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1 Acute Complications of Diabetes Diabetic Ketoacidosis 2 Introduction 3 DKA is an acute life threatening complication of DM ¼ of hospital admissions for DM Occurs predominantly in type I though may occur in II Incidence of DKA in diabetics 15 per 1000 patients 20-30% of cases occur in new-onset diabetes Mortality less than 5% Mortality higher in elderly due to underlying renal disease or coexisting infection Definition 4 Exact definition is variable Most consistent is: Blood glucose level greater than 250 mg/dL Bicarbonate less than 15 mEq/L Arterial pH less than 7.3 Moderate ketonemia Pathophysiology 5 Body’s response to cellular starvation Brought on by relative insulin deficiency and counter regulatory or catabolic hormone excess Insulin is responsible for metabolism and storage of carbohydrates, fat and protein Lack of insulin and excess counter regulatory hormones (glucagon, catecholamines, cortisol and growth hormone) results in: Hyperglycemia (due to excess production and underutilization of glucose) Osmotic diuresis Prerenal azotemia Ketone formation Wide anion-gap metabolic acidosis Clinical manifestations related to hyperglycemia, volume depletion and acidosis Pathophysiology 6 Free fatty acids released in the periphery are bound to albumin and transported to the liver where they undergo conversion to ketone bodies The metabolic acidosis in DKA is due to β-hydroxybutyric acid and acetoacetic acid which are in equilibrium Acetoacetic acid is metabolized to acetone, another major ketone body Depletion of baseline hepatic glycogen stores tends to favor ketogenesis Low insulin levels decrease the ability of the brain and cardiac and skeletal muscle to use ketones as an energy source, also increasing ketonemia Persistently elevated serum glucose levels eventually causes an osmotic diuresis Resulting volume depletion worsens hyperglycemia and ketonemia Electrolytes 7 Renal potassium losses already occurring from osmotic diuresis worsen due to renin-angiotensin- aldosterone system activation by volume depletion In the kidney, chloride is retained in exchange for the ketoanions being excreted Loss of ketoanions represents a loss of potential bicarbonate In face of marked ketonuria, a superimposed hyperchloremic acidosis is also present Presence of concurrent hyperchloremic metabolic acidosis can be detected by noting a bicarbonate level lower than explainable by the amount the anion gap has increased As adipose tissue is broken down, prostaglandins PGI2 and PGE2 are produced This accounts for the paradoxical vasodilation that occurs despite the profound levels of volume depletion DKA in Pregnancy 8 Physiologic changes in pregnancy makes more prone to DKA Maternal fasting serum glucose levels are normally lower Leads to relative insulin deficiency and an increase in baseline free fatty acid levels in the blood Pregnant patients normally have increased levels of counter regulatory hormones Chronic respiratory alkalosis Seen in pregnancy Leads to decreased bicarbonate levels due to a compensatory renal response Results in a decrease in buffering capacity DKA in Pregnancy 9 Pregnant patients have increased incidence of vomiting and infections which may precipitate DKA Maternal acidosis: Causes fetal acidosis Decreases uterine blood flow and fetal oxygenation Shifts the oxygen-hemoglobin dissociation curve to the right ◦ ◦ ◦ Maternal shifts can lead to fetal dysrhythmia and death Causes of DKA 25% have no precipitating causes found 10 Errors in insulin use, especially in younger population Omission of daily insulin injections Stressful events: Infection Stroke MI Trauma Pregnancy Hyperthyroidism Pancreatitis Pulmonary embolism Surgery Steroid use Clinical Features 11 Hyperglycemia Increased osmotic load Movement of intracellular water into the vascular compartment Ensuing osmotic diuresis gradually leads to volume loss and renal loss of sodium, chloride, potassium, phosphorus, calcium and magnesium ◦ ◦ Patients initially compensate by increasing their fluid intake Initially polyuria and polydipsia are only symptoms until ketonemia and acidosis develop Clinical Features 12 As acidosis progresses Patient develops a compensatory augmented ventilatory response Increased ventilation is stimulated physiologically by acidemia to diminish PCO2 and counter the metabolic acidosis ◦ ◦ Peripheral vasodilation develops from prostaglandins and acidosis Prostaglandins may contribute to unexplained nausea, vomiting and abdominal pain Vomiting exacerbates the potassium losses and contributes to volume depletion, weakness and weight loss ◦ ◦ Clinical Features 13 Mental confusion or coma may occur with serum osmolarity greater than 340 mosm/L Abnormal vital signs may be the only significant finding at presentation Tachycardia with orthostasis or hypotension are usually present Poor skin turgor Kussmaul respirations with severe acidemia Clinical Features 14 Acetone