Prof.

Iftikhar Ali Shah

Acute Complications of Diabetes

DKA HHNK Hypoglycemia

Other Complications
Hypoglycemic Unawareness

Somogyi Phenomenon
Dawn Phenomenon

Some things to know

Dawn Phenomenon vs Somogis effect Dawn phenomenon

Blood sugar rises in early morning

Somogis (rebound) effect

Blood sugar rise in morning as reaction to hypoglycemic time during the night

Chronic Complications
Macrovascular Complications

Microvascular Complications
Neuropathic Complications Mixed

Diabetic Ketoacidosis

Introduction
DKA is an acute life threatening complication of DM 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
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
Bodys 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
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 -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

10

Electrolytes
Renal potassium losses already occurring from osmotic diuresis worsen due to reninangiotensin-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

11

DKA in Pregnancy 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

12

DKA in Pregnancy 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

13

Causes of DKA
25% have no precipitating causes found 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
14

Clinical Features
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

15

Clinical Features
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

16

Clinical Features 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
17

Clinical Features
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

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Clinical Suspicion
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

19

 Elevated serum -hydroxybutyrate and acetoacetate cause

Acidosis

acidosis and ketonuria

acidosis

Elevated serum ketones may lead to a wide-anion gap metabolic 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

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ABGs
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

21

Potassium
Total body potassium is depleted by renal losses
Measured levels usually normal or elevated

22

Sodium
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
23

Symptoms of DKA
Abdominal pain Anorexia Dehydration Fuity breath Polyuria Somnolence Tachycardia Thirst Visual disturbances Warm, dry skin Weakness Wt. loss
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Kussmauls
Hypotension N&V

Electrolyte Loss:
Osmotic diuresis contributes to urinary losses and

total body depletion of:

Phosphorus Calcium Magnesium

25

 Creatinine

Other values elevated:

Some elevation expected due to prerenal azotemia May be factitiously elevated if laboratory assays for Cr and Acetoacetate interfere Due to fatty infiltration of the liver which gradually corrects as acidosis is treated

LFTs

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

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ECG changes
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
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Differential Diagnosis
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

28

Studies
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
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Assessment DKA
Hyperglycemia
Hyperosmolality Dehydration

Electrolyte imbalances
Metabolic acidosis Hypoglycemia Fluid overload

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Treatment Goals:
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
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Intervention
Rehydrate

Reverse shock
Give Potassium Corret pH Give insulin

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Treatment
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
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Fluid Administration
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 repletion

Normal saline is most frequently recommended fluid for initial volume

34

IV Fluids in DKA
Hour 1 N/S or Ringers lactate (15-20ml/kg) Hour 2 Continue fluid, consider half-strength NS Hour 3 Reduce fluid intake to 7.5ml/kg, use half-strength NS Hour 4 Consider urine output in adjusting fluids
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Fluid Administration
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
36

Fluid Administration
Add D5 to solution when glucose level is between 250-300 mg/dL
Change to hypotonic NS or D5 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
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Correct pH/Give Insulin

Give IV Insulin Give Regular Insulin only Initial bolus IV (0.15u/kg) Then Regular Insulin IV drip

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Insulin
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

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Insulin
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

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Insulin
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
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Potassium Replacement in DKA

Look at EKG

Replacement is based on plasma potassium level

Recheck potassium q 2 hours

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Potassium
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 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
43

Potassium 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

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Potassium
Fluid and insulin therapy alone usually lowers the

potassium level rapidly

by 0.5 mEq/L inversely

For each 0.1 change in pH, serum potassium concentration changes

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

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Phosphate
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

46

Magnesium
Osmotic diuresis may cause significant magnesium

depletion
Symptomatic hypomagnesemia in DKA is rare as is

need of IV therapy

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Bicarbonate
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
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Complications and Mortality

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

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Complications related to therapy

Hypoglycemia
Hypophosphatemia ARDS Cerebral edema

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Complications related to therapy

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
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Cerebral edema
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

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Disposition
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

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54

HHNK
Hyperglycemic, Hyperosmolar Noketotic Syndrome

Most commonly occurs in older adults with Type II

diabetes Always look for precipitating factors

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Factors Associated with HHNK

Drugs

Procedures
Chronic illness Acute illness

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Four Major Clinical Features

Severe hyperglycemia

No or slight ketosis
Profound dehydration Hyperosmolality

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Treatment
Similar to DKA

Find underlying cause

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Hyperosmolar Hyperglycemic State

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
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HHNS: Epidemiology
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

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Hyperosmolar Hyperglycemic State

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

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HHNS and DKA both

Hyperglycemia
Hyperosmolarity Severe volume depletion Electrolyte disturbances Occasionally acidosis
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HHNS
Acidosis in HHNS more likely due to: Tissue hypoperfusion

Lactic acidosis

Starvation ketosis Azotemia

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HHNS and DKA Lipolysis

DKA patients have much higher levels of lipolysis
Release and subsequent oxidation of free fatty acids to

ketone bodies

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

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HHNS: Pathophysiology
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

access to water

Fundamental risk factor for developing HHNS is impaired

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HHNS: Pathophysiology
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

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HHNS: Pathophysiology
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 profound volume depletion by replacing lost water with large free water intake

Patients with free access to water are often able to prevent

If water requirement is not met, volume depletion occurs

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 During osmotic diuresis, urine produced is markedly

HHNS: Pathophysiology
hypertonic

Significant loss of sodium and potassium and modest loss of

calcium, phosphate, magnesium and urea also occur GFR is reduced

As volume depletion progresses, renal perfusion decreases and 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

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HHNS: Pathophysiology
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

