2Diabetic Emergencies Case Presentation Pt is a 32yo female with a hx of type 1 DM who presents with a cc of N/V, and diffuse abdominal pain for 24 hoursWhat other questions would you like to ask
3Diabetic Emergencies Case Presentation Pt denies F/C, URI symptoms, urinary symptoms except for frequencyPt also states that she has been using her insulin correctly, but she had not taken any insulin for the last 24 hours because she wasn’t able to eat anything
4Diabetic Emergencies Case Presentation PMHx: Diagnosed with DM after episode of DKA approx 7 years ago.Meds: Insulin 70/30 28UqAM, 16UqPMNKMASHx: Single, no children, (+) Tob 1ppd for 12 years, occ EtOH use, no recreational drugsFHx: (+) HTNWhat are pertinent findings on physical exam?
5Diabetic Emergencies Physical Exam Gen: Mild distress but A&O x 3 97.4, 120, 34, 132/88HEENT: WNLHeart: RR Lungs: CTA-BAbd: (+) BS, diffuse tenderness, no reboundExt: WNL Neuro: WNLWhat Lab Data would you like to obtain?
6Diabetic Emergencies Case Presentation Lab Data WBC 15.7, H/H 15/45 Plt 229NA 132, K 5.2, CL 96, HCO 11, BUN 10, Cr 1.0 Glucose 612, Ca 12.1, Phos 6.6, Mg 2.1
7Diabetic Emergencies Case Presentation Lab Data Analysis NA 132, K 5.2, CL 96, HCO 11, BUN 10, Cr 1.0 Glucose 612, Ca 12.1, Phos 6.6, Mg 2.1What is the anion gap?What is the actual serum sodium?What is the differential diagnosis for wide anion gap metabolic acidosis?
8Formulas you may need sOsm = 2 (Na + K ) + Glu/18 + BUN/2.8 + ETOH/4.6 AG = Na - ( Cl + HCO3)Na = Na x (Glu - 100)/100
9Diabetic Emergencies Case Presentation Lab Data (Continued) UA: Protein 3+, Large ketonesSerum ketones were 1:16Serum osmolarity was 323mOsm/kg
10Diabetic Ketoacidosis (DKA) Life-threatening emergencyGross insulin deficiency is the predominant problem of DKAMost common in patients with type 1 diabetesCan occur in patients with type 2 diabetes due to progressive loss of β-cell reserveMortality is ~5%–10%In the absence of insulin to facilitate glucose entry into cells, the body metabolizes fat instead of glucose for energy, which results in an abnormally elevated concentration of ketones in the blood and urine. The accumulation of ketones leads to acidity, which can result in diabetic ketoacidosis (DKA), a life-threatening emergency. Although DKA is characteristic of type 1 diabetes, it can occur in type 2 diabetes under stress conditions or with progression to insulinopenia.Fishsbein H, Palumbo PJ. Acute metabolic complications in diabetes. In: National Diabetes Data Group. Diabetes in America. Bethesda (MD): National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases: 1995:
11Signs, Symptoms, and Treatment of Diabetic Ketoacidosis Blurred visionIncreased thirstIncreased urinationNausea/vomitingConfusionLoss of consciousnessSignsDeep respirationsFruity breathDehydrationHyperglycemiaKetosisAcidosisTreatmentGive insulin in a sufficient amountAttention to the potassium level is also importantHydration
12Type 1 DM hormonal pathophysiology - Insuln deficiency:decreased glucose utilization- Elevations in counterregulatory hormones:increased lipolysis in adipose tissueincreased proteolysis in muscleincreased glycogenolysisincreased gluconeogenesishepatic ketogenesisLeading to DKA
13Hyperosmolar Hyperglycemic State (HHS) Life-threatening emergencyOccurs in patients with type 2 diabetesCharacterized by very high blood glucose levels without ketonesinsulin secretion is maintained to prevent peripheral lipolysis , liver able to metabolize FFA in a nonketogenic mannerrelative insulin deficiency : decreased peripheral uptake and increased hepatic gluconeogenesishyperglycemia, hyperosmolalityosmotic diuresis and volume and electrolyte depletion
14DKA/HHS not mutually exclusive ! Criteria for DKA hyperglycemia ( glu>250 mg/dl)ketosisacidemia ( pH <7.3)
15Pathophysiology of DKA/HHS Insulin DeficiencyIncreased LipolysisHyperglycemiaIncreased ketogenesisOsmotic DiuresisKetoacidosisHyperosmolalityPure Diabetic KetoacidosisPure Hyperosmolar State
16DKAAbsolute insulin deficiency and counter-regulatory hormones promote lipolysisshift in hepatic lipid metabolism of incoming fatty acids due to high ratio of glucagon to insulin in portal flow - fall in malonyl co A levels and disinhibition of CPTCPT catalizes beta oxidative pathway- fatty acids are oxidized to form ketone bodies rather than re-esterified into TG
