DKA Diagnosis

• The presence of AG metabolic acidosis and ketonemia together is essential to diagnose DKA, the absence of one will rule out DKA.
• Hyperglycemia may or may not be present as in normoglycemic or Euglycemic DKA, where the serum glucose is normal or near normal.
• Normoglycemic or Euglycemic DKA can be seen in:
  • The use of Sodium-glucose co-transporter 2 (SGLT2) inhibitors, these agents promote urinary glucose loss minimizing plasma hyperglycemia.
  • Patients with poor oral intake
  • Patients who received insulin treatment before arrival in the emergency department.
  • Pregnancy.
• Abdominal pain, nausea, and vomiting are common presentations in DKA patients, but very unusual in NKHH!

NKHH diagnosis

• The presence of critical hyperglycemia (typically > 600 mg/dl) and hyperosmolarity is essential to diagnose NKHH.
• Ketonemia and acidosis may or may not be present, if present they are mild, and PH typically > 7.3.
• Neurological manifestations are common and prominent. Lethargy, confusion, obtundation, coma, stroke-like symptoms, and seizures, all can happen.

The distinction between DKA & NKHH

• The distinction between DKA and NKHH does not matter in the acute early phase as the treatment is the same.
• The presence of critical hyperglycemia that is out of proportion to the amount of ketonemia and acidosis, along with neurological symptoms, are strongly suggestive of NKHH. The critical hyperglycemia seen in NKHH would have caused a more profound acidosis and ketonemia had it been DKA!
• The presence of abdominal pain or the absence of neurological signs or symptoms makes NKHH very unlikely.

Precipitating factors for DKA & NKHH:

• Non-compliance remained, probably the most common reason, these patients are typically frequent fliers with recurrent DKA.
• Infections are the second most common triggers, especially in the elderly, particularly pneumonia and UTI. UA and CXR should be performed in all patients.
• Beware that severe leukocytosis is a common finding in DKA/NKHH! Please don’t start empiric antibiotics just because of leukocytosis in the absence of any evidence of infection!
• Acute pancreatitis may precipitate DKA and should be ruled out in patients presenting with abdominal pain, this can be challenging as DKA, as lipase and amylase are often elevated in DKA patients, CT abdomen/pelvis should be performed in these patients to evaluate for acute pancreatitis.
• Acute MI, don’t forget to order and review an EKG and troponins if suspected.
• Cocaine is known to cause recurrent DKA! Drug screening should be performed if drug use is suspected particularly in patients with recurrent DKA.
• Medications:
  • Glucocorticoids use.
  • SGL-2 inhibitors, discontinue them indefinitely if the patient develops normoglycemic DKA while on them.
  • Atypical antipsychotics, some data suggest an increased risk of diabetes and diabetic ketoacidosis in patients commenced on atypical antipsychotics (Clozapine and olanzapine).
• Any acute sickness can precipitate DKA and NKHH, let the patient history guide you in identifying the precipitating factor of DKA/NKHH.

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  Treatment

• The goal of treatment in DKA is:
  • To close the AG, not to normalize NaHCO3. Please remember that well, look at the gap, not the bicarb level!
  • To control hyperglycemia.

• AG (Anion gap) = (Na – (Cl + HCO3)).
• We use the measured Na, not the corrected one. The Measured Na is the Na value in the lab result.

• The goal of treatment in NKHH is:
  • For patients to become mentally clear.
  • For the effective plasma osmolality to fall below 315 mOsmol/kg.
  • To control hyperglycemia.

• Serum osmolality = 2 x Na + (glucose/18 + BUN/2.8).
• BUN moves freely between the intra and extracellular spaces and is considered ineffective osmoles.
• Na and glucose as effective osmoles.
• Effective plasma osmolality = 2 x Na mmol/L + (Glucose/18) mmol/L. We use the measured Na not the corrected one for hyperglycemia

• Admit to ICU or step-down unit if hospital policy permits that. Be prepared to manage your patient in the ED as the ICU may be full and will be a while before a bed becomes available.
• Keep the patient NPO until the insulin drip is switched off.
• Stop all home insulin and non-insulin diabetic medications, insulin pumps should be switched off.
• Central venous access is highly recommended, this will permit easier and quicker IVF resuscitation and potassium supplementation.