presents with odor in some patients Absence of fever does not exclude infection as a source of the ketoacidosis Hypothermia may occur due to peripheral vasodilatation Abdominal pain and tenderness may occur with gastric distension, ileus or pancreatitis Abdominal pain and elevated amylase in those with DKA or pancreatitis may make differentiation difficult Lipase is more specific to pancreatitis ◦ ◦ Clinical Suspicion 15 If suspect DKA, want immediately: Acucheck Urine dip ECG Venous blood gas Normal Saline IV drip Almost all patients with DKA have glucose greater than 300 mg/dL Acidosis 16 Elevated serum β-hydroxybutyrate and acetoacetate cause acidosis and ketonuria Elevated serum ketones may lead to a wide-anion gap metabolic acidosis Metabolic acidosis may occur due to vomiting, osmotic diuresis and concomitant diuretic use Some with DKA may present with normal bicarbonate concentration or alkalemia if other alkalotic processes are severe enough to mask acidosis In which case the elevated anion gap may be the only clue to the presence of an underlying metabolic acidosis ABGs 17 Help determine precise acid-base status in order to direct treatment Venous pH is just as helpful Studies have shown strong correlation between arterial and venous pH in patients with DKA Venous pH obtained during routine blood draws can be used to avoid ABGs Decreased PCO2 reflects respiratory compensation for metabolic acidosis Widening of anion gap is superior to pH or bicarbonate concentration alone Widening is independent of potentially masking effects concurrent with acid base disturbances Potassium 18 Total body potassium is depleted by renal losses Measured levels usually normal or elevated Sodium 19 Osmotic diuresis leads to excessive renal losses of NaCl in urine Hyperglycemia artificially lowers the serum sodium levels Two corrections: Standard-1.6 mEq added to sodium loss for every 100 mg of glucose over 100 mg/dL True-2.4 mEq added for blood glucose levels greater than 400 mg/dL Electrolyte Loss: 20 Osmotic diuresis contributes to urinary losses and total body depletion of: Phosphorus Calcium Magnesium Other values elevated: 21 Creatinine Some elevation expected due to prerenal azotemia May be factitiously elevated if laboratory assays for Cr and Acetoacetate interfere ◦ ◦ LFTs Due to fatty infiltration of the liver which gradually corrects as acidosis is treated ◦ CPK Due to volume depletion ◦ Amylase WBCs Leukocytosis often present due to hemoconcentration and stress response Absolute band count of 10,000 microL or more reliably predicts infection in this population ◦ ◦ ECG changes 22 Underlying rhythm is sinus tachycardia Changes of hypo/hyperkalemia Transient changes due to rapidly changing metabolic status Evaluate for ischemia because MI may precipitate DKA Differential Diagnosis 23 Any entity that causes a high-anion-gap metabolic acidosis Alcoholic or starvation ketoacidosis Uremia Lactic acidosis Ingestions (methanol, ethylene glycol, aspirin) If ingestion cannot be excluded, serum osmolarity or drug-level testing is required ◦ ◦ ◦ ◦ Patients with hyperosmolar non-ketotic coma tend to: Be older Have more prolonged course and have prominent mental status changes Serum glucose levels are generally much higher (>600 mg/dL) Have little to no anion-gap metabolic acidosis ◦ ◦ ◦ ◦ Studies 24 Diagnosis should be suspected at triage Aggressive fluid therapy initiated prior to receiving lab results Place on monitor and have one large bore IV with NS running Rapid acucheck, urine dip and ECG CBC Electrolytes, phosphorus, magnesium, calcium Blood cultures ABG optional and required only for monitoring and diagnosis of critically ill Venous pH (0.03 lower than arterial pH) may be used for critically ill Treatment Goals: 25 Volume repletion Reversal of metabolic consequences of insulin insufficiency Correction of electrolyte and acid-base imbalances Recognition and treatment of precipitating causes Avoidance of complications Treatment 26 Order of therapeutic priorities is volume first, then insulin and/or potassium, magnesium and bicarbonate Monitor glucose, potassium and anion gap, vital signs, level of consciousness, volume input/output until recovery is well established Need frequent monitoring of electrolytes (every 1-2 hours) to meet goals of safely replacing deficits and supplying missing insulin Resolving hyperglycemia alone is not the end point of therapy Need resolution of the metabolic acidosis or inhibition of ketoacid production to signify resolution of DKA Normalization of anion gap requires 8-16 hours and reflects clearance of ketoacids ◦ ◦ Fluid Administration 27 Rapid administration is single most important step in treatment Restores: Intravascular volume Normal tonicity Perfusion of vital organs Improve glomerular filtration rate Lower serum glucose and ketone levels Average adult patient has a 100 ml/Kg (5-10 L) water deficit and a sodium deficit of 7-10 mEq/kg Normal saline is most frequently recommended