Are you a protocol breaker? Lessons from Diabetic Ketoacidosis Dr Evelyn Tan, Endocrine AT Dr Christopher Rowe, Endocrinologist Department of Endocrinology and Diabetes
Outline 5 case vignettes: 1 typical, 4 atypical 2 audits Tertiary Inpatient Management of DKA (2010) Presentations of DKA in dialysis patients, 2006-2016 Reflection on the role of protocols and guidelines in medicine
Case 1 20yo male found at hotel bathroom unconscious PMHx: 1. T1DM dx age 5 HbA1c 10.9% Mar 17 ICU admissions for DKA 2017, 2016, 2009 x 2 Non-compliance Lantus 15 nocte Novorapid 6-18 TDS No known micro/macro complications 2. Hepatitis C (current IVDU) 3. ADHD 4. Asthma SHx: No fixed abode Released from jail Feb 16 IVDU amphetamines Current smoker Alcohol binge-drink In ED: 140/90, HR 100, afebrile Refused history or examination Verbally aggressive No obvious cellulitis/ injection marks Refused IDC
Investigations Admission VBG ph 7.17 Bicarbonate 11.7 Lactate N/A Base excess -16.1 Glucose 29.0 UEC Sodium 134 Potassium 4.1 Bicarbonate 12 Urea 7.7 Creatinine 125 egfr 71 Other LFT Bilirubin 16 GGT 421 ALP 304 ALT 509 AST 524 FBC WCC 10.3 Hb 160 Platelets 254 HbA1c 10.9% Urine drug screen Positive for amphetamines Capillary ketones 7.1 (<0.4) Beta-hydroxybutyrate 7.5 ( <0.4)
Diagnosis: DKA Admission VBG ph 7.17 Bicarbonate 11.7 Lactate N/A Base excess -16.1 Glucose 29.0 UEC Sodium 134 Potassium 4.1 Bicarbonate 12 Urea 7.7 Creatinine 125 egfr 71 Other LFT Bilirubin 16 GGT 421 ALP 304 ALT 509 AST 524 FBC WCC 10.3 Hb 160 Platelets 254 HbA1c 10.9% Urine drug screen Positive for amphetamines Capillary ketones 7.1 (<0.4) Beta-hydroxybutyrate 7.5 ( <0.4)
Diagnosis: DKA Admission VBG ph 7.17 Bicarbonate 11.7 Lactate N/A Base excess -16.1 Glucose 29.0 UEC Sodium 134 Potassium 4.1 Bicarbonate 12 Urea 7.7 Creatinine 125 egfr 71 Other LFT Bilirubin 16 GGT 421 ALP 304 ALT 509 AST 524 FBC WCC 10.3 Hb 160 Platelets 254 HbA1c 10.9% Urine drug screen Positive for amphetamines Capillary ketones 7.1 (<0.4) Beta-hydroxybutyrate 7.5 ( <0.4)
Diabetic Ketoacidosis (DKA) Diagnosis D: Known history of diabetes / elevated glucose AND K: Cap ketones > 3mmol/l AND or urine ketones 2+ A: ph<7.3 or Bicarb <15
Initial investigations 2 x large bore cannulae VBG, capillary/ urine ketones FBC/UEC/LFT/CMP/formal BGL Find a precipitant Infection blood cultures (x 2), CXR, urine m/c/s Infarction ECG History and physical examination
Treatment AIMS : RESOLUTION of ketones and acidosis (ph>7.3, Bicarb >18, cap ketones < 0.5) 1. Fluid status rapid initial fluid replacement in the first few hours (0.9% normal saline) Add 5% dextrose if BGL <15mmol/l Risk of cerebral oedema with children/young adults. 2. Insulin / Glycaemic control Fixed rate insulin (5 units/h) Reduce to 2 units/h if BGL <10 mmol/l Give usual long acting subcut insulin Target BGL 10-15 mmol/l Suppress ketogenesis 3. Electrolytes Significant potassium shifts Aim Potassium 4-5 mmol/l
IVF 1-2L K: 20mmol IVF 1-2L K: 20-40mmol IVF 1.5L K: 10-40mmol First 12 hours: 5L IVF and 50-100mmol
Progress VBG 0740h 0900h 1010h 1225h 1425h ph 7.17 7.24 7.27 7.33 7.35 Bicarbonate 11.7 12.3 13.1 16.5 19.5 Glucose 29.0 19.2 14.0 9.5 14.7 Potassium 4.2 4.2 5.1 4.4 5.3 Cap ketones 7.1-5.1 1.8 0.6 Normal saline Actrapid infusion Potassium replacement 5% dextrose
Estimate Case 1 IVF 1-2L K: 20mmol IVF 1-2L K: 20-40mmol IVF 1.5L K: 10-40mmol First 12 hours: 5L IVF and 50-100mmol K IVF 2.25L K: 10mmol IVF 2.85L K: 50mmol Resolution First 12 hours: 5.1L IVF and 60mmol K
