Transcript Alcohol Withdrawal and Delirium

James Stubenrauch, PA-C
April 8, 2016
Objectives:

Understand ETOH withdrawal physiology and
the typical progression of symptoms.

Anticipate patients at risk for DTs and utilize
the CIWA screening tool.

Review treatment modalities.

Increase awareness of potential complications.
Definitions:

Delirium Tremens:
 Severe alcohol withdrawal symptoms
characterized by altered mental status and
autonomic hyperactivity, which, if untreated,
will lead to cardiovascular collapse. (1)
1.
http://emedicine.medscape.com/article/166032-overview
What is too much?
Low risk for developing alcohol use disorder:

Women: ≤ 7 drinks per week and ≤ 3 drinks in a day.

Men: ≤ 14 drinks per week and ≤ 4 drinks in a day

Standard drink = 14 gm (0.6 oz) of pure alcohol. 5 oz wine
(12%), 12 oz beer (5%), 1.5 oz liquor (40% or 80-proof).

“Binge”: Men ≥ 5 and women ≥ 4 within about 2 hrs,
sufficient to raise BAC to 0.08%. (1)
1. http://www.niaaa.nih.gov/alcohol-health/overview-alcohol-consumption/moderate-binge-drinking
What is too much?
Low risk for developing alcohol use disorder:

Women: ≤ 7 drinks per week and ≤ 3 drinks in a day.

Men: ≤ 14 drinks per week and ≤ 4 drinks in a day

Standard drink = 14 gm (0.6 oz) of pure alcohol. 5 oz wine
(12%), 12 oz beer (5%), 1.5 oz liquor (40% or 80-proof).

“Binge”: Men ≥ 5 and women ≥ 4 within about 2 hrs,
sufficient to raise BAC to 0.08%. (1)
1. http://www.niaaa.nih.gov/alcohol-health/overview-alcohol-consumption/moderate-binge-drinking
ETOH by the Numbers:

At least 8 million alcoholics in US.

500,000 occurrences each year of withdrawals needing
pharmacologic tx. Incidence of DTs is 5% and mortality up to 5%.

Untreated withdrawal seizures lead to DTs in 33% of patients. (1)

38,000 people in US drink “too much”. Only 1 in 6 talk to their
provider about it. (2)

Tendency to underestimate is 76%-49% in low, moderate, heavy
drinkers, respectively. (3)
1.
Management of drug and alcohol withdrawal. AU Kosten TR, O'Connor PG SO N Engl J Med. 2003;348(18):1786.
http://www.cdc.gov/vitalsigns/alcohol-screening-counseling/index.html
http://nymag.com/scienceofus/2014/06/people-underestimate-how-much-they-drink.html
2.
3.
ETOH Metabolism:

Absorption rate varies (body fat, food consumption, etc).

Metabolized at about 1 standard drink per hour. (1)

From 0.08 BAC to zero = about 5 hours.(2)
1.
2.
http://www.drinkfox.com/information/alcohol-metabolism
http://forcon.ca/learning/alcohol.html
Withdrawal Pathophysiology:

The brain’s excitability stays in balance via GABA
(inhibitory NT) and Glutamate (excitatory NT).

ETOH enhances GABA’s effect on GABA receptors,
which leads to decreased overall brain excitability.
Overtime the brain becomes less sensitive to GABA’s
depressant effects (which accounts for increasing
tolerance of ETOH).

The body up-regulates the glutamate receptors to
compensate for the increased inhibitory GABA.
1.
http://www.aafp.org/afp/2004/0315/p1443.html
Withdrawal Pathophysiology:

Chronic ETOH: Glutamate receptors up-regulated
and GABA receptors are down-regulated.

