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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, dermatologic, infections, cataracts and glaucoma.
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, polyuria, volume depletion) • Dehydration / hypotension / tachycardia • Abdominal pain, abdominal tenderness • SOB / Kussmaul respiration • Fruity odor • Lethargy / coma • Cerebral edema (mostly in children)
Precipitating events • Inadequate insulin istration • 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. 2.
Confirm diagnosis Assess serum electrolytes, acid base status, renal function 3. Fluid replacement 4. Regular insulin (IV/IM) 5. Treat underlying condition 6. Measure capillary glucose (every 1-2h) 7. Measure electrolytes & anion gap (every 4h for 24h) 8. Monitor BP, pulse, respiration, mental status, I/O (every 1-4h) 9. Replace K 10. Continue above measure until patient is stable (glucose goal is 8-14mmol/L) 11. ister intermediate / long acting insulin as soon as patient is eating.
Fluid replacement 0.9% saline over first 1-3h (5mL/kg/h) Hemodynamic stability, or until shock corrected
0.45% saline (150-300mL/h) When plasma glucose reaches 14mmol/L
5% glucose and 0.45%saline (100-200mL/h)
Regular insulin (IV / IM) Regular insulin IV (0.1 units / kg) IM (0.4 units / kg)
Continuous IV infusion (0.1units / kg / h) (Increase to 2 to 10 fold if no response by 24h)
*** If initial serum K < 3.3mmol/L*** withhold insulin until corrected to > 3.3mmol/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. • Goal : maintain K+ > 3.5mmol/L. • Inclusion into IV fluid (KCL / KPO4 / K acetate) (10 mmol/L/h if K < 5.5mmol/L, 40-80mmol/L/h if K <3.5mmol/L)
Bicarbonate replacement • Usually not necessary, unless: – Severe acidosis (pH <7.0 after initial hydration) • ADA: • pH = 6.9 - 7 – 50mmol/L sodium bicarbonate in 200mL of 0.45% NS over 1h • pH < 6.9 – 100mmol/L sodium bicarbonate in 400mL of 0.45% NS over 2h
Phosphate • Usually low in DKA • Routine phosphate replacement does not improve outcomes in DKA • Give phosphate supplement if phosphate < 0.32mmol/L, (normal = 0.8-1.45mmol/L) • Give in form of potassium phosphate (potassium replacement) • Monitor serum calcium
HHS • Prototypical patient with HHS is elderly with type 2 DM, with several week history – Polyuria – Weight loss – Diminished oral intake – Lethargy – Mental confusion, coma
On examination :
Present
Absent
• Dehydration • Nausea • Hypotension • Vomiting • Tachycardia • Abdominal pain • Altered mental status. • Kussmaul respirations.
Laboratory values in DKA and HHS DKA
HHS
Glucose (mmol/L)
13.9 - 33.3
33.3 – 66.6
Na (mmol/L)
125-135
135-145
K (mmol/L)
Normal or high
High
Phosphate
Low
Normal
Creatinine
Slightly high
High
Osmolality (mOsm/mL)
300-320
330-380
Plasma ketones
++++
+/-
HCO3 (mmol/L)
< 15
Normal to slightly low
Arterial pH
6.8-7.3
> 7.3
Arterial pCO2 (mmHg)
20-30
Normal
Anion gap
High
Normal to slightly high
Magnesim, chloride
Normal
Normal
Chronic complications (Microvascular)
Possible molecular mechanisms Hyperglycemia (Increased intracellular glucose)
Complication of diabetes
• • • •
Increase Advanced glycation end products Sorbitol, Diacylglycerol, Fructose 6 phosphate
• • • •
Altered Cell function, Gene expression, Renal, Vascular connective tissue
Retinopathy • Proliferative diabetic retinopathy – Newly formed vessels appear near the optic nerve and macula and rupture easily – Lead to hemorrhage, fibrosis, retinal detachment • Non-proliferative diabetic retinopathy – Increased retinal vascular permeability, – Alterations in retinal blood flow, – Abnormal retinal microvasculature, – Lead to retinal ischemia.