Ketones
DKA management in HNE Retrospective audit over 12 months 1 Jan 2010 31 Dec 2010 John Hunter, Maitland Hospital, Belmont District Hospital DKA audit standards (UK) Blood gas within 60min from admission IV fluid started within 60min from admission IV insulin started within 120min from admission Cumulative period IV insulin stopped <60min per 24h while on IV insulin Received at least 2 UEC (excluding blood gas) in the first 24h from admission Interval between IV fluid and IV insulin <60min
DKA Audit Results: 90 DKA presentations Of which 50 at JHH (i.e. ~1/week) Precipitant 4% 27% 7% 35% 27% Infection Missed insulin New diagnosis Pump malfunction Others
DKA Audit - Results 64% received IV fluid within 60min 67% received blood gas within 60min 52% received IV insulin within 120min 33% had IV insulin delayed beyond 180min First 24 hours admission 9% had IV insulin interrupted beyond 60min 24% had potassium <3.5 mmol/l at some point Only 24% overall admissions met the set standards
Does a protocol improve efficacy and safety outcomes? Efficacy Safety
Cases that don t fit the guideline
Cases that don t fit the guideline Cases occurring in abnormal physiology Patients on dialysis Pregnancy Pharmacotherapy
Case 2a: Mr A 60 year old male. Diabetes Mellitus diagnosed in 1984 (age 28) On insulin since 1986 Prior episode of DKA in 2015 Social Lives alone, independent Occasional ETOH Non-smoker Microvascular complications Retinopathy (prior photocoagulation) Peripheral neuropathy Biopsy confirmed diabetic nephropathy Commenced PD 2 weeks prior Still passes some urine Hypoglyceamic unawareness (MVA 2016) Macro-vascular risk Treated HTN, Hypercholesterolaemia Medications Lantus 20 units nocte Humalog 10 units meals Verapamil 240mg Aspirin 100mg Rosuvastatin 10mg Calcitriol 0.5microg Calcium 1200mg TDS
Case 2a: Presentation 1-2 day history of confusion/vomiting Unclear when last had insulin/dialysis? Self harm Drowsy, confused Afebrile. BP 120/70. P110. Clinically not fluid overloaded No septic focus ph 6.96 7.32-7.43 HCO 3 5 22-30 CO 2 18 41-50 Anion Gap >47 7-17 Β-OH Butyrate 9 <0.4 Lactate 11 <2 Na + 125 135-145 Glucose 73 <11 K + 8 3.5-5 Urea 38 4-11 Creatinine 958 Osmolality 395 280-300
Case 2a: Presentation 1-2 day history of confusion/vomiting Unclear when last had insulin/dialysis? Self harm Drowsy, confused Afebrile. BP 120/70. P110. Clinically not fluid overloaded No septic focus ph 6.96 7.32-7.43 HCO 3 5 22-30 CO 2 18 41-50 Anion Gap >47 7-17 Β-OH Butyrate 9 <0.4 Lactate 11 <2 Na + 125 135-145 1. Define the key abnormalities 2. How does this situation differ from standard DKA? 3. What is your management priority Glucose 73 <11 K + 8 3.5-5 Urea 38 4-11 Creatinine 958 Osmolality 395 280-300
Case 2a: Presentation 1-2 day history of confusion/vomiting Unclear when last had insulin/dialysis? Self harm Drowsy, confused Afebrile. BP 120/70. P110. Clinically not fluid overloaded No septic focus ph 6.96 7.32-7.43 HCO 3 5 22-30 CO 2 18 41-50 Anion Gap >47 7-17 Β-OH Butyrate 9 <0.4 Lactate 11 <2 Na + 125 135-145 1. Define the key abnormalities 2. How does this situation differ from standard DKA? 3. What are your management priorities? Glucose 73 <11 K + 8 3.5-5 Urea 38 4-11 Creatinine 958 Osmolality 395 280-300
