Delirium Flashcards
__% of patients arriving to the ED are altered.
__% metabolic or systemic derangements.
__% structural lesions
3% of patients arriving to the ED are altered.
85% metabolic or systemic derangements.
15% structural lesions
What are the two components of consciousness?
Arousal
Cognition
What is arousal?
How is it controlled?
Where does it act in the CNS?
- Awareness of self & surroundings
- Ascending reticular activating system
- Where in the CNS? Dorsal brainstem
- Controls input of somatic & sensory stimuli, arousal from sleep
- Vulnerable to small lesions in brainstem
What is cognition?
How is it controlled?
Where does it act in the CNS?
- Combo of orientation (accurate perception of experiences), judgment (process input into meaningful info), & memory (store & retrieve info)
- Located in cerebral cortex
- Unilateral lesions rarely cause AMS
- Possibly bilateral lesions (rare)
What is a coma?
How is it caused?
- Coma = unconsciousness >6 hours
- Cannot be awakened
- No response to painful stimuli, light or sound
- No normal sleep-wake cycle
- No voluntary actions
- Causes
- Damage to brainstem, cortex, both
- Susceptible to toxins, metabolic derangements, mechanical injury
What are the 3 most common causes of altered mental status?
- Dementia
- Delirium
- Psychosis
When you have acute mental status change, what is the difference between fluctuating & non-fluctuating when determining a differential?
-
Fluctuating
- Delirium
-
Non-fluctuating
- Acute confusional state
- Differential includes delirium or a long list of CNS insults including toxic metabolic derangement, infection, trauma
What are some common causes of Delirium? (7)
- Metabolic/Endocrine
- Infectious Disease
- Cerebrovascular event/Structural CNS
- Both hemispheres or brainstem
- Cardiovascular
- Drugs/Toxic
- Hypoperfusion
- Others
What are some examples of drugs that can cause delirium?
- Alcohol withdrawal
- Diuretics
- Anti-cholinergics
- Corticosteroids
- Digoxin
- Opioids
- Anti-depressants
- Anxiolytics
- Hallucinogens/Dissociatives
- Benzodiazepines
- Sympathomimetics
How do these differ btwn Delirium & Dementia?
- History
- Onset
- Duration
- Course
- Level of consciousness
- Orientation
- Memory
- Perception
- Sleep
- Reversibility
- Physiologic changes
- Attention span
- History
- Delirium: acute, identifiable date
- Dementia: chronic, can’t be dated
- Onset
- Delirium: rapid
- Dementia: insidious
- Duration
- Delirium: days to weeks
- Dementia: months to years
- Course
- Delirium: fluctuating
- Dementia: chronically progressive
- Level of consciousness
- Delirium: fluctuating
- Dementia: normal
- Orientation
- Delirium: impaired periodically
- Dementia: disorientation to person
- Memory
- Delirium: recent memory markedly impaired
- Dementia: remote memories seen as recent
- Perception
- Delirium: visual hallucinations
- Dementia: hallucinations less common
- Sleep
- Delirium: disrupted sleep-wake cycle
- Dementia: less sleep disruption
- Reversibility
- Delirium: reversible
- Dementia: mostly irreversible
- Physiologic changes
- Delirium: prominent
- Dementia: minimal
- Attention span
- Delirium: very short
- Dementia: not reduced
What are some common age-related causes of altered mental status or coma?
- Infant
- Child
- Adolescent, Young Adult
- Elderly
-
Infant
- Infection
- Trauma, abuse
- Metabolic
-
Child
- Toxic ingestion
-
Adolescent, Young Adult
- Toxic ingestion
- Recreational drug use
- Trauma
-
Elderly
- Medication changes
- Over-the-counter medications
- Infection
- Alterations in living environment
- Stroke
- Trauma
What are some diseases that are more likely to cause delirium?
- Severe illness
- Drug toxicity
- Fluid & electrolyte disturbances
- Hyponatremia & azotemia
- *central pontine myelinolysis*
- Infections
- Hypothermia or hyperthermia
What is Central Pontine Myelinolysis?
*stressed in class, info here from First Aid*
- Acute paralysis, dysarthria, dysphagia, diplopia & loss of consciousness
- Can cause “locked-in syndrome”
- Massive axonal demyelination in pontine white matter tracts
- Secondary to osmotic forces & edema
- Commonly iatrogenic, caused by overly rapid correction of hyponatremia
Delirium is a _____ that has an underlying cause that must be recognized & identified.
The most important clue to delirium is the _________ and _________.