Withdrawal: ↓GABA transmission (less inhibition)
and ↓Glutamate inhibition (more excitation).
1.
2.
http://emedicine.medscape.com/article/166032-overview
A McKeon, M A Frye and Norman Delanty J. Neurol. Neurosurg. Psychiatry 2008;79;854-862;
Three Sets of Symptoms:
1. Autonomic Hyperactivity
- Tremors, sweating, N/V, anxiety, agitation
2. Neuronal excitation
- Seizures, global confusion.
3. Delirium Tremens
- Auditory/visual hallucinations, confusion,
significant autonomic hyperactivity.
Alcohol Hallucinosis ≠ DTs. Self-limited hallucinations
occurring within 12-24 hrs without general sensorium
clouding and usually normal vital signs.
1.
http://www.uptodate.com/contents/management-of-moderate-and-severe-alcohol-withdrawalsyndromes?source=preview&search=alcohol+withdrawal&language=en-US&anchor=H22&selectedTitle=1~69#H8
Timing of Withdrawal Symptoms:
Diagnosis:

Better to diagnose early…
 Retrospective study in NZ of 2000 trauma patients: only 7.3% had
adequate screening history.
 Consider asking family/significant other privately.
 Inquire about hx of DTs, seizures, total # of all types of ETOH drinks.

Can be seen with an admission BAC of zero. (2)
(2) http://www.ncbi.nlm.nih.gov/pubmed/25062967
Predicting….?
• PAWSS may become useful
screening tool.
• Goal: find who is at risk for
complicated withdrawal (eg.
seizures and DTs).
• Questions based on previous
literature of sx associated with
complicated withdrawal.
• Good prediction model in
validating study of 403 patients
using cut off score of 4.
CIWA-ar Protocol:
Scored 0 (best) to 7 (worst)
1. Nausea/vomiting.
2. Tremors
3. Paroxysmal Sweats
4. Anxiety
5. Agitation
6. Orientation (0-4)
7. Tactile Disturbances
8. Auditory Disturbances
9. Visual Disturbances
10. Headache
CIWA Scores:

Maximum Score = 67




0 to 9 Points: Very mild withdrawal.
10 to 15 Points: Mild withdrawal.
16 to 20 Points: Modest withdrawal.
21 to 67 Points: Severe withdrawal. (1)

ARRMC: Treat scores ≥ 8.

CIWA on admission, q 1-4 hrs x 72 hrs, prior to
treatment and 1 hr after treatment, and prn.

Continue x 72 hrs. D/C after 72 hrs and when score
< 8 x 24 hrs.
1.
http://www.uptodate.com/contents/management-of-moderate-and-severe-alcohol-withdrawalsyndromes?source=search_result&search=ciwa&selectedTitle=1%7E6
General Tx and Care:

Calm, quiet room.

Side rails up per protocol.

Vitamin replacement (MVI, folate, thiamine).

Volume and electrolyte management.
Treatment:

Benzodiazepines are cornerstone of tx.

Mechanism: Increases GABA transmission.
 ?which one to use
 ?scheduled vs prn
 ?short acting vs long-acting
Benzodiazepines:

One BZD not superior to the other. However…
 Short acting better for rapid sx control
○ Diazepam and lorazepam more rapidly absorbed
 Long acting = ?smoother detox (eg chlordiazepoxide).
 Liver dz: Prefer shorter acting (eg Lorazepam). (1-2)
 Lorazepam gtt > 0.1 mg/kg/hr = propylene glycol toxicity.
Name
Equiv dose
Onset (oral)
Duration
Lorazepam
1 mg
0.5-1 hr
Medium
Diazepam
5 mg
0.25-0.5 hr
Long
Alprazolam
0.5 mg
1 hr
Short
Chlordiazepoxide
10 mg
1 hr
Long
1. http://www.ncbi.nlm.nih.gov/pubmed/8700792
2. http://www.uptodate.com/contents/image?imageKey=PC%2F65653&topicKey=PSYCH%2F14631&rank=2%7E150&source=see_link&sea
rch=benzodiazepines&utdPopup=true
Treatment:
Symptom driven vs fixed schedule dosing?

Symptom driven therapy is better.
 Less BZD use.
 Shorter treatment duration.
 No significant differences in severity of withdrawal
during tx or incidence of seizures or DTs.
1.
2.
3.
4.
JAMA. 1994;272(7):519.
Arch Intern Med. 2002;162(10):1117.
Emerg Med J. 2012 Oct;29(10):802-4. Epub 2011 Oct 19.
Intensive Care Med. 2003;29(12):2230.
Dexmedetomidine:

IV selective alpha-2 agonist (“clonidine properties”).

Induces “cooperative sedation” with anesthetic, anxiolytic,
analgesic properties.

Peak: 15-30 minutes. Dose-dependent duration of action:
60-120 min. Suggest avoiding loading doses. (2)

Watch for bradycardia and hypotension, rebound.