Case 2a: Presentation Severe high anion gap metabolic acidosis - With respiratory compensation - Explained by ketones + lactate > uraemia Marked hyperglycaemia with compensatory hyponatremia (corrected Na = 146mEq/L) Hyperkalemia with ECG changes Hyperosmolality due to urea and glucose 1. Define the key abnormalities 2. How does this situation differ from standard DKA? 3. What are your management priorities? ph 6.96 7.32-7.43 HCO 3 5 22-30 CO 2 18 41-50 Anion Gap >47 7-17 Β-OH Butyrate 9 <0.4 Lactate 11 <2 Na + 125 135-145 Glucose 73 <11 K + 8 3.5-5 Urea 38 4-11 Creatinine 958 Osmolality 395 280-300
Case 2a: Presentation Severe high anion gap metabolic acidosis - With respiratory compensation - Explained by ketones + lactate > uraemia Marked hyperglycaemia with compensatory hyponatremia (corrected Na = 146mEq/L) Hyperkalemia with ECG changes Hyperosmolality due to urea and glucose 1. Define the key abnormalities 2. How does this situation differ from standard DKA? 3. What are your management priorities? ph 6.96 7.32-7.43 HCO 3 5 22-30 CO 2 18 41-50 Anion Gap >47 7-17 Β-OH Butyrate 9 <0.4 Lactate 11 <2 Na + 125 135-145 Glucose 73 <11 K + 8 3.5-5 Urea 38 4-11 Creatinine 958 Osmolality 395 280-300
Case 2a: Presentation Severe high anion gap metabolic acidosis - With respiratory compensation - Explained by ketones + lactate > uraemia Marked hyperglycaemia with compensatory hyponatremia (corrected Na = 146mEq/L) Hyperkalemia with ECG changes Hyperosmolality due to urea and glucose 1. Define the key abnormalities 2. How does this situation differ from standard DKA? 3. What are your management priorities? ph 6.96 7.32-7.43 HCO 3 5 22-30 CO 2 18 41-50 Anion Gap >47 7-17 Β-OH Butyrate 9 <0.4 Lactate 11 <2 Na + 125 135-145 Glucose 73 <11 K + 8 3.5-5 Urea 38 4-11 Creatinine 958 Osmolality 395 280-300
K 8.0 K 6.7
K 8.0 Prolonged QRS Prolonged PR Then loss of P waves Peaked T K 6.7
Case 2a: Presentation Severe high anion gap metabolic acidosis - With respiratory compensation - Explained by ketones + lactate > uraemia Marked hyperglycaemia with compensatory hyponatremia (corrected Na = 146mEq/L) Hyperkalemia with ECG changes Hyperosmolality due to urea and glucose 1. Define the key abnormalities 2. How does this situation differ from standard DKA? 3. What are your management priorities? ph 6.96 7.32-7.43 HCO 3 5 22-30 CO 2 18 41-50 Anion Gap >47 7-17 Β-OH Butyrate 9 <0.4 Lactate 11 <2 Na + 125 135-145 Glucose 73 <11 K + 8 3.5-5 Urea 38 4-11 Creatinine 958 Osmolality 395 280-300
Case 2a: Presentation ph 6.96 7.32-7.43 HCO 3 5 22-30 CO 2 18 41-50 Anion Gap >47 7-17 Β-OH Butyrate 9 <0.4 Lactate 11 <2 Na + 125 135-145 1. Define the key abnormalities 2. How does this situation differ from standard DKA? 3. What are your management priorities? Glucose 73 <11 K + 8 3.5-5 Urea 38 4-11 Creatinine 958 Osmolality 395 280-300
Case 2a: Presentation Unable to generate osmotic diuresis Less likely to have Total body potassium deficit Significant dehydration Dominant cause of acidosis less clear More hyperglylceamic and hyperosmolar?role of dialysis in correcting these abnormalities 1. Define the key abnormalities 2. How does this situation differ from standard DKA? 3. What are your management priorities? ph 6.96 7.32-7.43 HCO 3 5 22-30 CO 2 18 41-50 Anion Gap >47 7-17 Β-OH Butyrate 9 <0.4 Lactate 11 <2 Na + 125 135-145 Glucose 73 <11 K + 8 3.5-5 Urea 38 4-11 Creatinine 958 Osmolality 395 280-300