fluid for initial volume repletion Fluid Administration 28 Recommended regimen: First L of NS within first 30 minutes of presentation First 2 L of NS within first 2 hours Second 2 L of NS at 2-6 hours Third 2 L of NS at 6-12 hours ◦ ◦ ◦ ◦ Above replaces 50% of water deficit within first 12 hours with remaining 50% over next 12 hours Glucose and ketone concentrations begin to fall with fluids alone Fluid Administration 29 Add D5 to solution when glucose level is between 250-300 mg/dL Change to hypotonic ½ NS or D5 ½ NS if glucose below 300 mg/dL after initially using NS If no extreme volume depletion, may manage with 500 ml/hr for 4 hours May need to monitor CVP or wedge pressure in the elderly or those with heart disease and may risk ARDS and cerebral edema ◦ Insulin 30 Ideal treatment is with continuous IV infusion of small doses of regular insulin More physiologic Produces linear fall in serum glucose and ketone body levels Less associated with severe metabolic complications such as hypoglycemia, hypokalemia and hypophosphatemia Insulin 31 Recommended dose is 0.1 unit/kg/hr Effect begins almost immediately after initiation of infusion Loading dose not necessary and not recommended in children Insulin 32 Need frequent glucose level monitoring Incidence of non-response to low-dose continuous IV administration is 1-2% Infection is primary reason for failure Usually requires 12 hours of insulin infusion or until ketonemia and anion gap is corrected Potassium Patients usually33with profound total body hypokalemia 3-5 mEq/kg deficient Created by insulin deficiency, metabolic acidosis, osmotic diuresis, vomiting 2% of total body potassium is intravascular Initial serum level is normal or high due to: Intracellular exchange of potassium for hydrogen ions during acidosis Total body fluid deficit Diminished renal function Initial hypokalemia indicates severe total-body potassium depletion and requires large amounts of potassium within first 24-36 hours Potassium 34 During initial therapy the serum potassium concentration may fall rapidly due to: Action of insulin promoting reentry into cells Dilution of extracellular fluid Correction of acidosis Increased urinary loss of potassium ◦ ◦ ◦ ◦ Early potassium replacement is a standard modality of care Not given in first L of NS as severe hyperkalemia may precipitate fatal ventricular tachycardia and ventricular fibrillation ◦ Potassium 35 Fluid and insulin therapy alone usually lowers the potassium level rapidly For each 0.1 change in pH, serum potassium concentration changes by 0.5 mEq/L inversely Goal is to maintain potassium level within 4-5 mEq/L and avoid life threatening hyper/hypokalemia Oral potassium is safe and effective and should be used as soon as patient can tolerate po fluids During first 24 hours, KCl 100-200 mEq usually is required Phosphate 36 Roll of replacement during treatment of DKA is controversial Recommended not treating until level less than 1 mg/dL No established roll for initiating IV potassium phosphate in the ED Magnesium 37 Osmotic diuresis may cause significant magnesium depletion Symptomatic hypomagnesemia in DKA is rare as is need of IV therapy Bicarbonate 38 Role in DKA debated for decades No clinical study indicates benefit of treating DKA with bicarbonate Routine use of supplemental bicarbonate in DKA is not recommended Routine therapy works well without adding bicarbonate Complications and Mortality 39 Complications related to acute disease Main contributors to mortality are MI and infection Old age, severe hypotension, prolonged and severe coma and underlying renal and cardiovascular disease Severe volume depletion leaves elderly at risk for vascular stasis and DVT Airway protection for critically ill and lethargic patients at risk for aspiration Complications related to therapy 40 Hypoglycemia Hypophosphatemia ARDS Cerebral edema Complications related to therapy 41 Cerebral edema Occurs between 4 and 12 hours after onset of therapy but may occur as late as 48 hours after start treatment Estimated incidence is 0.7 to 1.0 per 100 episodes of DKA in children Mortality rate of 70% No specific presentation or treatment variables predict development of edema Young age and new-onset diabetes are only identified potential risk factors Cerebral edema 42 Symptoms include: Severe headache Incontinence Change in arousal or behavior Pupillary changes Blood pressure changes Seizures Bradycardia Disturbed temperature regulation Treat with Mannitol Any change in neurologic function early in therapy should prompt immediate infusion of mannitol at 1-2 g/kg Disposition 43 Most require admission to ICU: Insulin drips If early in the course of disease and can tolerate oral liquids, may be managed in ED or observation unit and discharged after 4-6 hours of therapy Anion gap at discharge should be less than 20 Alcoholic Ketoacidosis 44 Alcoholic Ketoacidosis 45 Wide anion gap acidosis Most often associated with acute cessation of alcohol