DIABETIC KETOACIDOSIS: A CASE STUDY Dr. Prashant Kadam

COULD THIS HAVE BEEN PREVENTED? 9 year old HARDIK, a known diabetic since past one year, on insulin Rx, developed fever & cough with loss of appetite. Since he was not eating, the parents, fearing hypoglycemia, omitted his insulin dose. As the day progressed he developed abdominal pain and distension with vomiting and became breathless and drowsy

Capillary refill: mildly prolonged, EXAMINATION HR: 130 /min RR: 50 /min BP:100/60 Severe dehydration, Capillary refill: mildly prolonged, Drowsy but no other neurological signs, Air hunger with bilateral good air entry and no foreign sounds, Abdominal distension, liver 2 cm+

BEDSIDE DIAGNOSIS IN < 2 MIN Finger prick BG: HIGH (600 mg %) Urine Ketones ++++ Diagnosis: Diabetic ketoacidosis

Samples collected for: ABG: pH: 6.92; pCo2: 4.5; HCo3: 1.1 CBC Electrolytes Creatinine and BUN Serum Ketones Serum Amylase Blood and Urine Culture Urine Routine.

IV INFUSION STARTED BEFORE SAMPLES DESPATCHED TO LAB…. BG at the end of 1st hour : 497 mg% (down by 103 mg%) 300 ml NS over 1hr (10 ml/kg) No insulin No bicarbonate No antibiotics

BASELINE LAB REPORTS CBC: 15.1 /55/23600 – P85, no band forms,/6 lacs Serum Electrolytes: 139 / 5.2 / 100. BUN: 25 Creatinine: 0.9 Serum Ketones +ve Serum Amylase: 163

DO NOT TAKE LAB REPORTS AT FACE VALUE… Corrected Na + = 139 +( 500 x 1.6 / 100 ) = 147 Anion Gap = Na – ( Cl + HCo3 ) = 139 – ( 100 + 1.1 ) = 37.9 (normal = 12-16 ) Calculated Serum Osmolality = 2 x Na + BG /18+ BUN/2.8 = 2 x 139+600/18 +25/2.8 = 319 Effective serum Osmolality = 311

INSULIN INFUSION: STARTED AT END OF 1ST HOUR 50 IU INSULIN ‘R’ in 500 ml NS 1 ml/Kg/hr would provide 0.1U/kg/hr In our case, 30 ml / hr. 50 ml run off from tubing.

FLUID CALCULATION: 2ND HOUR ONWARD HOW MUCH TO GIVE? Maintenance: (M) 1700 ml / 23 hrs = 70 ml/hr Deficit: (D) 9 % dehydration 90ml/kg = 2700 ml – 300 ml (fluid bolus) = 2400 ml / 47 hrs = 50 ml/hr Ongoing losses: not added So, the fluid / hr = 70(M) + 50(D) = 120 ml/hr

WHICH FLUID? BG > 250 mg%: ½ NS + KCL BG < 250 mg%: ½ DNS + KCL

HOW MUCH POTASSIUM? SERUM K+ KCL in Meq/L > 5.5 NIL 3.5-5.5 20-30 (1-1.5ml/100mlfluid) 2.5-3.5 40-60 (2-3 ml/100mlfluid)

BLOOD GLUCOSE TREND WITH Rx PERIOD BLOOD GLUCOSE baseline 600 1 hr 497 2 hr 458 3 hr 380 4 hr 292 5 hr 240 6 hr 200

ELECTROLYTE & ABG TRENDS IN 1ST 6 HOURS Hr Electrolyte Na / K / Cl ABG Ph / PCo2 / HCO3 139 / 5.2 / 100 6.92 / 4.5 / 1.1 2 142 / 4.8 / 104 7.00 / 15 / 4.2 4 144 / 3.9 / 107 7.14 / 18 / 7.0 6 145 / 3.4 / 110 7.22 / 18.5 / 8.5

ANION GAP & OSMOLARITY TRENDS Hr Anion Gap Urine ketones Corrected Na+ Serum OSM 37.9 ++++ 147.0 311 2 33.8 147.5 308 4 30.0 146.7 303 6 26.5 146.6 301

By the end of 6 hours Hardik was alert and his breathlessness settled .

