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This exercise is designed to test your comprehension of material presented in this issue of FOCUS as well as your ability to evaluate, diagnose, and manage clinical problems. Answer the questions below, to the best of your ability, on the basis of the information provided, making your decisions as you would with a real-life patient.
Questions are presented at “decision points” that follow a paragraph that gives information about the case. One or more choices may be correct for each question; make your choices on the basis of your clinical knowledge and the history provided. Read all of the options for each question before making any selections.
You are given points on a graded scale for the best possible answer(s), and points are taken away for answers that would result in a poor outcome or delay your arriving at the right answer. Answers that have little or no impact receive zero points. On questions that focus on differential diagnoses, bonus points are awarded if you select the most likely diagnosis as your first choice. At the end of the exercise, you will add up your points to obtain a total score.

Vignette part 1

You are the attending physician on the psychiatry consultation-liaison service at a large tertiary care hospital. You receive a consult request from the medicine service that reads: “Patient crying, trying to get out of bed. Please evaluate for depression.” You read the patient’s record in the hospital database and learn that he is a 62-year-old divorced man who was admitted to the hospital 1 month ago for a below-the-knee amputation of his left leg, which had been gangrenous. He has severe type 2 diabetes mellitus, and he has not adhered to his medication regimen. Since the amputation he has had “mental status changes” and been treated repeatedly with 5 mg i.m. of haloperidol. He developed aspiration pneumonia during his second week in the hospital and has had three urinary tract infections since admission. He has a sacral decubitus ulcer that is being treated with piperacillin, tazobactam, and gentamycin. He has lost 65 pounds since admission. His medical history is significant for hypertension, treated with 50 mg b.i.d. of atenolol and 0.2 mg b.i.d. of clonidine. His last transesophageal echocardiogram revealed a hypokinetic left ventricle, hypertrophic right ventricle, and an ejection fraction of 20%. He had a four-vessel coronary artery bypass graft 3 years ago after a myocardial infarction. The patient has chronic obstructive pulmonary disease from 80 pack-years of smoking, and obstructive sleep apnea was diagnosed 10 years ago. He has long refused to use a continuous positive airway pressure machine at night because he is “claustrophobic.”
The most recent physical examination revealed the patient to have a ruddy complexion. A nasal cannula was being used, delivering 3 liters of oxygen per minute. His heart rate was regular at 108 bpm, and his blood pressure was 197/100. He had a temperature of 99.5°F, treated 1 hour ago with 800 mg of acetaminophen. He had jugular venous distention at approximately 5 cm, S3 could be appreciated, and a 2/6 systolic murmur in the upper right sternal border and bilateral wheezing on auscultation of the chest could be heard. The patient had 2–3+ pitting edema on his right lower extremity to the knee. His left lower extremity above the knee incision was mildly erythematous, weeping clear fluid in three places where the incision was slightly dehisced. The examination was otherwise unremarkable.
The patient’s most recent lab results, from that morning, were as follows:
CBC: wbc 16.8, hem 10.8, hct 31.4, plt 82
BASIC: Na 127, K 2.4, Cl 99, HCO3 28, Cr 3.2, BUN 148, GLU 188
COMP: Cal 9.7, Alb 3.2, Prot 5.4, AST 26, ALT 22, Alk Phos 177
Urinalysis: leukocyte esterase positive, nitrite positive, wbc>25 per hpf, rbc 2–5 per hpf, hyaline casts 2–3 per hpf
Urine drug screen: positive for opiates, benzodiazepines
Oxygen saturation was 92% on 3 liters via nasal cannula
Chest X-ray showed enlarged heart silhouette, bilateral pleural effusion, no signs of infectious process; evidence of previous open heart surgery.

Decision Point A

Given this history, list the top five issues for this patient that could result in delirium or could exacerbate a delirium. (Check your responses against the list provided in the Answers section. Points are awarded for all correct responses specifically relating to this patient.)
1.
2.
3.
4.
5.