An adjunct to BZD, not a replacement.
1.
http://www.sccm.org/SiteCollectionDocuments/Dexmedetomidine%20for%20Acute%20Alcohol%20Withdrawal.pdf
http://www.uptodate.com/contents/dexmedetomidine-drug-information?source=preview&search=%2 Fcontents%2Fsearch &anchor= F158340&
selectedTitle=1~53#F158340
2.
Dexmedetomidine:

Randomized controlled trial of 72 ICU pts. CIWA-ar scores
25 at admission for both groups.

Intervention: Dex plus symptom-triggered Diazepam. Dose
0.2-1.4 mcg/kg/hr. Target RASS -2 to 0. Only one patient in
each group excluded due to severe sx.

Dex group got significantly less Diazepam (60 vs 90 mg).
More time at RASS goal. Less Haldol. Less oversedation.
Increased nursing satisfaction. No significant differences in
LOS. Non-significant increase in DTs in control group.
1.
Bielka et al. Ann. Intensive Care (2015) 5:33. DOI 10.1186/s13613-015-0075-7
Dexmedetomidine:

Randomized controlled trial of 72 ICU pts. CIWA-ar scores
25 at admission for both groups.

Intervention: Dex plus symptom-triggered Diazepam. Dose
0.2-1.4 mcg/kg/hr. Target RASS -2 to 0. Only one patient in
each group excluded due to severe sx.

Dex group got significantly less Diazepam (60 vs 90 mg).
More time at RASS goal. Less Haldol. Less oversedation.
Increased nursing satisfaction. No significant differences in
LOS. Non-significant increase in DTs in control group.
1.
Bielka et al. Ann. Intensive Care (2015) 5:33. DOI 10.1186/s13613-015-0075-7
What about Alcohol?
JAMA 2003 = majority of surveyed
hospitals had ETOH on formulary.
 Harmful secondary effects, drunkenness.
 Who titrates?
 Nihilistic
 Efficacy not proven.

1.
JAMA. 2003;289(5):552. doi:10.1001/jama.289.5.552.
Acute Complications:

Seizures
 Tonic-clonic, usually occur 12-48 hrs since last drink, but
can be within 2 hrs. ↑ risk = chronic ETOH).
 Tx with benzodiazepines. Phenytoin ineffective.

Respiratory failure
 SpO2, EtCO2, acoustic respiration monitor.
 ↑ benzo need = ↑ risk.

Electrolyte disturbances:
 Hypomagnesemia = ↑ risk dysrhythmias/seizures.
 Hypophosphatemia = if severe, then risk of cardiac failure,
rhabdomyolysis.
1.
http://www.uptodate.com
Wernicke Encephalopathy:
Thiamine (B1) deficiency.
 ETOH can ↓ thiamine absorption in S. intestine.
 Classic triad of ataxia, confusion, and ophthalmoplegia
(only seen in 33%).
 If untreated progresses to coma and death.
 Primarily a clinical diagnosis.

1.
http://www.uptodate.com
Wernicke Encephalopathy:

Treatment:
 Thiamine 500 mg IV tid x 2 days, then 250 mg
IV/IM qd x 5 days.
 Prophylactic dose: 100 mg IV/PO daily.

Prolonged administration of glucose without
thiamine may precipitate or worsen WE.

Do not delay necessary glucose! (1)
1.
Ann Emerg Med. 2007 Dec;50(6):715-21. Epub 2007 Aug 3.
Summary:

Common.

Easier to treat early than late.

If you don’t ask you won’t know.

Use prn benzo protocol with validated
monitoring tool (CIWA).

Be vigilant for complications.
Intermission…
Next year’s conference location
ICU Delirium:

Understand prevalence and dangers of delirium.

Identify risk factors for developing delirium.

Review the screening tool for delirium.

Review risks/benefits of pharmacologic tx.

Understand non-pharmacologic interventions.