SUBSEQUENT MANAGEMENT Fluids were tailored to maintain BG in range of 150-250 mg%, Electrolytes in normal range D10% with CRL was used to provide 5-10% dextrose whenever BG < 150 mg% Insulin drip continued till acidosis was corrected. Clinical assessment of CNS monitored with gradual normalization of serum Osmolality.

7TH- 14TH HOUR Hr BG PH HcO3 AG OSM 7 172 7.22 8.5 26.5 301 8 110 9 148 10 188 7.28 12.8 23 298 11 154 12 140 13 130 14 144 7.32 15.0 21 300 18 179 7.38 18.0 17 297

IV treatment continued till the child accepted oral feeds in morning. Subcutaneous insulin started as combination ( regular + NPH ) ,total dose of 1 u /kg/day, 2/3 of which (20 U) given as mix of 8R+12NPH BBF. Insulin infusion & IV fluids discontinued after 45 mins of SC insulin.

DIABETIC KETOACIDOSIS: TAKE HOME MESSAGES

THM-1) DKA CAN & SHOULD BE PREVENTED HARDIK, …. “developed fever & cough with loss of appetite. Since he was not eating, the parents, fearing hypoglycemia, omitted his insulin dose”.

SICK DAY GUIDELINES: (follow your BG not your appetite) Continue usual insulin dose (except: BG< 80) Check BG & urine ketones every 4 hours. If BG > 250, take extra ‘R’ insulin STAT!!. Consume plenty of salty liquids. (sweet liquids if BG < 100).

THM-2) DO NOT DELAY IN STARTING Rx: diagnosis does not need a lab Clinical picture plus Finger prick BG: >250 mg% Urine Ketones ++++  START IV NORMAL SALINE BOLUS!!

THM-3) BEWARE OF FALLACIES IN LAB TESTS High WBC: correlates with ketosis Raised amylase correlates with ketosis. Raised BUN dehydration.

DKA: INTERPRETING LAB REPORTS Factitious hyponatremia dilutional. True serum sodium: Add 1.6 meq for every 100 mg% BG above 100 mg% S.K+  overestimation of total body K+. True serum potassium: Lab Potassium value – (0.6x A) (A = 7.4 minus prevailing pH)

ECG IN POTASSIUM DISTURBANCES HYPOKALEMIA: Flat / inverted T waves, depressed S-T segment, prolonged Q-T interval, U waves. HYPERKALEMIA: Peaked T waves, wide QRS, depressed P waves, A-V dissociation

DKA: INTERPRETING LAB REPORTS Ketone bodies B-OH-B & AcAc Test measures AcAc, but predominant ketone body in DKA is B-OHB. Initial underestimation, later apparent persistence. Anion gap: (Na) – (HCo3 + Cl) N: 8-16 meq/L. A better measure of the degree of ketosis in DKA

THM 4) FLUIDS IN DKA: start early, go slow….. Volume expansion: 10 cc / kg in 1 hr. Repeat only if shock, hypotension, poor tissue perfusion persist. Maintenance: evenly over 24 hours. Deficit: >2 yrs: 3%, 6%, 9% <2 yrs: 5%, 10%, 15%. evenly over 36-48 hours or more ?Ongoing losses only if excessive (GIT, osmotic losses).

FLUIDS IN DKA: AVOID HYPOTONIC FLUIDS Initial bolus: NS. BG > 250-300 mg%: ½ NS + KCL. (continue NS if hypo / hypernatremia, severe hyperosmolarity) BG < 250-300 mg%: ½ D5NS + KCL. BG < 150 mg%: D10 with CRL + KCL.

…at outset if < 3.5 meq / L / ECG changes. THM-5) POTASSIUM: START SOON & REPLACE OVER 2 WKS; EXPECT DROP, MONITOR CLOSELY Start… after initial bolus fluid & only if urine output (+) & S. K+ <5.5 meq/L. …at outset if < 3.5 meq / L / ECG changes. Continue oral potassium till pre-DKA weight. If > 40 meq / L required (S.K<3.5), use central line & ECG monitoring. May give part oral by RT. 2/3 as KCl & 1/3 as KPo4 (ideal).

