Hypoglycaemia & HHS final

In the Name of God, Most Gracious, Most Merciful: 

In the Name of God, Most Gracious, Most Merciful

DIABETIC EMERGENCIES - HYPOGLYCEMIA - HYPEROSMOLAR HYPERGLYCEMIC STATE: 

DIABETIC EMERGENCIES - HYPOGLYCEMIA - HYPEROSMOLAR HYPERGLYCEMIC STATE Dr. Mohammed Sadiq Azam Dr. D. Sudeepta Rao II yr. Postgraduates: MD (Gen Med) Deccan College of Medical Sciences

HYPOGLYCEMIA: 

HYPOGLYCEMIA - Dr. Mohammed Sadiq Azam

HYPOGLYCEMIA - OUTLINE: 

HYPOGLYCEMIA - OUTLINE Definition Glucose Homeostasis Clinical Features Mechanisms Diagnosis Clinical Classification Hypoglycemia in DM Impact & Frequency Risk factors Hypoglycemia asso. autonomic failure

HYPOGLYCEMIA - OUTLINE: 

HYPOGLYCEMIA - OUTLINE Drugs asso. with hypoglycemia Hyperinsulinemic hypoglycemia – D/D Endogenous hyperinsulinemia – D/D, and, a word on insulinoma Hypoglycemia in Infancy & Childhood Diagnostic approach to an adult with hypoglycemia Management – Emergency management & prevention

DEFINITION: 

DEFINITION “Glucose levels <55mg/dl (<3.0mmol/l) with symptoms that are relieved promptly after the glucose level is raised document hypoglycemia.” Hypoglycemia is most convincingly documented by, Whipple’s triad, i.e : Symptoms consistent with hypoglycemia Low plasma glucose concentration (measured with a precise method) Relief of symptoms when plasma glucose concentration is increased.

GLUCOSE HOMEOSTASIS – Key roles: 

GLUCOSE HOMEOSTASIS – Key roles RESPONSE GLYCEMIC THRESHOLD (mg/dl) PHYSIOLOGIC EFFECTS ROLE IN GLUCOSE REGULATION ↓ Insulin 80-85 ↑ Ra ( ↓ Rd) 1 st line of defense (Primary glucose regulatory factor) ↑ Glucagon 65-70 ↑ Ra 2 nd line of defense (Primary glucose counterreg. factor) ↑ Epinephrine 65-70 ↑ Ra ↓ Rc 3 rd line of defense (critical when glucagon ↓ ) ↑ Cortisol & GH 65-70 ↑ Ra ↓ Rc Defense against prolonged hypoglycemia, not critical Symptoms 50-55 Recognition of hypoglycemia Prompt behavioral defense(food ingestion) ↓ Cognition < 50 ----- Compromises behavioral defense against hypoglycemia Ra = Rate of glucose appearance, Rd = Rate of glu disappearance, Rc = Rate of glu clearance

PowerPoint Presentation: 

PANCREAS BRAIN ADR CORTEX KIDNEY MUSCLE FAT LIVER PITUITARY ↓ ARTERIAL GLUCOSE ACTH ↑GH ↑ CORTISOL ADR MEDULLA Post Gn SymN ↑ SYM ADR OUTFLOW ↑ E ↑ NE ↑ Ach SYMPTOMS INGESTION ↑ ARTERIAL GLUCOSE ↓ GLU CLEARANCE ↓ INSULIN ↑ GLUCAGON ↑ GLUCOSE PRODUCTION ↑ GLUCONEOGENIC PRECURSORS

CLINICAL FEATURES - Symptoms: 

CLINICAL FEATURES - Symptoms Neurogenic symptoms: Sweaty Hungry Tingly Shaky (Tremulous) Poundy (Palpitations) Nervy (Anxious/Nervous) These symptoms are the result of the perception of physiologic changes caused by the ANS discharge ( Adr & Chol ) triggered by hypoglycemia.

CLINICAL FEATURES - Symptoms: 

CLINICAL FEATURES - Symptoms Neuroglycopenic symptoms: Warm Weak Confused/Difficulty thinking Tired/Drowsy Faint Dizzy Difficulty speaking Blurred vision These symptoms are the result of direct CNS glucose deprivation .