Case 2a: Presentation 1. Address hyperkalemia 2. Correct acidosis 3. Do no harm with treatment 1. Fluid overload 2. Overly rapid osmotic correction 4. Treat the underlying cause ph 6.96 7.32-7.43 HCO 3 5 22-30 CO 2 18 41-50 Anion Gap >47 7-17 Β-OH Butyrate 9 <0.4 Lactate 11 <2 Na + 125 135-145 1. Define the key abnormalities 2. How does this situation differ from standard DKA? 3. What are your management priorities? Glucose 73 <11 K + 8 3.5-5 Urea 38 4-11 Creatinine 958 Osmolality 395 280-300
Case 2a: Resolution Hour 0 1 3 4 6 8 10 12 15 24 ph 6.96 7.05 7.17 7.30 7.37 7.39 7.40 7.39 7.38 7.38 HCO3 4.7 4.7 7.9 14.2 20.2 22.3 21.7 22.2 21.8 22 CO2 19 18 22 30 31 34 36 37 38 39 BOHB 9.1 0.7 0.2 Lactate 11 9 6 3 2 1 1 1 1 1 PD exchange x2 + 700mL Insulin 10 units stat then 5 units / hour 3 units / hour K 8 6.7 5.0 4.3 4.1 4.3 3.9 4.1 4.1 4.1 24 hour totals Na 125 128 130 130 130 132 134 135 137 136 Corr Na 146 145 142 142 Gluc 73 59 >38 >38 >38 >38 31.0 24.1 IVF 1000 1000 1000 1000 4L IV K + Nil 20mmol 20mmol 40mmol U/O IDC 120 160 60 360 190 150 160 260 1.4L
Case 2a: Resolution Hour 0 1 3 4 6 8 10 12 15 24 ph 6.96 7.05 7.17 7.30 7.37 7.39 7.40 7.39 7.38 7.38 HCO3 4.7 4.7 7.9 14.2 20.2 22.3 21.7 22.2 21.8 22 CO2 19 18 22 30 31 34 36 37 38 39 BOHB 9.1 0.7 0.2 Lactate 11 9 6 3 2 1 1 1 1 1 PD exchange x2 + 700mL Insulin 10 units stat then 5 units / hour 3 units / hour K 8 6.7 5.0 4.3 4.1 4.3 3.9 4.1 4.1 4.1 24 hour totals Na 125 128 130 130 130 132 134 135 137 136 Corr Na 146 145 142 142 Gluc 73 59 >38 >38 >38 >38 31.0 24.1 IVF 1000 1000 1000 1000 4L IV K + Nil 20mmol 20mmol 40mmol U/O IDC 120 160 60 360 190 150 160 260 1.4L
Case 2a: Resolution Hour 0 1 3 4 6 8 10 12 15 24 ph 6.96 7.05 7.17 7.30 7.37 7.39 7.40 7.39 7.38 7.38 HCO3 4.7 4.7 7.9 14.2 20.2 22.3 21.7 22.2 21.8 22 CO2 19 18 22 30 31 34 36 37 38 39 BOHB 9.1 0.7 0.2 Lactate 11 9 6 3 2 1 1 1 1 1 PD exchange x2 + 700mL Insulin 10 units stat then 5 units / hour 3 units / hour K 8 6.7 5.0 4.3 4.1 4.3 3.9 4.1 4.1 4.1 24 hour totals Na 125 128 130 130 130 132 134 135 137 136 Corr Na 146 145 142 142 Gluc 73 59 >38 >38 >38 >38 31.0 24.1 IVF 1000 1000 1000 1000 4L IV K + Nil 20mmol 20mmol 40mmol U/O IDC 120 160 60 360 190 150 160 260 1.4L
Case 2a: Resolution Hour 0 1 3 4 6 8 10 12 15 24 ph 6.96 7.05 7.17 7.30 7.37 7.39 7.40 7.39 7.38 7.38 HCO3 4.7 4.7 7.9 14.2 20.2 22.3 21.7 22.2 21.8 22 CO2 19 18 22 30 31 34 36 37 38 39 BOHB 9.1 0.7 0.2 Lactate 11 9 6 3 2 1 1 1 1 1 PD exchange x2 + 700mL Insulin 10 units stat then 5 units / hour 3 units / hour K 8 6.7 5.0 4.3 4.1 4.3 3.9 4.1 4.1 4.1 24 hour totals Na 125 128 130 130 130 132 134 135 137 136 Corr Na 146 145 142 142 Gluc 73 59 >38 >38 >38 >38 31.0 24.1 IVF 1000 1000 1000 1000 4L IV K + Nil 20mmol 20mmol 40mmol U/O IDC 120 160 60 360 190 150 160 260 1.4L
Case 2a: Resolution Hour 0 1 3 4 6 8 10 12 15 24 ph 6.96 7.05 7.17 7.30 7.37 7.39 7.40 7.39 7.38 7.38 HCO3 4.7 4.7 7.9 14.2 20.2 22.3 21.7 22.2 21.8 22 CO2 19 18 22 30 31 34 36 37 38 39 BOHB 9.1 0.7 0.2 Lactate 11 9 6 3 2 1 1 1 1 1 PD exchange x2 + 700mL Insulin 10 units stat then 5 units / hour 3 units / hour K 8 6.7 5.0 4.3 4.1 4.3 3.9 4.1 4.1 4.1 24 hour totals Na 125 128 130 130 130 132 134 135 137 136 Corr Na 146 145 142 142 Gluc 73 59 >38 >38 >38 >38 31.0 24.1 IVF 1000 1000 1000 1000 4L IV K + Nil 20mmol 20mmol 40mmol U/O IDC 120 160 60 360 190 150 160 260 1.4L
