Case study: Diabetic Ketoacidosis

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

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

Acute complications .

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

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

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

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

Diagnostic Criteria for DKA .

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

45%saline (100-200mL/h) .45% saline (150-300mL/h) When plasma glucose reaches 14mmol/L 5% glucose and 0.9% saline over first 1-3h (5mL/kg/h) Hemodynamic stability.Fluid replacement 0. or until shock corrected 0.

1units / kg / h) (Increase to 2 to 10 fold if no response by 24h) *** If initial serum K < 3.4 units / kg) Continuous IV infusion (0.Regular insulin (IV / IM) Regular insulin IV (0.1 units / kg) IM (0.3mmol/L .3mmol/L*** withhold insulin until corrected to > 3.

5mmol/L. 40-80mmol/L/h if K <3.5mmol/L) .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. • Inclusion into IV fluid (KCL / KPO4 / K acetate) (10 mmol/L/h if K < 5.5mmol/L. • Goal : maintain K+ > 3.

9 .45% NS over 1h • pH < 6.9 – 100mmol/L sodium bicarbonate in 400mL of 0.0 after initial hydration) • ADA: • pH = 6.7 – 50mmol/L sodium bicarbonate in 200mL of 0.45% NS over 2h .Bicarbonate replacement • Usually not necessary. unless: – Severe acidosis (pH <7.

Phosphate • Usually low in DKA • Routine phosphate replacement does not improve outcomes in DKA • Give phosphate supplement if phosphate < 0.45mmol/L) • Give in form of potassium phosphate (potassium replacement) • Monitor serum calcium .32mmol/L.8-1. (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.

9 .33.3 – 66.3 125-135 Normal or high Low Slightly high HHS 33. chloride 300-320 ++++ < 15 6.3 Normal Normal to slightly high Normal .Laboratory values in DKA and HHS DKA Glucose (mmol/L) Na (mmol/L) K (mmol/L) Phosphate Creatinine 13.6 135-145 High Normal High Osmolality (mOsm/mL) Plasma ketones HCO3 (mmol/L) Arterial pH Arterial pCO2 (mmHg) Anion gap Magnesim.8-7.3 20-30 High Normal 330-380 +/Normal to slightly low > 7.

Chronic complications (Microvascular) .

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

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

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.

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.Nephropathy • Related to chronic hyperglycemia.

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

8 .Patient’s Identity • • • • • • • Name Age Gender Race Height Weight BMI : : : : : : : 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. red. macerated for a few days • Blurred vision for quite some times. .

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

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

Review of System • BP • RR • PR •T • SPO2 • Dstix : 104/56 : 88 : 24 : 37.8oC : 91% : 24.6mmol/L (SC actrapid 16 units stat) • Lung : Clear • Abdomen : Soft & non tender • CVS : DRNM .

Impression / Diagnosis • Diabetic ketoacidosis (DKA) .

Lab Investigations .

5 97 17.3 4-8 pCO2 pO2 HCO3 28 61 14.2 .Arterial Blood Gas Day pH 1 7.3 2 3 7.5 31.

005 Negative Negative Yellow 3+ 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.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.

70 33.5% 181.0% 2 3 7.3 4.8 11.0 .6 12.0 4-8 Platelet 187.21 38.4 3.Full Blood Count Day TWBC Hb RBC HCT 1 11.

82 3 4.6 103.2 1.31 121 39.0 111 42.31 108.2 3.55 107.59 111.0 0.9 4.1 4-6 7 3.6 142.5 3.6 1 7.0 140.8 138.1 8 .8 2 4.3 4.Renal Profile Day Urea Na K Cl Ca Mg PO4SrCr ClCr Uric acid 128 37.1 400 110 43.5 140.

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

Lipid Profile Date Lipid profile 8.2008 Results (mmol/L) T.7 .0 0.7mmol/L) LDL (<3.7mmol/L) HDL (> 1.1 TG (< 1.1.9mmol/L) 2.7mmol/L) 6.Chol (<5.5 3.

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 .

Penicillin oxacillin .08 7.1. gentamicin.08 Genital swab staphylococcus spp.Culture and sensitivity Date Date sampling Sample Micro-organism Sensitivity Resistant 11.1. Erythromycin.

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 .

6mmol/L) Urine ketone: 2+ Patient dehydrated.8) High glucose (24. NS if GM>12) • 2 hourly GM monitor • Genital swab (C&S) • NS dressing • Continue medication: – T. Scrotal: Red. aspirin 150mg od Plan (10pm): • Add 1g KCL alternate pint • Impression: a) Uncontrolled DM – Missed medication b) Scrotal cellulitis . 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.Clinical progress: Day 1 • • • • • • • Low BP (104/56) High T (37.

7 13.4 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 (24.3 14 mmol/L .6 mmol/L) c) ABG : Metabolic acidosis Low pH: 7.6 6pm 8pm 10pm 20.3 Low pCO2: 28 Low HCO3: 14.5 d) Low phosphate (0.31mmol/L) Fluid replacement &insulin infusion 5 units/h had been given (Patient = 52kg) Time Glucose (mmol/L) 330pm 24.

