Case study: Diabetic Ketoacidosis

Hoo Yee Yin Hospital Putrajaya

Summary of previous presentation
• Classification of DM • Clinical presentations • Diagnosis • Pathophysiology • Management (OHA & Insulin)

Outline
• Comlications of DM • Acute : DKA
– Clinical features – Precipitating events – Pathophysiology – Diagnostic criteria – Management

• Chronic complications
– Retinopathy – Nephropathy

Complications of DM • Acute – Diabetic ketoacidosis (DKA) – Hyperglycemic hyperosmolar state (HHS) • Chronic – Microvascular – Macrovascular – Others : GIT / genitourinary dysfunction. infections. . cataracts and glaucoma. dermatologic.

Acute complications .

but also occur in type 2 DM. • Associated with – Absolute or relative insulin deficiency – Volume depletion – Acid base abnormalities .DKA • Hallmark of type 1 DM.

volume depletion) • Dehydration / hypotension / tachycardia • Abdominal pain. abdominal tenderness • SOB / Kussmaul respiration • Fruity odor • Lethargy / coma • Cerebral edema (mostly in children) . polyuria.Clinical features of DKA Symptoms usually develop over 24 hours • Nausea / vomiting • Hyperglycemia (Thirst.

Precipitating events • Inadequate insulin administration • Noncompliance • New onset diabetes • Infection • Infarction • Drugs • Pregnancy .

amino acids delivery to liver Alter hepatic metabolism Favor ketone body formation through activation of enzyme carnitine palmitoyltransferase I .Pathophysiology Insulin deficiency + Excess glucagon Normally: • • • • Gluconeogenesis FFA convert to TG / VLDL Glycogenolysis Marked increase in FFA release from adipocytes Increase in FFA.

Diagnostic Criteria for DKA .

Measure capillary glucose (every 1-2h) 7.Management of DKA 1. Monitor BP. pulse. Fluid replacement 4. Measure electrolytes & anion gap (every 4h for 24h) 8. 2. Confirm diagnosis Assess serum electrolytes. respiration. Regular insulin (IV/IM) 5. mental status. renal function 3. . Replace K 10. acid base status. Continue above measure until patient is stable (glucose goal is 8-14mmol/L) 11. Administer intermediate / long acting insulin as soon as patient is eating. Treat underlying condition 6. I/O (every 1-4h) 9.

9% saline over first 1-3h (5mL/kg/h) Hemodynamic stability. or until shock corrected 0.45%saline (100-200mL/h) .45% saline (150-300mL/h) When plasma glucose reaches 14mmol/L 5% glucose and 0.Fluid replacement 0.

3mmol/L*** withhold insulin until corrected to > 3.1units / kg / h) (Increase to 2 to 10 fold if no response by 24h) *** If initial serum K < 3.3mmol/L .Regular insulin (IV / IM) Regular insulin IV (0.4 units / kg) Continuous IV infusion (0.1 units / kg) IM (0.

• Goal : maintain K+ > 3.Potassium replacement • Treatment with insulin & fluids will deplete K+ by: – Insulin mediated K transport into cells – Resolution of acidosis – Urinary loss of K salts of organic acids • K+ repletion should commence as soon as – Adequate urine output – Normal serum K+ are documented.5mmol/L. 40-80mmol/L/h if K <3. • Inclusion into IV fluid (KCL / KPO4 / K acetate) (10 mmol/L/h if K < 5.5mmol/L.5mmol/L) .

45% NS over 2h .45% NS over 1h • pH < 6.0 after initial hydration) • ADA: • pH = 6.7 – 50mmol/L sodium bicarbonate in 200mL of 0. unless: – Severe acidosis (pH <7.9 .Bicarbonate replacement • Usually not necessary.9 – 100mmol/L sodium bicarbonate in 400mL of 0.

8-1.45mmol/L) • Give in form of potassium phosphate (potassium replacement) • Monitor serum calcium .32mmol/L.Phosphate • Usually low in DKA • Routine phosphate replacement does not improve outcomes in DKA • Give phosphate supplement if phosphate < 0. (normal = 0.