CLINICAL FEATURES - Signs: 

CLINICAL FEATURES - Signs Pallor Diaphoresis ↑ PR ↑ BP TIA occasionally (Permanent damage is rare) “The magnitude of the responses to hypoglycemia is an inverse function of the nadir plasma glucose concentration rather than the rate of decrease in plasma glucose.” (Ref: William’s T. of Endo 10/e)

MECHANISMS OF HYPOGLYCEMIA: 

MECHANISMS OF HYPOGLYCEMIA Hypoglycemia implies that the rate of glucose efflux from circulation > rate of glucose influx into circulation. ↑ Efflux ↓ Influx ↑ U tilisation ↑ Losses Exercise Pregnancy Sepsis Pregnancy Renal Glycosuria ↓ Endogenous glucose production in the absence of exogenous glucose delivery – Most Common cause

MECHANISMS OF HYPOGLYCEMIA: 

MECHANISMS OF HYPOGLYCEMIA Defects causing Hypoglycemia ↑ Secretion of Insulin OR ↓ Secretion of glucose counter regulatory hormones Failure to mobilize or utilize gluconeogenic substrates Primary OR May result from hepatic disease REGULATORY ENZYMATIC SUBSTRATE

DIAGNOSIS: 

DIAGNOSIS Whipple’s triad Venous plasma glucose after an overnight fast: > 70mg/dl (>3.9 mmol /) : Normal 50 - 70 mg/dl (2.8-3.9 mmol /l) : s/o Hypoglycemia < 50 mg/dl (<2.8 mmol /l) : => Postabsorptive hypoglycemia P ostprandial (=Reactive) hypoglycemia: Diagnosis requires documentation of Whipple’s triad after a mixed meal (low venous plasma concentration post oral glucose load is not sufficient for diagnosis). (Ref: William’s T. of Endo 10/e, Harrison’s Principles of Int Med 17/e, 339:2308)

CLINICAL CLASSIFICATION: 

CLINICAL CLASSIFICATION Postabsorptive (=Fasting) Hypoglycemia Postprandial (=Reactive) Hypoglycemia Significance: Reproducible hypoglycemia in the postabsorptive state, implies the presence of disease and requires diagnostic explanation and treatment. It may become apparent during the latter part of any interdigestive period (NOT necessarily in the fasting state) esp. post-exercise. Postprandial (=reactive) hypoglycemia does not usually imply a serious underlying disorder.

CLINICAL CLASSIFICATION: 

CLINICAL CLASSIFICATION I) POSTABSORPTIVE (=FASTING) HYPOGLYCEMIA: DRUGS: Esp. Insulin, SU, alcohol Pentamidine , quinine Rarely salicylates , sulphonamides Others CRITICAL ILLNESSES: Hepatic failure Cardiac failure Renal failure Sepsis Inanition contd …

CLINICAL CLASSIFICATION: 

CLINICAL CLASSIFICATION I) POSTABSORPTIVE (=FASTING) HYPOGLYCEMIA: HORMONAL DEFICIENCIES: Cortisol or GH or both Glucagon or Epinephrine NON β CELL TUMORS ENDOGENOUS HYPERINSULINISM Pancreatic β cell disorders β cell secretagogue ( eg : SU) Autoimmune hypoglycemia (IA, IRA, ? β cell Ab ) ? Ectopic insulin secretion HYPOGLYCEMIA OF INFANCY & CHILDHOOD

CLINICAL CLASSIFICATION: 

CLINICAL CLASSIFICATION II) POSTPRANDIAL (=REACTIVE) HYPOGLYCEMIA: Congenital deficiencies of enzymes of carbohydrate metabolism: Heriditary Fructose intolerance Galactosemia Alimentary Glycosuria : Post gastrectomy Idiopathic (=Functional) postprandial hypoglycemia

HYPOGLYCEMIA IN DM: 

HYPOGLYCEMIA IN DM IMPACT & FREQUENCY: Limiting factor in the glycemic management of DM Causes recurrent morbidity in MOST cases of T1DM and MANY with T2DM and is sometimes fatal. Precludes maintenance of euglycemia over a lifetime of diabetes and thus full realization of the benefits of glycemic control. Causes a vicious cycle of recurrent hypoglycemia by producing hypoglycemia associated autonomic failure – the clinical syndromes of defective glucose counterregulation and of hypoglycemia unawareness.

