PATHOGENESIS

BOTH : insulin deficiency

+ elevation of counterregulatory hormones

(glucagon, catecholamines, cortisol, growth hormone)↓

Increase hepatic & renal glucose productionImpaired glucose utilization in peripheral tissues

↓Hyperglycemia & increase plasma osmolality

PATHOGENESIS

DKA :

release of free fatty acids (lipolysis)↓

Hepatic fatty acid oxidation to ketone bodies(β-hydroxybutyrate & acetoacetate)

↓Ketonemia & metabolic acidosis

PATHOGENESIS

HHS : Plasma insulin – inadequate for glucose utilization ‒ adequate to prevent lipolysis & ketogenesis

DKA & HHS : ― magnitude of dehydration ― degree of ketosis (& acidosis)

PRECIPITATING FACTORS● Infection● Cerebrovascular accident● Alcohol abuse● Pancreatitis● Myocardial infarction● Trauma● Drugs e.g. steroids, thiazides, sympathomimetic agents (dobutamine & terbutaline)● Stop/inadequate insulin in DM type I● Elderly with new-onset DM

DIAGNOSIS

History & physical examination :1) Process : - HHS : over several days to weeks - DKA : much shorter (typically < 24 hr)

2) Classical clinical picture of both : - polyuria - polydipsia - polyphagia - weight loss - vomitting - abdominal pain (DKA) - dehydration - weakness - clouding of sensoria - coma

DIAGNOSIS

3) Physical finding : - poor skin tugor - Kussmaul respiration (DKA) - tachycardia - hypotension - alteration of conscious (lethargy coma :HHS) - emesis (coffee-ground) - hypothermia (peripheral vasodilatation) - abdominal pain (DKA : Rx dehydration & metabolic acidosis)

LABORATORY FINDINGS :1)Initial lab : - BS, BUN, Cr, serum ketone - electrolyte (with calculated anion gap) • pseudohypoNa : osmotic gradient from hypergly. • true hypoNa from severe hyperTG • hyperK from insulin deficiency,hypotonicity& acidemia(cell shift) - osmolality : ≥ 320 mOsm/kg stupor/coma = 2 [measured Na (mEq/L) + BS (mg/dl)/18) - CBC with diff count (leukocytosis ὰ serum ketone) - U/A, urine ketone

LABORATORY FINDINGS :

1)Initial lab: - EKG - HbA1C : acute or chronic poor control

2) Suspected infection : - bacterial cultures of urine,blood & throat ,etc - CxR - abdominal pain : pancreatitis serum lipase (DKA : increase serum amylase & liver enz )

DIFFERENTIAL DIAGNOSIS :1) Ketoacidosis : - Starvation ketosis - Alcoholic ketoacidosis mildly elevation BS (rarely > 250 mg/dl) serum HCO3 not < 18 mEQ/L

2) High-anion gap metabolic acidosis : - Lactic acidosis (Ix : serum lactate) - drugs : • salicylate (Ix : serum salicylate), • methanol (Ix : serum methanol) • ethylene glycol (Ix : U/A-calcium oxalate &hippurate crystal),

DIFFERENTIAL DIAGNOSIS : 2) High-anion gap metabolic acidosis : - paraldehyde (strong odor breathing-osmolar gap- anion gap acidosis) - Chronic renal failure (hyperchloremic

acidosis)

TREATMENT :

1) Correction of dehydration, hyeprglycemia & E’lyte imbalance

2) Correct precipitating factor

3) Guideline for management

Fluid therapy :

1) Adult patients : - initial fluid Rx in no cardiac compromise : 0.9%NaCl ≥ 15-20 ml/kg/hr in 1st hour ( ~ 1-1.5 L ) - subsequent choice for fluid depend on hydration, serum E’lyte & urine output • if N/↑serum Na 0.45% NaCl 4 – 14 ml/kg • if ↓ serum Na 0.9% NaCl - monitor BP; fluid input/output ; clinical exam ; sermo osmolality not > 3 mOsm/kg/H2O/hr - fluid replacement correct deficit in 24 hr

FLUID THERAPY :

2) Pediatric patients (< 20 yrs) : - 1st hr : 0.9%NaCl 10-20 ml/hr ( not > 50 ml/kg in first 4 hr of therapy ) - Continued fluid therapy = fluid deficit in 48 hr or 1.5 times of 24 hr maintenance or 5 ml/kg/hr • 0.45-0.9% NaCl rate • ↓ osmolality not > 3 mOsm/kg/hr - serum glucose = 250 mg/dl change 5%DN/2 or 5%D/N/3 with potassium

INSULIN THERAPY :