HHS • Prototypical patient with HHS is elderly with type 2 DM. coma On examination : Present Absent • Dehydration • Nausea • Hypotension • Vomiting • Tachycardia • Abdominal pain • Altered mental status. . with several week history – Polyuria – Weight loss – Diminished oral intake – Lethargy – Mental confusion. • Kussmaul respirations.

33.9 .3 Normal Normal to slightly high Normal .3 – 66.3 125-135 Normal or high Low Slightly high HHS 33.Laboratory values in DKA and HHS DKA Glucose (mmol/L) Na (mmol/L) K (mmol/L) Phosphate Creatinine 13.3 20-30 High Normal 330-380 +/Normal to slightly low > 7. chloride 300-320 ++++ < 15 6.8-7.6 135-145 High Normal High Osmolality (mOsm/mL) Plasma ketones HCO3 (mmol/L) Arterial pH Arterial pCO2 (mmHg) Anion gap Magnesim.

Chronic complications (Microvascular) .

Diacylglycerol. Vascular connective tissue . Renal. Fructose 6 phosphate Complication of diabetes • • • • Altered Cell function. Gene expression.Possible molecular mechanisms Hyperglycemia (Increased intracellular glucose) • • • • Increase Advanced glycation end products Sorbitol.

– Abnormal retinal microvasculature. fibrosis. . retinal detachment • Non-proliferative diabetic retinopathy – Increased retinal vascular permeability. – Alterations in retinal blood flow.Retinopathy • Proliferative diabetic retinopathy – Newly formed vessels appear near the optic nerve and macula and rupture easily – Lead to hemorrhage. – Lead to retinal ischemia.

4-8mmol/L – BP:130/80 • Aspirin (650mg/day) does not appear to influence the natural history of retinopathy • Treatment : Laser photocoagulation .1mmol/L – Non fasting: 4.Treatment • Prevention : • Regular eye examinations • Intensive glycemic and BP control – Fasting: 4.4-6.

Nephropathy • Related to chronic hyperglycemia. glomerular hyperthrophy) • Leads to ESRF . • Involve effects of – Growth factor – Angiotensin II • Hemodynamic alterations in renal microcirculation – glomerular hyperfiltration • Structural changes of glomerulus (Ex: basement membrane thickening.

Natural history of diabetic nephropathy

Management of diabetic nephropathy
• Good glycaemic Control – FBS < 6 mmol/l – HbA1c < 6.5% • Tight control of BP – DM: 130/80 – Proteinuria >1g/d: 125/75 • Reduce proteinuria with ACEI / ARB • Smoking cessation • Lipid control • Salt and protein restriction – 0.6-0.8g / kg / day protein in patient with overt nephropathy and/or renal impairment – < 5g NaCL / day

Case Presentation

1.8 7.2008 14.1.2008 .Patient’s Identity • • • • • • • • • Name Age Gender Race Height Weight BMI DoA DoD : : : : : : : : : MH 66 Male Malay 158cm 52kg 20.

Presenting complaint • Fever X 3/7 • Vomited a few times • Noted by family the glucometer result was too high .

History of presenting complaint • Not taking OHA X 3/7 • Lethargic and bed bound X 3/7 • Scrotal area was swollen. . macerated for a few days • Blurred vision for quite some times. red.

Metformin 1g tds – HbA1C : Nov 2007 : 11. Gliclazide (Diamicron ® MR) 120mg OM – T.Past Medical History & Drug History • Type 2 DM (10 years) – T. Amlodipine 5mg od . Perindopril 4mg od – T.5 • Hypertension (8 years) – T.

Social / Family History • Staying with family in Klang • Brother has Type 2 DM .

Review of System • BP • RR • PR •T • SPO2 • Dstix : 104/56 : 88 : 24 : 37.6mmol/L (SC actrapid 16 units stat) • Lung : Clear • Abdomen : Soft & non tender • CVS : DRNM .8oC : 91% : 24.

Impression / Diagnosis • Diabetic ketoacidosis (DKA) .

Lab Investigations .

3 4-8 pCO2 pO2 HCO3 28 61 14.5 97 17.5 31.2 .Arterial Blood Gas Day pH 1 7.3 2 3 7.