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HHNS: Pathophysiology
Controversy how counter regulatory hormones glucagons

and cortisol, growth hormone and epinephrine play in HHNS

and this may help prevent lipolysis

Compared to DKA, glucagon and growth hormone levels are lower

Compared to DKA, significantly higher levels of insulin are

found in peripheral and portal circulation in HHNS

they appear to be sufficient to overcome lipolysis

Though insulin levels are insufficient to overcome hyperglycemia,

Animal studies have shown the hyperosmolar state and

severe hyperglycemia inhibit lipolysis in adipose tissue

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HHNS: Clinical Features

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

71

HHNS
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

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HHNS
Those predisposed to HHNS often have some level of
Self-referral for medical treatment in early stages is rare

baseline cognitive impairment such as senile dementia

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
73

HHNS
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

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HHNS Causes 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
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HHNS Causes 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 nondiabetics who present with an acute medical insult such as CVA, severe burns, MI, infection, pancreatitis or other acute illness
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HHNS: Physical findings

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

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HHNS: Physical findings

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

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HHNS: Physical findings

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

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Laboratory tests
Essential Serum glucose Electrolytes Calculated and measured serum osmolality BUN Ketones Creatinine CBC

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Laboratory tests
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
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 Electrolyte abnormalities usually reflect a contraction alkalosis due to profound

Electrolyte abnormalities

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 because the concurrent presence of both metabolic alkalosis and acidosis may result in each canceling out the others effect of the severity of underlying abnormalities, including volume loss

Initial serum electrolyte determinations can be reported as seemingly normal

Lack of careful analysis of serum chemistries may lead to delayed appreciation

82

Sodium
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

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
83

Osmolarity 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 osmolari

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
84

Potassium
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 deficit

Presence of acidemia may mask a potentially life-threatening potassium 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

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Labs 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

86

 Hypophosphatemia may occur during periods of prolonged hyperglycemia Acute consequences such as CNS abnormalities, cardiac dysfunction, and

Phosphate
unless severe

rhabdomyolysis are rare and are usually if level is <1.0 mg/dL

Routine replacement of phosphate and magnesium usually unnecessary 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
87

 Improvement in tissue perfusion is the key to effective recovery Treat hypovolemia, identify and treat precipitating causes,

Treatment

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 reserved for potentially life-threatening electrolyte abnormalities only

Due to potential complications, rapid therapy should only be

88

 Initial aim is reestablishing adequate tissue perfusion and

Fluid resuscitation

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 patients current weight in

kilograms and normal total body water

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 One-half of fluid deficits should be replaced over the initial 12

Fluid resuscitation

hours and the balance over the next 24 hours when possible

Actual rate of fluid administration should be individualized for Initial rates of 500-1500 ml/hr during first 2 hours followed by

each patient based on presence of renal and cardiac impairment rates of 250-500 ml per hour are usually well tolerated
volume repletion

Patients with cardiac disease may require a more conservative rate of

Renal and cardiovascular function should be carefully monitored Central venous and urinary tract catheterization should be

considered

90

 Rate of fluid administration may need to be limited in children A limited number of reports of cerebral edema occurring during or soon after

Fluid resuscitation

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 cerebral edema in HHNS patients

Little credible data on incidence or clinical indicators that may predispose to

91

 Current recommendations based on available data include limiting rate of

Fluid resuscitation

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 plasma volume

NS is hypotonic to the patients serum osmolality and will more rapidly restore Once hypotension, tachycardia and urinary output improve, NS can be used

to replace the remaining free water deficit

92

 Potassium deficits are most immediate electrolyte-based risk for a

Potassium
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

93

 When adequate urinary output is assured, potassium

Potassium

replacement should begin

may require 40 mEq/hr

Should replace at 10-20 mEq/hr though if life threatening 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 a steady state has been achieved

Monitoring of serum potassium should occur every hour until

94

Sodium Sodium deficits replenished rapidly since given NS or 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
95

Insulin
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
96

Insulin 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 NS

and insulin infusion should be reduced to half or 0.05 U/kg/hr.

97

Disposition
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
98

Questions
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:
99

Hypoglycemia
Also known as insulin reaction or hypoglycemic

reaction

100

Hypoglycemia
Weak, sweaty
Confused/irritable/ disoriented

Risk Factors
Overdose of insulin Omitting a meal

Overexertion
Nausea and vomiting Alcohol intake

102

Symptoms of Hypoglycemia
Adrenergic

Neuroglycopenic

Shakiness Irritability Nervousness Tachycardia Tremor Hunger Diaphoresis Pallor Paresthesias

Headache Mental illness Inability to concentrate Slurred speech Blurred vision Confusion Irrational behavior Lethargy LOC, coma, seizure
103

Interventions
Mild carbohydrate 10-15 gram Moderate 20-30 gram of carbs Glucagon, 1 mg SC or IM Severe 50% dextrose 25 g IV Glucagon 1 mg IM or IV
104

Helping others is good, teaching

them to help themselves is better. George Orwell

Slides current until 2008

Chronic Complications of DM

Macrovascular Retinopathy , Cataract Nephropathy Peripheral Neuropathy Autonamic Neuropathy Foot Disease

Macrovascular Coronary Circulation

Cerebral Circulation
Peripheral Circulation

RETINOPATHY- Pathophysiology
Hyperglycaemia increased Retinal blood flow Retinal endothelial cells & pericytes Impaired vascular autoregulation Dilated capillaries + production of vasoactive subsdtances +endothelial cell proliferation Capillary closure CHRONIC RETINAL HYPOXIA Vascular endothelial growth factor(VEGF)