fall by 50 to 70 mg per dL (2.8 to 3.9 mmol per L) in the first hour, the intravenous infusion rate should be doubled or additional intravenous 10-unit boluses of insulin should be given every hour. Either of these treatments should be continued until the blood glucose level falls by 50 to 70 mg per dL. Low-dose insulin therapy typically produces a linear fall in the glucose concentration of 50 to 70 mg per dL per hour.
More rapid correction of hyperglycemia should be avoided because it may increase the risk of cerebral edema. This dreaded treatment complication occurs in approximately 1 percent of children with diabetic ketoacidosis. The typical presentation is onset of headache and decreased mental status occurring several hours after the start of treatment. Cerebral edema is associated with a mortality rate of up to 70 percent.
When a blood glucose concentration of 250 mg per dL has been achieved, the continuous or hourly insulin dosage can be reduced to 0.05 unit per kg per hour. The insulin and fluid regimens are continued until ketoacidosis is controlled. This requires the achievement of at least two of these acid-base parameters: a serum bicarbonate concentration of greater than 18 mEq per L, a venous pH of 7.3 or greater and an anion gap of less than 14 mEq per L. The ketosis and acidemia in DKA take longer to resolve than the elevation of glucose. For this reason, the insulin therapy must be continued even when the blood glucose levels have improved to near normal levels. When the glucose levels begin to approach 250 mg/dl, insulin infusions are continued, but the fluid composition is changed to include 5-10% dextrose in water to avoid hypoglycemia.
Regardless of the serum potassium level at the initiation of therapy, during treatment of DKA there is usually a rapid decline in the potassium concentration in the patient with normal kidney function. Patients who have life-threatening elevation of potassium should be treated in the same manner as any other patient with severe hyperkalemia. The drop in potassium is a result of hydration and resolution of acidemia, but in particular is due to insulin administration. As insulin is given potassium is driven into the intracellular compartment. Additionally, early in the course of therapy potassium is usually still being lost in the urine due to ongoing osmotic diuresis and ketonuria. Since potassium is normally an intracellular ion, it is not well conserved as these mechanisms begin to take effect.
While it is not uncommon to have hyperkalemia, the development of severe hypokalemia is usually a greater threat. Total body deficits are estimated at 3-5 mEq/kg. When treating the patient with DKA the clinician should be able to anticipate all of these shifts and maintain potassium levels at near normal throughout therapy. General recommendations for potassium replacement are as follows. If the patient does not have marked elevation of potassium, is not in renal failure, the ECG does not show evidence of hyperkalemia beyond peaked T-waves, potassium therapy is initiated once good urine output has been established. Potassium is usually added to the intravenous fluids and should not exceed 40 mEq per liter of intravenous fluids. Some authors recommend spitting the potassium replacement as KCL and KPO4. The potassium level should be checked every one to two hours initially since this is when the greatest shift occurs. After the patient has stabilized the potassium can be checked every 6 to 8 hours.
To prevent hypokalemia, potassium replacement is initiated after serum levels fall below 5.5 mEq/l, assuming the presence of adequate urine output. Generally, 20-30 mEq potassium (2/3 KCl and 1/3 KPO4) in each liter of infusion fluid is sufficient to maintain a serum potassium concentration within the normal range of 4-5 mEq/l. Rarely, DKA patients may present with significant hypokalemia. In such cases, potassium replacement should begin with fluid therapy, and insulin treatment should be delayed until potassium concentration is restored to >3.3 mEq/l to avoid arrhythmias or cardiac arrest and respiratory muscle weakness. During treatment of diabetic ketoacidosis, a rapid decline in the serum potassium level is typical. When the serum potassium concentration is less than 5.5 mEq per L, 20 to 30 mEq per L of potassium chloride is added to the intravenous fluids.
During treatment of DKA and HHS with hydration and insulin, there is typically a rapid decline in plasma potassium concentration as potassium reenters the intracellular compartment. However, potassium replacement should not be initiated until the serum potassium concentration is <5.5 mEq/l.
The use of bicarbonate in the treatment of DKA is highly controversial. The advocates of bicarbonate suggest that acidosis is detrimental to cardiac function, while opponents of this therapy point out several problems. These include: (1) paradoxical lowering of intracellular pH from diffusion into cells of CO2 which is produced from the bicarbonate, (2) a decrease in tissue oxygenation from a shift in the oxygen dissociation curve, (3) sodium overload, (4) increased chance of acute hypokalemia. There are a limited number of studies evaluating the use of bicarbonate but those that are present have found that bicarbonate therapy does not significantly alter the recovery or outcome in DKA. To date there are not studies looking at the use of bicarbonate in severely acidotic patients (those with pH less than 6.9) and it is generally felt that this group should probably receive bicarbonate therapy. Current recommendations for bicarbonate therapy are as follows. Use of bicarbonate is considered unnecessary when the blood pH is greater than 7.1. For those patients with pH between 6.9 and 7.1 there are no clear guidelines. If the patient is elderly or very debilitated there may be some benefit to the bicarbonate in this range. If it is given it should be given with the intravenous fluids and not as IV push. For those patients with pH below 6.9 bicarbonate should be added to the intravenous fluids. One ampule of bicarbonate has 44 mEq of sodium bicarbonate. Attempts should be made to create an isotonic fluid with the bicarbonate being added to either one-half normal saline or D5W.