Estimate Case 1 IVF 1-2L K: 20mmol IVF 1-2L K: 20-40mmol IVF 1.5L K: 10-40mmol First 12 hours: 5L IVF and 50-100mmol K IVF 2.25L K: 10mmol IVF 2.85L K: 50mmol Resolution First 12 hours: 5.1L IVF and 60mmol K Case 2a IVF 2L K: Nil IVF 1L K: Nil IVF 1L K: 30mmol First 12 hours: 4L IVF and 30mmol K
Case 2a: Summary Severe DKA in a PD patient with lactic acidosis (hypoperfusion) With hyperkalemia Trigger: missed insulin and missed dialysis Resolution: Less IVF and K required than for standard severe DKA PD may have assisted with rapid resolution of acidosis Insulin infusion rate reduced to slow rate of correction of glucose once acidosis resolved
Case 2b: Ms B 49 year old Indigenous female. Type 2 diabetes mellitus Anti-GAD antibodies >2000iu/L (<10) Autoimmune hypothyroidism Sister has Type 1 Diabetes Microvascular complications End stage renal disease (diabetic nephropathy) Recently commenced on HD via permacath (previous PD peritonitis) Still passes urine Medications Lantus 90 units Novorapid 15 units TDS Metoprolol 12.5mg bd Aspirin 100mg Atorvastatin 40mg Clopidogrel 75mg Frusemide 80mg BD Calcitriol 0.25mcg Caltrate 2 tabs TDS Amlodipine 5mg Ezetimibe 10mg Macro-vascular complications IHD with 2x prior AMI
Case 2b: Presentation Epigastric pain and vomiting for 2 days Missed Lantus last night 2 episodes of diarrhoea Attended for HD at peripheral site Hyperglycaemic, unwell sent to JHH ED BP 160/64. P100. Afebrile Does not appear clinically overloaded Dry weight 88kg, Wt today 90.3kg ph 7.26 7.32-7.43 HCO 3 16 22-30 CO 2 41 41-50 Anion Gap 26 7-17 Β-OH Butyrate 4.6 <0.4 Lactate 2.7 <2 Na + 126 135-145 Glucose 50 <11 K + 5.3 3.5-5 Urea 23.1 4-11 Creatinine 602
Case 2b: Presentation Epigastric pain and vomiting for 2 days Missed Lantus last night 2 episodes of diarrhoea Attended for HD at peripheral site Hyperglycaemic, unwell sent to JHH ED BP 160/64. Afebrile Does not appear clinically overloaded Dry weight 88kg, Wt today 90.3kg 1. Define the key abnormalities 2. What is your management priority 3. How does this situation differ from standard DKA? ph 7.26 7.32-7.43 HCO 3 16 22-30 CO 2 41 41-50 Anion Gap 26 7-17 Β-OH Butyrate 4.6 <0.4 Lactate 2.7 <2 Na + 126 135-145 Glucose 50 <11 K + 5.3 3.5-5 Urea 23.1 4-11 Creatinine 602
Case 2b: Presentation Epigastric pain and vomiting for 2 days Missed Lantus last night 2 episodes of diarrhoea Attended for HD at peripheral site Hyperglycaemic, unwell sent to JHH ED BP 160/64. Afebrile Does not appear clinically overloaded Dry weight 88kg, Wt today 90.3kg 1. Define the key abnormalities 2. What is your management priority 3. How does this situation differ from standard DKA? ph 7.26 7.32-7.43 HCO 3 16 22-30 CO 2 41 41-50 Anion Gap 26 7-17 Β-OH Butyrate 4.6 <0.4 Lactate 2.7 <2 Na + 126 135-145 Glucose 50 <11 K + 5.3 3.5-5 Urea 23.1 4-11 Creatinine 602
Case 2b: Presentation Mild high anion gap metabolic acidosis - Explained by ketones Hyperglyceamia with secondary hyponatremia ph 7.26 7.32-7.43 HCO 3 16 22-30 CO 2 41 41-50 Anion Gap 26 7-17 Β-OH Butyrate 4.6 <0.4 Lactate 2.7 <2 Na + 126 135-145 1. Define the key abnormalities 2. What is your management priority 3. How does this situation differ from standard DKA? Glucose 50 <11 K + 5.3 3.5-5 Urea 23.1 4-11 Creatinine 602