POTASSIUM: EXPECT A DROP…. Proteolysis & Glycogenolysis liberation of K+ in the cell Acidosis, Insulin def draws K+ extracellularly Polyuria, ketonuria K+ loss from body With improvement in GFR K+ wash out With correction of acidosis & provision of insulin K+ moves intracellularly

THM-6) INSULIN IN DKA: no urgency, low dose infusion, till acidosis corrected!! Initial drop in BG due to volume expansion & improved GFR. More rapid drop in BG with insulin sudden fluid shift ECF to ICF vascular collapse & ?cerebral edema. Insulin before potassium shift of potassium to ICF acute hypokalemia.

INSULIN IN DKA Short / ultra short acting insulins only. Bolus unnecessary, unless delay in starting insulin. Run off 50 cc (insulin adheres to glass & polyvinyl). Dose @ 0.1 unit / kg / hr. Double dose if BG fall <50-70 mg%/ hour. Optimum rate of BG drop= <100mg%/hour.

INSULIN IN DKA: TILL CORRECTION OF ACIDOSIS Keep BG between 150-250 mg% till ketosis is corrected so that insulin can be continued without risk of: Osmotic diuresis. Hypoglycemia. CRH response.

THM-7) BICARBONATE : RARELY IF EVER NEEDED Over correction of acidosis  true alkalosis. Acute hypokalemia. Acute hypernatremia. Before repletion of RBC 2,3, DPG  shift of O2 dissociation curve to left  tissue hypoxia lactic acidosis. Paradoxical CNS acidosis ( CO2 crosses B-B-B but HCo3 does not )

ADVERSE EFFECTS OF PROFOUND ACIDEMIA Negative ionotropism Peripheral vasodilatation CNS depression Insulin resistance

BICARBONATE IN DKA When? * pH < 6.9 * pH < 7.0 after 1 hr of hydration (ADA) * Circulatory failure due to acidosis * Hyperkalemia with ECG changes How much? * 1-2 meq / kg as slow infusion over 1-2 hours (never bolus)

THM-8) DKA: MONITOR CLOSELY, ALERT FOR CEREBRAL EDEMA Clinical: every 30-60 mins. Accurate I & O record. BG every hour. Electrolytes, blood gases, urea, HCT every 2-4 hours. Serum Na+ should rise with Rx, anion gap should reduce.

CEREBRAL EDEMA: WHEN TO SUSPECT? Vomiting, headache, lethargy, age inappropriate incontinence Declining / fluctuating mental state, coma, Dilated, unresponsive, sluggish, unequal pupils, Sudden hyper / hypotension, Bradycardia, Decorticate / decerebrate posturing, papilledema Unexpected decline in urine output without clinical improvement, Falling Nacorr to < 130 or Eosm < 275 mOm/kg

CEREBRAL EDEMA 1-3% of children with DKA. 1/3 die, 1/3 have permanent CNS sequel. Accounts for 30% of DKA deaths & 20% of overall childhood diabetes deaths. Onset during Rx (2-24 hrs), rarely before Rx.

THM-9) EMERGENCY RX ON SUSPICION OF CEREBRAL EDEMA Immediate mannitol: 0.2-1.0 gm/kg IV over 30 mins. Can be repeated every hour till desired response. Hypertonic saline (3%) 5 ml/kg over 30 min. Reduce fluid administration rate. Mechanical hyperventilation (but intubation & hyperventilation to PCo2 < 22 mm Hg ass with poor prognosis). Dexamethasone? Furosemide? Urgent CT to exclude other possibilities.

THM-10) COMPLICATIONS ARE IATROGENIC, PREVENTABLE THERAPEUTIC ERROR COMPLICATION Delay in starting IV Shock, thrombosis Rapid / hypotonic fluids Cerebral edema, ARDS High dose insulin Hypoglycemia, hypoK+, CE Injudicious use of HCo3 Alkalosis, hyperNa+, hypoK+, CNS acidosis CE Delay in giving K+ / Over Rx with K+ Hypokalemia / Hyperkalemia ?Excess chloride Hyperchloremic acidosis ?Non provision of Po4 2,3 DPG deficiency

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