17Physiology of DKA 3 hydroxybutyrate Acetone Triglyceride Insulin glucagonTriglycerideFree Fatty AcidsFatty Acyl Co AAcetyl Co AHMA Co AAcetoaceteateHormone Sensitive LipaseAdipocyteSerumGlucagonMalonyl Co AHepatocyteCarnitine palmitoyl transferase 1Mitochondria3 hydroxybutyrateAcetone
18Evaluation of patient history of DM , medications and symptoms history of complicationsutilization of medicationssocial history ( including alcohol)vomitingprecipitating factor - pregnancy, infection, omission of insulin, MI, CVAasses hemodynamic statusexamine for infection
19Laboratory Evaluation BMPCBCserum ketonescalculate serum osmolality and AGmeasure serum osmolality if ingestion of osmotically active substance other than glucose suspectedUA and cultureconsider blood cultureCXRconsider HCGABG if indicated clinicallyHbA1c
20“Euglycemic ketoacidosis “ Glu < 300 mg/dlHCO3 < 10 mEq/lUsually in pump pts ( no “back-up insulin)
21Other expected labs in DKA Hyponatermia unless pt is dehydratedHyperkalemia due to cellular shiftLeukocytosis in the absonce of infectionElevation of amylase and lipase in the absence of pancreatitis
22“Serum Ketone Negative DKA” Alcoholic ketoacidosisHypoxiaBeta hydroxybutirate is the dominant ketoneNot detected by nitroprusside reaction
23Gudelines ofr therpay of DKA/HHS addapted from Joslin’s Diabetes Mellitus 14th edtion , 2005
24Suggested Fluid Replacement in DKA/HHS Administer NS as indicated to maintain hemodynamic status than follow general guidelines:NS for first 4 hoursconsider 1/2 NS thereafterChange to D5 1/2 NS when BG < 259 mg/dlmay need to adjust type and rate of fluid administration in the elderly and in patients with CHF and CRF
26Guidelines for Insulin Management in DKA/ HHS regular insulin 10U I.v. stat ( for adults) or U/kg I.v. statstart regular insulin infusion 0.1 u /kg per hour or 5 U per hourIncrease insulin by 1 U per hour every 1-2 hours if less than 10 % decrease in glucose or no improvement in acid - base statusdecrease insulin by 1-2 U/hr when BG < 250 mg/dl and/or progressive improvement in clinical status with decrease in glucose >75 mg/dl /hrdo not decrease insulin infusion to < 1 u /hrmaintain BG mg/dlif BG < 80 mg/dl , stop insulin infusion for no more than 1 hour and restart the infusionif BG drops consistently to <100 mg/dl , change I.V. fluids to D 10 to maintain BG mg/dl
27Insulin Infusion Algorithm 1. Discontinue all subcutaneous insulin use2. Measure blood glucose every hourmeasure urine ketones after each void every 4 hours3. Give D5%W iv via insulin infusion pump4. Make insulin solution using regular insulin to a concentration of 0.5 U/ml
28Insulin Infusion Algorithm Newton et al:Arch Intern Med 164,sept 27, 2004
29Guidelines for K replacement in DKA/HHS Do not administer K if serum K > 5.5 mEq/l or if patient is anuricUse KCl but alternate with KPO4 if there is severe phosphorus depletion and patient is unable to take phosphorus by mouthAdd I.V. KCl to each liter of fluid administered unless contraindicated
30Guidelines for K replacement in DKA/HHS serum K ( mEq/L) Additional K required< mEq/LmEq/LmEq/L> Stop K infusion
31Guidelines for Bicarbonate Therapy in DKA PRO: severe acidosis is associated with adverese effects:hypotension, decreased cardiac output decreased peripheral vascular resistance, increased pulmonary arterterial resistance , bardycardia, arrhytimas , renal and mesenteric ischemia, cerebral vasodilatationCONS: no studies have shown any benefit of bicarbonate if pH isSIDE EFF : overshoot alkalosis, paradoxical CSF acidosis , hypokalemia, volume overload, overproduction of ketoacids
32Guidelines for Bicarbonate Therapy in DKA Use clinical judgement in deciding if bicarbonate therapy is indicatedif pH is < 7.0 consider 100 ml HCO3 over 45 min( mix 100 ml NaHCO3 with 400 ml sterile water and administer at rate of 200 ml/hr)check ABG 30 min later
33Phosphate replacement Phos depletion is common: renal loss, intracellular uptake during insulin Rxproblem: low cardiac output, respiratory muscle weakness, rhabdomyolisis , CNS deppression , seizures , coma, renal failureCAVE : iv Phos leads to hypocalcemiano benefit in routine replacementreserve replacement Rx if phos < 1.5 mg/dl AND in whom Ca is normaluse of small amount of Kphos and KCL iv is safe and effectivebut oral replacement preferred to I.V.
