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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 ↑
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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
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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)
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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
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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
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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
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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
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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
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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
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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
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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
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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.
Bicarbonate is in equilibrium with C02 Giving HCO3 raises CO2
HCO3 H2CO3 CO2 + H2O HCO3 H2CO3 CO2
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BBB “Rules” If you give HCO3 rapidly IV:
•Serum HCO3 will rise •pCO2 crosses freely • Thus serum pH will rise •HCO doesn’t cross 3 • If pH rises, less hyperventilation
• Ventilation rate (pCO2) determined • Serum pCO2 will rise on venous side by venous pH • Causing pCO2 to rise on CSF side too
Push Bicarb ONLY For:
Children are at Real Risk • Hyperkalemic emergency for Cerebral Edema.
• Impending cardiopulmonary arrest Be Careful!
Phosphate Therapy in DKA
• No proven benefit • Rarely used in adults Hyperosmolar • Up to ½ of K requirements given as Hyperglycemia
K2 PO4 in pediatric patients
• Check with your pediatrician
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Hyperosmolar Hyperglycemic State (HHS) Hyperosmolar Hyperglycemic State (HHS) (HONK, NKHC, HHNK) (HONK, NKHC, HHNK) A disease usually of the elderly • Not enough insulin to move glucose A mortality of up to 20% • Enough insulin to drive K into cell Profound dehydration • Glucose > 600 • Enough insulin to block catabolic state • pH > 7.30 • Enough to not breakdown fat & protein •HCO3 > 18 • Extreme glucose elevations • Osm > 350
Hyperosmolar Hyperglycemic State (HHS) HHS (HONK, NKHC, HHNK) • AMS in most patients DKA HHS Insulin levels very low may be normal • Up to 50% present in coma Ketoacidosis profound minimal Glucose 600 1,000+ • Seizures in up to 1/4 of patients HCO3 5 - 15 20 – 24 OSM 300 - 325 350+ • Often focal (20 - 85% of reported cases) Age young old Onset acute chronic Associated diseases rare common • Patients usually lethargic or comatose Seizures very rare common Coma rare common • 10% present without AMS Mortality approaches 0 10 – 20%
When you see HHS think: • It takes hours to 1-2 days to • Precipitating cause develop DKA - Pneumonia –Treat aggressively -UTI • It takes many days to weeks to • Beware develop NKHC -AMI -CVA – Do not treat aggressively -Sepsis
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HHS Insulin in NKHC
• Volume resuscitate like DKA • ADA guidelines recommend bolus and maintenance like in DKA • Then 250-500 cc/hr • 0.1 units/kg bolus and 0.1 units/kg per hour • KCL at about 10meq/hr • My bias, follow very, very closely • Be careful: older, risk of HF, fluid overload • I use less insulin until rate of glucose known • I go slow with fluids post bolus
Therapy and Rationales in DKA • Volume – Enough to re-hydrate – But don’t wash out ketones • Insulin Summary – Saturate receptors – And keep saturated • Potassium – Avoid hyperkalemia early – But avoid hypokalemia later
Therapy and Rationales in DKA - 2 HHS
• Bicarbonate – Rarely needed • Find cause – Use only for decompensation • Treat carefully • Phosphate – Only cachectic patients • Mortality – much higher – Use for values below 1.0 – 1.5
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DKA DKA 10 “Pearls” 10 “Pearls”
NSS or LR, not insulin to start Refractory acidosis: Dead gut, abscess, sepsis Bolus then infuse NSS or LR SGLT-2: glucose WNL, pH Beware “WNL” sodium in DKA Bicarbonate is hyperosmolar and hypercarbic
Check K before starting insulin K2PO4 only if PO4 below 1-1.5 VpH not ABG Hyperosmolar Glu state = precipitating cause
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