diabetic ketoacidosis dr jayesh vaghela
TRANSCRIPT
DIABETICKETOACIDOSIS (DKA)
&HYPEROSMOLAR HYPERGLYCEMIC
SYNDROME (HHS)
DR. JAYESH VAGHELA
KETONE BODIESSYNTHESIS
2
SPECTRUM OFDKA AND HYPEROSMOLAR COMA
Pure Ketoacidosis
Ketoacidosis-Hyperosmolar
Coma
PureHyperosmolar
Coma
Rapid OnsetMarked Insulin
Lack
Intermediate Slow OnsetMild Insulin Lack
DIABETICKETOACIDOSIS
INTRODUCTION
•Diabetic : Glucose >250 mg/dL
•Keto – :ketones produced
Blood concentration: 90mg/100ml
Urinary excretion: 5000mg/24 hr
•Acidosis :
Anion gap metabolic acidosis;
HCO3- : <15mEq/L,
pH : <7.30
[N: 70-110mg/dL]
[N : < 3mg/100 ml]
[N : 125mg/24 hr]
[N: 5-16 mEq/L]
[N: 22-26 mEq/L]
[N: 7.35-7.45]
• DKA - potentially life-threatening complication
• Medical emergency,
• Predominantly in those with type 1 diabetes ,It may be the first symptom of previously undiagnosed diabetes.
• can occur in patients with type 2 diabetes .
HISTORY
• The first full description of DKA : Julius Dreschfeld
• In 1886,described the main ketones, acetoacetate and -hydroxybutyrate, and βtheir chemical determination.
• DKA remained almost universally fatal until the discovery of insulin in the 1920s;
• 1930s, mortality had fallen to 29%
• 1950s : less than 10%
HISTORY CONTD.
• The entity of “ketosis-prone type 2 diabetes” was first fully described in 1987.
• It was initially thought to be a form of maturity onset diabetes of the young
• Then went through several other names, such as,
• "idiopathic type 1 diabetes",
• "Flatbush diabetes",
• "atypical diabetes“
• "type 1.5 diabetes"
CLASSIFICATION2006, American Diabetes Association (for adults)
Grade Blood pH S. Bicarbonate Status of patient
Mild 7.25 - 7.3015–18 mEq/L
( N: > 20) Patient is alert
Moderate 7.00–7.25 10–15 mEq/L Mild drowsiness may
be present
Severe < 7.00 < 10 mEq/L Stupor or coma may
occur
2004, European Society for Paediatric Endocrinology and the Lawson Wilkins Pediatric Endocrine Society (for children)