005 Negative Negative Yellow 3+ 1.UFEME Day Bacteria Glucose Ketones pH Protein RBC Count Leucocytes 1 Negative 2 Negative 3 Negative 4-8 4+ 2+ 5 2+ 2+ 5 1+ 1+ 6 1+ 1+ Negative 1.005 Negative Negative Yellow Other cells a) SG b) UBG c) Bil d) Colour .015 Negative Negative Yellow 2+ Negative 2+ Negative 3+ 1.

21 38.6 12.Full Blood Count Day TWBC Hb RBC HCT 1 11.5% 181.8 11.70 33.0% 2 3 7.3 4.0 4-8 Platelet 187.0 .4 3.

5 3.1 400 110 43.Renal Profile Day Urea Na K Cl Ca Mg PO4SrCr ClCr Uric acid 128 37.8 138.31 108.6 142.1 4-6 7 3.82 3 4.0 111 42.6 1 7.0 140.2 1.9 4.59 111.55 107.31 121 39.5 140.3 4.2 3.6 103.1 8 .8 2 4.0 0.

Bilirubin T.Protein 1 2 23 9 72 3-8 ALP ALT AST 140 57 79 .Liver Profile Day Albumin T.

7mmol/L) HDL (> 1.Chol (<5.9mmol/L) 2.2008 Results (mmol/L) T.7mmol/L) 6.1.Lipid Profile Date Lipid profile 8.7mmol/L) LDL (<3.7 .5 3.0 0.1 TG (< 1.

8 37 37 37 37 37 37 37 RR PR 22 80 20 104 20 80 20 100 20 91 20 91 20 91 20 100 .Vital Signs Day BP T 1 104/ 58 2 123/ 71 3 129/ 60 4 150/ 79 5 139/ 80 6 121/ 76 7 142/ 72 8 139/ 73 37.

Input / Output chart Day 1 2 3 4 5 6 7 Input 1000 3340 955 1265 1090 695 700 Output 600 1150 1200 900 1650 1700 1500 Balance +400 +2190 -245 +1365 -560 -1005 -800 .

1.08 Genital swab staphylococcus spp.Culture and sensitivity Date Date sampling Sample Micro-organism Sensitivity Resistant 11. Erythromycin.08 7. Penicillin oxacillin .1. gentamicin.

Ward Medications .

Ward medications Drug Day start Day stop IV Ceftriaxone 2g od IV Amoxycillin / clavulanate potassium Tablet aspirin 150mg od Tablet amlodipine 5mg od SC actrapid 16 units stat SC insulatard 14 units ON SC actrapid 10 units tds SC actrapid 8 units tds SC actrapid 14 units tds SC insulatard 16 units ON Cream aqueous prn 1 2 1 7 1 3 3 4 7 7 7 8 8 8 8 1 7 4 7 8 8 8 .

Clinical Progress & Pharmaceutical Care plans .

NS if GM>12) • 2 hourly GM monitor • Genital swab (C&S) • NS dressing • Continue medication: – T. aspirin 150mg od Plan (10pm): • Add 1g KCL alternate pint • Impression: a) Uncontrolled DM – Missed medication b) Scrotal cellulitis . Scrotal: Red. marcerated Groin: erythematous + blister • Fundoscope: – Dense cataract – Diabetic retinopathy Plan (4pm): • Withhold anti HPT • IV ceftriaxone 2g stat & od • IV drip 4 pints/24h • IV insulin 5 units/h (Change to IVD D5% once GM<12.6mmol/L) Urine ketone: 2+ Patient dehydrated.Clinical progress: Day 1 • • • • • • • Low BP (104/56) High T (37.8) High glucose (24.

3 14 mmol/L .7 13.6 mmol/L) c) ABG : Metabolic acidosis Low pH: 7.3 Low pCO2: 28 Low HCO3: 14.31mmol/L) Fluid replacement &insulin infusion 5 units/h had been given (Patient = 52kg) Time Glucose (mmol/L) 330pm 24.4 11.PCI (Day 1) PCI Pharmacist Recommendation • Monitor a) Vital signs b) Glucose level c) Serum electrolyte d) ABG e) Renal function f) I/O chart • Add PO4 to IV infusion •Change to IVD D5% when glucose level reach Outcome Management of DKA Patient had: a) Low BP (104/56) b) High glucose (24.5 d) Low phosphate (0.6 6pm 8pm 10pm 20.