IVF resuscitation

• Fluids are more important than insulin in the early acute phase! patients die from dehydration and electrolyte imbalance rather than lack of insulin in this phase.
• DKA and NKHH patients have profound volume depletion, estimated to be around 5-6 L in DKA, and 9-10 L in NKHH, so be generous with volume replacement.
• Give 15-20 ml/kg of IV fluid fluid in the first hour, with a maximum of 50 ml/kg in the first 4 hours.
• The fluid bolus received in the ED should be included in the total amount.

• The fluid type used in the first 4 hours must be isotonic preferably NS or LR.
• After the first 4 hours, We continue IV fluid resuscitation at 250-500 ml/hour but the fluid type here shall be guided by the corrected Na level (not the measured one).
• Change the fluid to 0.45 NS at the same rate if the corrected Na is normal or high.

A history of cardiomyopathy or ESRD (End-stage renal disease) isn’t a contraindication to agrresssive IVF fesuscitation! The only contraindication to IV fluid is active pulmonary edema.

• In DKA, I typically continue IVF for the next 12 hours and re-assess volume status! if the patient has stable vital signs and adequate urine output, the IVF can be discontinued once the patient can eat and the insulin drip is off.
• There is a subset of DKA patients that may not require this initial fluid resuscitation, as in those with early and mild DKA and those with normoglycemic DKA, these patients can be directly started on IVF at 200 -250 ml/hour with dextrose solution, but again look at their volume status and hemodynamics.
• In NKHH, the volume deficit is larger than DKA, we may need to continue IV fluid beyond the first 24 hours guided by volume status, corrected Na level, and the drop in effective plasma osmolality.

K & PO4 hemostasis:

• Almost all patients with DKA or HHS have a significant potassium deficit due to urinary losses generated by the glucose osmotic diuresis and secondary hyperaldosteronism
• Despite the total body potassium deficit, the serum potassium concentration can be normal or elevated at presentation! This is largely due to insulin deficiency and hyperosmolality which shift potassium out of the cells, imagine how profound the level of K depletion is if the initial K is low!
• Don’t start the insulin drip until the potassium level is > 3.3 meq/l, otherwise, a profound and dangerous hypokalemia can develop!
• The potassium replacement should be started ASAP if K < 3.3 meq/l, this safe level must be confirmed on lab before starting insulin, IT’S OKAY TO DELAY INSULIN THERAPY!
• K < 3.3:
  • Delay the initiation of insulin drip.
  • Give KCL 20-40 meq IV over one hour (it’s safe), and check serum K level after each replacement, repeat until K is > 3.3.
• K is 3.3- 5.3:
  • Add KCL 20 meq to each liter of IVF ( ensure the liter is infused no faster than over an hour!), if fluid boluses are given at a faster rate, infuse KCL through a separate bag!
  • Okay to start insulin drip.
• K > 5.3:
  • Start insulin drip.
  • Don’t give potassium.

   

• If the serum K drops below 3.3, hold insulin and repeat the steps mentioned earlier.

All this talk about K replacement is valid only in those with adequate UO (remember UO may be diminished initially but typically improves quickly with fluid resuscitation). K replacement should be done at a much slower rate in patients on dialysis or those with AKI who is oliguric or anuric. Remember that 90% of K regulation is done through the kidney.

• Similar to potassium, PO4 is depleted in DKA and NKHH despite the initial normal or elevated serum PO4, unless severe hypophosphatemia occurs (serum phosphate concentration below 1 mg/dL), replacement isn’t required.
• If the initial PO4 >=2, serial PO4 testing is not needed, maybe repeat with the next morning’s lab.