Grade Blood pH S. Bicarbonate
Mild 7.20 - 7.30 10–15 mEq/L
Moderate 7.1 – 7.2 5-10 mEq/L
Severe < 7.1 < 5 mEq/L
PRECIPITATING FACTORS
1. Inadequate insulin administration
2. Infections (Pneumonia, UTI, Gastroenteritis, Sepsis)
3. Infarction (Cerebral, myocardial, coronary, mesenteric, etc.)
4. Pregnancy
5. Use of medications: steroids (glucocorticoids), thiazide diuretics, calcium-channel blockers, propranolol, Cocaine
PATHOPHYSIOLOGY
↑ Glycogenolysis↑ Gluconeogenesis,
↑ Protein catabolism
↑ Hyperglycemia
Glucosuria
Osmotic diuresis
Dehydration
↓
↓
↓
↓
Diabetic ketoacidosis
Insulin deficiency
↑ Lipolysis
↑ Free fatty acids
↓
↓
↑ Ketone bodies
Hyperketonemia
↓
↓
Acidosis
CLINICAL
PRESENTATION
SYMPTOMS
• Nausea & vomiting
• Polyuria / ↑ Thirst
• Abdominal pain
• Shortness of breath
SIGNS
Dehydration
• Mild: Dry mouth
• Severe: Tachycardia, Low BP ( d/t ↓ circulatory volume)
Abdominal tenderness (may resemble acute pancreatitis / Acute Appendicitis)
• Tachypnoea, Kussmaul’s respiration, “Fruity” smell of breath, Respiratory distress
• Lethargy, cerebral edema & coma
DIAGNOSIS1. History and physical examination:
2. Laboratory investigations:
PARAMETER NORMAL VALUE VALUE in DKA
1. B. Glucose 70-110 mg/dL 250 -600 mg/dL
2. S. Bicarbonate 22-26 mEq/ L < 15 mEq/ L
3. Ketone bodies
• Plasma concentration < 3 mg/ 100 ml 90 mg/ 100 ml (++++)
• Urine excretion 125 mg/ 24 hr 5000 mg/ 24 hr(++++)
4. S. Osmolality 275-295 mosm/L 300-320 mosmol/L
5. Art. pH 7.35-7.45 6.8 - 7.3
6. Art. pCo2 35-45 mmHg 20-30 mmHg
PARAMETER NORMAL VALUE VALUE in DKA
7. S. Electrolytes
• K + 3.5 – 6.5mEq/ L N to ↑
• Na + 135 – 148 mEq/ L125-135 mEq /L
(100mg ↑ in glucose asso. with 1.6 mEq reduction in S. Na )
• Mg +2 1.5 -2.5 mg/dL N
• Phosphate 2.2 -4.8 mg/dL ↓
• Chloride 46-112 mEq/ L N
• Anion gap [ Na – (Cl + Hco3) ]
5-16 mEq/ L ↑
TREATMENT
1. Initial evaluation & admission to hospital
2. Dehydration (fluid therapy)
3. Hyperglycemia (insulin)
4. Electrolyte deficits (potassium , sodium, phosphate therapy)
5. Ketoacidosis ( insulin as well as bicarbonate therapy)
6. Other measures.
1.Initial evaluation
&Admission to
hospital
If vomiting Or altered mental status : insert nasogastric tube.
Intensive care is necessary for frequent monitoring, If pH is < 7.0 or pt is unconscious.
Assess patient:
History & Physical examination
Blood sugar.
S. Electrolytes
Acid base status
Renal function
CBC with differential count, ECG
TREATMENT Contd…
• Start I.V. Fluids 1 L, 0.9 % Normal saline / Hr (15-20ml/kg/hr)
• Confirm the Diagnosis :
• Blood Glucose : > 250 mg/dl
• Arterial pH : < 7.3
• S. Bicarbonate < 15 mEq/L
• ketonuria & ketonemia
2.Fluid Therapy
(Dehydration)THESE IS THE MAINSTAY OF THERAPY…
• Deficit : 3-5 L
• 2-3 L → Isotonic Saline ( 0.9 % NaCl) → over 1-3 hrs (Bolus) ( 10-15ml/ kg/ hr)
↓ followed by
• 150 – 300 ml/ hr → Hypotonic Saline ( O.45 % NaCl)
• Only when Haemodynamic stability & adequate Urine output are achieved
↓
• When Blood Glucose comes to 250-300 mg/dL
• 100-200 ml/ hr → ½ NS ( O.45 % NaCl) + 5 % Glucose
• Amount of i. v. fluids to be used: ~ 3L /m2/24 hr
Advantages of early rehydration:1. Dehydration :Restores circulatory volume
2. Hyperglycemia is treated
3. Hyperkalemia is reversed
Complications of fluid therapy:1. Excessive therapy may result in ARDS
2. Cerebral edema
3. Hyperchloremic acidosis
3.Insulin therapy
(Hyperglycaemia)
INSULIN TREATMENT 1. Type of insulin: Plain / Regular insulin
2. Route : Bolus I.V. → CLDII (Continuous low dose i.v. infusion)
3. Dose : 0.1 U /kg → I. V. Bolus immediately
↓
0.1U/kg/hr → CLDII (Conti. low dose i.v. inf.)
Mix to run @ 10ml/hr
(regular insulin equal to wt. in kg x 2.5, mixed in 250ml bag of saline)
Example: weight = 50kg
[50 x 2.5 = 125 units in 250ml = 5u/hr (i.e. 0.1 U/kg/hr)
INSULIN TREATMENT CONTD.