HYPOGLYCEMIA IN DM – The Burden: 

HYPOGLYCEMIA IN DM – The Burden T1DM- Fact of life Average of 2 episodes of symptomatic hypoglycemia per week and at least one episode of sever, at least temporarily disabling hypoglycemia each year. Estimated 2-4% of people with T1DM die due to hypoglycemia. T2DM- Less frequent than T1DM. Metformin , TZDs, AGIs, GLP-1 analogues, DDP-4 inhibitors should not cause hypoglycemia, however the risk increases when combined with insulin/SU. As insulin resistance increases and patients require insulin the risk of hypoglycemia in T2DM approaches that in T1DM.

RISK FACTORS – THE PREMISE: 

RISK FACTORS – THE PREMISE “The conventional risk factors for hypoglycemia in diabetes are based on the premise that relative or absolute insulin excess is the sole determinant of risk.” - Harrison’s Principles of Int Med 17/e, 339:2306 “Iatrogenic hypoglycemia in T1DM is the result of the interplay of therapeutic insulin excess and compromised glucose counterregulation. ” -William’s T. of Endo 10/e

CONVENTIONAL RISK FACTORS: 

CONVENTIONAL RISK FACTORS Absolute/Relative Insulin Excess occurs when: Insulin (or secretogogue ) doses are excessive, ill-timed or of the wrong type The influx of exogenous glucose is reduced (e.g., overnight fast or following missed meals/snacks) Insulin-independent glucose utilization is increased (e.g., exercise) Sensitivity to insulin is increased (e.g., improved glycemic control, in the middle of the night, late of the exercise, or with increased fitness or weight loss) Endogenous glucose production is reduced (e.g., alcohol ingestion) Insulin clearance is reduced (e.g., renal failure)

COMPROMISED GLUCOSE COUNTERREGULATION: 

COMPROMISED GLUCOSE COUNTERREGULATION Absolute insulin deficiency (C-peptide negativity): β cell destruction: No decrease insulin in response to fall in glucose Unknown: No increase glucagon in response to fall in glucose H/O severe hypoglycemia/aggressive treatment per se: Lower glucose goals, low HbA1c Attenuated autonomic activation & symptoms in response to fall in glucose.

HYPOGLYCEMIA ASSOCIATED AUTONOMIC FAILURE: 

HYPOGLYCEMIA ASSOCIATED AUTONOMIC FAILURE Defective glucose counterregulation Hypoglycemia unawareness Defective glucose counterregulation compromises physiologic defense, and hypoglycemia unawareness compromises behavioral defense.

DEFECTIVE GLUCOSE COUNTERREGULATION: 

DEFECTIVE GLUCOSE COUNTERREGULATION Fa i lure of ALL 3 lines of defense . Result of antecedent iatrogenic hypoglycemia Glycemic threshold is shifted to lower plasma glucose concentrations. 25x or more risk of sever iatrogenic hypoglycemia during aggressive glycemic therapy . ↓ Glucose No ↓ Insulin No ↑ Glucagon No ↑ Epinephrine ↑ Glucose

HYPOGLYCEMIA UNAWARENESS: 

HYPOGLYCEMIA UNAWARENESS Caused by the attenuated sympathoadrenal response (largely the ↓ sympathetic neural response) to hypoglycemia. Characterised by the loss of warning adrenergic & cholinergic symptoms that previously allowed the patient to recognise developing hypoglycemia ad therefore abort the episode by ingesting carbohydrates. 6x increased risk of severe iatrogenic hypoglycemia during aggressive treatment .

HYPOGLYCEMIA ASSOCIATED AUTONOMIC FAILURE: 

HYPOGLYCEMIA ASSOCIATED AUTONOMIC FAILURE Insulin deficient diabetes (Imperfect insulin replacement) (No ↓insulin, No ↑ Glucagon) Antecedent hypoglycemia Reduced sympathoadrenal responses to hypoglycemia Reduced sympathetic neural responses Hypoglycemia unawareness Defective glucose counterregulation Reduced epinephrine responses Recurrent hypoglycemia Sleep Antecedent exercise

ADDITIONAL RISK FACTORS – T1DM: 

ADDITIONAL RISK FACTORS – T1DM Insulin deficiency that indicates that insulin levels will not decrease and glucagon levels will not increase as plasma glucose falls A h/o severe hypoglycemia or of hypoglycemia unawareness , implying recent antecedent hypoglycemia, that indicates that the sympathoadrenal response will be attenuated; and Lower HbA1c levels or lower glycemic goals that, all other factors being equal, increase the probability of recent antecedent hypoglycemia.

