9/28/2018 ACEP 2018 DKA and Hyperosmolar Syndrome Pearls and Pitfalls Corey M. Slovis, M.D. DKA Vanderbilt University Medical Center Metro Nashville Fire Department Nashville International Airport Nashville, TN Mastering Emergency Medicine A 21 year old grad student Presents in DKA. • Secure the ABC’s • Consider or give NGT • Five Causes How many causes of •Five Steps DKA are there? • Five Reasons for almost everything DKA – Insulin Lack 5 Causes of DKA 5 Actions of Insulin • Infection • Drives Glucose into cell → Glu ↑ • Infarction • Drives K into cell → K ↑ • Infant • Anabolic → Catabolic • Indiscretion • Blocks Fat breakdown → FFA Acids ↑ • Insulin lack • Blocks protein breakdown → Keto Acids ↑ 1 9/28/2018 Diabetes Care 2009;32:1335-1343 • Current State of the Art Metabolism 2016;65:507-21 Med Clin N Am 2017;101:587-606 • Standard of Care • Consensus Statement of ADA Three Levels of DKA Although DKA is much more Mild Moderate Severe common in Type 1 DM, 1/3 of DKA pH 7.25 – 7.30 7.00 – 7.24 below 7.0 cases occur in patients classified as Type 2 DM (“Adult onset”) HCO3 15 - 18 10 - 15 below 10 Stupor or J Clin Endocrinol Metab 2015;100:2849-52 MS Alert Alert + Coma How Sick in DKA? • Mental Status • BP/Pulse Can an adult patient have • Respiratory Rate “euglycemic DKA”? • Finger Stick Glucose • Serum pH 2 9/28/2018 SGLT2 Inhibitors Sodium Glucose Cotransporter 2 Inhibitors J Clin Endocrinol Metab 2015;100:2849-52 • The Good Case Rep Crit Care 2016:ID 1656182 J Diab and Comp 2017;31:611-14 - Inhibits proximal tubular reabsorption of glucose - May decrease the rate of diabetic kidney disease • SGLT-2 may cause Euglycemic DKA • Glucose values 200-300 • The Bad • Yet severe acidosis - Increases reabsorption of ketones - Increases glucagon levels • May take longer to clear keto acids - Thus promoting hepatic ketogenesis • Be wary, use PE, VS & pH, not just glucose Acad Emerg Med 2003;10:836-841 Do you need an ABG in DKA? • 200 ABGs and VpHs in DKA Patients •ABG pO2 and pCO2 changed Rx in 2/200 • Very high Art pH/V pH correlation (0.95) Venous pH How many therapies should Routinely Use VpH in DKA you consider in DKA? Very high Art pH/V pH correlation (0.95) 3 9/28/2018 Five Therapies to Consider in DKA Therapy and Rationales in DKA • Volume • Volume – Enough to re-hydrate – But don’t wash out ketones v• Insulin • Insulin • Potassium – Saturate receptors ...................... – And keep saturated • Bicarbonate • Potassium • Phosphate – Avoid hyperkalemia early – But avoid hypokalemia later Therapy and Rationales in DKA - 2 • Bicarbonate – Rarely needed – Use for decompensation How dehydrated are DKA patients? • Phosphate – Only cachectic adult patients – Common in children – Use for values below 1.0 – 1.5 VOLUME in DKA Deficits: Is aggressive fluid • 3 - 5 liters is usual deficit in management optimal mild-moderate DKA in adults? • 5 - 6 liters is usual fluid deficit in severe DKA 4 9/28/2018 JAMA 1989;262:2108-13 Don’t “wash out” all the Keto Acids …. Let the Patient Metabolize Them Volume Therapy in DKA Begin Therapy: • Bolus healthy patients with at least 1,000 cc of NSS (20 cc/kg) rapidly For mild DKA you can just Stable Patients: • NSS at 500 cc/hr x 4 hours begin therapy at 250cc/hr • Switch to NSS at 250 cc/hour with smaller or no bolus Profound Dehydration: • NSS wide open until well perfused NSS vs. ½ NS • NSS is the “standard” Should you ever use half • Use initially to volume load normal saline in treating DKA? • Consider ½ NS if corrected serum sodium is elevated above normal 5 9/28/2018 The easiest way to correct for Na in DKA is 2 meq ↓ Na for every 100mg/dl glucose “Real Formula” – 1.6 ↓ Na/100 mg/dl glucose to 400 2.4 ↓ Na/100 mg/dl > 400 134 96 Glu = 750 5.0 10 What is better fluid in DKA . Corrected Na = 134 + 2/100 glu ↑ Normal saline (NSS) or Lactated Ringer’s (LR)? . Corrected Na = above 140 (145-148) Use ½ NS in this patient Resolution of DKA: pH and Glucose NSS vs LR Q J Med 2012;105:337-43 683 Q J Med 2012;105:337-43 700 540 600 • 57 pts randomized to NSS vs LR 410 500 P=0.251 300 P=0.014 • pH 6.9-7.2, average glucose 470 400 300 • Double-blind, randomized 200 100 0 • Evaluated time to pH 7.32 and glucose < 250 NSS LR NSS LR pH to 7.32 Glucose to 250 6 9/28/2018 LR vs NSS in DKA Take Homes • A small study that does show N Engl J Med 2018;378:829-39 bicarbonate rises sooner but glucose Is LR or NSS more advantageous in ED falls slower with LR patients admitted to the ICU? • 15,802 adult pts from 1 hospital • No proven benefit