↓
Double the dose : if B. Glucose does not fall in 2 hrs
When decrease in B. Glucose level = 10% /hr : Adequate response
Hyperglycemia improves at a rate of 75-100 mg/dl/hr
DURATION OF INSULIN THERAPY
Until acidosis recovers&
Metabolism is normal
↓
Dose: 0.05-0.1U/Kg/hr
Intermediate or Long actingInsulin
+Short acting s.c. insulin
↓
As patient resumes eating
It is crucial to continueInsulin infusion
Until adequate insulin levelsAre achieved by s.c. injection
↓Even brief episode of
Insulin lack↓
DKA relapse
With insulin regimen, patient recovers within 36 – 48 hoursInitial S. K+ : < 3mEq/L, Don’t administer insulin until it is corrected to > 3mEq/L
• Role of insulin
Hyperglycemia: Insulin mediated glucose disposal
↓ Hepatic glucose release
Ketoacidosis: ↓ lipolysis
↓ hepatic Ketone Body formation
↑ Peripheral Ketone Body use
Hyperkalemia: Transport of K+ In to cell
4.Electrolyte deficit
(Na+, K+, PO4-)
POTASSIUM TREATMENT :
Deficit : 3-5 mEq / kg
During treatment with insulin & I.V. fluids, dangerous hypokalemia can occur
So K+ repletion is commenced as soon as,
• Adequate Urine output : >1ml /min
• Normal Serum Creatinine
• Normal ECG
• Normal Serum K+ level is achieved
B. SODIUM TREATMENT :
Initial s. sodium may be ‘low’ : Depletion secondary to urinary losses / vomiting
“Pseudohyponatremia” is often present
Corrected Na= Measured Na + 0.016(measured glucose - 100)If Na+ does not rise, true hyponatremia may be present (possibly increasing
cerebral edema risk) and should be treated
C. PHOSPHATE TREATMENT :
Any patient with phosphate concentration
< 1mg/ dL → should receive phosphate Therapy.
↓
5-10 mmol / hr Na+ Or K+ phosphate .
5.Bicarbonate
therapy
(Acidosis)
Bicarbonate therapy:
When SEVERE acidosis ( pH < 7 after initial hydration) : l/t cardio-respiratory compromise
pH : 6.9-7.0 → 50 mEq /L NaHCo3 in 200 ml sterile water with 10 mEq/L KCl over 1 hr.
pH : < 6.9 → 100mEq /L NaHCo3 in 400 ml sterile water with 20 mEq/L KCl over 2 hr
Until pH > 7.0.
OTHER MEASURES
Assess patient for Precipitating factors:
• Non compliance, Infection, Trauma, Infarction, Drugs history
• Initiate appropriate workup for that event like history, Culture, ECG etc
• Based on that treat the patient with antibiotics & supportive measures.
• Appropriate treatment ↓es the mortality of DKA to < 5%, That is mainly related to precipitating factors
Measurements:
• Capillary B. Glucose → every 1-2 hrly
• S. Electrolytes → every 4 hrly for first 24 hrs
• Monitor BP /Pulse / Respi./Mental status /Fluid intake & output → every 1-4 hrly
• Nursing care of patient about skin, mouth, position & bladder.
Remember, The Ideal Treatment For DKA Is Prevention
Educate the patient about,
• Symptoms of DKA,
• Its precipitating factors
• Management of diabetes during concurrent illness
• Frequent measurement of blood glucose.
• Measure Urinary Ketones when S. Glucose > 300mg/dl
• Drink fluids
• Continuous/Increase insulin
• Seek medical attention, If persistent Vomiting, uncontrolled hyperglycemia & dehydration
COMPLICATIONS
OF
DKA TREATMENT
1) Dehydration / shock
2) Hypokalemia (Cardiac arrhythmia) / hyperkalemia (Cardiac arrest)
3) Hypoglycemia
4) Aspiration pneumonia
5) Sepsis
6) ATN/ MI/ stroke
7) Insulin resistance (unremitting acidosis after 4-6hrs of treatment)
8) Cerebral edema
CEREBRAL OEDEMA
• Almost exclusively a condition of childhood.
• The pathophysiology is not completely understood
• Usually occurs between 4-12 hours from the start of treatment,
• but may be present at onset of DKA and can occur up to 24 hours later.
• Responsible for 50-60% of all diabetes-related deaths in children
Causes:
Excessive use of fluids
Large doses of insulin
Use of bicarbonate
Manifestations:
Headache - Alteration in level of consciousness
Bradycardia - Emesis
Diminished responsiveness to painful stimuli
Unequal or fixed, dilated pupils
TREATMENT:
• Mannitol 0.5-1 gm/kg IV over 15 minutes
• Reduce IV fluid rate to 70% maintenance
• Hypertonic saline ( 3% N.S.)