Not mild DKA : Rx of choice = regular insulin continuous IV infusion Exclude hypoK (< 3.3 mEq/l) Start regular insulin 0.15 units/kg iv bolus (iv bolus nit recommend in pediatric) Cont. infusion 0.1 units/kg/hr (5-7 units/hr in adult) Aim decrease BS 50-75 mg/dl/hr If in 1st hr BS not decrease > 50 mg/dl • check hydration • double dose insulin infusion every hr

INSULIN THERAPY :

when BS = 250 mg/dl in DKA or = 300 mg/dl in HHS • ↓ insulin infusion rate = 0.05 - 0.1 unit/kg/hr (3-6 units/hr) • 5-10% Dextrose

Keep until acidosis in DKA mental status hyperosmolarity in HHS resolve

INSULIN THERAPY :

Ketonemia • longer ot clear than hyperglycemia • monitor by measure serum β-OHB during Rx β-OHB acetoacetic ȃ worse ketosis then not use urine / serum ketone level for Rx

During Rx : monitor serum E’lyte , BS, BUN, Cr, osmolality & venous pH (for DKA) q 2-4 hr ( venous pH < arterial pH = 0.03 units ) anion gap resolution of acidosis

Mild DKA :

Regular insulin SC or IM q 1 hr - priming dose of RI = 0.4 – 0.6 unit/kg • half IV bolus • half SC or IM - then RI 0.1 unit/kg/hr SC or IM

CRITERIA FOR RESOLUTION OF DKA : ● Glucose < 200 mg/dl ● Serum bicarbonate ≥ 18 mEq/l ● Venous pH > 7.3

When DKA resolve

1) If NPO : • continue IV insulin & fluid replacement • RI sc q 4 hr (RI 5 unit / BS 50 mg/dl if BS > 150 mg/dl until RI 20 unit for BS ≥ 300 mg/dl)

When DKA resolve :

2) Patient is able to eat : - multiple-dose schedule : use combination of short/rapid-acting + intermediate/long-acting RI - continue IV insulin infusion for 1-2 hr after the spit-mixed regimen - DM : insulin dose = before the onset of DKA/HHS - new Dx DM : 0.5-1 units/kg/day divide two doses regimen of short + long-acting RI - type-2 DM : oral antihyperglycemic agent & diet

POTASSIUM :

• Insulin Rx, correct ȃ & volume expansion HypoK• Prevent hypoK : replace K < 5.5 mEq/l & adequate urine output• General 20-30 mEq K (2/3 KCl + 1/3 KPO4 ) in each liter of infusion fluid keep serum K = 4-5 mEq/l• hypoK (< 3.3 mEq/l) : - K replacement begin with fluid Rx - insulin Rx delayed until K > 3.3 mEq/l

BICARBONATE :• controversial• keep pH > 7 for - reestrablish insulin activity blocks lipolysis - resolve ketoacidosis without add HCO3 • if pH < 6.9 100 mmol NaHCO3 in 400 ml sterile iv rate 200 ml/hr • if pH 6.9-7.0 50 mmol NaHCO3 in 200 ml sterile iv rate 200 ml/hr • if pH > 7.0 no NaHCO3 • mornitor venous pH q 2 hr until pH > 7.0 • caution : hypoK NaHCO3 in NaCl not Na > 155 mEq/l

PHOSPHATE :

Whole-body phosphate deficit in DKA = 1 mmol/kgSerum phosphate decrease with insulin Rx I/C phosphate replacement • cardiac dysfunction • anemia • respiratory depressionSerum phosphate < 1 mg/dl 20-30 mEq/l K2PO4 No Rx phosphate in HHS Over phosphate Rx hypoCa without tetany

COMPLICATIONS :

● hypoglycemia : over insulin Rx

● hypoK : insulin Rx & Rx acidosis with NaHCO3

● hyperglycemia : interrupt/stop iv insulin after recovery without subsequent sc insulin

● hyperchloremia : excessive saline for fluid & E’lyte replacement

COMPLICATION :

● transient non-anion gap metabolic acidosis (except acute renal failure or extreme oliguria)

● hypoxemia & noncardiogenic pulmonary edema be careful in widen A-a oxygen gradient

COMPLICATION :

● Cerebral edema from osmolality : - rapid alteration of consciousness - headache - seizure - incontinence - bradycardia - pupillary changes - rapid papilledema - respiratory arrest ☺ prevent by gradual replacement of Na & water deficit in hyperosmolality (max ↓ 3 mOsm/kg/hr) ☺ In HHS : keep BS 250-300 mg/dl until hyperosmolality & mental status improve

PREVENTION :

1) Check up or F/U

2) Pt education

3) BS goals & use short-acting RI during illness

4) self monitor if BS > 300 mg/dl be careful 5) suppress fever & Rx infection

6)Early recovery : take easily digestible liquid diet (carbohydrate + salt)