Diabetic Emergencies

Andjela Drincic M.D.

Diabetic 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 hours

What other questions would you like to ask

Diabetic Emergencies

Case Presentation Pt denies F/C, URI symptoms, urinary

symptoms except for frequency Pt 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

Diabetic Emergencies

Case Presentation PMHx: Diagnosed with DM after episode of

DKA approx 7 years ago. Meds: Insulin 70/30 28UqAM, 16UqPM NKMA SHx: Single, no children, (+) Tob 1ppd for 12

years, occ EtOH use, no recreational drugs FHx: (+) HTN What are pertinent findings on physical

exam?

Diabetic Emergencies

Physical Exam Gen: Mild distress but A&O x 3 97.4, 120, 34, 132/88 HEENT: WNL Heart: RR Lungs: CTA-B Abd: (+) BS, diffuse tenderness, no

rebound Ext: WNL Neuro: WNL What Lab Data would you like to obtain?

Diabetic Emergencies

Case Presentation Lab Data

WBC 15.7, H/H 15/45 Plt 229 NA 132, K 5.2, CL 96, HCO 11, BUN 10, Cr

1.0 Glucose 612, Ca 12.1, Phos 6.6, Mg 2.1

Diabetic 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 2.1

What is the anion gap? What is the actual serum sodium? What is the differential diagnosis for wide

anion gap metabolic acidosis?

Formulas you may need

sOsm = 2 (Na + K ) + Glu/18 + BUN/2.8 + ETOH/4.6

AG = Na - ( Cl + HCO3) Na = Na + 1.6 x (Glu - 100)/100

Diabetic Emergencies

Case Presentation Lab Data (Continued)

UA: Protein 3+, Large ketones Serum ketones were 1:16 Serum osmolarity was 323mOsm/kg

Diabetic Ketoacidosis (DKA)

Life-threatening emergency Gross insulin deficiency is the

predominant problem of DKA Most common in patients with

type 1 diabetes Can occur in patients with type 2

diabetes due to progressive loss of β-cell reserve

Mortality is ~5%–10%

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: 1995:283-291.

Signs, Symptoms, and Treatment of Diabetic Ketoacidosis

Symptoms Blurred vision Increased thirst Increased urination Nausea/vomiting Confusion Loss of consciousness

Signs Deep respirations Fruity breath Dehydration Hyperglycemia Ketosis Acidosis

Treatment Give insulin in a sufficient

amount Attention to the potassium

level is also important Hydration

Type 1 DMhormonal pathophysiology

- Insuln deficiency: decreased glucose utilization - Elevations in counterregulatory hormones: increased lipolysis in adipose tissue increased proteolysis in muscle increased glycogenolysis increased gluconeogenesis hepatic ketogenesisLeading to DKA

Hyperosmolar Hyperglycemic State (HHS)Life-threatening emergency Occurs in patients with type 2 diabetes Characterized by very high blood glucose

levels without ketones insulin secretion is maintained to prevent

peripheral lipolysis , liver able to metabolize FFA in a nonketogenic manner

relative insulin deficiency : decreased peripheral uptake and increased hepatic gluconeogenesis

hyperglycemia, hyperosmolality osmotic diuresis and volume and electrolyte

depletion

DKA/HHS

not mutually exclusive ! Criteria for DKA

hyperglycemia ( glu>250 mg/dl) ketosis acidemia ( pH <7.3)

Pathophysiology of DKA/HHS

Insulin Deficiency

Increased Lipolysis Hyperglycemia

Increased ketogenesis Osmotic Diuresis

Ketoacidosis Hyperosmolality

Pure Diabetic Ketoacidosis Pure Hyperosmolar State

DKA

Absolute insulin deficiency and counter-regulatory hormones promote lipolysis

shift 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 CPT

CPT catalizes beta oxidative pathway- fatty acids are oxidized to form ketone bodies rather than re-esterified into TG