In general, supplemental bicarbonate therapy is no longer recommended for patients with diabetic ketoacidosis, because the plasma bicarbonate concentration increases with insulin therapy. Insulin administration inhibits ongoing lipolysis and ketone production and also promotes the regeneration of bicarbonate. Insulin, as well as bicarbonate therapy, lowers serum potassium; therefore, potassium supplementation should be maintained in intravenous fluid as described above and carefully monitored. Thereafter, venous pH should be assessed every 2 h until the pH rises to 7.0, and treatment should be repeated every 2 h if necessary.
Antibiotics In most instances, it may be necessary to start treatment with a broad spectrum antibiotic without waiting for specific proof of the presence of an infection and a culture and sensitivity test.
Frequency of monitoring in DKA
Brain Edema: Clinical brain edema occurs in less than one percent of the pediatric population and even less frequently in adults. When it does occur the mortality rate is high It is probably prudent to prevent overvigorous correction of severe hyperosmolarity and hypernatremia.
When this complication does develop it typically has a rapid onset of severe headache and depression of the mental status. CT scan will show characteristic changes. Treatment must be started rapidly with intravenous mannitol and intubation as indicated.
Adult Respiratory Distress Syndrome: This complication usually occurs during therapy with fluids, insulin, and electrolyte replacement. Fluid therapy causes an increase in the right atrial pressure and additionally, decreases colloid oncotic pressure. These conditions could favor the development of pulmonary edema in a normal patient, but those with DKA may also have an increased pulmonary capillary permeability for unclear reasons.
Patients who have a widened A-a gradient or who have rales on lung exam at the time that they present with DKA seem to be at an increased risk for developing ARDS. In patients with these risk factors it is probably wise to use lower rates of fluid replacement. Hyperchloremic Acidosis: This complication can be recognized by a low bicarbonate level, low to normal pH, normal anion gap, and an increased serum chloride level. The cause of this condition is multifactorial: (1) ketoacid anions are metabolized by the regeneration of bicarbonate. Therefore, the prior loss of the ketoacids in the urine prevents regeneration of bicarbonate, This causes a hyperchloremic acidosis, (2) During the development of ketoacidosis, sodium is lost preferentially to chloride leaving more of this anion in the body.
Generally, this condition causes no adverse outcome and will usually resolve on its own with ongoing therapy. It may be minimized by switching to hypotonic fluids during therapy and by using smaller amounts of chloride during therapy (KPhos rather than KCl).
Hypokalemia: As the patient is being treated for DKA, the volume expansion, and insulin therapy can rapidly lower potassium. As long as these therapies are ongoing, the potassium level will continue to decline unless it is being aggressively replaced. To avoid sudden decompensation due to severe hypokalemia, it is prudent to recheck a serum potassium, following each liter of fluid. If large doses of insulin are required to control the patient's blood glucose, the potassium level will need to be checked more frequently.
Hypoglycemia: As discussed previously, during DKA therapy, the serum glucose typically normalizes before the ketotic state has been corrected. To reverse this state it is necessary to continue insulin therapy after the glucose levels have improved. Without close monitoring, this can result in life-threatening hypoglycemia. To help avoid this, glucose measurements should be done frequently, and as the glucose level nears 250 mg/dl, the insulin infusion rate should be slowed, and glucose infusion with D5W should be started.
The two major precipitating factors in the development of DKA are inadequate insulin treatment (including noncompliance) and infection. In many cases, these events may be prevented by better access to medical care, including intensive patient education and effective communication with a health care provider during acute illnesses.
Goals in the prevention of hyperglycemic crises precipitated by either acute illness or stress have been outlined. These goals included controlling insulin deficiency, decreasing excess stress hormone secretion, avoiding prolonged fasting state, and preventing severe dehydration. Therefore, an educational program should review sick-day management with specific information on administration of short-acting insulin, including frequency of insulin administration, blood glucose goals during illness, means to suppress fever and treat infection, and initiation of an easily digestible liquid diet containing carbohydrates and salt.
