Why dka is dangerous?

The body does this when it doesn't have enough insulin to use glucose, the body's normal source of energy. When ketones build up in the blood, they make it more acidic. They are a warning sign that your diabetes is out of control or that you are getting sick. High levels of ketones can poison the body.

Diabetes-related ketoacidosis (DKA) is a serious and life-threatening, but treatable, complication that affects people with diabetes and those who have undiagnosed diabetes.

Diabetes-related ketoacidosis occurs when your body doesn't have enough insulin (a hormone that's either produced by your pancreas or injected). Your body needs insulin to turn glucose, your body’s go-to source of fuel, into energy. If there’s no insulin or not enough insulin, your body starts breaking down fat for energy instead. As fat is broken down, ketones are released into the bloodstream.

For a person with diabetes, a high amount of ketones causes their blood to become acidic (the blood pH is too low). This creates an emergency medical situation that requires immediate attention and treatment.

Diabetes-related ketoacidosis can develop in people of any age who have diabetes or undiagnosed diabetes.

Hyperglycemia (high blood sugar) and diabetes-related ketoacidosis both happen when your body doesn't have enough insulin or isn't using the insulin it has properly.

The difference is that DKA is an acute complication, meaning it has a severe and sudden onset. While very high blood sugar (above 250 mg/dL) is almost always a contributing factor to DKA, other conditions need to be present to have DKA, including ketones in your blood and/or urine. You can have high blood sugar without having ketones in your blood and/or urine.

Untreated high blood sugar can lead to DKA. This is why it’s important to treat high blood sugar with insulin as soon as possible.

Although it’s not as common, you can be in DKA even if your blood sugar is lower than 250 mg/dL. This is known as euglycemic diabetes-related ketoacidosis (euDKA).

Even though they sound alike, diabetes-related ketoacidosis and ketosis are two different things.

Ketosis occurs when you have ketones in your blood and/or urine but not enough to turn your blood acidic. It usually happens if you are eating a low-carbohydrate diet, if you’re fasting or if you’ve drunk too much alcohol. Ketosis isn't harmful.

Fluid resuscitation and maintenance, insulin therapy, electrolyte replacement, and supportive care are the mainstays of management in diabetic ketoacidosis.

Hydration

In patients with DKA, the fluid deficit could be up to 10-15% of the body weight.[1] Immediate fluid resuscitation is vital to correct hypovolemia, restore tissue perfusion, and to clear ketones. Hydration improves glycemic control independent of insulin.

Choice of Fluids

Isotonic fluids have been well established for more than 50 years as preferred fluids. Colloids vs. crystalloids were compared for critically ill patients, in a 2013 meta-analysis, and crystalloid was found to be non-inferior.[24] Traditionally, 0.9% normal saline has been used. There has been a concern that normal saline may contribute to hyperchloremia and hyperchloremic metabolic acidosis; however, this typically occurs when it is used for large volumes. There have been small studies comparing normal saline with other solutions like Ringer lactate. These studies did not show differences in clinical outcomes.[25][26][27] Normal saline continues to be used for initial hydration.

Infusion Rate

Initial:

Infusion of 15-20 ml per Kg body weight in the first 1 hour is typically appropriate. Aggressive hydration with 1 liter/hour for 4 hours has been compared in a study to a slower rate of hydration at half the rate. Slower hydration was found to be equally effective.[28] However, in critically ill patients, including those with hypotension, aggressive fluid therapy is preferred. There has been extensive debate regarding the risk of cerebral edema in patients with aggressive early volume resuscitation. There are studies that have demonstrated rates of increased cerebral edema with aggressive volume, particularly in the pediatric population. Yet other studies show no difference in outcome and theorize that patients at greatest risk from cerebral edema present at a later stage and are the most severe volume depleted.[29]

Maintainance:

The subsequent choice for fluid replacement depends on hemodynamics, the state of hydration, serum electrolyte levels, and urinary output.[1] In patients who have high serum sodium level, 0.45% NaCl infused at 4–14 ml/kg/hour or 250–500 mL/hr is appropriate, and for patients with hyponatremia, 0.9% NaCl at a similar rate is preferred.[30] Maintenance fluids may need to be adjusted if hyperchloremic metabolic acidosis becomes a concern, then you can switch to the Ringer lactate solution.

Insulin Therapy

The discovery of insulin, along with the antibiotics, has led to a drastic decrease in mortality with DKA, down to 1%. Intravenous insulin by continuous infusion is the standard of care. Previous treatment protocols have recommended the administration of an initial bolus of 0.1 U/kg, followed by the infusion of 0.1 U/kg/h. A more recent prospective randomized trial demonstrated that a bolus is not necessary if patients are given hourly insulin infusion at 0.14 U/kg/hr.[31] When the plasma glucose reaches 200-250 mg/dl, and if the patient still has an anion gap, then dextrose containing fluids should be initiated, and the insulin infusion rate may need to be reduced.