Physiology of DKA

Triglyceride

Free Fatty Acids

Free Fatty Acids

Free Fatty Acids

Fatty Acyl Co A

Acetyl Co A

HMA Co A

Acetoaceteate

Acetone 3 hydroxybutyrate

Adipocyte

Serum

Hepatocyte

Mitochondria

Hormone Sensitive Lipase

Carnitine palmitoyl transferase 1 Malonyl Co A

Glucagon

Insulin glucagon

Evaluation of patient

history of DM , medications and symptoms history of complications utilization of medications social history ( including alcohol) vomiting precipitating factor - pregnancy, infection,

omission of insulin, MI, CVA asses hemodynamic status examine for infection

Laboratory Evaluation

BMP CBC serum ketones calculate serum osmolality and AG measure serum osmolality if ingestion of osmotically

active substance other than glucose suspected UA and culture consider blood culture CXR consider HCG ABG if indicated clinically HbA1c

“Euglycemic ketoacidosis “

Glu < 300 mg/dl HCO3 < 10 mEq/l Usually in pump pts ( no “back-up

insulin)

Other expected labs in DKA

Hyponatermia unless pt is dehydrated

Hyperkalemia due to cellular shift Leukocytosis in the absonce of

infection Elevation of amylase and lipase in

the absence of pancreatitis

“Serum Ketone Negative DKA”

Alcoholic ketoacidosis Hypoxia Beta hydroxybutirate is the

dominant ketone Not detected by nitroprusside

reaction

Gudelines ofr therpay of DKA/HHS

addapted from Joslin’s Diabetes Mellitus 14th edtion , 2005

Suggested Fluid Replacement in DKA/HHS

Administer NS as indicated to maintain hemodynamic status than follow general guidelines: NS for first 4 hours consider 1/2 NS thereafter Change to D5 1/2 NS when BG < 259

mg/dl may need to adjust type and rate of fluid

administration in the elderly and in patients with CHF and CRF

Suggested fluid replacement in DKA /HHS

1st hour : 1 l 2nd hour : 1 l 3rd hour : 500 ml - 1 l 4th hour: 500 ml - 1 l 5th hour : 500 ml - 1 l Total 1st - 5th hour 3.5 - 5 l 6th - 12th hour : 250 - 500

ml/hr

Guidelines for Insulin Management in DKA/ HHS

regular insulin 10U I.v. stat ( for adults) or 0.15 U/kg I.v. stat start regular insulin infusion 0.1 u /kg per hour or 5 U per hour Increase insulin by 1 U per hour every 1-2 hours if less than 10

% decrease in glucose or no improvement in acid - base status decrease 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 /hr

do not decrease insulin infusion to < 1 u /hr maintain BG 140 - 180 mg/dl if BG < 80 mg/dl , stop insulin infusion for no more than 1 hour

and restart the infusion if BG drops consistently to <100 mg/dl , change I.V. fluids to D

10 to maintain BG 140 - 180 mg/dl

Insulin Infusion Algorithm

1. Discontinue all subcutaneous insulin use

2. Measure blood glucose every hour measure urine ketones after each void

every 4 hours 3. Give D5%W iv via insulin infusion

pump 4. Make insulin solution using regular

insulin to a concentration of 0.5 U/ml

Insulin Infusion AlgorithmNewton et al:Arch Intern Med 164,sept 27, 2004

Blood glucosemg/dl

Insulin infusionU/h

D5%Wml/h

<7071-100101-150151-200201-250251-300301-350351-400401-450451-500>500

0.51.02.03.04.06.08.010.012.015.020.0

250225200175150100500000

Guidelines for K replacement in DKA/HHS

Do not administer K if serum K > 5.5 mEq/l or if patient is anuric

Use KCl but alternate with KPO4 if there is severe phosphorus depletion and patient is unable to take phosphorus by mouth

