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diabetic ketoacidosis (DKA)

Etiology: 1) new onset type 1 diabetes 2) inappropriate use of insulin or non-adherence by a type-1 diabetic 3) type 1 diabetic with a systemic infection 4) type 1 diabetic with an acute myocardial infarction or other vascular event 5) type 1 diabetic with trauma or stress 6) use of glucocorticoids or adrenergic agonists by type 1 diabetic 7) type 1 diabetic with hyperthyroidism or pheochromocytoma 8) pancreatitis 9) new onset ketosis-prone type 2 diabetes [2] 10) pharmaceuticals that increase risk - glucocorticoids - atypical antipsychotics - SGLT2 inhibitors (serum glucose may be normal) [2] Pathology: 1) deficiency of insulin 2) increase in glucagon 3) increase in catecholamines 4) increase in cortisol Clinical manifestations: 1) nausea/vomiting 2) anorexia 3) abdominal pain 4) fatigue 5) weight loss 6) shortness of breath 7) muscle cramps 8) tachycardia 9) tachypnea 10) orthostatic hypotension 11) polyuria 12) polydipsia 13) hypothermia Laboratory: 1) serum chemistries a) serum glucose (> 250 mg/dL) b) urea nitrogen generally mildy increased c) serum creatinine d) electrolytes 1] hyponatremia: expected decrease in Na+ due to glucose (glucose - 100) x 0.016 - expect serum sodium to increase with insulin administration 2] hyperkalemia (decreased total body K+) - expect serum potassium to decrease with insulin administration 3] serum bicarbonate < 15 meq/L - generally anion gap metabolic acidosis [8] e) serum amylase & serum lipase if suspected pancreatitis - serum amylase is often elevated in DKA (> 1000 U/L) [2] - metabolic decompensation given as the reason [2] - not specified if increase is due to pancreatic amylase - no explanation why 'metabolic decompensation' should cause a release of amylase 2) arterial blood gas, pH < 7.30 3) serum ketones positive 4) serum osmolality 5) complete blood count with differential - non specific leukocytosis often present - WBC may be > 20,000/uL 6) cultures when indicated: blood, urine, throat, sputum, cerebrospinal fluid 7) hemoccult stool for suspected GI blood loss 8) urinalysis [2] 9) monitor serum electrolytes & serum glucose during insulin infusion Diagnostic criteria: - serum glucose > 250 mg/dL - arterial blood gas: pH < 7.30 - serum HCO3- < 18 meq/L - positive serum or urine ketones - increased anion gap Special laboratory: - electrocardiogram a) monitor significant hyperkalemia or hypokalemia b) rule out acute myocardial infarction & arrhythmias Radiology: - chest radiograph - abdominal CT not needed if abdominal pain resolves with resolution of ketoacidosis [2,4] Differential diagnosis: 1) diabetic ketoacidosis* a) glucose > 250 mg/dL b) pH < 7.35 or HCO3- < 15 meq/L c) positive serum or urine ketones d) increased anion gap 2) alcoholic ketoacidosis* 3) starvation ketoacidosis* 4) inherited disorders of branched-chain amino acids (uncommon) 5) lactic acidosis 6) renal failure with GFR < 20 mL/min 7) salicylate intoxication 8) methanol ingestion 9) ethylene glycol ingestion 10) paraldehyde ingestion 11) formaldehyde ingestion 12) toluene ingestion *Criteria for diabetic, alcoholic & starvation ketoacidosis overlap. A higher glucose favors DKA. A very low glucose favors starvation ketoacidosis. Complications: 1) infection a) pyelonephritis b) pneumonia 2) shock a) hypovolemia b) aggravation of hypovolemia by acidosis c) cardiogenic shock from myocardial infarction 3) thrombosis a) increased factor VIII in DKA b) decreased antithrombin III in DKA c) hyperosmolar state d) low cardiac output with acidosis e) coronary artery disease 4) cerebral edema a) generally observed in children b) more rapid fall in plasma glucose than in intracerebral glucose 5) pancreatitis 6) disseminated intravascular coagulation (DIC) Management: 1) goals a) reverse metabolic acidosis b) replace fluid & electrolytes 2) fluid replacement a) normal saline (1st line) - 15 mL/kg/hr for 1 hour - 7.5 mL/kg/hr for 2-4 hr - 3.75 mL/kg/hr for 24-36 hr until fluid loss is corrected - 15-20 mL/kg/hr for 1st few hours [3] b) if serum Na+ > 145 meq/L, use 1/2 normal saline c) use of lactated Ringer's solution results in faster resolution of DKA by 3 hours [7] 3) insulin therapy a) do not start insulin therapy until serum K+ > 3.3 meq/L - use KCl at 20-30 meq/hour through central line - do not start KCl until adequate urine output b) 0.1 units/kg regular insulin IV bolus (or 10 units) - if serum glucose does not decline by 10% in 1st hour, an additional IV bolus of 0.14 units/kg of regular insulin may be given [1] c) insulin drip - 0.1 units/kg/hr of regular insulin - once serum glucose drops to 200 mg/dL, change IV fluid to contain dextrose (D5W-1/2NS, D5W-NS) 150-250 mL/hr - adjust insulin infusion to maintain serum glucose 150-200 mg/dL - ([serum glucose (mg/dL)] - 60) x 0.03 units/hr - the 60 may be adjusted to the lowest level of acceptable serum glucose - the 0.03 may be adjusted for sensitivity of the patient to insulin - monitor serum electrolytes & serum glucose during insulin infusion d) change to subcutaneous insulin (70/30) when ketoacidosis has resolved & the patient is eating e) stop insulin drip one hour after 1st dose of SQ insulin f) reducing insulin infusion too early, before clearance of ketones, will cause relapse of DKA [2] 4) glucose replacement: - IV fluid is switched to D5 normal saline when glucose < 200 mg/dL [2] - decrease rate of insulin infusion to diminish risk of hypoglycemia [2] 5) K+ replacement a) if serum K+ < 3 meq/L, add 0.5 meQ/kg/hr in IV fluid b) if serum K+ 3-4 meq/L, add 0.4 meQ/kg/hr in IV fluid c) if serum K+ 4-5 meq/L, add 0.3 meQ/kg/hr in IV fluid d) or add KCl 20-30 meq to each liter of IV fluids e) K+ replacement if serum K+ < 5.3 meq/L [2] f) serum K+ should be checked every 2 hours g) do not start K+ replacement until adequate urine output [2] 6) phosphate replacement a) does not improve recovery or mortality [1] b) may prevent rhabdomyolysis from hypophosphatemia [2] 7) bicarbonate replacement a) does not improve recovery or mortality b) do not use unless pH < 6.9 [2] c) 200 mmol of sodium bicarbonate in 100 mL of water + KCl 20 meq infused over 2 hours 8) magnesium sulfate 2 g IV for magnesium deficiency 9) subcutaneous heparin for patients at risk for DVT 10) identify precipitating factors 11) diet a) nothing by mouth until ketoacidosis & nausea/vomiting resolve b) ADA diet L) Diabetes education