Case 2b: Presentation Mild high anion gap metabolic acidosis - Explained by ketones Hyperglyceamia with secondary hyponatremia ph 7.26 7.32-7.43 HCO 3 16 22-30 CO 2 41 41-50 Anion Gap 26 7-17 Β-OH Butyrate 4.6 <0.4 Lactate 2.7 <2 Na + 126 135-145 1. Define the key abnormalities 2. What is your management priority 3. How does this situation differ from standard DKA? Glucose 50 <11 K + 5.3 3.5-5 Urea 23.1 4-11 Creatinine 602
Case 2b: Presentation ph 7.26 7.32-7.43 HCO 3 16 22-30 CO 2 41 41-50 Anion Gap 26 7-17 Β-OH Butyrate 4.6 <0.4 Lactate 2.7 <2 Na + 126 135-145 1. Define the key abnormalities 2. What is your management priority 3. How does this situation differ from standard DKA? Glucose 50 <11 K + 5.3 3.5-5 Urea 23.1 4-11 Creatinine 602
Case 2b: Presentation Priorities: 1. Correct acidosis by addressing ketosis 2. Correct hyperglycaemia 3. Manage volume status/hyperosmolality ph 7.26 7.32-7.43 HCO 3 16 22-30 CO 2 41 41-50 Anion Gap 26 7-17 Β-OH Butyrate 4.6 <0.4 Lactate 2.7 <2 Na + 126 135-145 1. Define the key abnormalities 2. What is your management priority 3. How does this situation differ from standard DKA? Glucose 50 <11 K + 5.3 3.5-5 Urea 23.1 4-11 Creatinine 602
Case 2b: Presentation ph 7.26 7.32-7.43 HCO 3 16 22-30 CO 2 41 41-50 Anion Gap 26 7-17 Β-OH Butyrate 4.6 <0.4 Lactate 2.7 <2 Na + 126 135-145 1. Define the key abnormalities 2. What is your management priority 3. How does this situation differ from standard DKA? Glucose 50 <11 K + 5.3 3.5-5 Urea 23.1 4-11 Creatinine 602
Case 2b: Presentation Differences: - Lower likelihood of potassium and water deficit due to lack of osmotic diuresis - Greater hyperosmolality / hyperglyceamia ph 7.26 7.32-7.43 HCO 3 16 22-30 CO 2 41 41-50 Anion Gap 26 7-17 Β-OH Butyrate 4.6 <0.4 Lactate 2.7 <2 Na + 126 135-145 1. Define the key abnormalities 2. What is your management priority 3. How does this situation differ from standard DKA? Glucose 50 <11 K + 5.3 3.5-5 Urea 23.1 4-11 Creatinine 602
Case 2b: Resolution Hour 0 2 4 6 10 14 19 24 Total ph 7.26 7.26 7.31 7.31 7.36 7.34 7.33 7.35 HCO 3 16 16 17 18 20 22 22 21 CO 2 40 41 38 36 37 41 41 40 B-OH-B 4.6 3 1.8 0.7 0.2 0.1 Lactate 2.7 3.1 4.0 4.1 3.3 2.9 2.1 1.0 Dialysis withheld Dialysis given Insulin 5 units/hr 2 units/hr 1.5u/hr Stop K + 5.3 5.3 5.4 5.5 5.2 4.5 4.5 4.8 Na + 126 126 126 128 127 131 133 139 Corr Na + 139 139 139 140 140 141 140 140 Glucose 50 >38 37 33 30 16 7 8 IVF IV K + U/O Nil Not recorded 1000mL
Case 2b: Resolution Hour 0 2 4 6 10 14 19 24 Total ph 7.26 7.26 7.31 7.31 7.36 7.34 7.33 7.35 HCO 3 16 16 17 18 20 22 22 21 CO 2 40 41 38 36 37 41 41 40 B-OH-B 4.6 3 1.8 0.7 0.2 0.1 Lactate 2.7 3.1 4.0 4.1 3.3 2.9 2.1 1.0 Dialysis withheld Dialysis given Insulin 5 units/hr 2 units/hr 1.5u/hr Stop K + 5.3 5.3 5.4 5.5 5.2 4.5 4.5 4.8 Na + 126 126 126 128 127 131 133 139 Corr Na + 139 139 139 140 140 141 140 140 Glucose 50 >38 37 33 30 16 7 8 IVF IV K + U/O Nil Not recorded 1000mL
Case 2b: Resolution Hour 0 2 4 6 10 14 19 24 Total ph 7.26 7.26 7.31 7.31 7.36 7.34 7.33 7.35 HCO 3 16 16 17 18 20 22 22 21 CO 2 40 41 38 36 37 41 41 40 B-OH-B 4.6 3 1.8 0.7 0.2 0.1 Lactate 2.7 3.1 4.0 4.1 3.3 2.9 2.1 1.0 Dialysis withheld Dialysis given Insulin 5 units/hr 2 units/hr 1.5u/hr Stop K + 5.3 5.3 5.4 5.5 5.2 4.5 4.5 4.8 Na + 126 126 126 128 127 131 133 139 Corr Na + 139 139 139 140 140 141 140 140 Glucose 50 >38 37 33 30 16 7 8 IVF IV K + U/O Nil Not recorded 1000mL