Add I.V. KCl to each liter of fluid administered unless contraindicated

Guidelines for K replacement in DKA/HHS

serum K ( mEq/L) Additional K required

<3.5 40 mEq/L 3.5 - 4.5 20 mEq/L 4.5 - 5.5 10 mEq/L > 5.5 Stop K

infusion

Guidelines 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 vasodilatation

CONS: no studies have shown any benefit of bicarbonate if pH is 6.9-7.1

SIDE EFF : overshoot alkalosis, paradoxical CSF acidosis , hypokalemia, volume overload, overproduction of ketoacids

Guidelines for Bicarbonate Therapy in DKA

Use clinical judgement in deciding if bicarbonate therapy is indicated

if 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

Phosphate replacement

Phos depletion is common: renal loss, intracellular uptake during insulin Rx

problem: low cardiac output, respiratory muscle weakness, rhabdomyolisis , CNS deppression , seizures , coma, renal failure

CAVE : iv Phos leads to hypocalcemia no benefit in routine replacement reserve replacement Rx if phos < 1.5 mg/dl AND in

whom Ca is normal use of small amount of Kphos and KCL iv is safe

and effective but oral replacement preferred to I.V.

Monitoring of RX

BG hourly electrolytes and acid base status every 2-4

hours ok 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 hydroxybutirate

repeat CXR after 4 l fluids administered

Complications 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 Cl

hypoalcemia cerebral edema - children DVT/PE ( dehydration as a risk factor)

DKA - is it always type 1 DM?

Arch Int Med 1999 159:2317 - epidemiology of pts admitted for DKA :

type 1 DM in 80 % of whites 53% of African Americans 34 % of Hispanics

no difference in electrolytes,glu, pH, AG, pOsm or level of ketosis

majority of pts with type 2 , no preciptating event !

A” Real Life “ case

55 y/o AAF no previous h/o DM comes with polyuria,, polydipsia, fatigue Vitals: 96.9, 130, 24, 122/63 Labs: WBC 19, BS 502, K 6.0, Na 128, CO2

5

Orders

Dx DKA IVF NS 3l bolus than 200 cc/hour 2 amps HCO3 blood cultures, sputum

cultures,accucheck q 1hour diabetic education in am cbc , bmp in am bmp q 2hours x 4, UA Mg, PO4 levels

Insulin gtt: U/hour

0-50 off 70 - 100 0.3 101- 129 0.4 130 - 170 0.5 171 - 200 0.6 201 -230 0.8 231 - 270 1.0 271 - 300 2.0 300 - 330 4.0 >330 4.0

Orders - 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/hour 6 hours later: phos 1.2 order : 40 mEq K phos IV soft diet for pt 24 hours later , BS 350

Diabetic Emergencies

Hypoglycemia Whipple Triad

Consistent signs and symptoms Low blood glucose Relief with supplemental glucose

Two categories of hypoglycemia Reactive Nonreactive

Diabetic Emergencies

Hypoglycemia Reactive Hypoglycemia

Develops in response to a nutrient challenge

Seen in pts with type 2 DM (???) and post GI surgery pts

Idiopathic form Nonreactive Hypoglycemia

Iatrogenic Fasting/Factious

Diabetic Emergencies

Hypoglycemia Fasting/Factious Hypoglycemia

3 main causes Factitious taking of oral hypoglycemics/insulin Autoimmune etiology Insulinoma from an islet cell tumor

Heavy EtOH can also cause hypoglycemia Three tests for workup of nonreactive

hypoglycemia Serum insulin C-peptide Urinary sulfonylurea test

Diabetic Emergencies

Hypoglycemia C-peptide

Elevated indicates endogenous insulin secretion and is low if there is factitious insulin injection

High levels seen in autoimmune hypoglycemia, insulinoma, and sulfonylurea ingestion

Urinary sulfonylurea test will rule in or out oral hypoglycemic use

Insulin levels < 100 suggest insulinoma > 100 suggest autoimmune