consumption after chronic alcohol abuse Metabolism of alcohol with little or no glucose sources results in elevated levels of ketoacids that typically produce metabolic acidosis present in the illness Usually seen in chronic alcoholics but may be seen in first time drinkers who binge drink, especially in those with volume depletion from poor oral intake and vomiting Epidemiology 46 No gender difference Usually presents between age 20 to 60 Many with repeated episodes of ketoacidosis Incidence is unknown but mirrors incidence of alcoholism Usually self-limited Poor outcomes may occur 7-25% of deaths of known alcoholics due to AKA Pathophysiology 47 Key features Ingestion of large quantities of alcohol Relative starvation Volume depletion Pathophysiology 48 Pathophysiologic state occurs with: Depletion of NAD Aerobic metabolism in the Krebs cycle is inhibited Glycogen stores are depleted and lipolysis is stimulated Occurs in patients with: Recently intoxicated Volume-contraction Poor nutrition Underlying liver disease Pathophysiology 49 Insulin secretion is suppressed Glucagon, catecholamines, and growth hormone are all stimulated Aerobic metabolism is inhibited and anaerobic metabolism causes lipolysis and ketones are produced β-hydroxybutyrate is increased More ketones are produced with malnourishment and vomiting or with hypophosphatemia Clinical Features 50 Usually occurs after episode of heavy drinking followed by decrease in alcohol and food intake and vomiting Nausea, vomiting and abdominal pain of gastritis and pancreatitis may exacerbate progression of illness With anorexia continuing, symptoms worsen leading to seeking medical help Symptoms are nonspecific and diagnosis is difficult without labs No specific physical findings solely with AKA Most commonly tachycardia, tachypnea, diffuse mild to moderate abdominal tenderness Volume depletion resulting from anorexia, diaphoresis and vomiting may explain the tachycardia and hypotension Clinical Features 51 Most are alert Mental status changes in patients with ketoacidosis should alert to other causes: Toxic ingestion Hypoglycemia Alcohol-withdrawal seizures Postictal state Unrecognized head injury Labs EtOH52levels usually low or undetectable Some may have elevated levels Elevated anion gap caused by ketones is essential in diagnosis Since β hydroxybutyrate predominates, degree of ketonemia may not be appreciated Initial anion gap is 16-33 usually, mean of 21 Frequently mild hypophosphatemia, hyponatremia and/or hypokalemia Severe derangements are rare Labs Most have elevated bilirubin and53liver enzymes due to liver disease from chronic EtOH use BUN and creatine kinase are frequently elevated due to relative volume depletion Serum lactate mildly elevated Glucose usually mildly elevated Some have hypoglycemia Rarely glucose greater than 200 mg/dL Acid-Base Balance 54 Need to evaluate the anion gap in every patient at risk for AKA Diagnosis can easily be missed otherwise Anion gap greater than baseline or 15 signifies a wide-anion-gap acidosis regardless of bicarbonate concentration or pH, even if alkalemic ABG not needed to arrive at correct diagnosis Acid-Base Balance 55 Serum pH usually acidemic (55% of time) though may be normal or alkalemic early in course of disease Degree of acidosis typically less than in DKA Since volume loss is virtually always present, some degree of metabolic acidosis is present Ketones 56 Clinical application is variable Most ketones in AKA are β-hydroxybutyrate The serum and urine nitroprusside test for ketones detects acetoacetate and may show only mildly elevated ketones As treatment progresses the acetoacetate will increase and indicates improving condition Most suggest measuring β-hydroxybutyrate and acetoacetate only if diagnosis is unclear or other methods are not available to follow patient’s response to therapy Diagnosis 57 May be established with classic presentation of: The chronic alcoholic with: Recent anorexia Vomiting Abdominal pain Unexplained metabolic acidosis with a positive nitroprusside test, elevated anion gap and a low or mildly elevated serum glucose level Classic Presentation is Uncommon 58 Difficult to establish diagnosis Blood alcohol level may be zero May not provide history of alcohol consumption Urine nitroprusside testing may be negative or weakly positive despite significant ketoacidosis pH may vary from significant acidemia to mild alkalemia Wide anion gap is variable Initial studies 59 Electrolytes BUN Creatinine Liver enzymes Pancreatic enzymes WBC count Hematocrit Urinalysis Calculate anion gap Serum lactic acid level and serum osmolarity may be helpful if diagnosis is in doubt ABG is unnecessary unless a primary respiratory acid-base disturbance is suspected Differential diagnosis 60 Very broad Same as for wide-anion-gap metabolic acidosis Lactic acidosis Uremia Ingestions such as: Methanol Ethylene glycol Methanol and ethylene glycol do not produce ketosis but do have severe acidosis