Related

diabetes mellitus hyperglycemic-hyperosmolar syndrome; hyperglycemic-hyperosmolar nonketotic coma (HHNC) hypokalemia hypophosphatemia

General

ketoacidosis diabetes mellitus complication

References

  1. Saunders Manual of Medical Practice, Rakel (ed), WB Saunders, Philadelphia, 1996, pg 632-634
  2. Medical Knowledge Self Assessment Program (MKSAP) 11, 14, 16, 17, 18. American College of Physicians, Philadelphia 1998, 2006, 2012, 2015, 2018. - Medical Knowledge Self Assessment Program (MKSAP) 19 Board Basics. An Enhancement to MKSAP19. American College of Physicians, Philadelphia 2022
  3. UpToDate Online 15.3 http://www.utdol.com
  4. Umpierrez G, Freire AX. Abdominal pain in patients with hyperglycemic crises. J Crit Care. 2002 Mar;17(1):63-7. PMID: 12040551
  5. Wilson JF In clinic. Diabetic ketoacidosis. Ann Intern Med. 2010 Jan 5;152(1):ITC1-1, ITC1-2, ITC1-3, ITC1-4, ITC1-5, ITC1-6, ITC1-7, ITC1-8, ITC1-9, ITC1-10, ITC1-11, ITC1-12, ITC1-13, ITC1-14, ITC1-15, table of contents; quiz ITC1-16 PMID: 20048266
  6. Fayfman M, Pasquel FJ, Umpierrez GE. Management of Hyperglycemic Crises: Diabetic Ketoacidosis and Hyperglycemic Hyperosmolar State. Med Clin North Am. 2017 May;101(3):587-606. Review. PMID: 28372715
  7. Catahay JA et al. Balanced electrolyte solutions versus isotonic saline in adult patients with diabetic ketoacidosis: A systematic review and meta-analysis. Heart Lung 2022 Jul-Aug; 54:74. PMID: 35358905 https://www.heartandlung.org/article/S0147-9563(22)00068-1/fulltext
  8. NEJM Knowledge+ Nephrology/Urology
  9. ElSayed NA, Aleppo G, Aroda VR, et al. 16. Diabetes care in the hospital: standards of care in diabetes - 2023. Diabetes Care. 2023;46:S267-S278. PMID: 36507644