34Monitoring of RX BG hourly electrolytes and acid base status every 2-4 hoursok to check venous pH if you can’t get art line ( 0.03 unit less than arterial )frequent measurement of ketones may be misleading ( hydroxybutirate is converted to acetoacetate)consider using bedside measurement of ß hydroxybutiraterepeat CXR after 4 l fluids administered
35Complications of RX hypoglycemia hypokalemia hypophosphatemia hyperchloremia and hyperchloremic acidosis - chloride losses are less severe than sodium losses but replacement solutions have equal par tof Na and Clhypoalcemiacerebral edema - childrenDVT/PE ( dehydration as a risk factor)
36DKA - is it always type 1 DM? Arch Int Med :2317 -epidemiology of pts admitted for DKA : type 1 DM in80 % of whites53% of African Americans34 % of Hispanicsno difference in electrolytes,glu, pH, AG, pOsm or level of ketosismajority of pts with type 2 , no preciptating event !
37A” Real Life “ case 55 y/o AAF no previous h/o DM comes with polyuria,, polydipsia, fatigueVitals: 96.9, 130, 24, 122/63Labs: WBC 19, BS 502, K 6.0, Na 128, CO2 5
38Orders Dx DKA IVF NS 3l bolus than 200 cc/hour 2 amps HCO3 blood cultures, sputum cultures,accucheck q 1hourdiabetic education in amcbc , bmp in ambmp q 2hours x 4, UAMg, PO4 levels
40Orders - cont 4 hours later - K 3.0 , BS 347 order : 40 mEq KCl now change IVF to D5 NS with 40 KCl at 200 cc/hour6 hours later: phos 1.2order : 40 mEq K phos IVsoft diet for pt24 hours later , BS 350
41Diabetic Emergencies Hypoglycemia Whipple Triad Consistent signs and symptomsLow blood glucoseRelief with supplemental glucoseTwo categories of hypoglycemiaReactiveNonreactive
42Diabetic Emergencies Hypoglycemia Reactive Hypoglycemia Develops in response to a nutrient challengeSeen in pts with type 2 DM (???) and post GI surgery ptsIdiopathic formNonreactive HypoglycemiaIatrogenicFasting/Factious
43Diabetic Emergencies Hypoglycemia Fasting/Factious Hypoglycemia 3 main causesFactitious taking of oral hypoglycemics/insulinAutoimmune etiologyInsulinoma from an islet cell tumorHeavy EtOH can also cause hypoglycemiaThree tests for workup of nonreactive hypoglycemiaSerum insulinC-peptideUrinary sulfonylurea test
44Diabetic Emergencies Hypoglycemia C-peptide Insulin levels Elevated indicates endogenous insulin secretion and is low if there is factitious insulin injectionHigh levels seen in autoimmune hypoglycemia, insulinoma, and sulfonylurea ingestionUrinary sulfonylurea test will rule in or out oral hypoglycemic useInsulin levels< 100 suggest insulinoma> 100 suggest autoimmune