Absence of urinary ketones cannot exclude diagnosis of AKA if concurrent methanol or ethylene glycol ingestion is suspected Isopropyl alcohol ingestion Produces ketones and may have mild lactic acidosis Salicylate poisoning Sepsis Renal failure DKA Starvation ketosis Concurrent Illnesses Promoting Alcohol Cessation and Anorexia 61 Need to evaluate for these illnesses: Pancreatitis Gastritis Upper GI bleeding Seizures Alcohol withdrawal Pneumonia Sepsis Hepatitis Treatment 62 Glucose administration and volume repletion Fluid of choice is D5NS Glucose stimulates insulin production, stopping lipolysis and halts further formation of ketones Glucose increases oxidation of NADH to NAD and further limits ketone production Patients are not hyperosmolar Cerebral edema is not a concern with large volumes of fluid administration Treatment 63 Insulin No proven benefit May be dangerous as patients have depleted glycogen stores and normal or low glucose levels Treatment 64 Sodium bicarbonate is not indicated unless patients are severely acidemic with pH 7.1 or lower This level of acidemia not likely explained by AKA alone Vigorous search for alternate explanation must be undertaken Treatment 65 Hypophosphatemia Frequently seen in alcoholic patients Can retard resolution of acidosis Phosphorous is necessary for mitochondrial utilization of glucose to produce NADH oxidation Phosphate replacement is generally unwarranted in ED unless levels less than 1 are encountered Oral replenishment is safe and effective Treatment Nitroprusside tests useful because as 66 become more positive signifies improvement To prevent theoretical progression to Wernicke’s disease, all patients should receive 50-100 mg of thiamine prior to administration of glucose Concomitant administration of magnesium sulfate and multivitamins should be considered and guided by laboratory results Acidosis may clear within 12-24 hours If uncomplicated ED course, may be safely discharged if resolution of acidosis over time and patient able to tolerate oral fluids If complicated course, underlying illness or persistent acidosis, admit for further evaluation and treatment Hyperosmolar Hyperglycemic State 67 Hyperosmolar Hyperglycemic State 68 Syndrome of severe hyperglycemia, hyperosmolarity and relative lack of ketonemia in patients with poorly uncontrolled DM type II ADA uses hyperosmolar hyperglycemic state (HHS) and hyperosmolar hyperglycemic non ketotic syndrome (HHNS) Both commonly used and appropriate Frequently referred to as non ketotic hyperosmolar coma Coma should not be used in nomenclature Only 10 % present with coma HHNS: Epidemiology 69 HHNS is much less frequent than DKA Mortality rate higher in HHNS 15-30 % for HHNS 5% for DKA Mortality for HHNS increases substantially with advanced age and concomitant illness Hyperosmolar Hyperglycemic State 70 Defined by: Severe hyperglycemia With serum glucose usually greater than 600 mg/dL Elevated calculated plasma osmolality Greater than 315 mOsm/kg Serum bicarbonate greater than 15 Arterial pH greater than 7.3 Serum ketones that are negative to mildly positive Values are arbitrary Profound metabolic acidosis and even moderate degrees of ketonemia may be found in HHNS HHNS and DKA both 71 Hyperglycemia Hyperosmolarity Severe volume depletion Electrolyte disturbances Occasionally acidosis HHNS 72 Acidosis in HHNS more likely due to: Tissue hypoperfusion Lactic acidosis Starvation ketosis Azotemia HHNS and DKA Lipolysis 73 DKA patients have much higher levels of lipolysis Release and subsequent oxidation of free fatty acids to ketone bodies β hydroxybutyrate and Acetoacetate Contribute additional anions resulting in a more profound acidosis Inhibition of lipolysis and free fatty acid metabolism in HHNS is poorly understood See table 214-1 on page 1307 HHNS: Pathophysiology 74 Three main factors: Decreased utilization of insulin Increased hepatic gluconeogenesis and glycogenolysis Impaired renal excretion of glucose Identification early of those at risk for HHNS is most effective means of preventing serious complications Must be vigilant on helping those who are non-ambulatory with inadequate hydration status Fundamental risk factor for developing HHNS is impaired access to water HHNS: Pathophysiology 75 With poorly controlled DM II, inadequate utilization of glucose due to insulin resistance results in hyperglycemia Absence of adequate tissue response to insulin results in hepatic glycogenolysis and gluconeogenesis resulting in further hyperglycemia As serum glucose increases, an osmotic gradient is produced attracting water from the intracellular space and into the intravenous compartment HHNS: Pathophysiology 76 Initial increase in intravascular volume is accompanied by a temporary increase in the GFR As serum glucose concentration exceeds 180 mg/dL, capacity of kidneys to reabsorb glucose is exceeded and glucosuria and a profound osmotic diuresis occurs Patients with free access to water are often able