Case 2b: Resolution Hour 0 2 4 6 10 14 19 24 Total ph 7.26 7.26 7.31 7.31 7.36 7.34 7.33 7.35 HCO 3 16 16 17 18 20 22 22 21 CO 2 40 41 38 36 37 41 41 40 B-OH-B 4.6 3 1.8 0.7 0.2 0.1 Lactate 2.7 3.1 4.0 4.1 3.3 2.9 2.1 1.0 Dialysis withheld Dialysis given Insulin 5 units/hr 2 units/hr 1.5u/hr Stop K + 5.3 5.3 5.4 5.5 5.2 4.5 4.5 4.8 Na + 126 126 126 128 127 131 133 139 Corr Na + 139 139 139 140 140 141 140 140 Glucose 50 >38 37 33 30 16 7 8 IVF IV K + U/O Nil Not recorded 1000mL
Estimate Case 1 IVF 1-2L K: 20mmol IVF 1-2L K: 20-40mmol IVF 1.5L K: 10-40mmol First 12 hours: 5L IVF and 50-100mmol K IVF 2.25L K: 10mmol IVF 2.85L K: 50mmol Resolution First 12 hours: 5L IVF and 60mmol K Case 2a IVF 2L K: Nil IVF 1L K: Nil IVF 1L K: 30mmol First 12 hours: 4L IVF and 30mmol K Case 2b IVF: Nil K: Nil IVF: Nil K: Nil IVF 1L K: Nil First 12 hours: 1L IVF and Nil K
Case 2b: Summary Mild metabolic acidosis due to DKA Resolved with IV insulin alone (no IVF or K) Trigger: Viral illness + inadequate Sick Day Education Not appropriate for DKA protocol Excess IVF + K + replacement? Too rapid correction of glucose Withholding dialysis to minimize osmotic shifts may have been beneficial
DKA in Dialysis patients Uncommon Altered physiology
How uncommon? ICD10 Audit : 2006 2016 DKA codes (T1/T2DM) ESRD codes (dialysis, CKD) Manual review 10 patients, 11 episodes Approximately 1 case per year in HNE DKA Dialysis DKA Non-Dialysis p Presentations, n 11 (1%) 619 (99%) Patients, n 10 305 Presentations, n per patient 1.1 1.8 Age (mean, SD) 44 (10.2) 32.2 (14.3) p=0.01 Gender ratio (M:F, n, %) 6 : 5 (54 : 46) 256 : 363 (41 : 59) ns Mortality (n, %) 1/11 (9%) 12/619 (0.02%) p=0.09 LOS (median, IQR) 5 (3-9) 2 (1-4) p=0.01 Transferred from other facility 2 / 11 (18%) 85 / 619 (14%) ns
DKA in Dialysis patients Uncommon Longer insulin half-life Survivor bias Routine service contact Altered physiology Main difference is or lack of osmotic diuresis Minimal fluid loss Minimal potassium loss Insulin infusion is often the only treatment required.
DKA in Dialysis patients Uncommon Longer insulin half-life Survivor bias Routine service contact Altered physiology Main difference is or lack of osmotic diuresis Minimal fluid loss Minimal potassium loss Insulin infusion is often the only treatment required.
Tonicity = without urea Osmolality = with urea Rohrscheib, Adv Perit Dialy 2005
Serum Potassium mmol/l Serum K + at presentation DKA Non-DKA DKA Non-DKA Dialysis Non-Dialysis Tzamaloukas, Int Urol Neph 2011
Treatment with insulin alone Pooled analysis of observational studies of 130 patients with dialysis associated hyperglyceamia, treated with insulin alone (no fluids, no potassium). Study 18 includes 22 patients with DKA. Remainder have non-ketotic hyperglyceamia Strong correlation between magnitude of fall in potassium level and starting level of potassium in all studies. Tzamaloukas, Int Urol Neph 2011
Comments: DKA in Dialysis DKA in dialysis patients is uncommon About 1 per year in our area. First principles management is probably right DKA protocol not appropriate gives more fluid and K + than required Many patients may not require supplemental K + or fluids Insulin is the main treatment required. Unclear if a slower rate of infusion is optimum given tendency to significant hyperglycaemia Recommended rate of fall of glucose: 3-5mmol/hour
Case 3: Ms B 35. Female T1DM, diagnosed age 28 Levemir 13 units BD Novorapid 2-3 units / 15g CHO TDS HbA1c 8.5% Autoimmune hypothyroidism Social Lives alone. Independent Works in Pharmaceutical Industry Non smoker. Minimal alcohol.