• Elevate Head end to 45o
• Consider intubation
• hyperventilation
• keep pCO2 > 22mmHg
HYPOGLYCEMIC REACTIONS(INSULIN SHOCK)
• Is a life threatening complication: blood Glucose < 50 mg/dl
Symptoms and signs : pallor, sweating, apprehension, trembling, tachycardia, hunger, drowsiness, mental confusion, seizures and coma
Management :
• If conscious: - Carbohydrate - containing snack or drink
• If patient is unconscious: - Glucagon 0.5 mg (S.C. or I.M.) or
Glucose solution 20-50 ml I.V. infusion
HYPEROSMOLAR HYPERGLYCEMIC
SYNDROME(HHS)
Synonym:
• Hyperosmolar hyperglycemic non-ketotic coma (HHNKC)
• Mainly seen in elder individuals with Type 2 DM.
• Is characterized by profound hyperglycemia & dehydration.
• Mortality
• Variable 10-50%
• Most often due to the precipitating illness
Difference Between DKA & HHS
Parameters DKA HHS
Type of DM Mc in Type 1 DM Mc in Type 2 DM
Precipitating factor
Mc : Inadequate or omitted insulinMC :Serious concurrent illness + debilitating condition that compromises water intake
Symptoms Abdominal pain, Kussmaul’s respi. Absent
Signs
Dry mouth,hypotension, tachycardiaAbdominal tenderness,Fruity smell of breath
Profound dehydration ↓Tachycardia, hypotension & altered mental status
Dehydration(loss of water)
3 - 5 L 8 - 10 L
Parameters Normal value DKA HHS
Blood Glucose 70-110 mg/dL 250 - 600 mg/dL 600 - 1200 mg/dL
S. Bicarbonate 22-26 mEq/ L < 15 mEq/ LN to slight ↓Mild or no acidosis
Ketone bodies
ABSENT / Mild ketosis
• Plasma conc. < 3 mg/ 100 ml 90 mg/ 100 ml (++++)
• Urine excretion
125 mg/ 24 hr 5000 mg/ 24 hr (++++)
S. Osmolality 275-295 mosmol/L 300-320 mosmol/L 330– 380 mosmol/L
Arterial pH 7.35-7.45 < 7.3 > 7.3
Arterial pCo2 35-45 mmHg 20-30 mmHg N
BUN 2.8 -7.9mmol/L 11.4 (mean) 21.8 (mean)
Parameter Normal Value Value In DKA HHS
K + 3.5 – 6.5 mEq/ L N to ↑ (4.5) N (3.9)
Na + 135 – 148 mEq/ L 125-135 mEq /L
(100mg ↑ in glucose asso. with 1.6 mEq ↓ in S. Na+ )
135-145 mEq /L
Mg +2 1.5 -2.5 mg/dL N N
Phosphate 2.2 -4.8 mg/dL ↓ N
Chloride 46-112 mEq/ L N N
Anion gap 5-16 mEq/ L ↑ N to ↑
TREATMENT
Initial Evaluation: ABCs; Exam; Labs; Causes
Close Monitoring
Fluid Replacement : vigorous
Insulin Therapy
Electrolyte Replacement
Patients are prone to develop thrombosis : prophylactic heparin
REFERENCES
• Standaert DG & Roberson E. Endocrine Pancreas and Pharmacotherapy of Diabetes Mellitus and Hypoglycemia.In : Bruton LL, editor. Goodman & Gilman’s – The Pharmacological basis of therapeutics. 12th edition. New York : Mc Graw Hill Publication; 2011. p. 609- 28.
• Tripathi KD. Essentials of Medical Pharmacology. 6th ed. Jaypee brothers medical publishers; New Delhi 2009. p. 425-34.
• Sharma HL & Sharma KK. Principles of Pharmacology. 2nd ed. Paras publication; New Delhi 2012. p. 532-42.
• Olanow CW, Schapira AH. Diabetes Mellitus. In: LongoDL, editor :Harrisons’s principles of internal medicine.18th edition. New york:Mc Grew hill;2012. P.3317-35.