1Acute Complications of Diabetes

2

Diabetic Ketoacidosis

Introduction3

DKA is an acute life threatening complication of DM

¼of 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

Definition4

Exact definition is variable

Most consistent is:Blood glucose level greater than 250 mg/dLBicarbonate less than 15 mEq/L Arterial pH less than 7.3Moderate ketonemia

Pathophysiology5

Body’s response to cellular starvation Brought on by relative insulin deficiency and counter regulatory or

catabolic hormone excessInsulin 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 diuresisPrerenal azotemiaKetone formationWide anion-gap metabolic acidosis

Clinical manifestations related to hyperglycemia, volume depletion and acidosis

Pathophysiology6

Free fatty acids released in the periphery are bound to albumin and transported to the liver where they

undergo conversion to ketone bodiesThe metabolic acidosis in DKA is due to β-hydroxybutyric acid

and acetoacetic acid which are in equilibriumAcetoacetic acid is metabolized to acetone, another major

ketone bodyDepletion of baseline hepatic glycogen stores tends to favor

ketogenesisLow 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

Electrolytes7

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 Pregnancy8

Physiologic changes in pregnancy makes more prone to DKA

Maternal fasting serum glucose levels are normally lowerLeads to relative insulin deficiency and an increase in baseline

free fatty acid levels in the bloodPregnant 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 responseResults in a decrease in buffering capacity

DKA in Pregnancy9

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 DKA10

25% have no precipitating causes found

Errors in insulin use, especially in younger population

Omission of daily insulin injections

Stressful events :InfectionStrokeMITraumaPregnancyHyperthyroidismPancreatitisPulmonary embolismSurgerySteroid use

Clinical Features11

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 Features12

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 Features13

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 Features14 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 Suspicion15

If suspect DKA, want immediately:AcucheckUrine dipECGVenous blood gasNormal Saline IV drip

Almost all patients with DKA have glucose

greater than 300 mg/dL

Acidosis16

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 acidosisIn which case the elevated anion gap may be the only clue to

the presence of an underlying metabolic acidosis

ABGs17

Help determine precise acid-base status in order to direct treatment

Venous pH is just as helpfulStudies have shown strong correlation between arterial

and venous pH in patients with DKAVenous 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

Potassium18

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/dLTrue-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:

PhosphorusCalciumMagnesium

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 changes22

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 Diagnosis23

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

Studies24 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

Treatment26 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 Administration27

Rapid administration is single most important step in treatment

Restores:Intravascular volume Normal tonicityPerfusion 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 Administration28

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 Administration29

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

Insulin30

Ideal treatment is with continuous IV infusion of small doses of regular insulin

More physiologicProduces linear fall in serum glucose and ketone body

levelsLess associated with severe metabolic complications

such as hypoglycemia, hypokalemia and hypophosphatemia

Insulin31

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

Insulin32

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

Potassium33 Patients usually with 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

acidosisTotal body fluid deficitDiminished renal functionInitial hypokalemia indicates severe total-body potassium depletion

and requires large amounts of potassium within first 24-36 hours

Potassium34

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

Potassium35

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

Phosphate36

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

Magnesium37

Osmotic diuresis may cause significant magnesium depletion

Symptomatic hypomagnesemia in DKA is rare as is need of IV therapy

Bicarbonate38

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 Mortality39

Complications related to acute diseaseMain contributors to mortality are MI and infectionOld age, severe hypotension, prolonged and severe

coma and underlying renal and cardiovascular diseaseSevere volume depletion leaves elderly at risk for

vascular stasis and DVTAirway protection for critically ill and lethargic patients

at risk for aspiration

Complications related to therapy40

Hypoglycemia

Hypophosphatemia

ARDS

Cerebral edema

Complications related to therapy41

Cerebral edema Occurs between 4 and 12 hours after onset of therapy

but may occur as late as 48 hours after start treatmentEstimated incidence is 0.7 to 1.0 per 100 episodes of