HYPOGLYCEMIA IN T2DM: 

HYPOGLYCEMIA IN T2DM THERAPY N HBA1C % ANY HYPO % MAJOR HYPO Diet 379 8.0 3.0 0.2 Sulphonyl urea 922 7.1 45.0 3.3 Insulin 689 7.1 76.0 11.2 Diet 297 8.2 2.8 0.4 Metformin 251 7.4 17.6 2.4 Ref: UKPDS, Diabetes 1995-44-1249-1258

DRUGS CAUSING HYPOGLYCEMIA: 

DRUGS CAUSING HYPOGLYCEMIA ESTABLISHED DRUGS: DISORDER DRUG DM Insulin, SU, other secretogogues , metformin , alcohol Infection Pentamidine , Quinine, Sulphonamides Arrhythmias Quinidine , dispyramide , cibenzoline Pain Acetylsalicylic acid

DRUGS CAUSING HYPOGLYCEMIA: 

DRUGS CAUSING HYPOGLYCEMIA PUTATIVE DRUGS: Fluroquinolones esp. Gatifloxacin Acetaminophen ACEI, BB ( nonsel > sel ), Frusemide MAOI, Haloperidol, CPZ, Fluoxetine Diphenhydramine , Clofibrate , P henytoin , Pencillamine Enflurane , Halothane, Ranitidine, Colchicine

HYPERINSULINEMIC HYPOGLYCEMIA – D/D: 

HYPERINSULINEMIC HYPOGLYCEMIA – D/D INSULIN C-PEPTIDE PROINSULIN SU INSULIN ANTIBODY DIAGNOSIS ↑ ↓ ↓ - - Exogenous insulin ↑ ↑ ↑ - - Insulinoma, Congenital hyperinsulinism ↑ ↑ ↑ + - Suphonylurea ↑ ↑ (Free ↓) ↑ (Free ↓) - + Insulin autoimmune ↑ +/- ↓ ↓ - - Insulin Receptor autoimmune (Insulin receptor Antibody +)

ENDOGENOUS HYPERINSULINEMIA: 

ENDOGENOUS HYPERINSULINEMIA Hypoglycemia related to endogenous hyperinsulinemia can be caused by- A primary pancreatic islet ( β ) cell disorder , typically a β cell tumour (insulinoma), sometimes multiple insulinomas , or, esp. in infants/young children, a functional β cell disorder with β cell hyperplasia or without an anatomic correlate. A β cell secretogogue , often a SU, theoritically a β cell stimulating antibody. An antibody to insulin Ectopic insulin secretion (rare).

ENDOGENOUS HYPERINSULINEMIA: 

ENDOGENOUS HYPERINSULINEMIA Fundamental pathophysiologic feature of endogenous hyperinsulinemia caused due to a primary β cell disorder or an insulin secretogogue is failure of insulin secretion to fall to very low levels during hypoglycemia . Critical diagnostic findings: Plasma insulin ≥3 uU /ml Plasma C-Peptide concentration ≥ 0.6 ng /ml Plasma proinsulin concentration ≥ 5.0 pmol /l, w hen the plasma glucose concentration is < 55 mg/dl with symptoms of hypoglycemia.

INSULINOMA: 

INSULINOMA Uncommon, 1/250,000; > 90% benign, treatable cause of potentially fatal hypoglycemia. Median age of presentation – 50 yrs (sporadic cases), third decade in MEN 1. Symptoms: Various combinations of diplopia , blurred vision, sweating, palpitations or weakness: 85% Confusion or abnormal behaviour : 80% Unconsciousness or amnesia: 53% Grand mal seizures: 12%

HYPOGLYCEMIA IN INFANCY/CHILDHOOD: 

HYPOGLYCEMIA IN INFANCY/CHILDHOOD Transient Intolerance of fasting: Preterm/ SGA infants. Hypopitutrism , adrenal hypoplasia , congenital adrenal hyperplasia Ketotic hypoglycemia of childhood. Hyperinsulinism : IDM Maternal drugs (SU,B2, adr . Agonist) Congenital hyperinsulinism , insulinoma Misc – Rh incompatibility, Beckwith Wiedemann syndrome, exchange transfusion.