Develop a practical step-wise approach to assessing and
managing delirium.
Waxing and
waning mental
status
Decreased
awareness of
environment
Inattention and
confusion
DELIRIUM
Transient
and
usually
reversible
Acute change from
baseline
The DSM-V Five Key Features:
1.
Disturbance in attention (reduced ability to direct, focus, sustain, and shift
attention) and awareness.
2.
The disturbance develops over a short period of time (usually hours to days),
represents a change from baseline, and tends to fluctuate during the course
of the day.
3.
An additional disturbance in cognition (memory deficit, disorientation,
language, visuospatial ability, or perception).
4.
The disturbances are not better explained by another preexisting, evolving or
established neurocognitive disorder, and do not occur in the context of a
severely reduced level of arousal, such as coma.
5.
There is evidence from the history, physical examination, or laboratory findings
that the disturbance is caused by a medical condition, substance
intoxication or withdrawal, or medication side effect. (1)
1.
http://www.uptodate.com/contents/diagnosis-of-delirium-and-confusional-states?source=preview&language=enUS&anchor=H3&selectedTitle=1~150#H8
Delirium Etiologies:

Disease specific (eg infectious).

Drug/ETOH withdrawal.

Drug/ETOH toxicity (eg DTs, benadryl OD).

Iatrogenic.
1.
http://www.learnicu.org/SiteCollectionDocuments/Pain,%20Agitation,%20Delirium.pdf
Delirium Types:

Hyperactive: easy to recognize. Occurs in only
5-22% of delirium patients.

Hypoactive is under recognized and treated

Most delirium is hypoactive or mixed.

Patient with hypoactive delirium often “peacefully smile, nod, and say
yes to all questions. “

Hyper: more delusions/hallucinations. Hypo: more confusion/sedation.

Easy to miss signs of “inattention and decreased awareness of the
environment.” (1,2)
1.
2.
http://www.medscape.com/viewarticle/709975_2
http://www.learnicu.org/SiteCollectionDocuments/Pain,%20Agitation,%20Delirium.pdf
Differential Diagnosis:
Sundowning: (pre-existing in dementia patients).



A predictable increase in neuropsychiatric symptoms developing
later afternoon or after. Etiology: ?melatonin decrease,
environmental. If NEW, this should be presumed to be delirium.
Non-convulsive status epilepticus.

Dementia.

Primary psychiatric illness. (1,2)
1.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3246134/
http://www.uptodate.com/contents/diagnosis-of-delirium-and-confusional-states?source=preview&language=en-US&anchor=H3&selectedTitle=1~150#H8
2.
Delirium vs Dementia:
1.
http://www.cancernetwork.com/oncology-nursing/cognitive-impairment-older-adults-cancer
How Common is it?

Nearly 30% of older medical patients in hospital.

Surgical patients: 10 to > 50%. (1)

Up to 80% of mechanically ventilated patients. (2)
Key – assess risk factors and anticipate delirium.
1.
2.
http://www.uptodate.com/contents/diagnosis-of-delirium-and-confusional-states?source=preview&language=enUS&anchor=H3&selectedTitle=1~150#H3
ICUdelirium.org
Why treat delirium?
 Prolonged hospital stay.
 Functional and cognitive decline. A study of CT surgery patients
showed a persistent drop in MMSE scores at 6 months. (1)
Another study showed deficits in some patients at 12 months to
be similar to patients with moderate TBI. (2)
 Higher risk for institutionalization.
 Delirium is an independent marker for mortality. (3)
 Distressing to patients, to family, and to staff.
 Estimated $4-16 billion annually to treat. (4)
1.
2.
3.
4.
N Engl J Med. 2013;369(14):1306.
N Engl J Med. 2012 Jul;367(1):30-9.
http://www.uptodate.com/contents/diagnosis-of-delirium-and-confusional-states?source=preview&language=enUS&anchor=H3&selectedTitle=1~150#H8
http://www.learnicu.org/SiteCollectionDocuments/Pain,%20Agitation,%20Delirium.pdf
What can we do?

Anticipate/prevent

Recognize

Treat

Educate
Anticipate Who’s at Risk:

Advancing age and frailty.

Complex procedures (cardiac surgery).

Underlying brain diseases: eg dementia, stroke,
Parkinson disease.

Presence of precipitating factors…
1.
http://www.uptodate.com/contents/diagnosis-of-delirium-and-confusional-states?source=preview&language=enUS&anchor=H3&selectedTitle=1~150#H3
Precipitating Factors








1.
Polypharmacy.
Infection.
Dehydration.
Immobility.
Restraints.
Malnutrition.
Foley catheters.
Sleep deprivation.
http://www.uptodate.com/contents/diagnosis-of-delirium-and-confusionalstates?source=preview&language=en-US&anchor=H3&selectedTitle=1~150#H3
Common Drugs causing Delirium:

Opiates, especially Demerol.