to prevent profound volume depletion by replacing lost water with large free water intake If water requirement is not met, volume depletion occurs HHNS: Pathophysiology 77 During osmotic diuresis, urine produced is markedly hypertonic Significant loss of sodium and potassium and modest loss of calcium, phosphate, magnesium and urea also occur As volume depletion progresses, renal perfusion decreases and GFR is reduced Renal tubular excretion of glucose is impaired which further worsens the hyperglycemia A sustained osmotic diuresis may result in total body water losses that often exceeds 20-25% of total body weight or approximately 8-12 L in a 70 kg person HHNS: Pathophysiology 78 Absence of ketosis in HHNS not clearly understood Some degree of starvation does occur but a clinically significant ketoacidosis does not occur Lack of ketoacidosis may be due to: Lower levels of counter regulatory hormones Higher levels of endogenous insulin that strongly inhibits lipolysis Inhibition of lipolysis by the hyperosmolar state HHNS: Pathophysiology 79 Controversy how counter regulatory hormones glucagons and cortisol, growth hormone and epinephrine play in HHNS Compared to DKA, glucagon and growth hormone levels are lower and this may help prevent lipolysis Compared to DKA, significantly higher levels of insulin are found in peripheral and portal circulation in HHNS Though insulin levels are insufficient to overcome hyperglycemia, they appear to be sufficient to overcome lipolysis Animal studies have shown the hyperosmolar state and severe hyperglycemia inhibit lipolysis in adipose tissue HHNS: Clinical Features 80 Typical patient is usually elderly Often referred by a caretaker Abnormalities in vital signs and or mental status May complain of: Weakness Anorexia Fatigue Cough Dyspnea Abdominal pain HHNS 81 Many have undiagnosed or poorly controlled type II diabetes Precipitated by acute illness Pneumonia and urinary tract infections account for 30-50% of cases Noncompliance with or under-dosing of insulin has been identified as a common precipitant also HHNS 82 Those predisposed to HHNS often have some level of baseline cognitive impairment such as senile dementia Self-referral for medical treatment in early stages is rare Any patient with hyperglycemia, impaired means of communication and limited access to free water is at major risk for HHNS Presence of hypertension, renal insufficiency or cardiovascular disease is common in this patient population and medications commonly used to treat these diseases such as blockers predispose the development of HHNS HHNS 83 An insidious state goes unchecked Progressive hyperglycemia Hyperosmolarity Osmotic diuresis Alterations in vital signs and cognition follow and signal a severity of illness that is often advanced HHNS Causes 84 A host of metabolic and iatrogenic causes have been identified Diabetes Parental or enteral alimentation GI bleed PE Pancreatitis Heat-related illness Mesenteric ischemia Infection MI HHNS Causes 85 Severe burns Renal insufficiency Peritoneal or hemodialysis Cerebrovascular events Rhabdomyolysis Commonly prescribed drugs that may predispose to hyperglycemia, volume depletion or other effects leading to HHNS HHNS may unexpectedly be found in non-diabetics who present with an acute medical insult such as CVA, severe burns, MI, infection, pancreatitis or other acute illness HHNS: Physical findings 86 Non-specific Clinical signs of volume depletion: Poor skin turgor Dry mucus membranes Sunken eyeballs Hypotension Signs correlate with degree of hyperglycemia and hyperosmolality and duration of physiologic imbalance Wide range of findings such as changes in vital signs and cognition to clear evidence of profound shock and coma may occur Normothermia or hypothermia is common due to vasodilation HHNS: Physical findings 87 Seizures Up to 15% may present with seizures Typically focal Generalized seizures that are often resistant to anticonvulsants may occur Other CNS symptoms may include: Tremor Clonus Hyperreflexia Hyporeflexia Positive plantar response Reversible hemiplegia or hemisensory defects without CVA or structural lesion HHNS: Physical findings 88 Degree of lethargy and coma is proportional to the level of osmolality Those with coma tend to have: Higher osmolality Higher hyperglycemia Greater volume contraction Not surprising that misdiagnosis of stroke or organic brain disease is common in the elderly Laboratory tests 89 Essential Serum glucose Electrolytes Calculated and measured serum osmolality BUN Ketones Creatinine CBC Laboratory tests 90 Consider Urinalysis and culture Liver and pancreatic enzymes Cardiac enzymes Thyroid function Coagulation profiles Chest x-ray ECG Other CT of head LP Toxicology ABG Of value only if suspicion of respiratory component to acid-base abnormality Both PCO2 and pH can be predicted from bicarbonate concentration obtained from venous electrolytes Electrolyte abnormalities 91 Electrolyte abnormalities usually