HYPOGLYCEMIA IN INFANCY/CHILDHOOD: 

Enzyme defects: CARBOHYDRATE METABOLISM : Glycogen storage disease Types I / II/ VI Glycogen synthase deficiency Fructose 1,6 bis phosphatase deficiency Fructose 1-phosphate – aldolase deficiency Gal 1-phosphate – uridyl transferase deficiency HYPOGLYCEMIA IN INFANCY/CHILDHOOD

HYPOGLYCEMIA IN INFANCY/CHILDHOOD: 

Enzyme defects: PROTEIN METABOLISM : Branched chain α ketoacid dehydrogenase complex deficiency FAT METABOLISM : FA oxidation defects induding d eficiencies in the carnitine cycle β – oxidation s piral defects ETC defects Ketogenesis sequence defects HYPOGLYCEMIA IN INFANCY/CHILDHOOD

NEONATAL HYPOGLYCEMIA: 

NEONATAL HYPOGLYCEMIA Diagnostic Criteria ( Cornblath et al): < 2.5 mmol /l (<45mg/dl) in infants with clinical manifestations compatible with hypoglycemia, and, <2.0 mmol / l (<30mg/dl) in infants at risk for hypoglycemia Now outdated, current guidelines suggest higher cutoff values around 50 mg/dl to prevent neonatal mortality & morbidity.

DIAGNOSTIC APPROACH: 

DIAGNOSTIC APPROACH

DIAGNOSTIC APPROACH - ALGORITHM: 

DIAGNOSTIC APPROACH - ALGORITHM Suspected/Documented Hypoglycemia Diabetes No diabetes Treated with: Insulin Sulphonylurea Other secretogogue Adjust regimen Document improvement and monitor Clinical clues Drugs Organ failure Sepsis Hormone deficiencies Non- β -cell tumor Previous gastric Sx Provide adequate glucose, treat underlying cause Apparently healthy

PowerPoint Presentation: 

Apparently healthy Suspected/Documented Hypoglycemia No diabetes Fasting glucose < 55 mg/dl ≥ 55 mg/dl History Strong Extended fast G lucose ↑ Insulin, Whipple’s triad < 55 mg/dl ↑ C-peptide Insulinoma Autoimmune SU Likely Factitious Weak ≥ 55 mg/dl Mixed meal Exogenous insulin Whipple’s triad Reactive hypoglycemia Hypoglycemia excluded ↓ C-peptide + --

TREATMENT: 

TREATMENT Oral treatment with glucose tablets or glucose containing fluids, candy or food is appropriate if the patient is able & willing to take these. Initial dose = 20 g of glucose Unable to take oral foods  parenteral therapy IV glucose 25 g bolus followed by infusion guided by serial plasma glucose measurements. Inj.Glucagon 0.1 mg sc/ im can be used esp in T1DM. (it has no role in alcohol induced hypoglycemia) Eat ASAP  restore glycogen stores.

PREVENTION: 

PREVENTION Identifying & addressing the cause Encouraging SMBG by patient Education & empowerment of patient Flexible insulin or OAD regimens Rational, individual glycemic goals Ongoing professional guidance & support Integrated approach between patient, family & health care professionals

HYPEROSMOLAR HYPERGLYCEMIC STATE: 

HYPEROSMOLAR HYPERGLYCEMIC STATE - Dr. D. Sudeepta Rao

Hyperosmolar Hyperglycemic State: 

Hyperosmolar Hyperglycemic State Dr Sudeepta Rao , PG 2 nd yr – Gen Med DCMS

Introduction: 

Introduction Hyperosmolar hyperglycemic state (HHS) and diabetic ketoacidosis (DKA) represent two distinct metabolic derangements manifested by insulin deficiency and severe hyperglycemia DKA is defined as the presence of all three of the following: (i) hyperglycemia (glucose >250 mg/ dL ), (ii) ketosis, and (iii) acidemia (pH <7.3) . HHS is characterized by severe hyperglycemia and hyperosmolarity . HHS and DKA are not mutually exclusive but rather two conditions that both result from some degree of insulin deficiency. They can and often do occur simultaneously

Incidence of DKA 1980-2003 : 

Incidence of DKA 1980-2003

Mortality rate of DKA 1980-2001 : 

Mortality rate of DKA 1980-2001

Introduction: 

Introduction Age adjusted mortality rates in the U.S. have dropped by 22% between 1980 and 2001 Contrary to DKA mortality, the mortality rate of HHS has remained high, ~ 15%, compared to less than 5% in patients with DKA Severe dehydration, older age, and the presence of comorbid conditions in patients with HHS, account for the higher mortality in these patients .