Treatment • Prevention : • Regular eye examinations • Intensive glycemic and BP control – Fasting: 4.4-6.1mmol/L – Non fasting: 4.4-8mmol/L – BP:130/80 • Aspirin (650mg/day) does not appear to influence the natural history of retinopathy • Treatment : Laser photocoagulation
Nephropathy • Related to chronic hyperglycemia. • Involve effects of – Growth factor – Angiotensin II • Hemodynamic alterations in renal microcirculation – glomerular hyperfiltration • Structural changes of glomerulus (Ex: basement membrane thickening, glomerular hyperthrophy) • Leads to ESRF
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
Patient’s Identity • • • • • • • • •
Name Age Gender Race Height Weight BMI DoA DoD
: : : : : : : : :
MH 66 Male Malay 158cm 52kg 20.8 7.1.2008 14.1.2008
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.
Past Medical History & Drug History • Type 2 DM (10 years) – T. Gliclazide (Diamicron ® MR) 120mg OM – T. Metformin 1g tds – HbA1C : Nov 2007 : 11.5 • Hypertension (8 years) – T. Perindopril 4mg od – T. Amlodipine 5mg od
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 : 37.8oC : 91% : 24.6mmol/L (SC actrapid 16 units stat)
• Lung : Clear • Abdomen : Soft & non tender • CVS : DRNM
Impression / Diagnosis • Diabetic ketoacidosis (DKA)
Lab Investigations
Arterial Blood Gas Day
1
2
3
pH
7.3
7.3
pCO2
28
31.5
pO2
61
97
HCO3
14.5
17.2
4-8
UFEME Day
1
2
3
Bacteria
Negative
Negative
Negative
Glucose
4+
2+
1+
Ketones
2+
2+
1+
pH
5
5
6
Protein
1+
2+
2+
RBC Count
1+
Negative
Negative
Leucocytes
Negative
3+
3+
Other cells a) SG b) UBG c) Bil d) Colour
1.015 Negative Negative Yellow
1.005 Negative Negative Yellow
1.005 Negative Negative Yellow
4-8
Full Blood Count Day
1
TWBC
11.6
7.8
Hb
12.3
11.4
RBC
4.21
3.70
HCT
38.0%
33.5%
Platelet 187.0
2
3
181.0
4-8
Renal Profile Day
1
2
3
Urea
7.8
4.6
4.5
3.0
Na
138.3
142.9
140.2
140.5
K
4.6
4.31
3.59
3.55
Cl
103.8
108.2
111.1
107.1
Ca
4-6
7
1.82
Mg PO4-
0.31
SrCr
128
121
110
111
ClCr
37.0
39.1
43.0
42.6
Uric acid
400
8
Liver Profile Day
1
2
Albumin
23
T.Bilirubin
9
T.Protein
72
ALP
140
ALT
57
AST
79
3-8
Lipid Profile Date
8.1.2008
Lipid profile
Results (mmol/L)
T.Chol (<5.7mmol/L) 6.1
TG (< 1.7mmol/L)
2.0
HDL (> 1.7mmol/L)
0.5
LDL (<3.9mmol/L)
3.7
Vital Signs Day
1
2
3
4
5
6
7
8
BP
104/ 58
123/ 71
129/ 60
150/ 79
139/ 80
121/ 76
142/ 72
139/ 73
T
37.8
37
37
37
37
37
37
37
RR
22
20
20
20
20
20
20
20
PR
80
104
80
100
91
91
91
100
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
Culture and sensitivity Date
11.1.08
Date sampling
7.1.08
Sample
Genital swab
Micro-organism
staphylococcus spp.