Delirium most commonly occurs in ______ and patients with underlying ____________.
Delirium is very common in _______ patients over the age of ____.
symptom
acuity of onset, fluctuation in course
older persons, neurologic disease
sick, hospitalized, 65
What are some predictors of delirium? (7)
- Abnormal sodium level
- Severe illness
- Chronic cognitive impairment
- Hypothermia or hyperthermia
- Moderate illness
- Psychoactive drug use
- Azotemia
What are the first steps in management of a patient presenting with delirium?
ABCDEs
-
Airway
- hypoxia –> CNS dysfunction –> delirium
-
Breathing
- low minute ventilation
- respiratory acidosis
-
Circulation
- hypoperfusion of the brain
- check pulses
- Trendelenburg position (picture)
-
Disability
- Glasgow coma scale
-
Exposures
- trauma, transdermal meds, dialysis devices, infections, catheter, skin
AMS =
LOC =
AMS = altered mental status
LOC = loss/level of consciousness
What type of information gathering is performed with a delirium patient?
- All sources of information
- EMS (Emergency Medical Services)
- Family
- EMR (Electronic Medical Record)
- GCS for classification
- Glasgow Coma Scale
What is the Glascow Coma Scale?
*Study this table*
What is the next step after ABCs & the GCS?
- Basic neuro exam
- Differential
-
Work-up
- “DON’T” coma cocktail
- Labs
- Imaging
- Other tests (EKG, lumbar puncture)
- Treatment
- Antidotes, antibiotics, surgery, supportive care, metabolic cofactors (thiamine, folate)
What is the “coma cocktail”?
What is it used for?
Alleviates common causes of delirium
- Dextrose
- Oxygen
- Naloxone
- Thiamine
What causes of delirium could be alleviated by DEXTROSE?
Hypoglycemia
- Insulin (+ don’t eat)
- Sulfonylureas (+ don’t eat)
- Anorexia
- Alcohol (malnourished, children)
- Drinks, hand sanitizer
- Beta blockers
What causes of delirium could be alleviated by OXYGEN?
Decreased respiratory drive
- Carbon monoxide exposure
- Opiates (opioids)
- Alcohol (drug combos)
What causes of delirium could be alleviated by NALOXONE?
Opioids
(morphine, heroin, oxycodone, fentanyl, tramadol, etc.)
What is the Confusion Assessment Method? (CAM)
What is the sensitivity & specificity?
Best-validated tool for diagnosing delirium
-
CAM is positive when a patient fulfills both criteria a and b as well as either c or d:
- A) the mental status change is of acute onset & fluctuating course
- B) there is inattention
- C) there is disorganized thinking (or incoherent)
- D) there is an altered level of consciousness
- The test characteristics surpass those of an unaided physician assessment
- Sensitivity: 86%, specificity: 93%
Patient’s who experienced delirium had a higher risk of _______, ____________, & _______ during follow-up.
What are the percentages?
death, institutionalization, dementia
- mortality rate = 38%
- institutionalization = 33.4%
- dementia = 62.5%
Many acutely ill, older patients who have an acute deterioration in mental status are suffering from ______.
Delirium can occasionally “unmask” an underlying ______.
delirium
dementia
1 day old male born at term, still in hospital, & you are called bedside because he is lethargic. He had a C-section due to large gestational size. Poor suck. Mother IDDM.
- A - intact
- B - slow respirations
- C - femoral pulses intact, cap refill 5 seconds
What bedside test do you do? What is most likely?
What should be considered?
- Blood glucose, could give dextrose
- Hypoglycemia, Sulfonylureas
- Consider:
- Opioid withdrawal (irritable, poor suck, shrill cry)
- Infection (low immune system, group B strep, birth trauma)
- Hypoventilation (hypoxia, low cap refil, full lungs)
- Trauma (head bleed, intentional trauma)
- Inborn errors of metabolism
What would your differential diagnosis be if the child was 6 wks old, had no prenatal care, and was febrile to 38 degrees C & came in lethargic?
- Meningitis (bacteria)
- Herpetic lesions on head = HSV
- Dehydration
- Alcohol (whiskey)
- Nitrites in well water
- Methemoglobinemia
- Abuse (shaking)
- Honey - botulism
What would your differential diagnosis be if this child were 1 year old, hypoglycemic, lethargic, just at grandma’s house, who has a PMH of DM & HTN?
- Drug cabinet & pill containers
- Boys > girls (65% of poisoned 1 year olds)
- TCAs = seizure, hypoglycemia, altered state
-
“1 pill can kill” for toddler
- Sulfonylureas
- Beta blockers
- High risk for child with manual dexterity
What are some examples of “1 pill can kill” for a toddler?