reflect a contraction alkalosis due to profound water deficit 50% of patients with HHNS will have increased anion gap metabolic acidosis Lactic acidosis, azotemia, starvation ketosis, severe volume contraction Acute or concurrent illnesses such as ischemic bowel will contribute anions such as lactic acid causing varying degrees of an anion gap metabolic acidosis Initial serum electrolyte determinations can be reported as seemingly normal because the concurrent presence of both metabolic alkalosis and acidosis may result in each canceling out the other’s effect Lack of careful analysis of serum chemistries may lead to delayed appreciation of the severity of underlying abnormalities, including volume loss Sodium Serum sodium is suggestive but not a reliable indicator of degree of volume contraction 92 Though patient is total body sodium depleted, serum sodium (corrected for glucose elevation) may be low, normal or elevated Measured serum sodium is often reported as factitiously low due to dilutional effect of hyperglycemia Need to correct the sodium level Serum sodium decreases by 1.6 mEq for every 100 mg/dL increase in serum glucose above 100 mg/dL See formula page 1309 Elevated corrected serum sodium during sever hyperglycemia is usually explainable only by profound volume contraction Normal sodium level or mild hyponatremia usually but not invariably suggests modest dehydration Osmolarity 93 Serum osmolarity has also been shown to correlate with severity of disease as well as neurologic impairment and coma Calculated effective serum osmolarity excludes osmotically inactive urea that is usually included in laboratory measures of osmolarity See formula page 1309 Normal serum osmolarity range is approximately 275 to 295 mOsm/kg Values above 300 mOsm/kg are indicative of significant hyperosmolarity and those above 320 mOsm are commonly associated with alterations of cognitive function Potassium Hypokalemia is most immediate electrolyte based risk and should be anticipated 94 Total body deficits of 500-700 mEq/l are common Initial values may be reported as normal during a period of severe volume contraction and with metabolic acidosis when intravascular hydrogen ions are exchanged for intracellular potassium ions Presence of acidemia may mask a potentially life-threatening potassium deficit As intravascular volume is replaced and acidemia is reversed, potassium losses become more apparent Patients with low serum potassium during the period of severe volume contraction are at greatest risk for dysrhythmia Importance of potassium replacement during periods of volume repletion and insulin therapy cannot be overemphasized Labs 95 BUN and Cr Both prerenal azotemia and renal azotemia are common with BUN/Cr ratios often exceeding 30/1 WBC Leukocytosis is variable and a weak clinical indicator When present usually due to infection or hemoconcentration Phosphate 96 Hypophosphatemia may occur during periods of prolonged hyperglycemia Acute consequences such as CNS abnormalities, cardiac dysfunction, and rhabdomyolysis are rare and are usually if level is <1.0 mg/dL Routine replacement of phosphate and magnesium usually unnecessary unless severe Both electrolytes tend to normalize as metabolic derangements are addressed When necessary, gradual replacement minimizes risks of complications such as renal failure or hypocalcemia Metabolic acidosis is of a wide-anion-gap type, often due to lactic acidosis from poor tissue perfusion, resulting in uremia, mild starvation ketosis or all three Treatment 97 Improvement in tissue perfusion is the key to effective recovery Treat hypovolemia, identify and treat precipitating causes, correct electrolyte abnormalities, gradual correction of hyperglycemia and osmolarity Cannot overstate importance of judicious therapeutic plans that adjusts for concurrent medical illness such as LV dysfunction or renal insufficiency Due to potential complications, rapid therapy should only be reserved for potentially life-threatening electrolyte abnormalities only Figure 214-1 Fluid resuscitation 98 Initial aim is reestablishing adequate tissue perfusion and decreasing serum glucose Replacement of intravascular fluid losses alone can account for reductions in serum glucose of 35-70 mg/hr or up to 80 % of necessary reduction Average fluid deficit is 20-25% of total body water or 8-12 L In elderly 50% of body weight is due to total body water Calculate the water deficit by using patient’s current weight in kilograms and normal total body water Fluid resuscitation 99 One-half of fluid deficits should be replaced over the initial 12 hours and the balance over the next 24 hours when possible Actual rate of fluid administration should be individualized for each patient based on presence of renal and cardiac impairment Initial rates of 500-1500 ml/hr during first 2 hours followed by rates of 250- 500 ml per hour are usually well tolerated Patients with cardiac disease may require a more conservative rate of