Sensitivity
Erythromycin, gentamicin, Penicillin
Resistant
oxacillin
Ward Medications
Ward medications Drug
Day start
Day stop
IV Ceftriaxone 2g od
1
8
IV Amoxycillin / clavulanate potassium
2
8
Tablet aspirin 150mg od
1
8
Tablet amlodipine 5mg od
7
8
SC actrapid 16 units stat
1
1
SC insulatard 14 units ON
3
7
SC actrapid 10 units tds
3
4
SC actrapid 8 units tds
4
7
SC actrapid 14 units tds
7
8
SC insulatard 16 units ON
7
8
Cream aqueous prn
7
8
Clinical Progress & Pharmaceutical Care plans
Clinical progress: Day 1 • • • • • • •
Low BP (104/56) High T (37.8) High glucose (24.6mmol/L) Urine ketone: 2+ Patient dehydrated. Scrotal: Red, marcerated Groin: erythematous + blister • Fundoscope: – Dense cataract – Diabetic retinopathy
• Impression: a) Uncontrolled DM – Missed medication b) Scrotal cellulitis
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, 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
PCI (Day 1) PCI
Pharmacist Recommendation
Management of DKA
• Monitor a) Vital signs b) Glucose level c) Serum electrolyte d) ABG e) Renal function f) I/O chart
Patient had: a) Low BP (104/56) b) High glucose (24.6 mmol/L) c) ABG : Metabolic acidosis Low pH: 7.3 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)
• Add PO4 to IV infusion •Change to IVD D5% when glucose level reach
14
mmol/L
Outcome
Time
Glucose (mmol/L)
330pm 24.6 6pm
20.7
8pm
13.4
10pm
11.3
PCI (Day 1) PCI
Pharmacist Recommendation
Outcome
Management of cellulitis
• T. paracetamol 1g stat and prn • Monitor Temperature, WBC count. • Review antibiotics used in cellulitis
• Antibiotics remained unchanged.
Patient a) Scrotal: Red, marcerated b) Groin: erythematous + blister c) High WBC: (11.6X10/L) d) Fever (37.8oC) IV ceftriaxone 2g od had been given.
Sanford 2007 (pg18, 86, 92): Early mild disease • T. Trimetoprim sulfamethoxazole double strength (160TMP/800SMX) 2 tab bd with T. Rifampin 300mg bd. Severe disease • IV Imipenem (1g IV od) / IV meropenem (0.5g IV qid) / IV ertapenem (0.5-1g tds) Plus • IV / PO linezolid 600mg bd / IV vancomycin (based on weight)
PCI (Day 1) PCI
Pharmacist Recommendation
Retinopathy screening & treatment
ADA 2007: • Patient was referred to • Optimal glycemic control ophthalmologist. • Optimal BP control • Refer to ophthalmologist. • Perform examination annually by ophthalmologist. (Examinations will be required more frequently if retinopathy is progressing)
Patient: • Dense cataract • Diabetic retinopathy
Outcome
Clinical progress: Day 2 • BP: 123/71 • Dry tongue, patient dehydrated • Scrotal & groin: red, inflammed Time
Glucose (mmol/L)
12am
6.3
2am
7.2
4am
9.2
6am
12.6
8am
14.4
10am
12.3
1220pm
8.4
4pm
6.7
6pm
5.8
820pm
6.2
10pm
3.3
Plan: • Increase to 5 pints NS/24h • IV insulin 2 units/h • IV Augmentin ® 1.2g stat and tds • 2 hourly GM monitor • I/O charting
• Withold insulin infusion
PCI (Day 2) PCI
Pharmacist Recommendation
Outcome
Prevention of hypoglycemia
• Monitor glucose level. • Withhold insulin infusion • Oral glucose (10-20g) – Treatment effect should be apparent in 15 min.
• Insulin infusion was withhold.
Patient’s glucose level dropped to 3.3mmol/L.
PCI (Day 2) PCI
Pharmacist Recommendation
Outcome
Lipid management
• ADA 2007: For those over 40 years old, Statin therapy to achieve an LDL reduction of 30-40% regardless of baseline LDL levels.
• No lipid lowering agent was given.
Patient’s lipid profile shown: Patient was 66 years old.
• Can be Initiated with: a) Lovastatin (20mg ON) b) Simvastatin (10-20mg ON) c) Atorvastatin (10-20mg od)
Clinical progress: Day 3 • Imp: Fluid overload • Not sleep well yesterday • Groin: still erythematous with blister Time
Glucose (mmol/L)
12am
4.4
1am
5.1
4am
4.8
6am
4.3
8am
3.9
10am
4.7
12pm
4.3
2pm
7.2
640pm
8.3
10pm
7.1
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
PCI (Day 3) PCI
Review of Oral hypoglycemic agent
Pharmacist Recommendation
Pharmacotherapy handbook: • Insulin therapy Patient HbA1C was 15.1 (0.7 – 2.5 (11.5 - Nov 2007) units/kg/day) • Can be started Patient was on maximum dose on basal bolus of OHA insulin regimen a) T. Gliclazide MR 120mg OM • Perform HbA1C b) T. Metformin 1g tds test in 3 months time. Patient’s CLcr trend: D1: 37.0mL/min D2: 39.1mL/min
Outcome • Patient was started with a) SC actrapid (10 units tds) b) SC insulatard (14 units ON) Total: 44 units/day (0.85 units/kg/day)
Clinical progress: Day 4 • C&S: Staphylococcus spp • Taking orally (not much)
Time
Glucose (mmol/L)
1225am 6.6 2am
6.5
4am
6.6
6am
5.6
4pm
5.3
8pm
6.7
1030pm 6.4
Plan: • Continue IV antibiotics • Daily dressing with NS • GM 4 hourly • Off IV D5% • Reduce dose: – SC actrapid 8 units tds
PCI (Day 4) PCI
Pharmacist Recommendation
ABG monitoring Patient’s ABG was monitored on day 1 and 3.