of modifying current American Diabetes Association • Pragmatic, multiple cross overs recommendations for treatment of DKA • ED pts who were then ICU admitted • 1,000 ml LR/Plasma-Lyte vs 1,020 ml NSS (median) • Compared mortality, new RRT, persistent Cr 2 x N Engl J Med 2018;378:829-39 N Engl J Med 2018;378:829-39 Death, Renal Replacement Therapy and Cr 2 x N Engl J Med 2018;378:829-39 11.1% 12% 10.3% 11% Ped Emerg Care 2018 Aug;ePub ahead of print 10% Hundreds 9% Is LR superior to NSS in Pediatric DKA? 6.6% 8% 6.4% 7% p < 0.06 • 49,737 pts ages 0-17, retrospective study 6% 5% 2.9% 2.5% • Pediatric Health Information System Database 4% p < 0.6 3% p < 0.08 • 43,841 NSS vs 1,762 (4%) LR 2% 1% 0% • Most DKA “mild to moderate” NSS LR NSS LR NSS LR Mortality RRT Cr • Evaluated LOS and incidence of cerebral edema 7 9/28/2018 Cerebral Edema Ped Emerg Care 2018 Aug;ePub ahead of print Ped Emerg Care 2018 Aug;ePub ahead of print 5% Study shows more than a 4x increase 3.6% 4% incidence of cerebral edema with NSS 3% vs LR (3.6% vs 0.8%) 2% 0.8% However 5.9% of NSS had “severe” or 1% “extreme” DKA vs only 1.6% treated with LR or about 4x as many seriously 0% LR NSS ill patients at risk for cerebral edema What Fluid Should You Use In DKA Once Serum Glucose Not clear… approaches 250 mg%: ADA recommends NSS Switch to Glucose but it’s from 2009 containing fluids (D51/2 NS at 150 - 250 cc/hr) My bias is LR Insulin Insulin Dosing Current recommendation: • Loading Dose • Provide a loading dose, and then – 0.1 units/kg IV Push • Keep all receptor sites saturated • Maintenance Dose Each unit of insulin moves about – 0.1 units/kg per hour 4-5 grams of glucose into cell In general load adults, not children 8 9/28/2018 J Emerg Med 2010;38:422-427 J Emerg Med 2010;38:422-427 • ADA recommends insulin loading in adults Conclusions • Loading dose saturates receptors • IV insulin bolus not of proven benefit • Loading may cause hypoglycemia in children • Loading not recommended in Peds DKA • May cause more hypoglycemia • Hypoglycemia seen in adults too! J Emerg Med 2015;48:530-8 What do you need to know about SQ Can you use SQ insulin insulin treatment of DKA? in DKA? • 5 small studies, mild-moderate DKA • All show SQ is similar to IV • But requires SQ injections Q 1-2 h • Close following of blood glucose • Never in severe acidosis, hypotension, AMS SQ Insulin in DKA Potassium in DKA Take Homes • SQ can avoid ICU admission • The average K deficit in DKA • But floor RNs often can’t do is 3 - 5 meq/kg IBW • Still requires close monitoring • The ECG does not accurately • Yes for a step down unit predict hypokalemia • Not for sick patients 9 9/28/2018 Potassium Dosing in DKA KCL Replacement in First Hours of DKA In general Hyperkalemia (above 5.3) Hold K for 1 hr, recheck K 10 meq/hr “DKA Kalemia” (4.0 - 5.3) KCL 10 meq/hr Hypokalemia (3.5 - 4.0) KCL 20 meq/hr But … Severe HypoK (below 3.5) Hold Insulin KCL 20 - 60 meq/hr/constant ECG Unexpected Death in DKA • First hour or two when sick: Should you begin insulin – Hyperkalemia along with the IV fluids? • Later while “stabilizing”: NO!! – Hypokalemia Glucose + insulin drives K into the cell Always determine the serum Hypokalemia + DKA + insulin = potassium before starting insulin VF, VT or Toursades 10 9/28/2018 Refractory Acidosis in DKA What should you immediately • Dead Gut consider if glucose is falling but •Sepsis bicarbonate values are not rising too? • Abscess Bicarbonate Use Potential Benefits Potential Risks Reverses Acidosis Intracellular Acidosis Improves Cardiac Output Increased Ca, H+, K fluxes Should you use bicarbonate Increases Fibrillatory Threshold Hypokalemia, Tissue Hypoxia in DKA? Improves Insulin Sensitivity Hyperosmolarity, Hypernatremia Decreased Work of Breathing Increased CO2 Generation, Respiratory Acidosis Decreased Length of Coma Paradoxical CSF Acidosis Recommendations on Bicarbonate It is generally agreed that: NEJM 2001;344:264-269 The only therapeutic variable associated with • pH above 6.9 requires NO bicarbonate cerebral edema in children with DKA was the administration of Bicarbonate • pH below 6.9 probably requires bicarbonate • Low pH, low pCO2 levels and amount of • Be “forced” into using bicarbonate dehydration also important determinants 11 9/28/2018 Rule 1: CO2 freelyBBB Crosses BBB Rapid IV administration of CO2 bicarbonate in DKA can cause a CO respiratory acidosis in the brain 2 CO2 CO2 Rule 2: HCO3 does not cross BBB HCO3 Rule 3: Hyperventilation is based on venous pH not CSF pH.