volume repletion Renal and cardiovascular function should be carefully monitored Central venous and urinary tract catheterization should be considered Fluid resuscitation 100 Rate of fluid administration may need to be limited in children A limited number of reports of cerebral edema occurring during or soon after the resuscitation phase of patients with both DKA and HHNS have been described Most cases have occurred in children with DKA and mechanism is unclear One review showed cerebral edema was found with similar frequency before treatment with replacement fluids New study shows rehydration of children with DKA during first 4 hours at a rate greater than 50 mL/kg was associated with increased risk of brain herniation Little credible data on incidence or clinical indicators that may predispose to cerebral edema in HHNS patients Fluid resuscitation 101 Current recommendations based on available data include limiting rate of volume depletion during first 4 hours to <50 ml/kg of NS Mental status should be closely monitored during treatment CT of brain should be obtained with any evidence of cognitive impairment Most authors agree use of NS is most appropriate initial crystalloid for replacement of intravascular volume NS is hypotonic to the patient’s serum osmolality and will more rapidly restore plasma volume Once hypotension, tachycardia and urinary output improve, ½ NS can be used to replace the remaining free water deficit Potassium 102 Potassium deficits are most immediate electrolyte-based risk for a bad outcome On average potassium losses range from 4-6 mEq/kg though may be as high as 10mEq/kg of body weight Initial measurements may be normal or even high with acidemia Patients with levels <3.3 are at highest risk for cardiac dysrhythmia and respiratory arrest and should be treated with urgency Insulin therapy precipitously lowers intravascular potassium further and potassium must be vigorously replaced Potassium 103 When adequate urinary output is assured, potassium replacement should begin Should replace at 10-20 mEq/hr though if life threatening may require 40 mEq/hr Central line needed if given more than 20 mEq/hr Some believe potassium through central line poses risk for conduction defects and should be avoided if good peripheral line sites are available Monitoring of serum potassium should occur every hour until a steady state has been achieved Sodium 104 Sodium deficits replenished rapidly since given NS or ½ NS during fluid replacement Phosphate and Magnesium should be measured Current guideline recommend giving 1/3 of potassium needed as potassium phosphate to avoid excessive chloride administration and to prevent hypophosphatemia Unless severe, alleviation of hypophosphatemia or hypomagnesemia should occur after the patient is admitted into the ICU setting Insulin 105 Volume repletion should precede insulin therapy If given before volume repletion, intravascular volume is further depleted due to shifting of osmotically active glucose into the intracellular space bringing free water with it and this may precipitate vascular collapse Absorption of insulin by IM or SC route is unreliable in patients with HHNS and continuous infusion of IV insulin is needed No proven benefit to bolus of insulin Continuous infusion of 0.1U/kg/hour is best Insulin 106 Want one unit of regular insulin for every mL of NS in infusion Steady states utilizing infusion pumps occur within 30 minutes of infusion Decrease plasma glucose by 50-75 mg/dL per hour along with adequate hydration If adequate hydration, may double infusion rate until 50-75 mg/dL/hr is achieved Some patients are insulin resistant and require higher doses Once level less than 300 mg/dL, should change IV solution to D5 ½ NS and insulin infusion should be reduced to half or 0.05 U/kg/hr. Disposition 107 Need to track pH, vital signs and key lab values in the ED for appropriate management and disposition of these patients ICU Most require for initial 24 hours of care SDU Patients with no significant co morbid conditions and who demonstrate a good response to initial therapy as evidenced by documented improvement in vital signs, urine output, electrolyte balance and mentation Questions 108 1. T/F: The venous pH is just as helpful as arterial pH in patients with DKA and may be obtained during routine blood draws. 2. T/F: Alcoholic ketoacidosis is usually seen in chronic alcoholics but may be seen in first time drinkers who binge drink, especially in those with volume depletion from poor oral intake and vomiting. 3. T/F: In treating DKA, the order of therapeutic priorities is volume first, then insulin and/or potassium, magnesium and bicarbonate. 4. T/F: DKA patients have much higher levels of lipolysis, resulting in release and subsequent oxidation of free fatty acids to ketone bodies contributing additional anions resulting in a more profound acidosis than in HHNS. 5. T/F: Volume repletion should precede insulin therapy in HHNS Answers: T,T,T,T,T