DKA in childrenMortality rate of 70%No specific presentation or treatment variables predict

development of edemaYoung age and new-onset diabetes are only identified

potential risk factors

Cerebral edema42

Symptoms include:Severe headacheIncontinenceChange in arousal or behaviorPupillary changesBlood pressure changesSeizuresBradycardiaDisturbed temperature regulation

Treat with MannitolAny change in neurologic function early in therapy should

prompt immediate infusion of mannitol at 1-2 g/kg

Disposition43

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

44

Alcoholic Ketoacidosis

Alcoholic Ketoacidosis45

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

Epidemiology46

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

Pathophysiology47

Key featuresIngestion of large quantities of alcoholRelative starvationVolume depletion

Pathophysiology48

Pathophysiologic state occurs with:Depletion of NADAerobic metabolism in the Krebs cycle is inhibitedGlycogen stores are depleted and lipolysis is

stimulated

Occurs in patients with:Recently intoxicatedVolume-contractionPoor nutritionUnderlying liver disease

Pathophysiology49

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 Features50 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 AKAMost commonly tachycardia, tachypnea, diffuse mild to moderate

abdominal tendernessVolume depletion resulting from anorexia, diaphoresis and

vomiting may explain the tachycardia and hypotension

Clinical Features51

Most are alertMental status changes in patients with ketoacidosis

should alert to other causes:Toxic ingestionHypoglycemiaAlcohol-withdrawal seizuresPostictal stateUnrecognized head injury

Labs

52 EtOH levels usually low or undetectableSome 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

53Most have elevated bilirubin and liver 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 hypoglycemiaRarely glucose greater than 200 mg/dL

Acid-Base Balance54

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 Balance55

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

Ketones56

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

Diagnosis57

May be established with classic presentation of:

The chronic alcoholic with:Recent anorexiaVomitingAbdominal painUnexplained 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 studies59 Electrolytes

BUNCreatinineLiver enzymesPancreatic enzymesWBC countHematocritUrinalysis Calculate anion gapSerum lactic acid level and serum osmolarity

may be helpful if diagnosis is in doubtABG is unnecessary unless a primary

respiratory acid-base disturbance is suspected

Differential diagnosis60

Very broadSame as for wide-anion-gap metabolic acidosis

Lactic acidosisUremia Ingestions such as:

MethanolEthylene 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 poisoningSepsisRenal failureDKAStarvation ketosis

Concurrent Illnesses Promoting Alcohol Cessation and Anorexia61

Need to evaluate for these illnesses:PancreatitisGastritisUpper GI bleedingSeizuresAlcohol withdrawalPneumoniaSepsis Hepatitis

Treatment62

Glucose administration and volume repletionFluid of choice is D5NSGlucose stimulates insulin production, stopping

lipolysis and halts further formation of ketonesGlucose 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

Treatment63

Insulin No proven benefit May be dangerous as patients have depleted glycogen

stores and normal or low glucose levels

Treatment64

Sodium bicarbonate is not indicated unless patients are severely acidemic with pH 7.1 or

lowerThis level of acidemia not likely explained by AKA aloneVigorous search for alternate explanation must be

undertaken

Treatment65

Hypophosphatemia Frequently seen in alcoholic patientsCan 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

Treatment66 Nitroprusside tests useful because as 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

67

Hyperosmolar Hyperglycemic State

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 nomenclatureOnly 10 % present with coma

HHNS: Epidemiology69

HHNS is much less frequent than DKA

Mortality rate higher in HHNS15-30 % for HHNS5% 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/dLElevated calculated plasma osmolality

Greater than 315 mOsm/kgSerum bicarbonate greater than 15Arterial pH greater than 7.3 Serum ketones that are negative to mildly positive