- Beta blockers
- Sulfonylureas
- Ca2+ channel blockers
- Clonidine
- Buprenorphine
- Oxycotin
- Methadone
- Fentanyl
- Anti-psychotics
What kinds of symptoms predominate with hypoglycemia?
CNS symptoms predominate
- Brain relies almost entirely on glucose
- During prolonged starvation, the brain can use ketones
- Other major organs (heart, liver, skeletal muscle) function during hypoglycemia (use various fuel sources
How does insulin receptor density vary in diabetes?
What is the mean glucose in hypoglycemia?
- In diabetes, density of neuronal insulin receptors varies w/ glycemic control
- Poor glycemic control –> fewer neuronal glucose receptors
- Hypoglycemic symptoms at higher concentrations of glucose
- Mean [glucose] for symptomatic hypoglycemia 78 + 5 mg/dL vs. 53 + mg/dL
What is the interaction btwn sulfonylureas & insulin?
- Normally, insulin released w/ elevation of intracellular ATP
- Sulfonylureas potentiate the effects of ATP at its “sensor”
- Increased intracellular K –> increased intracellular potential opens voltage-gated Ca2+ channels –> increases intracellular Ca2+ concentration
- Increased calcium –> release of insulin
- Binding of sulfonylureas to receptor sites –> insulin release
What is the interaction btwn Meglitinides & insulin?
- Bind to K channels on pancreatic cells –> increased insulin secretion
- Hypoglycemic effects shorter duration
What is the mechanism of Metformin?
Does this cause hypoglycemia?
does NOT cause hypoglycemia
-
Glucose stabilizing by several mechanisms
- Inhibits gluconeogenesis –> decreased hepatic glucose output
- Enhanced peripheral glucose uptake
- Decreased fatty acid oxidation
- Increased intestinal use of glucose
- In skeletal muscle & adipose cells, enhanced activity & translocation of glucose transporters
Previously healthy 17 year old male presenting with AMS. He was found on doorstep by parents, acting paranoid & inappropriate. Has a history of drug & alcohol abuse. Had been at a party with friends, possibly used drugs.
- A - intact
- B - normal breath sounds bilaterally
- C - bounding peripheral pulses, tachycardic
What is the most likely diagnosis? What else is on the differential?
Sympathomimetics
- Stimulant use
- Amphetamines (adderall, cocaine)
- Methamphetamines
- PCP
- Robutussin
- Salvia divinorum (dysphoria)
- MDMA (SIADH)
- Bath salts, anticholinergic toxicity (diphenhydramine), thyrotoxicosis, psychiatric break, hypoglycemia, head trauma, meningitis, withdrawal (alcohol, barbiturates)
What would be your differential if he was a known alcoholic?
If he lived in New Mexico?
Withdrawal
Methamphetamine
All of the following sympathomimetic drugs inhibit the uptake of NE except:
- Cocaine
- Amphetamine
- Venlafaxine
- Buproprion
- Dobutamine
Dobutamine
ß1 > ß2, alpha
What is the action of sympathomimetics?
What are the two types?
- Stimulate sympathetic nervous system
-
Direct-acting
- Bind post-synaptic receptors
- Direct stimulation
-
Indirect-acting
- Increase synaptic concentration of NTs
Describe the components of the monoamininergic synapse
- VMAT
- MAO
- Presynaptic receptor
- Post-synaptic receptor
- DAT, NET, SERT
- COMT
What are the post-synaptic receptors in the NE synapse and what are their effects?
- Galpha(i)
- CNS: inhibition
- Peripheral: vasoconstriction
- Galpha(s)
- CNS: excitation
- Peripheral: bronchodilation, increased HR, vasodilation
What are the cellular responses at the dopamine synapse?
- Brain
- Addiction
- Drug craving
- Choreoathetosis
- Tourette syndrome
- Psychoses
- Peripheral
- Vasodilation
What are the mechanisms of these indirect acting sympathomimetics?
- Cocaine
- Amphetamines
- Molly/Ecstasy (MDMA)
- Bath salts/cathinones
-
Cocaine
- Transport blocker
- DAT, NET, SERT
-
Amphetamines
- False substrate
- DAT, NET, VMAT
-
Molly/Ecstasy (MDMA)
- False substrate
- DAT, NET, SERT, VMAT
-
Bath salts/cathinones
- False substrates/transport blocker
- DAT, NET, SERT, VMAT
What are the mechanisms of these indirect acting sympathomimetics?