The use of NaHCO3

• Severe metabolic acidosis with PH < 7 may occur in DKA but, fortunately, it improves quickly with IVF and insulin therapy, most of these patients, despite extremely low PH < 7, are still awake and alert with stable cardiac rhythm and function!
• Some recommend giving NaHCO3 only if PH =< 6.9 and only to bring up to PH =>7
• NaHCO3 is given as pushes or as a drip, Hospitals have prefilled 50 cc ampules or syringes of NaHCO3, each ampule has 100 meq of NaHCO3 ( 50 of Na + 50 of HCO3).
• The proper way of ordering NaHCO3 drip is by mixing 3 amps of NaHCO3 in 1000 ml of free water or 1.5 amp in 1000 ml of 0.45 NS, avoid mixing with D5W, we don’t want to give more glucose to these patients!

Insulin therapy:

• K must be > 3.3 meq/l.
• Give 0.1 unit/kg of IV insulin as an initial bolus.
• Skip the initial bolus in normoglycemic DKA patients (BS < 250 mg/dl), these patients should be started directly on insulin drip.
• Human regular insulin and Insulin glulisine come in IV form but insulin glulisine is way more expensive and not superior to IV human regular insulin.
• The initial drip rate is similar to the bolus amount, 0.1 unit/kg/hour.
• Hold insulin drip if K drops below 3.3 meq/l. Resume the insulin drip once K > 3.3 meq/l.

Early and mild DKA

• Early and mild DKA usually have:
  • Mild increase in AG.
  • HCO3 level > 15
  • Patients are hemodynamically stable, and most of them present early to the ED.
• These patients can be treated similarly to more severe DKA but alternatively rapid-acting insulin can be used, In such a case, administer o.3/kg units SQ followed by 0.2/kg one hour later then O.2/kg every two hours until BS is <= 250then reduce to 0.1/KG every two hours until the gap is closed. BMP Monitoring and changing fluid are similar to what we explained earlier.

Monitoring

• While on an insulin drip:
  • Check blood sugar (BS) every hour.
  • Check BMP every 2-4 hours except when the K drops <3.3, in such a case, hold the insulin drip, replete K, and order BMP every 2 hours.

Blood sugar targets

• Aim to reduce blood sugar (BS) levels by 50-100 within the first hour. If the desired drop is not achieved, we double the drip rate.
• When the serum glucose drops to 250 mg/dL:
  • Add dextrose to the IV fluid.
  • Decrease the insulin infusion rate to 0.02 to 0.05 units/kg per hour.

The goal of this switch is to prevent hypoglycemia while waiting for AG to close in DKA and to avoid a quick drop in effective serum osmolality which may promote cerebral edema in NKHH.

 

Transition

• Transition in DKA starts when the AG is closed.

• In NKHH, we continue insulin drip until all the following are achieved:
  • The glucose level is 250-300 mg/dL.
  • The effective plasma or serum osmolality is < 315 mos/kg.
  • And the patient becomes more alert.
• Calculate the total amount of IV insulin received in the last 24 hours before the gap closed, if we can’t find the exact amount, a rough estimate can be used by finding the last two or four readings, summing them up, and multiplying by 12 (if two readings) or 6 (if four readings).
• The next step is the two-thirds/one-third rule. We divide the total amount received in the last 24 hours by 3. Two-thirds of the amount is given as basal insulin and one-third as scheduled premeal insulin (if the patient is expected to have adequate oral intake only).
  

  Give only basal insulin if the patient is NPO, with poor, or unreliable oral intake.

• Give the first dose of basal insulin and communicate the following to the patient’s nurse:
• Switch insulin drip 2 hours after giving the first dose of basal insulin.
• Once the insulin drip is switched off:
  • switch off any IV dextrose solution.
  • Start a diabetic diet.
  • Start the scheduled premeal insulin, and add a correction sliding scale.
  • Switch BS checks to AC/HS.
  • Stop serial BMP.

• For patients previously treated with insulin, their pre-DKA or pre-HHS insulin regimen may be restarted. If we feel their home insulin regimen wasn’t enough we can follow the ⅔-⅓ rule mentioned earlier.
• For patients treated with continuous subcutaneous insulin infusion(insulin pump), start the previous pump basal rate, and then switch the drip off two hours later. However, if the IV insulin requirements are significantly higher than their usual insulin requirements, it is reasonable to increase the basal rate temporarily.
• For patients treated with non-insulin medications, it’s preferred to delay their transition back to non-insulin medications as an outpatient or before their discharge.