Monitor ABG daily until metabolic acidosis resolved.
ABG trend Day
1
3
pH
7.3
7.3
pCO2
28
31.5
pO2
61
97
HCO3 14.5
17.2
Outcome
Clinical progress: Day 5 • Sleep well • Afebrile
Time
Glucose (mmol/L)
430am
9.8
8am
10.3
11am
20.1
530pm
16.7
Plan (8am): • Continue medications
PCI (Day 5) PCI
Pharmacist Recommendation
Glucose level was high.
• Assess patient on present of
Time
Glucose (mmol/L)
430am
8.0
8am
10.3
11am
20.1
530pm
16.7
hypoglycemic symptoms • Increase dose of: Insulatard from 14 to 16 units. Actrapid from 8 to 14 units. Novo Nordisk Diabetes Care Services leaflet: Blood Glucose Level Above Target Value
Add
Up to 1 mmol/L
2iu
1 to 2 mmol/L
4iu
> 2 mmol/L
6iu
Outcome
Clinical progress: Day 6 • GM 8am: 13.7 • GM trend (Day 5) 9.8/20.1/16.7/9.3 • Afebrile Time
Glucose (mmol/L)
12am
9.3
4am
6.4
8am
13.7
1220pm
9.9
6pm
10.4
1030pm
5.1
1140pm
5.1
Plan: • Increase dose – SC actrapid 14 unit tds • GM monitor 4 hourly
Clinical progress: Day 7 • Afebrile • Respond to Antibiotics for scrotal cellulitis Time
Glucose (mmol/L)
2am
5.2
6am
6.4
8am
8.0
1240am
6.0
6pm
6.1
1030pm
4.9
Plan: • GM monitoring qid • Increase dose – SC insulatard 16 units ON • GM monitor 4 hourly • Restart T. Amlodipine 5mg od • Aqueous cream prn at scrotal area.
Clinical progress: Day 8 • Patient slept well. • Afebrile Time
Glucose (mmol/L)
8am
5.6
1230pm
4.6
Plan: • Off IV antibiotics • Start oral Augmentin ® 625mg bd • Discharge today
Discharge Medications • T. Aspirin 150mg od • SC Insulatard 16 units ON • SC Actrapid 14 units tds • T. Amlodipine 5mg od • T. Amoxycillin / clavulanic acid 625mg bd X 3/7
PCI (Day 8) PCI
Pharmacist Recommendation
Outcome
Management of hypertension T. amlodipine restarted on D7
Patient have DM and renal insufficiency, give anti-hypertensive a) T. perindopril 4mg od
Patient discharge with T. amlodipine 5mg od
Patient BP trend in ward
ADA 2007 recommend: ACEI for DM patients > 55 years old at high risk of CVD. ACEI may be superior to dihydropyridine CCB in reducing cardiovascular events.
Patient’s CLcr in ward ACEI and ARB delay progression to macroalbuminuria.
References • Malaysian Practice guideline (2004): – Management of Type 2 Diabetes Mellitus – Diabetic nephropathy
• American Diabetes Association (2007): Standards of Medical Care in Diabetes.Diabetes Care 2007;30:S4-41 • BSPED Recommended DKA Guidelines. • JNC 7 hypertension guideline • Sanford guide to antimicrobial therapy • Diabetic ketoacidosis, David E. Trachtenbarg, MD. American family physician. • DiPiro,J.TTalbert,R.L. Yee,G.C.et al (2005).Pharmacotherapy, A pathophysiology Approach. 6th Edition,Appleton & Lange • Harrison’s principle of internal medicine
THANK YOU
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, dermatologic, infections, cataracts and glaucoma.