Values are arbitraryProfound metabolic acidosis and even moderate

degrees of ketonemia may be found in HHNS

HHNS and DKA both71

Hyperglycemia

Hyperosmolarity

Severe volume depletion

Electrolyte disturbances

Occasionally acidosis

HHNS72

Acidosis in HHNS more likely due to:Tissue hypoperfusion

Lactic acidosisStarvation ketosis Azotemia

HHNS and DKA Lipolysis73

DKA patients have much higher levels of lipolysis

Release and subsequent oxidation of free fatty acids to ketone bodies

β hydroxybutyrate and AcetoacetateContribute 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: Pathophysiology74

Three main factors :Decreased utilization of insulinIncreased hepatic gluconeogenesis and glycogenolysisImpaired 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: Pathophysiology75

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: Pathophysiology76

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: Pathophysiology77

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: Pathophysiology78

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 hormonesHigher levels of endogenous insulin that strongly

inhibits lipolysisInhibition of lipolysis by the hyperosmolar state

HHNS: Pathophysiology79

Controversy how counter regulatory hormones glucagons and cortisol, growth hormone and

epinephrine play in HHNSCompared 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 Features80

Typical patient is usually elderlyOften referred by a caretaker

Abnormalities in vital signs and or mental status

May complain of:WeaknessAnorexiaFatigueCoughDyspneaAbdominal pain

HHNS81

Many have undiagnosed or poorly controlled type II diabetes

Precipitated by acute illnessPneumonia 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

HHNS82

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

HHNS83

An insidious state goes uncheckedProgressive hyperglycemia Hyperosmolarity Osmotic diuresis

Alterations in vital signs and cognition follow and signal a severity of illness that is often

advanced

HHNS Causes84

A host of metabolic and iatrogenic causes have been identified

DiabetesParental or enteral alimentationGI bleedPEPancreatitisHeat-related illnessMesenteric ischemiaInfectionMI

HHNS Causes85

Severe burnsRenal insufficiencyPeritoneal or hemodialysisCerebrovascular eventsRhabdomyolysisCommonly 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 findings86 Non-specific

Clinical signs of volume depletion:Poor skin turgorDry mucus membranesSunken eyeballsHypotension

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 findings87

SeizuresUp to 15% may present with seizuresTypically focalGeneralized seizures that are often resistant to

anticonvulsants may occur

Other CNS symptoms may include:TremorClonusHyperreflexiaHyporeflexiaPositive plantar responseReversible hemiplegia or hemisensory defects

without CVA or structural lesion

HHNS: Physical findings88

Degree of lethargy and coma is proportional to the level of osmolality

Those with coma tend to have:Higher osmolalityHigher hyperglycemia Greater volume contraction

Not surprising that misdiagnosis of stroke or organic brain disease is common in the

elderly

Laboratory tests89

EssentialSerum glucoseElectrolytesCalculated and measured serum osmolalityBUN KetonesCreatinineCBC

Laboratory tests90 Consider

Urinalysis and cultureLiver and pancreatic enzymesCardiac enzymesThyroid functionCoagulation profilesChest x-rayECG

OtherCT of headLPToxicology 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 abnormalities91

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

Sodium92

Serum sodium is suggestive but not a reliable indicator of degree of volume contraction

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

Osmolarity93

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

94 Hypokalemia is most immediate electrolyte based risk and should be anticipated

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

Labs95

BUN and CrBoth prerenal azotemia and renal azotemia are common

with BUN/Cr ratios often exceeding 30/1

WBCLeukocytosis is variable and a weak clinical indicatorWhen present usually due to infection or

hemoconcentration

Phosphate96

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

Treatment97

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 resuscitation98

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 resuscitation99

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 resuscitation100

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 resuscitation101

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

Potassium102

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

Potassium103

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

Sodium104

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

Insulin105

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

Insulin106

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.

Disposition107

Need to track pH, vital signs and key lab values in the ED for appropriate management

and disposition of these patients

ICUMost require for initial 24 hours of care

SDUPatients 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

Questions108

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