- Clorgyline, Pargyline, Selegiline
- Tolcapone
- Clorgyline, Pargyline, Selegiline: MAO
- Tolcapone: COMT
- Note: 5-HT is indolamine, not catecholamine
Describe the False Substrate Mechanism of sympathomimetics
- Amphetamine fills up vesicles
- High amphetamine transport into the presynaptic cell
- Transporters can reverse, amphetamine takes DA with it when it leaves
- High concentration of presynaptic DA in the cytoplasm
- DA purged from presynaptic terminal via reverse transport through transporters
- Activity independent purging of DA & NE from the presynaptic terminals
- High concentrations can have profound pharmacologic effects
- Catecholamines (DA, NE) are very oxidizable
- Brain only has a limited capacity to inhibit oxidation of these compounds
- DA will form oxidized products –> mitochondrial damage in presynaptic terminals (distressed terminals)
- Summary: false substrates can be dangerous!
What is a toxidrome?
- Describes groups of signs & symptoms consistently attributed to particular toxins
- Usually a combination of vital signs & end organ damage (clinically apparent)
What are the components of the sympathomimetic toxidrome?
- Hypertension
- Hyperthermia
- Tachycardia
- Mydriasis
- Diaphoresis
What are the components of the Anticholinergic toxidrome?
Low potency antipsychotics, oxybutinin, ipratropium, ACh receptor antagonists
- Increased HR & BP
- Increased temp
- Mydriasis
- Decreased bowel sounds
- Decreased diaphoresis
What are the components of the Cholinergic toxidrome?
ACh receptor agonists, AChEIs (Donepezil)
- Miosis
- Increased bowel sounds
- Increased diaphoresis
What are the components of the Opioid toxidrome?
morphine, heroin, hydromorphone
- Decreased HR & BP
- Decreased RR
- Decreased temp
- Miosis
- Decreased bowel sounds
- Decreased diaphoresis
What are the components of the Sympathomimetic toxidrome?
epinephrine, cocaine, amphetamine, methylphenidate
- Increased HR & BP
- Increased RR
- Increased temp
- Mydriasis
- Increased bowel sounds
- Increased diaphoresis
What are the components of the Sedative-Hypnotic toxidrome?
benzos, barbs, Z-drugs, anti-histamines
- Decreased HR & BP
- Decreased RR
- Decreased temp
- Decreased bowel sounds
- Decreased diaphoresis
What medications would you give to a patient with a sympathomimetic toxidrome?
What if they became too sedated?
What caution should you take with this?
- Give benzodiazepines
- If too sedated, give flumazenil
- Be concerned about withdrawal
What is the mechanism of Flumazenil?
Why is it’s use limited?
Who is the ideal recipient of it?
- Competitive benzodiazepine receptor antagonist
- Role in patients w/ unknown overdose is limited because seizures & dysrhythmias may develop
- Can induce benzo withdrawal symptoms, including seizures in those who are benzo dependent
-
Ideal antidote for the few patients who:
- Are both naive to benzos & who overdose soley on a benzo OR
- benzo-naive patients whose benzo component must be reverse after procedural sedation
50 year old male found down by family in bathroom. History of chronic back pain. Has multiple ED visits for pain in the last month.
- A - intact
- B - RR 4
- C - weak pulses, cyanotic
What is the most likely diagnosis? What do you give?
- Could be hypnotic, but classic presentation for opioid toxidrome
- Altered mental status
- Decreased respiration
- Pinpoint pupils (left out of history)
- Administer Naloxone
What are the 3 components of the opioid toxidrome?
- Altered mental status (stupor, coma)
- Miosis
- Respiratory depression
What is the mechanism by which opioids such as morphine produce respiratory depression?
- They decrease chemoreceptor sensitivity to carbon dioxide
- Don’t have the “drive to breathe”
What are some examples of amino acid sequence similarities among endogenous opiates?
-
ß-endorphin
- Tyr-Gly-Gly-Phe-_Met_
-
Methionine enkephalin
- Tyr-Gly-Gly-Phe-_Met_
-
Leucine enkephalin
- Tyr-Gly-Gly-Phe-_Leu_
-
Dynorphin A
- Tyr-Gly-Gly-Phe-_Leu_
-
alpha-neoendorphin
- Tyr-Gly-Gly-Phe-_Leu_
Which endogenous peptides are selective for µ and δ receptors? What about κ receptors?