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, polyuria, volume depletion) • Dehydration / hypotension / tachycardia • Abdominal pain, abdominal tenderness • SOB / Kussmaul respiration • Fruity odor • Lethargy / coma • Cerebral edema (mostly in children)
Precipitating events • Inadequate insulin istration • 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. 2.
Confirm diagnosis Assess serum electrolytes, acid base status, renal function 3. Fluid replacement 4. Regular insulin (IV/IM) 5. Treat underlying condition 6. Measure capillary glucose (every 1-2h) 7. Measure electrolytes & anion gap (every 4h for 24h) 8. Monitor BP, pulse, respiration, mental status, I/O (every 1-4h) 9. Replace K 10. Continue above measure until patient is stable (glucose goal is 8-14mmol/L) 11. ister intermediate / long acting insulin as soon as patient is eating.
Fluid replacement 0.9% saline over first 1-3h (5mL/kg/h) Hemodynamic stability, or until shock corrected
0.45% saline (150-300mL/h) When plasma glucose reaches 14mmol/L
5% glucose and 0.45%saline (100-200mL/h)
Regular insulin (IV / IM) Regular insulin IV (0.1 units / kg) IM (0.4 units / kg)
Continuous IV infusion (0.1units / kg / h) (Increase to 2 to 10 fold if no response by 24h)
*** If initial serum K < 3.3mmol/L*** withhold insulin until corrected to > 3.3mmol/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. • Goal : maintain K+ > 3.5mmol/L. • Inclusion into IV fluid (KCL / KPO4 / K acetate) (10 mmol/L/h if K < 5.5mmol/L, 40-80mmol/L/h if K <3.5mmol/L)
Bicarbonate replacement • Usually not necessary, unless: – Severe acidosis (pH <7.0 after initial hydration) • ADA: • pH = 6.9 - 7 – 50mmol/L sodium bicarbonate in 200mL of 0.45% NS over 1h • pH < 6.9 – 100mmol/L sodium bicarbonate in 400mL of 0.45% NS over 2h
Phosphate • Usually low in DKA • Routine phosphate replacement does not improve outcomes in DKA • Give phosphate supplement if phosphate < 0.32mmol/L, (normal = 0.8-1.45mmol/L) • Give in form of potassium phosphate (potassium replacement) • Monitor serum calcium
HHS • Prototypical patient with HHS is elderly with type 2 DM, with several week history – Polyuria – Weight loss – Diminished oral intake – Lethargy – Mental confusion, coma
On examination :
Present
Absent
• Dehydration • Nausea • Hypotension • Vomiting • Tachycardia • Abdominal pain • Altered mental status. • Kussmaul respirations.
Laboratory values in DKA and HHS DKA
HHS
Glucose (mmol/L)
13.9 - 33.3
33.3 – 66.6
Na (mmol/L)
125-135
135-145
K (mmol/L)
Normal or high
High
Phosphate
Low
Normal
Creatinine
Slightly high
High
Osmolality (mOsm/mL)
300-320
330-380
Plasma ketones
++++
+/-
HCO3 (mmol/L)
< 15
Normal to slightly low
Arterial pH
6.8-7.3
> 7.3
Arterial pCO2 (mmHg)
20-30
Normal
Anion gap
High
Normal to slightly high
Magnesim, chloride
Normal
Normal
Chronic complications (Microvascular)
Possible molecular mechanisms Hyperglycemia (Increased intracellular glucose)
Complication of diabetes
• • • •
Increase Advanced glycation end products Sorbitol, Diacylglycerol, Fructose 6 phosphate
• • • •
Altered Cell function, Gene expression, Renal, Vascular connective tissue
Retinopathy • Proliferative diabetic retinopathy – Newly formed vessels appear near the optic nerve and macula and rupture easily – Lead to hemorrhage, fibrosis, retinal detachment • Non-proliferative diabetic retinopathy – Increased retinal vascular permeability, – Alterations in retinal blood flow, – Abnormal retinal microvasculature, – Lead to retinal ischemia.