Rifampin 300mg bd. Trimetoprim sulfamethoxazole double strength (160TMP/800SMX) 2 tab bd with T. Management of cellulitis Patient a) Scrotal: Red.PCI (Day 1) PCI Pharmacist Recommendation • T.5-1g tds) Plus • IV / PO linezolid 600mg bd / IV vancomycin (based on weight) Outcome • Antibiotics remained unchanged. marcerated b) Groin: erythematous + blister c) High WBC: (11. • Review antibiotics used in cellulitis Sanford 2007 (pg18. 86. Severe disease • IV Imipenem (1g IV od) / IV meropenem (0. paracetamol 1g stat and prn • Monitor Temperature. 92): Early mild disease • T. .5g IV qid) / IV ertapenem (0.6X10/L) d) Fever (37.8oC) IV ceftriaxone 2g od had been given. WBC count.

PCI (Day 1) PCI Pharmacist Recommendation Outcome Retinopathy screening & treatment Patient: • Dense cataract • Diabetic retinopathy ADA 2007: • Patient was referred to • Optimal glycemic control ophthalmologist. • Perform examination annually by ophthalmologist. (Examinations will be required more frequently if retinopathy is progressing) . • Optimal BP control • Refer to ophthalmologist.

4 12.2 12.2g stat and tds • 2 hourly GM monitor • I/O charting • Withold insulin infusion . inflammed Time 12am 2am 4am 6am 8am 10am 1220pm 4pm 6pm 820pm 10pm Glucose (mmol/L) 6.8 6.2 9.Clinical progress: Day 2 • BP: 123/71 • Dry tongue.7 5.3 7.6 14. patient dehydrated • Scrotal & groin: red.3 Plan: • Increase to 5 pints NS/24h • IV insulin 2 units/h • IV Augmentin ® 1.2 3.4 6.3 8.

. Prevention of hypoglycemia Patient’s glucose level dropped to 3.PCI (Day 2) PCI Pharmacist Recommendation • Monitor glucose level. • Withhold insulin infusion • Oral glucose (10-20g) – Treatment effect should be apparent in 15 min. Outcome • Insulin infusion was withhold.3mmol/L.

Lipid management Patient’s lipid profile shown: Patient was 66 years old. Statin therapy to achieve an LDL reduction of 30-40% regardless of baseline LDL levels. • Can be Initiated with: a) Lovastatin (20mg ON) b) Simvastatin (10-20mg ON) c) Atorvastatin (10-20mg od) . Outcome • No lipid lowering agent was given.PCI (Day 2) PCI Pharmacist Recommendation • ADA 2007: For those over 40 years old.

8 4.3 7.3 7.1 Plan (1am): • IVD 2 pints D5% • Start IV insulin 0.Clinical progress: Day 3 • Imp: Fluid overload • Not sleep well yesterday • Groin: still erythematous with blister Time 12am 1am 4am 6am 8am 10am 12pm 2pm 640pm 10pm Glucose (mmol/L) 4.9 4.3 3.7 4.4 5.5units / h • GM 2 hourly Plan (8am) • Reduce drip to 1 pint D5% • Overlap with sc insulin – SC actrapid (10 units tds) – SC insulatard (14 units ON) • Withhold insulin infusion • Continue daily dressing .2 8.1 4.

Patient’s CLcr trend: D1: 37.5 .7 – 2.85 units/kg/day) Review of Oral hypoglycemic agent Pharmacotherapy handbook: • Insulin therapy Patient HbA1C was 15.5 (11.0mL/min D2: 39.1 (0.Nov 2007) units/kg/day) • Can be started Patient was on maximum dose on basal bolus of OHA insulin regimen a) T.1mL/min . Metformin 1g tds test in 3 months time. Gliclazide MR 120mg OM • Perform HbA1C b) T.PCI (Day 3) PCI Pharmacist Recommendation Outcome • Patient was started with a) SC actrapid (10 units tds) b) SC insulatard (14 units ON) Total: 44 units/day (0.