Benzos. Benzos. Benzos.

Anticholinergics (benadryl, Flowmax, meclizine, promethazine).

H2 blockers (famotidine, scopolamine). (1)

Medications may account for 12-39% of delirium. (2)
1.
2.
http://www.uptodate.com/contents/diagnosis-of-delirium-and-confusional-states? source=preview& language=enUS&anchor=H3&selectedTitle=1~150#H3
Crit Care Nurse 2009;29:85-87 doi: 10.4037/ccn2009986
Ativan and delirium:

Cohort study of 198 pts on ventilator.
Ativan independent risk factor for delirium.

Fentanyl, Morphine, propofol not
statistically significant odds ratios. (1)

Take home : avoid benzos if possible.
1.
Anesthesiology. 2006 Jan;104(1):21-6.
Getting “rest” in the ICU:

Sleep deprivation is very common.

Total sleep time may be normal, but percentage of time in stage
2, 3, 4, and REM sleep is poor.

Sleep is highly fragmented. 50% of sleep occurs during the day
in short bouts.

Noise levels in the ICU have been shown to range from mean
levels of 53 to 65 dB to peak levels greater than 80 dB
throughout a 24-hour period. (1)

Vacuum cleaner is 70 decibels.

Benzodiazepines, antipsychotics, and opiates are all associated
with REM suppression.
1.
2.
SLEEP 2006;29(5): 707-716.
https://www.chem.purdue.edu/chemsafety/Training/PPETrain/dblevels.htm
(2)
Screening:
 “If delirium is not screened for using a
validated delirium screening tool it is missed
~75% of time. “
 Inouye SK Arch Intern Med. 2001;161:2467-2473.
 Devlin JW Crit Care Med. 2007;35:2721-2724.
 Spronk PE Intensive Care Med. 2009;35:1276-1280.
 van Eijk MM Crit Care Med. 2009;37:1881-1885.
1.
http://www.icudelirium.org/docs/abcdef_educationalslides.pdf
Confusion Assessment Method for the
ICU: (CAM-ICU)
Focuses on:

Onset (acute onset or fluctuating RASS).

Inattention.

Disorganized thinking.
Notice that orientation questions aren’t featured.
Delirium Assessment:
First assess LOC…
Delirium Assessment:
First assess LOC…
Then assess the CONTENT OF CONSCIOUSNESS…
CAM-ICU:

If Features 1, 2, & 3 are present, then
there is NO need to assess Feature 4.

If either features 1 or 2 are absent then
you do not have to proceed because the
patient cannot be CAM + without them.

Check at least q shift.
Management:

Consider and treat alternate causes.

Non-pharmacologic treatments.

Medications to treat delirium?

Medications to prevent delirium?
Alternative Causes:
D: drugs (don’t forget ETOH, street drugs).
E: Eyes, ears, and other sensory deficits.
L: Low O2 states (e.g. heart attack, stroke, PE).
I: Infection.
R: Retention (of urine or stool).
I: Ictal state.
U: Underhydration/undernutrition.
M: Metabolic causes (DM, post-op state, sodium
abnormalities).
(S)Subdural hematoma.
http://www.icudelirium.org/terminology.html
Management: Non-pharmacologic:

Keep Oriented: clocks, calendars, etc.

Encourage interaction with family, care-givers.

Provide hearing aids, glasses, etc.

Manage pain.

Avoid restraints and remove foleys if possible.

Increase mobility and physical therapy. (1)

Physiologic sleep (one study showed that ear-plugs reduced
delirium). (2)
1.
http://www.uptodate.com/contents/delirium-and-acute-confusional-states-prevention-treatment-and-prognosis?source=preview&language=enUS&anchor=H104295692&selectedTitle=2~150#H104295698
Crit Care. 2012 May;16(3):R73. Epub 2012 May 4.
2.
Prevention in Ventilated Patients:

MENDS trial: Double-blind RCT of 106 medical and
surgical vented patients. Sedated with Precedex vs
Lorazepam up to 120 hours. (1)
 Evaluated with RASS and CAM-ICU.
 Precedex use “resulted in more days alive without delirium or
coma (median days, 7.0 vs 3.0; P = .01) and more time at the
targeted level of sedation” (median percentage of days, 80% vs
67%; P = .04).