Treatment • Prevention : • Regular eye examinations • Intensive glycemic and BP control – Fasting: 4.4-6.1mmol/L – Non fasting: 4.4-8mmol/L – BP:130/80 • Aspirin (650mg/day) does not appear to influence the natural history of retinopathy • Treatment : Laser photocoagulation
Nephropathy • Related to chronic hyperglycemia. • Involve effects of – Growth factor – Angiotensin II • Hemodynamic alterations in renal microcirculation – glomerular hyperfiltration • Structural changes of glomerulus (Ex: basement membrane thickening, glomerular hyperthrophy) • Leads to ESRF
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
Patient’s Identity • • • • • • • • •
Name Age Gender Race Height Weight BMI DoA DoD
: : : : : : : : :
MH 66 Male Malay 158cm 52kg 20.8 7.1.2008 14.1.2008
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.
Past Medical History & Drug History • Type 2 DM (10 years) – T. Gliclazide (Diamicron ® MR) 120mg OM – T. Metformin 1g tds – HbA1C : Nov 2007 : 11.5 • Hypertension (8 years) – T. Perindopril 4mg od – T. Amlodipine 5mg od
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 : 37.8oC : 91% : 24.6mmol/L (SC actrapid 16 units stat)
• Lung : Clear • Abdomen : Soft & non tender • CVS : DRNM
Impression / Diagnosis • Diabetic ketoacidosis (DKA)
Lab Investigations
Arterial Blood Gas Day
1
2
3
pH
7.3
7.3
pCO2
28
31.5
pO2
61
97
HCO3
14.5
17.2
4-8
UFEME Day
1
2
3
Bacteria
Negative
Negative
Negative
Glucose
4+
2+
1+
Ketones
2+
2+
1+
pH
5
5
6
Protein
1+
2+
2+
RBC Count
1+
Negative
Negative
Leucocytes
Negative
3+
3+
Other cells a) SG b) UBG c) Bil d) Colour
1.015 Negative Negative Yellow
1.005 Negative Negative Yellow
1.005 Negative Negative Yellow
4-8
Full Blood Count Day
1
TWBC
11.6
7.8
Hb
12.3
11.4
RBC
4.21
3.70
HCT
38.0%
33.5%
Platelet 187.0
2
3
181.0
4-8
Renal Profile Day
1
2
3
Urea
7.8
4.6
4.5
3.0
Na
138.3
142.9
140.2
140.5
K
4.6
4.31
3.59
3.55
Cl
103.8
108.2
111.1
107.1
Ca
4-6
7
1.82
Mg PO4-
0.31
SrCr
128
121
110
111
ClCr
37.0
39.1
43.0
42.6
Uric acid
400
8
Liver Profile Day
1
2
Albumin
23
T.Bilirubin
9
T.Protein
72
ALP
140
ALT
57
AST
79
3-8
Lipid Profile Date
8.1.2008
Lipid profile
Results (mmol/L)
T.Chol (<5.7mmol/L) 6.1
TG (< 1.7mmol/L)
2.0
HDL (> 1.7mmol/L)
0.5
LDL (<3.9mmol/L)
3.7
Vital Signs Day
1
2
3
4
5
6
7
8
BP
104/ 58
123/ 71
129/ 60
150/ 79
139/ 80
121/ 76
142/ 72
139/ 73
T
37.8
37
37
37
37
37
37
37
RR
22
20
20
20
20
20
20
20
PR
80
104
80
100
91
91
91
100
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
Culture and sensitivity Date
11.1.08
Date sampling
7.1.08
Sample
Genital swab
Micro-organism
staphylococcus spp.