86.8oC) IV ceftriaxone 2g od had been given.5g IV qid) / IV ertapenem (0.5-1g tds) Plus • IV / PO linezolid 600mg bd / IV vancomycin (based on weight) Outcome • Antibiotics remained unchanged. paracetamol 1g stat and prn • Monitor Temperature. marcerated b) Groin: erythematous + blister c) High WBC: (11. 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. Severe disease • IV Imipenem (1g IV od) / IV meropenem (0. WBC count. • Review antibiotics used in cellulitis Sanford 2007 (pg18. . 92): Early mild disease • T. Rifampin 300mg bd.6X10/L) d) Fever (37.

• Perform examination annually by ophthalmologist. (Examinations will be required more frequently if retinopathy is progressing) .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. • Optimal BP control • Refer to ophthalmologist.

2 9.3 8.4 12.7 5.8 6.Clinical progress: Day 2 • BP: 123/71 • Dry tongue.3 7.2 3.2g 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) 6.3 Plan: • Increase to 5 pints NS/24h • IV insulin 2 units/h • IV Augmentin ® 1.4 6.2 12. patient dehydrated • Scrotal & groin: red.6 14.

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

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) . Lipid management Patient’s lipid profile shown: Patient was 66 years old.PCI (Day 2) PCI Pharmacist Recommendation • ADA 2007: For those over 40 years old. Outcome • No lipid lowering agent was given.

7 4.1 Plan (1am): • IVD 2 pints D5% • Start IV insulin 0.5units / 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 .3 7.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) 4.8 4.2 8.3 7.4 5.1 4.9 4.3 3.

Gliclazide MR 120mg OM • Perform HbA1C b) T.5 (11.1 (0.85 units/kg/day) Review of Oral hypoglycemic agent Pharmacotherapy handbook: • Insulin therapy Patient HbA1C was 15.5 .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 (0.1mL/min .Nov 2007) units/kg/day) • Can be started Patient was on maximum dose on basal bolus of OHA insulin regimen a) T. Patient’s CLcr trend: D1: 37.0mL/min D2: 39.7 – 2. Metformin 1g tds test in 3 months time.

6 2am 4am 6am 4pm 8pm 1030pm 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) 6.3 6.6 5.6 5.5 6.7 1225am 6.4 .

PCI (Day 4) PCI Pharmacist Recommendation Monitor ABG daily until metabolic acidosis resolved.3 31. Outcome ABG monitoring Patient’s ABG was monitored on day 1 and 3.2 HCO3 14.5 .3 28 3 7.5 pO2 61 97 17. ABG trend Day pH pCO2 1 7.

Clinical progress: Day 5 • Sleep well • Afebrile Plan (8am): • Continue medications Time 430am 8am 11am 530pm Glucose (mmol/L) 9.7 .1 16.8 10.3 20.

Actrapid from 8 to 14 units. • Assess patient on present of Time 430am 8am 11am 530pm Glucose (mmol/L) 8.PCI (Day 5) PCI Pharmacist Recommendation Outcome Glucose level was high.7 hypoglycemic symptoms • Increase dose of: Insulatard from 14 to 16 units. 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 .0 10.1 16.3 20.

3 6.1 5.Clinical progress: Day 6 • GM 8am: 13.1 Plan: • Increase dose – SC actrapid 14 unit tds • GM monitor 4 hourly .8/20.7 9.4 5.3 • Afebrile Time 12am 4am 8am 1220pm 6pm 1030pm 1140pm Glucose (mmol/L) 9.4 13.7/9.7 • GM trend (Day 5) 9.1/16.9 10.

4 8. Amlodipine 5mg od • Aqueous cream prn at scrotal area.Clinical progress: Day 7 • Afebrile • Respond to Antibiotics for scrotal cellulitis Time 2am 6am 8am 1240am 6pm 1030pm Glucose (mmol/L) 5.0 6. .2 6.9 Plan: • GM monitoring qid • Increase dose – SC insulatard 16 units ON • GM monitor 4 hourly • Restart T.0 6.1 4.

Clinical progress: Day 8 • Patient slept well.6 Plan: • Off IV antibiotics • Start oral Augmentin ® 625mg bd • Discharge today 1230pm 4.6 . • Afebrile Time 8am Glucose (mmol/L) 5.

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

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

et al (2005). MD.TTalbert. American family physician.L.Diabetes Care 2007.30:S4-41 • BSPED Recommended DKA Guidelines. Trachtenbarg. A pathophysiology Approach. • JNC 7 hypertension guideline • Sanford guide to antimicrobial therapy • Diabetic ketoacidosis. 6th Edition.References • Malaysian Practice guideline (2004): – Management of Type 2 Diabetes Mellitus – Diabetic nephropathy • American Diabetes Association (2007): Standards of Medical Care in Diabetes. • DiPiro.J.Pharmacotherapy.C. David E.R.G.Appleton & Lange • Harrison’s principle of internal medicine . Yee.

THANK YOU .