4 .6 5.7 1225am 6.3 6.Clinical progress: Day 4 • C&S: Staphylococcus spp • Taking orally (not much) Plan: • Continue IV antibiotics • Daily dressing with NS • GM 4 hourly • Off IV D5% • Reduce dose: – SC actrapid 8 units tds Time Glucose (mmol/L) 6.6 2am 4am 6am 4pm 8pm 1030pm 6.6 5.5 6.

Outcome ABG monitoring Patient’s ABG was monitored on day 1 and 3.5 .PCI (Day 4) PCI Pharmacist Recommendation Monitor ABG daily until metabolic acidosis resolved.3 28 3 7.5 pO2 61 97 17. ABG trend Day pH pCO2 1 7.3 31.2 HCO3 14.

8 10.3 20.Clinical progress: Day 5 • Sleep well • Afebrile Plan (8am): • Continue medications Time 430am 8am 11am 530pm Glucose (mmol/L) 9.1 16.7 .

Novo Nordisk Diabetes Care Services leaflet: Blood Glucose Level Above Target Value Add Up to 1 mmol/L 1 to 2 mmol/L > 2 mmol/L 2iu 4iu 6iu .PCI (Day 5) PCI Pharmacist Recommendation Outcome Glucose level was high. Actrapid from 8 to 14 units. • Assess patient on present of Time 430am 8am 11am 530pm Glucose (mmol/L) 8.1 16.3 20.7 hypoglycemic symptoms • Increase dose of: Insulatard from 14 to 16 units.0 10.

7/9.1 Plan: • Increase dose – SC actrapid 14 unit tds • GM monitor 4 hourly .7 9.Clinical progress: Day 6 • GM 8am: 13.4 5.1 5.1/16.9 10.3 6.3 • Afebrile Time 12am 4am 8am 1220pm 6pm 1030pm 1140pm Glucose (mmol/L) 9.8/20.7 • GM trend (Day 5) 9.4 13.

Amlodipine 5mg od • Aqueous cream prn at scrotal area.9 Plan: • GM monitoring qid • Increase dose – SC insulatard 16 units ON • GM monitor 4 hourly • Restart T.4 8.0 6.2 6. .Clinical progress: Day 7 • Afebrile • Respond to Antibiotics for scrotal cellulitis Time 2am 6am 8am 1240am 6pm 1030pm Glucose (mmol/L) 5.1 4.0 6.

Clinical progress: Day 8 • Patient slept well. • Afebrile Time 8am Glucose (mmol/L) 5.6 .6 Plan: • Off IV antibiotics • Start oral Augmentin ® 625mg bd • Discharge today 1230pm 4.

Amlodipine 5mg od • T. Aspirin 150mg od • SC Insulatard 16 units ON • SC Actrapid 14 units tds • T.Discharge Medications • T. Amoxycillin / clavulanic acid 625mg bd X 3/7 .

amlodipine restarted on D7 Patient discharge with T.PCI (Day 8) PCI Pharmacist Recommendation Patient have DM and renal insufficiency. perindopril 4mg od ADA 2007 recommend: ACEI for DM patients > 55 years old at high risk of CVD. give anti-hypertensive a) T. Outcome Management of hypertension T. amlodipine 5mg od Patient BP trend in ward Patient’s CLcr in ward ACEI and ARB delay progression to macroalbuminuria. . ACEI may be superior to dihydropyridine CCB in reducing cardiovascular events.

et al (2005). A pathophysiology Approach. American family physician.L.Diabetes Care 2007.J.30:S4-41 • BSPED Recommended DKA Guidelines. • DiPiro.Appleton & Lange • Harrison’s principle of internal medicine .C.TTalbert. • JNC 7 hypertension guideline • Sanford guide to antimicrobial therapy • Diabetic ketoacidosis. Trachtenbarg.References • Malaysian Practice guideline (2004): – Management of Type 2 Diabetes Mellitus – Diabetic nephropathy • American Diabetes Association (2007): Standards of Medical Care in Diabetes. MD.G. Yee.Pharmacotherapy. 6th Edition. David E.R.

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