Sensitivity
Erythromycin, gentamicin, Penicillin
Resistant
oxacillin
Ward Medications
Ward medications Drug
Day start
Day stop
IV Ceftriaxone 2g od
1
8
IV Amoxycillin / clavulanate potassium
2
8
Tablet aspirin 150mg od
1
8
Tablet amlodipine 5mg od
7
8
SC actrapid 16 units stat
1
1
SC insulatard 14 units ON
3
7
SC actrapid 10 units tds
3
4
SC actrapid 8 units tds
4
7
SC actrapid 14 units tds
7
8
SC insulatard 16 units ON
7
8
Cream aqueous prn
7
8
Clinical Progress & Pharmaceutical Care plans
Clinical progress: Day 1 • • • • • • •
Low BP (104/56) High T (37.8) High glucose (24.6mmol/L) Urine ketone: 2+ Patient dehydrated. Scrotal: Red, marcerated Groin: erythematous + blister • Fundoscope: – Dense cataract – Diabetic retinopathy
• Impression: a) Uncontrolled DM – Missed medication b) Scrotal cellulitis
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, 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
PCI (Day 1) PCI
Pharmacist Recommendation
Management of DKA
• Monitor a) Vital signs b) Glucose level c) Serum electrolyte d) ABG e) Renal function f) I/O chart
Patient had: a) Low BP (104/56) b) High glucose (24.6 mmol/L) c) ABG : Metabolic acidosis Low pH: 7.3 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)
• Add PO4 to IV infusion •Change to IVD D5% when glucose level reach
14
mmol/L
Outcome
Time
Glucose (mmol/L)
330pm 24.6 6pm
20.7
8pm
13.4
10pm
11.3
PCI (Day 1) PCI
Pharmacist Recommendation
Outcome
Management of cellulitis
• T. paracetamol 1g stat and prn • Monitor Temperature, WBC count. • Review antibiotics used in cellulitis
• Antibiotics remained unchanged.
Patient a) Scrotal: Red, marcerated b) Groin: erythematous + blister c) High WBC: (11.6X10/L) d) Fever (37.8oC) IV ceftriaxone 2g od had been given.
Sanford 2007 (pg18, 86, 92): Early mild disease • T. Trimetoprim sulfamethoxazole double strength (160TMP/800SMX) 2 tab bd with T. Rifampin 300mg bd. Severe disease • IV Imipenem (1g IV od) / IV meropenem (0.5g IV qid) / IV ertapenem (0.5-1g tds) Plus • IV / PO linezolid 600mg bd / IV vancomycin (based on weight)
PCI (Day 1) PCI
Pharmacist Recommendation
Retinopathy screening & treatment
ADA 2007: • Patient was referred to • Optimal glycemic control ophthalmologist. • Optimal BP control • Refer to ophthalmologist. • Perform examination annually by ophthalmologist. (Examinations will be required more frequently if retinopathy is progressing)
Patient: • Dense cataract • Diabetic retinopathy
Outcome
Clinical progress: Day 2 • BP: 123/71 • Dry tongue, patient dehydrated • Scrotal & groin: red, inflammed Time
Glucose (mmol/L)
12am
6.3
2am
7.2
4am
9.2
6am
12.6
8am
14.4
10am
12.3
1220pm
8.4
4pm
6.7
6pm
5.8
820pm
6.2
10pm
3.3
Plan: • Increase to 5 pints NS/24h • IV insulin 2 units/h • IV Augmentin ® 1.2g stat and tds • 2 hourly GM monitor • I/O charting
• Withold insulin infusion
PCI (Day 2) PCI
Pharmacist Recommendation
Outcome
Prevention of hypoglycemia
• Monitor glucose level. • Withhold insulin infusion • Oral glucose (10-20g) – Treatment effect should be apparent in 15 min.
• Insulin infusion was withhold.
Patient’s glucose level dropped to 3.3mmol/L.
PCI (Day 2) PCI
Pharmacist Recommendation
Outcome
Lipid management
• ADA 2007: For those over 40 years old, Statin therapy to achieve an LDL reduction of 30-40% regardless of baseline LDL levels.
• No lipid lowering agent was given.
Patient’s lipid profile shown: Patient was 66 years old.
• Can be Initiated with: a) Lovastatin (20mg ON) b) Simvastatin (10-20mg ON) c) Atorvastatin (10-20mg od)
Clinical progress: Day 3 • Imp: Fluid overload • Not sleep well yesterday • Groin: still erythematous with blister Time
Glucose (mmol/L)
12am
4.4
1am
5.1
4am
4.8
6am
4.3
8am
3.9
10am
4.7
12pm
4.3
2pm
7.2
640pm
8.3
10pm
7.1
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
PCI (Day 3) PCI
Review of Oral hypoglycemic agent
Pharmacist Recommendation
Pharmacotherapy handbook: • Insulin therapy Patient HbA1C was 15.1 (0.7 – 2.5 (11.5 - Nov 2007) units/kg/day) • Can be started Patient was on maximum dose on basal bolus of OHA insulin regimen a) T. Gliclazide MR 120mg OM • Perform HbA1C b) T. Metformin 1g tds test in 3 months time. Patient’s CLcr trend: D1: 37.0mL/min D2: 39.1mL/min
Outcome • Patient was started with a) SC actrapid (10 units tds) b) SC insulatard (14 units ON) Total: 44 units/day (0.85 units/kg/day)
Clinical progress: Day 4 • C&S: Staphylococcus spp • Taking orally (not much)
Time
Glucose (mmol/L)
1225am 6.6 2am
6.5
4am
6.6
6am
5.6
4pm
5.3
8pm
6.7
1030pm 6.4
Plan: • Continue IV antibiotics • Daily dressing with NS • GM 4 hourly • Off IV D5% • Reduce dose: – SC actrapid 8 units tds
PCI (Day 4) PCI
Pharmacist Recommendation
ABG monitoring Patient’s ABG was monitored on day 1 and 3.