SAT and SBT
 Awake and Breathe (ABC Trial). 2008. Decreased time on the
ventilator, reduced time spent in the ICU and hospital, and
improved one-year survival. (2) (3)
1.
2.
1.
JAMA. 2007 Dec 12;298(22):2644-53.
http://www.icudelirium.org/docs/abcdef_educationalslides.pdf
http://www.thelancet.com/article/S0140-6736(08)60105-1/abstract
When to use Drugs?

If behavior is dangerous to patient/others.

NOT a substitute for non-pharmacologic
management!

Limited data supports the use of neuroleptics.

Hypoactive delirium probably has similar
response to haloperidol as agitated delirium.
Antipsychotics:

Bind to various dopamine receptors, blocking the NT
dopamine from binding to that receptor.

“Typical” or 1st Generation: eg. Haloperidol. Blocks all D2
receptors, including receptors involved in movements
(potential for undesirable motor side effects).

“Atypical” or 2nd Gen: eg. Quetiapine, Olanzapine. Lower
affinity for D2 receptors, readily bind to D3/D4 receptors.(1)

Newer atypical antipsychotics have fewer side effects and
appear to have similar efficacy. (2)
1.
2.
https://web.williams.edu/imput/synapse/pages/IIIB5.htm
http://www.uptodate.com/contents/delirium-and-acute-confusional-states-prevention-treatment-and-prognosis?source=preview&language=en-US&anchor=H7363389&selectedTitle=7~117#H104295711
Haloperidol:

Most studied neuroleptic.

A first generation antipsychotic.

Inhibits dopamine-mediated effects.

Lower incidence of anticholinergic effects compared to
other anti-psychotics.

Low affinity for histamine H1 and muscarinic M1 receptors
(less hypotension and sedation).

Weak antiemetic effects. (1)
1.
https://www.glowm.com/resources/glowm/cd/pages/drugs/h001.html
IV Haloperidol:

Onset: 5-10 minutes. Peak 20-30 minutes. Duration: 4-5 hrs. (1)

Avoid in Parkinsonism (use atypicals instead).

Vanderbilt protocol: 2-5 mg IV once (0.5-2mg in elderly), then q 6 hrs up
to 20 mg per day. (2)

QT prolongation – caution if QT > 440 msec. Hold if QT > 25% from
baseline. (2)

Review baseline QT. Consider serial EKGs. Avoid hypokalemia.
lower seizure threshold in ETOH patients. (1)

Don’t confuse Decanoate (IM depot only) with lactate (IV ok).

IV Haldol may be associated with less EPS effects than oral
(4)
3.
http://dig.pharm.uic.edu/faq/2013/Feb/faq2.aspx
http://www.uptodate.com/contents/delirium-and-acute-confusional-states-prevention-treatment-and-prognosis?source=preview&language=enUS&anchor=H7363389&selectedTitle=7~117#H7363389
http://www.icudelirium.org/docs/Delirium_Protocol_2001_30_07.pdf
4.
http://www.drugs.com/monograph/haloperidol-lactate.html
1.
2.
(3)
May
2nd Generation Antipsychotics:

Quetiapine (Seroquel). PO.
 No renal adjustment.
 Start 25 mg q 12 hrs. Increase by 25 mg daily as needed.
Max 800 mg day.
 Lower incidence of EPS (doesn’t bind D2 receptors tightly).

Olanzapine (Zyprexa). PO, IM, SL.
 No renal adjustment.
 Start 2.5 mg q hs. Max 20 mg/day.

Risperdone (Risperdal). PO.
 Needs renal and hepatic adjustment.
 Start 1 mg q 12 hrs. ↑ 0.5-1mg q 2-3 days. Max 6 mg.
1.
http://www.uptodate.com/
Seroquel plus Haldol Study:
“Efficacy and safety of quetiapine in critically ill patients with delirium: a
prospective, multicenter, randomized, double-blind, placebo-controlled pilot
study.” (1)

DESIGN: Three academic medical centers. Thirty-six adult ICU patients
with delirium (Intensive Care Delirium Screening Checklist score >or = 4),
tolerating enteral nutrition, and without a complicating neurologic condition.

INTERVENTIONS: Randomized to quetiapine 50 mg q 12 hrs or placebo.
Quetiapine ↑ q 24 hrs if > 1 dose of haldol given in the previous 24 hrs.