-
µ and δ
- Met-enkephalin
- Leu-enkephalin
- ß-Endorphin
-
κ
- Dynorphin A
- Dynorphin B
- α-Neoendorphin
What is the structure of the opioid receptor?
- Gα1 coupled
- Reduction in AC –> decreased cAMP
- Open K+ channels –> hyperpolarization
What are the opioid clinical effects on each of these systems?
- Cardiovascular
- Dermatologic
- Endocrinologic
- Gastrointestinal
- Neurologic
- Ophthalmologic
- Pulmonary
- Cardiovascular
- Orthostatic hypotension, bradycardia, peripheral vasodilation
- Dermatologic
- Itching, Flushing (histamine)
- Endocrinologic
- Prolactin release, reduced ADH & gonadotropin release
- Gastrointestinal
- Increased anal sphincter tone, increased biliary tract pressure, reduced gastric acid secretion, reduced motility
- Neurologic
- Analgesia, anti-tussive, euphoria, sedation, coma, seizures (meperidine, propoxyphene)
- Ophthalmologic
- Miosis
- Pulmonary
- Acute lung injury, bronchospasm (histamine), respiratory depression
What is the classic triad of Wernicke’s Encephalopathy?
- Confusion
- Ophthalmoplegia
- Ataxia
What are the 2 types of Thiamine deficiency?
What is the difference between them?
-
Wet beriberi: CV disease
- High output cardiac failure
- Peripheral vasodilation & formation of arteriovenous fistulae
-
Dry beriber: Wernicke-Korsakoff Syndrome
- Classic Wernicke triad
- Confusion
- Ophthalmoplegia
- Ataxia
- Korsakoff Syndrome
- Confabulation, memory loss, personality change
- Chronic
- 10-20% mortality
- Peripheral neuropathy common
- Classic Wernicke triad
What are the 2 major molecular targets of ethanol?
What are their functions?
-
GABA receptors
- Suppress neuronal transmission
- Help maintain resting membrane potential in some neurons
-
NMDA receptors
- Learning & memory
What is the structure of the GABA-A receptor?
What is the mechanism of action?
- Pentameric receptor complex
- 2 alpha
- 2 beta
- 1 gamma
- Activation promotes hyperpolarization via chloride flux
What is the interaction btwn alcohol & GABA-A?
What other drugs interact with this receptor?
- Alcohol potentiates GABA & sedative hypnotics
- Chronic alcohol use results in cross tolereance to sedative hypnotics
- Other interactions
- Benzodiazepines (Flumazenil)
- Diprivan (propofol)
- Neurosteroids
- Barbiturates
- Volatile anesthetics (isoflurane)
What are the 2 major pathways and 2 minor pathway of alcohol metabolism?
-
Alcohol dehydrogenase (ADH)
- lower stomach ADH in women
-
Microsomal Ethanol-Oxidizing System (MEOS)
- Primarilty CYP450 2E1 (induced in alcoholics), 1A2, 3A4
- Induction by chronic alcohol intake
- Increases in clearance of other drugs
- Catalase is a minor metabolic pathway of alcohol
How does alcohol react with NMDA receptors?
What about Ketamine & PCP?
What is a common side effect?
- Alcohol is an antagonist of NMDA receptors
- Ketamine & PCP are also antagonists
- Depolarization to remove Mg2+ block
- Side effect: Nystagmus
What are the symptoms & chronology of alcohol withdrawal?
What are the symptoms of Delirium Tremens?
- Hallucinations (visual & tactile)
- Disorientation
- Hypertension
- Tachycardia
- Fever
What are the high risks of Delirium Tremens?
When does this usually occur?
Mortality?
- High risk for seizures & dangerous ventricluar arrhythmias
- Seen in 5% of patients w/ alcohol withdrawal
- 2-4 days after the last drink
- Untreated mortality = 30%
- <5% with treatment
Elderly man with mild COPD. Had surgery complicated by transient hypotension & excessive blood loss. After extubation, wife noted him to be confused on post-op day 3.
- A - intact
- B - RR 12
- C - good distal pulses
What is the diagnosis? differential?
Delirium
- Hyponatremia, electrolyte imbalance
- Infection
- Stroke
- Alcohol withdrawal
- Opioids
- Hypoxic, hypercardic, elevated CO2
- Acute MI
- Seizure
What are 6 things we can do to treat & minimize delirium?
- Treat the underlying cause
- Administer fluids to treat & prevent dehydration
- Avoid sleep deprivation
- Provide a quiet environment
- Keep nightime awakenings to a minimum
-
Protect from falls or self-inflicted injury
- Sitters
- Low-dose neuroleptics
