Acute Complications of DM

1. Acute Complications of DM Dr. ghanei Endocrinologist

2. Acute Complications of DM • Diabetic ketoacidosis (DKA) and hyperglycemic hyperosmolar state (HHS) are acute complications of diabetes. DKA was formerly considered a hallmark of type 1 DM, but also occurs in individuals who lack immunologic features of type 1 DM and who can sometimes subsequently be treated with oral glucose-lowering agents.

3. Both disorders are associated with absolute or relative insulin deficiency, volume depletion, and acid-base abnormalities. DKA and HHS exist along a continuum of hyperglycemia, with or without ketosis.

4. Diabetic KetoacidosisClinical Features • DKA may be the initial symptom complex that leads to a diagnosis of type 1 DM, but more frequently it occurs in individuals with established diabetes. Nausea and vomiting are often prominent, and their presence in an individual with diabetes warrants laboratory evaluation for DKA. Abdominal pain may be severe and can resemble acute pancreatitis or ruptured viscus.

5. CLINICAL MANIFESTATION • HHS usually evolves over several days to weeks • DKA and HHS, the classical clinical picture includes a history of polyuria, polydipsia,, weight loss, vomiting, abdominal pain (only in DKA), dehydration, weakness, clouding of sensoria, and finally coma. Physical findings may include • poor skin turgor, tachycardia, hypotension, alteration in mental status

6. Physical examination reveals signs of dehydration including • loss of skin turgor • Dry mucous membranes • Tachycardia • hypotension • Mental status can vary from • Full alertness to lethargy • 20% of patients with HHS are hospitalized with loss of consciousness • Mental obtundation and coma are more frequent because the majority of patients, are hyperosmolar • In some FND and seizures may be the dominant

7. Lethargy and central nervous system depression may evolve into coma with severe DKA but should also prompt evaluation for other reasons for altered mental status (infection, hypoxemia, etc.).

8. Signs of infection, which may precipitate DKA, should be sought on physical examination, even in the absence of fever

10. Pathophysiology • DKA results from relative or absolute insulin deficiency combined with counterregulatory hormone excess .The decreased ratio of insulin to glucagon promotes gluconeogenesis, glycogenolysis, and ketone body formation in the liver, as well as increases in substrate delivery from fat and muscle (free fatty acids, amino acids) to the liver.

11. PRECIPITATING EVENTS • Infections ;The most common are pneumonia ,UTI ( 30–50% of cases precipitating) • Alcohol abuse • Trauma • Pulmonary embolism • MI • Corticosteroids • Pentamidine • Sympathomimetic agents, and adrenergic blockers • Diuretics • Omission of insulin therapy

12. DKA is often precipitated by increased insulin requirements, as occurs during a concurrent illness. Failure to augment insulin therapy often compounds the problem. Complete omission or inadequate administration of insulin by the patient or health care team (in a hospitalized patient with type 1 DM) may precipitate DKA.

13. Laboratory Abnormalities and Diagnosis • DKA is characterized by hyperglycemia, ketosis, and metabolic acidosis (increased anion gap) along with a number of secondary metabolic derangements. Occasionally, the serum glucose is only minimally elevated.

15. Diagnostic criteria for HHS include • plasma glucose 600 mg/dl, serum total osmolality 330 mOsm/kg, and absence of severe ketoacidosis • patients with HHS have a serum pH 7.3, a serum HCO3 18 mEq/l, and mild ketonemia and ketonuria • Approximately 50% of the patients with HHS have an increased AG metabolic acidosis as the result of concomitant ketoacidosis and/or an increase in serum lactate levels

16. Calculated total and effective osmolalities can be correlated with mental status, stupor, and coma typically occurring with total and effective osmolalities of 340 and 320 mOsm/kg H2O, respectively

17. The presence of stupor or coma in the absence of such hyperosmolarity demands prompt consideration of other causes of • altered mental status

18. Laboratory Abnormalities and Diagnosis • Serum bicarbonate is frequently <10 mmol/L, and arterial pH ranges between 6.8 and 7.3, depending on the severity of the acidosis. Despite a total-body potassium deficit, the serum potassium at presentation may be mildly elevated, secondary to the acidosis..

19. Laboratory Abnormalities and Diagnosis • Total-body stores of sodium, chloride, phosphorus, and magnesium are reduced in DKA but are not accurately reflected by their levels in the serum because of dehydration and hyperglycemia. Elevated BUN and serum creatinine levels reflect intravascular volume depletion. Interference from acetoacetate may falsely elevate the serum creatinine measurement.

20. in HHS, the measured serum Na concentration is usually normal or elevated because of severe dehydration. • Corrected serum sodium concentrations of 140 mEq/l and calculated total osmolality of 340 mOsm/kg H2O are associated with large fluid deficits

21. Laboratory Abnormalities and Diagnosis • Leukocytosis, hypertriglyceridemia, and hyperlipoproteinemia are commonly found as well. Hyperamylasemia may suggest a diagnosis of pancreatitis, especially when accompanied by abdominal pain. However, in DKA the amylase is usually of salivary origin and thus is not diagnostic of pancreatitis. Serum lipase should be obtained if pancreatitis is suspected

22. Laboratory Abnormalities and Diagnosis • In DKA, the ketone body, β-hydroxybutyrate, is synthesized at a threefold greater rate than acetoacetate; however, acetoacetate is preferentially detected by a commonly used ketosis detection reagent (nitroprusside.