OUTCOMES WITH SEROQUEL GROUP:
 More likely to discharge to home or rehab.
 Associated with a shorter time to first resolution of delirium.
 Mortality and ICU LOS unchanged.
 Quetiapine group received less prn Haldol.
 QTc and EPS symptoms similar between groups.
 More somnolence with Quetiapine.
1.
Crit Care Med. 2010;38(2):419.
Prophylactic Medications?

No strong evidence yet to support routine use.
 Cholinesterase inhibitors (e.g. donepezil) did not reduce
incidence; increased side effects. (1)
 Anti-psychotics: 2013 meta-analysis showed reduced
incidence, but not in severity or duration, or reduced AEs.
2nd Gen antipsychotics better than haloperidol. (2)
 Possible role for Gabapentin, melatonin.
 Appropriate analgesia.
(1)
Crit Care Med. 2009;37(5):1762.
(2)
J Clin Psychiatry. 2013 Dec;74(12):e1136-44.
So why not use these more?
1st Generation Side Effects:

EPS*

NMS

Tardive dyskinesia

QT prolongation.

1.
* Extrapyramidal system : part of the motor system involved in modulation and regulation of movement. Distinct from
corticospinal and corticobulbar tracts. Connects cerebral cortex, basal ganglia, thalamus, cerebellum, reticular formation,
and spinal neurons. Includes red nucleus and substantia nigra.
http://radiopaedia.org/articles/extrapyramidal-system
BLACK BOX
Increased Mortality in Elderly Patients with Dementia-Related
Psychosis: Elderly patients with dementia-related psychosis treated
with antipsychotic drugs are at an increased risk of death. Analyses of
seventeen placebo-controlled trials (modal duration of 10 weeks),
largely in patients taking atypical antipsychotic drugs, revealed a risk of
death in drug-treated patients of between 1.6 to 1.7 times the risk of
death in placebo-treated patients. Over the course of a typical 10 week
controlled trial, the rate of death in drug-treated patients was about
4.5%, compared to a rate of about 2.6% in the placebo group.
Although the causes of death were varied, most of the deaths
appeared to be either cardiovascular (e.g., heart failure, sudden death)
or infectious (e.g., pneumonia) in nature. Observational studies
suggest that, similar to atypical antipsychotic drugs, treatment with
conventional antipsychotic drugs may increase mortality. The extent to
which the findings of increased mortality in observational studies
may be attributed to the antipsychotic drug as opposed to some
characteristic(s) of the patients is not clear. (1)
1.
http://www.rxlist.com/haldol-decanoate-drug.htm
Extrapyramidal (EPS) Symptoms:

Akathisia: the most common EPS. Motor
restlessness and compelling urge to move.

Parkinsonism: resting tremor, shuffling gait,
bradykinesias.

Dystonia: involuntary contractions of major muscle
groups, torticollus, oculogyric crisis, opisthotonos.
Acute tx: diphenydramine.

Tardive Dyskinesias: Generally not seen with tx < 6
months. Usually tx > years.
1.
http://www.uptodate.com/contents/tardive-dyskinesia-etiology-and-epidemiology?source=
machineLearning&search=tardive+dyskinesia&selectedTitle=3%7E150&sectionRank=3&anchor=H15#H13
Management Algorithm:
CAM Positive
Check vitals. Consider DDX (infx, NH3, SZ, etc)
D/c deliriogenic drugs. Non-pharm protocol.
Assess catheters, restraints, insomnia, etc.
Check RASS
RASS > +2
RASS -1 to -5
RASS 0 to +1
Treat pain. Consider neuroleptic
http://www.icudelirium.org
Reassess sedation
Consider neuroleptic
Education:
Support for patient and family:
 Reassure and reorient patient.
 Educate family.
 Emphasize family’s role in promoting a safe,
familiar environment.
 Consult spiritual care, social work.
 Bring in home mementos.
Summary:

Anticipate delirium and look for hypoactive form.

Use validated screening tool. You won’t recognize it if you
don’t look for it!

Focus on prevention (timely removal of catheters,
offending meds, timely SATs and SBTs).

Emphasize non-pharmacologic measures.

Neuroleptics if needed. Start low dose.

Monitor for AE’s with neuroleptics.

Educate and support patient and family.