Treatment of adult patients who have uncomplicated, mild diabetic ketoacidosis can be treated with subcutaneous insulin lispro hourly in a non-intensive care setting may be safe and cost-effective as opposed to treatment with intravenous regular insulin in the intensive care setting as shown in many studies.[32] In one of these studies, the patients received subcutaneous insulin lispro at a dose of 0.3 U/kg initially, followed by 0.1 U/kg every hour until blood glucose was less than 250 mg/dl. Then insulin dose was decreased to 0.05 or 0.1 U/kg given every hour until the resolution of DKA.[32] Similarly, insulin aspart has been used and found to be similar in efficacy.[33]

Patients with DKA should be treated with insulin until resolution. Criteria for resolution of ketoacidosis include blood glucose less than 200 mg/dl and two of the following criteria: a serum bicarbonate level >=more than 15 mEq/l, a venous pH more than 7.3, or a calculated anion gap equal or less than 12 mEq/l. Patients can be transitioned to subcutaneously administered insulin when DKA has resolved, and they are able to eat. Those previously treated with insulin might be recommended on their home dose if they had been well controlled.

Insulin-naive patients should receive a multi-dose insulin regimen beginning at a dose of 0.5 to 0.8 U/kg/day. To prevent the recurrence of ketoacidosis in the transition period, insulin infusion should be continued for 2 hrs after the starting of subcutaneous insulin and check blood sugar and complete metabolic profile again before stopping the insulin drip. If the patient cannot tolerate oral intake, intravenous insulin, and fluids may be continued. The use of long-acting insulin analogs during the initial management of DKA may facilitate the transition from intravenous to subcutaneous insulin therapy.[34]

Electrolyte Replacement

Potassium

Patients with DKA are often found to initially have mild to moderate hyperkalemia, despite a total body deficit of potassium. The initiation of insulin causes an intracellular shift of potassium and lowers the potassium concentration, potentially resulting in severe hypokalemia.[35][36] Hence patients with serum potassium levels of less than 3.3 mmol/L need initial management with fluid resuscitation and potassium replacement while delaying commencement of insulin until after potassium levels are above 3.3 mmol/L, to avoid cardiac arrhythmias, arrest, and respiratory muscle weakness.[34] In other patients, potassium replacement should be started when the serum concentration is less than 5.2 mEq/L to maintain a level of 4 to 5 mEq/L. The administration of 20 to 30 mEq of potassium per liter of fluids is sufficient for most patients; however, lower doses are required for patients with acute or chronic renal failure.[37]

Magnesium

Hypokalemia is commonly associated with hypomagnesemia. Repletion of both potassium and magnesium may need to be done, and it may be difficult to improve potassium levels until magnesium levels are repleted.

Bicarbonate

Bicarbonate replacement does not appear to be beneficial. In one study, the difference in time to resolution of acidosis (8 hours vs. 8 hours; p = 0.7) and time to hospital discharge (68 hours vs. 61 hours; p = 0.3) was found to be statistically insignificant between patients who received intravenous bicarbonate (n = 44) compared with those who did not (n = 42).[38] In another pediatric study, children with diabetic ketoacidosis who have low PaCO2 and high BUN concentrations at presentation and those treated with bicarbonate were at increased risk for cerebral edema.[39] Proposed pitfalls of the use of sodium bicarbonate therapy in DKA may include paradoxical CSF acidosis, hypokalemia, large sodium bolus, and cerebral edema. However, it may be used in patients with severe acidemia. The most recent ADA guidelines do recommend the use of sodium bicarbonate therapy in patients with pH less than 7.1.[38]

Phosphate

The role of phosphate replacement in DKA has been looked at in different studies. In one randomized study with 44 patients, phosphate therapy did not alter the duration of DKA, insulin dosage required to correct the acidosis, abnormal muscle enzyme levels, glucose disappearance, or morbidity and mortality. Although theoretically appealing, phosphate therapy is not an essential part of the treatment for DKA in most patients, an unusual case of severe hypophosphatemia (1.0 mg/dl) related seizure in a child with diabetic ketoacidosis (DKA) has been described in the literature.[40]

Laboratory Monitoring

Intubation

There are multiple risks associated with intubation in patients with DKA. Intubation should be avoided if at all possible. Treating as above with a focus on administering fluids and insulin will almost always lead to an improvement in acidosis and overall clinical presentation. Patients attempt to compensate for severe acidosis by creating a compensatory respiratory alkalosis that manifests via tachypnea and Kussmaul breathing. If patients are no longer able to generate respiratory alkalosis due to comatose state or severe fatigue, intubation should be considered. However, the risks of intubation in DKA include a rise in PaCO2 during sedation and/or paralysis, which can decrease pH further, increasing the risk of aspiration due to gastroparesis, and difficulty matching the degree of respiratory compensation once the patient is on a ventilator. If a patient is intubated and placed on a ventilator, it is essential to attempt to match the patient's minute ventilation such that respiratory alkalosis is created to compensate for the metabolic acidosis of DKA. If not, there will be worsening acidosis, which can ultimately lead to cardiac arrest. It is reasonable to start with a tidal volume of 8 ml/kg based on ideal body weight and respiratory rate, similar to the patient's compensating respiratory rate. However, care should be taken that auto-PEEP is not occurring due to the rapid respiratory rate.[41]

Cerebral Edema

Mental status and neurologic exam should be monitored in all patients with DKA. In any patient who is severely obtunded or comatose or who has declining mental status despite treatment or focal neurologic deficits, there should be a very low threshold to treat for cerebral edema. Mannitol is typically the first-line agent, though there are also studies in both TBI literature and DKA literature regarding the use of 3% saline.

Precipitating Events