Monitor ABG daily until metabolic acidosis resolved.
ABG trend Day
1
3
pH
7.3
7.3
pCO2
28
31.5
pO2
61
97
HCO3 14.5
17.2
Outcome
Clinical progress: Day 5 • Sleep well • Afebrile
Time
Glucose (mmol/L)
430am
9.8
8am
10.3
11am
20.1
530pm
16.7
Plan (8am): • Continue medications
PCI (Day 5) PCI
Pharmacist Recommendation
Glucose level was high.
• Assess patient on present of
Time
Glucose (mmol/L)
430am
8.0
8am
10.3
11am
20.1
530pm
16.7
hypoglycemic symptoms • Increase dose of: Insulatard from 14 to 16 units. Actrapid from 8 to 14 units. Novo Nordisk Diabetes Care Services leaflet: Blood Glucose Level Above Target Value
Add
Up to 1 mmol/L
2iu
1 to 2 mmol/L
4iu
> 2 mmol/L
6iu
Outcome
Clinical progress: Day 6 • GM 8am: 13.7 • GM trend (Day 5) 9.8/20.1/16.7/9.3 • Afebrile Time
Glucose (mmol/L)
12am
9.3
4am
6.4
8am
13.7
1220pm
9.9
6pm
10.4
1030pm
5.1
1140pm
5.1
Plan: • Increase dose – SC actrapid 14 unit tds • GM monitor 4 hourly
Clinical progress: Day 7 • Afebrile • Respond to Antibiotics for scrotal cellulitis Time
Glucose (mmol/L)
2am
5.2
6am
6.4
8am
8.0
1240am
6.0
6pm
6.1
1030pm
4.9
Plan: • GM monitoring qid • Increase dose – SC insulatard 16 units ON • GM monitor 4 hourly • Restart T. Amlodipine 5mg od • Aqueous cream prn at scrotal area.
Clinical progress: Day 8 • Patient slept well. • Afebrile Time
Glucose (mmol/L)
8am
5.6
1230pm
4.6
Plan: • Off IV antibiotics • Start oral Augmentin ® 625mg bd • Discharge today
Discharge Medications • T. Aspirin 150mg od • SC Insulatard 16 units ON • SC Actrapid 14 units tds • T. Amlodipine 5mg od • T. Amoxycillin / clavulanic acid 625mg bd X 3/7
PCI (Day 8) PCI
Pharmacist Recommendation
Outcome
Management of hypertension T. amlodipine restarted on D7
Patient have DM and renal insufficiency, give anti-hypertensive a) T. perindopril 4mg od
Patient discharge with T. amlodipine 5mg od
Patient BP trend in ward
ADA 2007 recommend: ACEI for DM patients > 55 years old at high risk of CVD. ACEI may be superior to dihydropyridine CCB in reducing cardiovascular events.
Patient’s CLcr in ward ACEI and ARB delay progression to macroalbuminuria.
References • Malaysian Practice guideline (2004): – Management of Type 2 Diabetes Mellitus – Diabetic nephropathy
• American Diabetes Association (2007): Standards of Medical Care in Diabetes.Diabetes Care 2007;30:S4-41 • BSPED Recommended DKA Guidelines. • JNC 7 hypertension guideline • Sanford guide to antimicrobial therapy • Diabetic ketoacidosis, David E. Trachtenbarg, MD. American family physician. • DiPiro,J.TTalbert,R.L. Yee,G.C.et al (2005).Pharmacotherapy, A pathophysiology Approach. 6th Edition,Appleton & Lange • Harrison’s principle of internal medicine
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