Case 3: Presentation Self-presented to ED 0130 3 day history of nausea, abdominal pain Now developed thirst and polyuria Looks unwell Dry mucous membranes. T36. HR 100. BP 120/70. BGL 8.9mmol/L No septic focus. Taking canagliflozen (bought on internet) 1. Explain the biochemical abnormalities 2. What treatment does this patient need? ph 7.20 7.32-7.43 HCO 3 6 22-30 CO 2 21 41-50 Anion Gap 27 7-17 Β-OH Butyrate 6.1 <0.4 Lactate 0.9 <2 Na + 133 135-145 Glucose 9.6 <11 K + 4.3 3.5-5 Urea 8.4 4-11 Creatinine 71
Case 3: Presentation Euglycaemic diabetic ketoacidosis - Moderate severity - Clear ketosis Due to inadequate exogenous insulin - Pharmacological renal glucose wasting Insulin and glucose (and K + ) 1. Explain the biochemical abnormalities 2. What treatment does this patient need? ph 7.20 7.32-7.43 HCO 3 6 22-30 CO 2 21 41-50 Anion Gap 27 7-17 Β-OH Butyrate 6.1 <0.4 Lactate 0.9 <2 Na + 133 135-145 Glucose 9.6 <11 K + 4.3 3.5-5 Urea 8.4 4-11 Creatinine 71
Case 3: Presentation Euglycaemic diabetic ketoacidosis - Moderate severity - Clear ketosis Due to inadequate exogenous insulin - Pharmacological renal glucose wasting Insulin and glucose (and K + ) 1. Explain the biochemical abnormalities 2. What treatment does this patient need? ph 7.20 7.32-7.43 HCO 3 6 22-30 CO 2 21 41-50 Anion Gap 27 7-17 Β-OH Butyrate 6.1 <0.4 Lactate 0.9 <2 Na + 133 135-145 Glucose 9.6 <11 K + 4.3 3.5-5 Urea 8.4 4-11 Creatinine 71
Case 3: Resolution Time 0100 0200 0300 0500 0800 1100 Ref ph 7.20 7.16 7.18 7.21 7.22 7.32 7.32-7.43 HCO 3 6 8 10 11 12 16 22-30 CO 2 21 25 28 31 31 34 41-50 Anion Gap 27 7-17 Β-OH Butyrate 6.1 6.3 6.1 4.9 1.7 1.0 <0.4 Glucose 9.6 9 8 8 8 6 <11 K + 4.3 5 4.4 4.4 4.0 4.6 3.5-5 IV insulin 2 units / hr IV Saline 1000 500 500 IV Dextrose 125ml/hr IV K + 10 10 10
Case 3: Further history Current Pharmacotherapy Canagliflozen 100mg BD (internet pharmacy) Phentaramine 30mg daily Metformin 2000mg daily Self prescribed VLCD (<45g/day) No ketone monitoring at home Unwell for 2 days prior to presentation Vomiting, dehydration Treated with water as BGLs 9-10mmol/L, but no extra insulin Urinary ketones strongly positive!
Comments: SGLT2 associated DKA Euglycaemic DKA secondary to SGLT-2 inhibitors Many case reports in the literature Often a second hit required (SGLT2 probably reduces threshold for ketosis) - Low calorie diet further reduction of insulin requirements In T1DM Renal glucose wasting artificially lowers insulin requirements lipolysis and ketogenesis Early evidence emerging that SGLT2 may have a role in management of T1DM Patient education, safety monitoring are essential.
Early evidence for SGLT2 in T1DM HbA1c Weight Trials limited to ~100 pts and < 12 weeks Not TGA approved. Significant safety caveats not addressed Chen, Scientific Reports, 2017
SGLT2 in T2DM Empagliflozen (Jardiance) Dapagliflozen (Forxiga) Canagliflozen (Invokana) Independent of insulin action Dependent on GFR + glucose 0.5-0.7% reduction in HbA1c 2-3kg wt loss Modest antihypertensive effect 1 in 20 excess thrush / yr Osmotic diuresis (1 void/24 hrs) Second or third line agent as add on to metformin
What s all the fuss with Empa- Zinman, N Eng J Med 2015
Don t believe everything you re told The findings from this study need to be kept in perspective. The large benefit of empagliflozin, while impressive, was in a very high-risk population with established CVD at baseline. Moreover, the difference in glycemia between the treatment groups was minimal, suggesting that extra-glycemic effects of the drug were responsible for the CVD outcome. Whether the salutary cardiovascular effects in those with overt CVD are specific to empagliflozin, or represent a class effect of the SGLT2 inhibitors, will await publication of the canagliflozin and dapagliflozin cardiovascular trials in progress. In addition, it is unknown whether empagliflozin, or other SGLT2 inhibitors, will have similar CVD effects in the majority of persons with type 2 diabetes who do not have overt CVD. Anthony DeSantis, MD, Uptodate
In summary HNE DKA Protocol has been in use for 6 years Safe, effective protocol based care Appropriate for use in most circumstances Protocols do not replace need for thoughtful, individualised patient care Highlighted by cases of abnormal physiology (dialysis, pregnancy, pharmacotherapy)
Comments Protocols are part of 21 st Century medical care Senior clinical leadership in teams to model patient centered care through: Thoughtful adherence to protocols in most circumstances Cautious, considered and occasional protocol deviation Consult before you depart from standard of care. The DKA protocol has stood the test of time. Use it!