The second major hyperglycemic emergency is the Hyperosmolar Hyperglycemic State (HHS) and is one that is most commonly seen in an older population with type 2 diabetes. This complication is perhaps best known as hyperglycemic hyperosmolar nonketotic (HHNK) coma. However, since patients rarely present in coma (less than 10% of patients) other names have been suggested that might truly represent the condition in which the patient presents. Thus, this discussion will use the term HHS.
When considering the patient with HHS there are patients who present purely with this disorder while others seem to have a combination of both. Thus, DKA and NKH should be thought of as a continuum of disease. At one extreme is pure DKA without hyperosmolarity of significant amount. As noted above these patients may present with more modest degrees of glucose elevation. At the other extreme is NKH with extreme elevations of glucose, and hyperosmolarity, but without significant ketosis (see table below). Finally, there are a range of patients who will have features of both.
It is due to this continuum, that a significant discussion about aspects of HHS has been dealt with above in conjunction with the discussion on DKA. Some leading authorities, feel that DKA and HHS presenting with a comatose state should be considered the opposite boundaries of a spectrum of presentations, rather than thinking of them as different disease states.
It has been shown that HHS may be due to plasma insulin concentration inadequate to facilitate glucose utilization by insulin-sensitive tissues but adequate (as determined by residual C-peptide) to prevent lipolysis and subsequent ketogenesis. In addition, inadequate fluid intake contributes to hyperosmolarity without ketosis, the hallmark of HHS.
This happens when the body is stressed and needs greater insulin secretion but is unable to meet these increasing demands due to deficient reserves.
HONK is a slowly progressive disease and it is not uncommon to have 3-10 day history of increasing thirst, polyuria, and malaise. Patients usually have evidence of dehydration such as dry mucus membranes, tachycardia, poor skin turgor, and sometimes a low grade fever. The blood pressure is usually well preserved unless there is severe dehydration or infection. Respiratory symptoms are usually absent unless the patient has pneumonia. Central nervous system dysfunction is relatively common in these patients. Lethargy and disorientation are common, but frank coma is rare. It is critical to remember that these CNS symptoms rarely present unless the effective osmolarity is greater than 340-350 mOsm/L. Patients with altered sensorium and osmolarity less than this should have a different etiology searched for. Any area within the brain can be affected, and while focal neurologic findings are uncommon in DKA, they are fairly common in patients with HONK. Seizures may be present in up to one-fourth of patients and can be focal or generalized. Cerebral edema is rare in patients with HONK.
In general, HONK is defined as those individuals with: serum glucose levels in excess of 600 mg/dl, serum osmolality greater than 330 mOsm/kg, absent or minimal serum ketones, arterial pH above 7.3, and a serum bicarbonate above 20 mEq/L. It is characterized by severe fluid and electrolyte depletion due to the osmotic diuresis produced by the extreme levels of glucose in the serum. Serum potassium levels can be normal, high, or low, but as was true in DKA the total body amount of potassium is significantly depleted.
Elevations in white blood cell count are not uncommon in patients with HONK. Leukocytosis can result simply from the stress and not necessarily from infection. However, extreme elevations in WBC should probably be considered evidence for infection. It is wise to have a low threshold for doing complete septic workups and for obtaining a head CT to avoid missing the pathologic process that precipitated the patients.
The immediate aim of treatment is to rapidly expand the contracted intravascular volume to stabilize BP and to improve circulation and urine flow Treatment is started by infusing 2 to 3 L of 0.9% sodium chloride solution over 1 to 2 h. If this stabilizes BP and circulation and restores good urine flow, then the IV infusion can be changed to 0.45% sodium chloride solution to provide additional water. The rate of the 0.45% sodium chloride solution infusion must be adjusted in accordance with frequent assessments of BP, cardiovascular status, and the balance between fluid input and output.
K replacement is usually started by adding 20 mmol/L potassium as a phosphate salt to the initial liter of the IV-infused 0.45% sodium chloride solution, provided urine flow is adequate and the resulting initial rate of K infusion does not exceed 20 to 40 mmol/h Insulin treatment should not be aggressive and may be unnecessary because adequate hydration will usually decrease plasma glucose levels. Patients with NKHHC are often very sensitive to insulin, and large doses can precipitously decrease plasma glucose. A too-quick reduction in osmolality can lead to cerebral edema. However, many obese type II DM patients with HONK require larger insulin doses to reduce their marked hyperglycemia. If insulin is administered, 5% glucose should be added to the IV fluids when the plasma glucose reaches approximately 250 mg/dL (13.88 mmol/L) to avoid hypoglycemia. After recovery from the acute episode, patients are usually switched to adjusted doses of subcutaneous regular insulin at 4- to 6-h intervals.
The complications of HONK are essentially the same as those seen in DKA. The exception to this is the development of cerebral edema, which is quite rare in HONK.