Definitions: 

Definitions DKA consists of the biochemical triad of hyperglycemia , ketonemia and metabolic high anion gap acidosis The term “hyperglycemic hyperosmolar nonketotic coma” has been replaced with the term “ hyperglycemic hyperosmolar state ” (HHS) 1)the hyperglycemic hyperosmolar state may consist of moderate to variable degrees of clinical ketosis detected by nitroprusside method and 2) alterations in consciousness may often be present without coma .

Pathophysiology : 

Pathophysiology The underlying defects in DKA and HHS are reduced net effective action of circulating insulin as a result of decreased insulin secretion (DKA) or ineffective action of insulin in HHS elevated levels of counterregulatory hormones: glucagon, catecholamines , cortisol, and growth hormone, resulting in increased hepatic glucose production and impaired glucose utilization in peripheral tissues dehydration and electrolytes abnormalities mainly due to osmotic diuresis caused by glycosuria If insulin deficiency is severe enough, ketosis and ultimately acidosis develop .

Pathophysiology: 

Pathophysiology In HHS: there is enough insulin to prevent lipolysis and ketogenesis but not adequate to cause glucose utilization (as it takes 1/10 as much insulin to suppress lipolysis as it does to stimulate glucose utilization) possible smaller increases in counterregulatory hormones

Hyperglycemia: 

Hyperglycemia

Dehydration & Hyperosmolarity:: 

Dehydration & Hyperosmolarity : Hyperglycemia Osmotic Diuresis Dehydration Hyper Osmolarity Glycosuria Increased GFR Hypovolemia Decreased GFR & Renal Glucose Loss Hyperglycemia

Ketogenesis and Acidosis:: 

Ketogenesis and Acidosis:

Precipitating Causes:: 

Precipitating Causes:

History and Physical Examination:: 

History and Physical Examination: DKA usually evolves over a shorter period (usually less than 24 hours) than HHS, which tends to evolve over a few days. The common clinical pictures in DKA and HHS due to hyperglycemia include polyuria, polyphagia, polydipsia, weight loss, weakness and physical signs of dehydration such as dry buccal mucosa, sunken eye balls, poor skin turgor, tachycardia, hypotension and shock in severe cases. Kussmaul respiration, acetone breath, nausea, vomiting and abdominal pain may also occur primarily in DKA. Mental status in DKA may vary from full alertness to profound lethargy or coma but less frequent than HHS.

Initial Evaluation of the Patient:: 

Initial Evaluation of the Patient:

Assessment of the degree of dehydration: 

Assessment of the degree of dehydration Decreased tissue turgor suggests 5% dehydration. An orthostatic change in pulse alone suggests that there has been loss of approximately 10% of extracellular fluid volume (~2 L), orthostatic change in pulse and blood pressure (>15/10 mm Hg) suggests a 15% to 20% fluid deficit (3 to 4 L). Supine hypotension , when present, suggests either severe dehydration and a decrease in extracellular fluid volume of more than 20% or underlying sepsis. Assessment of degree of dehydration may be difficult in the elderly and those with underlying autonomic neuropathy, who may have orthostatic hypotension at baseline.

Relationship between serum osmolality and level of consciousness:: 

Relationship between serum osmolality and level of consciousness:

Admission Clinical And Biochemical Profile And Response To Therapy Of Comatose Vs. Non comatose Patients:: 

Admission Clinical And Biochemical Profile And Response To Therapy Of Comatose Vs. Non comatose Patients:

Laboratory Evaluation:: 

Laboratory Evaluation: * Blood urea nitrogen Serum chloride Carbon dioxide, also known as CO2 Creatinine Blood glucose Serum potassium Serum sodium *

Admission biochemical data in patients with HHS and DKA: 

Admission biochemical data in patients with HHS and DKA

Serum Sodium: 

Serum Sodium The serum sodium level may be low or normal. It may even be elevated in patients who are severely dehydrated even though total body sodium is depleted. True sodium concentration ( millimolar )can be obtained by multiplying excess glucose above 100 mg/dl by 1.6 /100 * . If the corrected sodium level is extremely low , hypertriglyceridemia (secondary to uncontrolled diabetes ) should be suspected. *

Serum Potassium: 

Serum Potassium Serum potassium levels at presentation may be high, normal, or low even though total body potassium may be depleted. Unless the initial serum potassium is elevated above 5.5 mEq /L or the patient is in acute renal failure or oliguric , potassium replacement is required when treatment is initiated

Laboratory Evaluation(contd): 

Laboratory Evaluation( contd ) level of consciousness correlates more closely with serum osmolality than with pH. Coma in an individual whose serum osmolality is less than 320 mOsm /kg warrants further evaluation for other causes of the coma . Leukocytosis is a common finding in patients with DKA or HHS, but leukocytosis greater than 25,000 / μL suggests ongoing infection.