23. Laboratory Abnormalities and Diagnosis • The metabolic derangements of DKA exist along a spectrum, beginning with mild acidosis with moderate hyperglycemia evolving into more severe findings. The degree of acidosis and hyperglycemia do not necessarily correlate closely since a variety of factors determine the level of hyperglycemia (oral intake, urinary glucose loss).

25. Treatment • Correction of Dehydration • Correction of Hyperglycemia • Correction of electrolyte imbalances • Correction of precipitating event

26. Therapeutic goals • The therapeutic goals for treatment of hyperglycemic crises consist of • 1) improving circulatory volume and tissue perfusion • 2) decreasing serum glucose and plasma osmolality toward normal levels • 3) correcting electrolyte imbalances • 4) identifying and treating precipitating events

30. Isotonic saline is hypotonic relative to the patient’s extracellular fluid and remains restricted to the extracellular fluid compartment • Administration of hypotonic saline, which is similar in composition to fluid lost during osmotic diuresis, leads to gradual replacement of deficits in both intracellular and extracellular • an initial liter of 0.9% NaCl over the 1st h is followed by either 0.45 or 0.9% NaCl, depending on the corrected serum sodium and the hemodynamic status of the patient.

31. Once BP stability is achieved with the use of 10–20 ml/kg/h 0.9% NaCl for 1–2 h one should become more conservative with hydrating fluid • 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 edem

32. Dextrose 5% should be added to replacement fluids when blood glucose concentrations are 300 mg/dl in HHS, avoids too rapid correction of hyperglycemia, which may be associated with development of cerebral edema. Failure to adjust fluid replacement for urinary losses leads to a delay in repair of Na, K, and water deficits.

33. The duration of intravenous fluid replacement in adults is 48 h depending on the clinical response to therapy.

35. INSULIN therapy • because of a greater level of mental obtundation in HHS, we have recommended only using the IV route for HHS • The important point to emphasize is that insulin should be used after initial serum electrolyte values are obtained while the patient is being hydrated with 1liter of 0.9% saline • Insulin therapy is then initiated with an IV bolus of 0.15U/kg or 10 U regular insulin, followed by either IV infusion of insulin at a rate of 0.1 U/ kg/ h or 7–10 U/h

36. The insulin rate is decreased to 0.05–0.1 U kg/h when blood glucose reaches 300 mg/dl. • DW 5% -10% is added to the hydrating solution at this time to keep blood glucose at its respective level (by adjusting the insulin rate) until the patient has recovered from HHS (osmolality 315 mOsm/kg and patient is alert).

37. Blood glucose monitoring every 60 min will indicate whether this is sufficient to produce a consistent reduction in blood glucose. • If blood glucose fails to decrease at a rate of 50–70 mg/dl/h, the patient’s volume status should be reassessed to ensure adequate volume repletion.

38. After resolution and when patients are able to take fluids orally, a multidose regimen may be initiated based on Hx of previous treatment. • for newly diagnosed patients, a total insulin dose of 0.6–0.7 U/kg/day may be initiated as a multidose regimen of short- and intermediate-/long-acting insulin, with subsequent modification based on glucose testing. • Finally, some may be discharged on OHA and dietary therapy.

40. Potassium • k deficits, which represent mainly intracellular losses, • Extracellular hyperosmolarity causes a shift of water and k from the intracellular to the extracellular space, resulting in normal or elevated serum k concentrations despite total-body k deficits of 500–700 mEq/l • This k shift is further enhanced by insulin deficiency.

41. Excessive urinary k losses, which occur as a result of osmotic diuresis with increased delivery of fluid and Na and k to secretory sites in the distal nephron, are ultimately responsible for the development of k depletion • Secondary hyperaldosteronism, further augment k losses. • During treatment HHS with hydration and insulin, there is rapid decline in plasma k concentration as it reenters the intracellular compartment. • k replacement should not be initiated until the serum k concentration is <5.5mEq/l.

42. hypokalemia is the most life-threatening derangement occurring during treatment, in patients (with hypokalemia )k should be initiated before insulin therapy and insulin therapy held until plasma k =3.3 mEq/l • IV k administration should not exceed 40mEq in the 1st h • thereafter, 20–30 mEq/h to maintain plasma k levels between 4 - 5 mEq/l

46. Resolution • DKA BS<200 + 2 of these 1) HCO3>15 2) PH>7.3 3) Anion gap<12 • HHS • Normal osmolality • Regain of mental status • If the patient is to remain • fasting/nothing by mouth, it is preferable • to continue the intravenous insulin infusion • and fluid replacement.

47. With appropriate therapy, the mortality rate of DKA is low (<1%) and is related more to the precipitating event, such as infection or myocardial infarction. Venous thrombosis, upper gastrointestinal bleeding, and acute respiratory distress syndrome occasionally complicate DKA.

48. The major nonmetabolic complication of DKA therapy is cerebral edema, which most often develops in children as DKA is resolving. The etiology of and optimal therapy for cerebral edema are not well established, but overreplacement of free water should be avoided.

49. Following treatment, the physician and patient should review the sequence of events that led to DKA to prevent future recurrences. Foremost is patient education about the symptoms of DKA, its precipitating factors, and the management of diabetes during a concurrent illness.

50. During illness or when oral intake is compromised, patients should (1) frequently measure the capillary blood glucose; (2) measure urinary ketones when the serum glucose > 300 mg/dL; (3) drink fluids to maintain hydration; (4) continue or increase insulin; and (5) seek medical attention if dehydration, persistent vomiting, or uncontrolled hyperglycemia develop. .