Pitfalls of Laboratory Tests : 

Pitfalls of Laboratory Tests elevation of serum creatinine , either as a result of dehydration or interference from ketone bodies if a colorimetric method is used. Most of the laboratory tests for ketone bodies use the nitroprusside method, which detects acetoacetate, but not β hydroxybutyrate (BOHB ) . Serum ketones may be negative in some situations, such as alcoholic ketoacidosis or DKA associated with hypoxia . Under “normal” conditions, the ratio of β- hydroxybutyrate to acetoacetate is 3:1. This increases to 8:1 in alcoholic ketoacidosis or DKA associated with severe hypoxia drugs that have sulfhydryl groups can interact with the reagent in the nitroprusside reaction, giving a false positive result. Particularly important in this regard is captopril , an angiotensin converting enzyme inhibitor prescribed for the treatment of hypertension and diabetic nephropathy.

Treatment: 

Treatment The goals of therapy in patients with DKA and HHS include Improvement of circulatory volume and tissue perfusion, Gradual reduction of serum glucose and plasma osmolarity , C orrection of electrolyte imbalance, and in DKA steady resolution of ketosis, Identification and prompt treatment of co-morbid precipitating causes

Fluid Therapy : 

Fluid Therapy DKA and HHS are volume-depleted states with water deficit of approximately 6 L in DKA and 9 L in HHS The initial fluid of choice is isotonic saline , which we recommend to be infused at the rate of 15–20 ml /kg body weight per hour or 1–1.5 L during the first hour. The choice of fluid for continued repletion depends on the hydration status, serum electrolyte levels, and urinary output. In patients who are hypernatremic or eunatremic , 0.45% NaCl infused at 4–14 ml/kg/hour is appropriate and in patients with hyponatremia 0.9% NaCl at a similar rate is preferred .

Fluid Therapy(Contd): 

Fluid Therapy( Contd ) The goal is to replace half of the estimated water deficit over a period of 12- 24 hours. In patients with hypotension, aggressive fluid therapy with isotonic saline should continue until blood pressure is stabilized. The administration of insulin without fluid replacement in such patients may further aggravate hypotension. Patients with DKA and HHS require calories for proper metabolism of ketone bodies.

Fluid Therapy(Contd): 

Fluid Therapy( Contd ) Therefore in DKA, as soon as blood glucose falls below 200 mg/dl, the sodium chloride solution should be replaced with 5% glucose containing saline solution with a reduced rate of insulin administration until acidosis and ketosis are controlled while avoiding too rapid correction of hyperglycemia (which may be associated with cerebral edema especially in children) and also inhibiting hypoglycemia. In HHS, the use of D5 ½ NS should start when blood glucose reaches 300 mg/dl, because overzealous replacement with hypotonic fluids has been associated with the development of cerebral edema

Insulin Therapy: 

Insulin Therapy starting with an intravenous loading dose of 0.15 U/kg body weight (usually 10 U in adults) followed by a continuous infusion of insulin at a rate of 0.1 U/kg per hour (usually 5 to 7 U per hour in adults) If the patient is in shock or the initial serum potassium level is less than 3.3 mEq /L, resuscitation with intravenous fluids or potassium replacement or both is instituted before commencing the insulin infusion An insulin infusion of 5 to 7 U per hour should lower serum glucose concentrations by 50 to 75 mg/ dL per hour

Insulin Therapy : 

Insulin Therapy The insulin infusion rate should be continually reassessed and increased if the rate of decrease in glucose is less than 50 mg/ dL per hour, providing that other causes for the lack of response to therapy have been excluded. The rate of insulin should be adjusted to maintain blood glucose between 150-200 mg/dl in DKA and 250-300 mg/dl for HHS until DKA is resolved or mental obtundation and hyperosmolar state are corrected in HHS

Potassium Therapy : 

Potassium Therapy

Ongoing Monitoring : 

Ongoing Monitoring

THANK YOU: 

THANK YOU