Vignette Part 2

At 7:30 p.m. you are paged by the medicine intern, who wishes to speak with you urgently. You call back and he reports that the patient has pulled out his IV and his Foley catheter. The patient struck two nurses and then a security guard with closed fists as they placed him in four-point restraints. The patient is now stiffening, his head is turning to the side, his tongue looks thickened, he is “making crazy faces,” and he is unable to respond to any external stimuli. The intern is very anxious and wants advice on how to manage this patient. He wants to know if it was appropriate to put the patient into restraints and whether to administer haloperidol.

Decision Point B

Based on this information, your next step should include which of the following? (More than one answer is possible. Points are taken away for incorrect answers. Answers should be prioritized.)
B1. ____Tell the intern that the patient is very likely “sundowning” and that the most appropriate step would be to give him 10 mg i.m. haloperidol immediately. Tell him that you will be there shortly to assess the patient and make further recommendations.
B2. ____ Tell the intern that the patient is likely “sundowning” and that the best course of action is to reorient him, maintain him in four-point restraints, and administer 2 mg of lorazepam intramuscularly or orally every 4 hours for agitation.
B3. ____ Tell the intern that the description of the patient suggests that he is suffering an acute dystonia, likely secondary to the large doses of haloperidol. Tell him that you will be there shortly, but he should immediately give the patient 50 mg i.v. of diphenhydramine. Tell him that an anticholinergic agent could worsen the delirium but that because patients can develop laryngeal dystonia, treatment is necessary. Tell him to remove the restraints as soon as the patient calms down.
B4. ____ Tell the intern that the patient probably has a CNS infection and should be transferred immediately to the intensive care unit. Tell him that an intravenous haloperidol drip of 0.2 mg per hour should be started and a lumbar puncture performed and that empirical treatment of bacterial meningitis should be considered while the patient’s cerebrospinal fluid is evaluated.
B5. ____ Tell the intern that the patient should be placed in a Posey restraint as well as the four-point leather restraints to keep him in bed. Tell him that there is no treatment for this condition and that the patient must “ride it out.” Assure him that this episode will be over within 4–6 hours.

Vignette Part 3

You check the patient’s current medications list, which includes the following:
1.
Glyburide 5 mg p.o. daily
2.
Metformin 500 mg p.o. b.i.d.
3.
Insulin sliding scale with Humalog
4.
Aspirin 81 mg p.o. daily
5.
Furosemide 160 mg p.o. daily
6.
Piperacillin/tazobactam 3.375 grams i.v. every 6 hours
7.
Gentamycin 2 grams i.v. every 8 hours
8.
Atenolol 50 mg p.o. b.i.d.
9.
Lisinopril 20 mg p.o. daily
10.
Clonidine 0.2 mg p.o. b.i.d.
11.
Fluoxetine 60 mg p.o. daily
12.
Fluticasone/salmeterol 5/500 2 puffs b.i.d.
13.
Albuterol 2 puffs b.i.d.
14.
Haloperidol 10 mg p.o. or i.m. every 6 hours p.r.n. for agitation (total 40 mg in 3 days)
15.
Trazodone 200 mg p.o. h.s.
16.
Zolpidem 10 mg p.o. h.s.

Decision Point C

Given the patient’s presentation and this list of medications, specify your degree of concern regarding drug interactions or direct adverse effects for each medication. (Scoring is individualized to each drug. Identify your level of concern in terms of the medication causing or exacerbating a delirium. Your choices are “No concern,” “Possibly dangerous,” or “Definitely dangerous.” Points are taken away for incorrect answers.)
MedicationNo ConcernPossibly DangerousDefinitely Dangerous
C1. Glyburide   
C2. Metformin   
C3. Insulin siding scale with Humalog   
C4. Aspirin   
C5. Furosemide   
C6. Piperacillin/tazobactam   
C7. Gentamycin   
C8. Atenolol   
C9. Lisinopril   
C10. Clonidine   
C11. Fluoxetine   
C12. Fluticasone/salmeterol   
C13. Albuterol   
C14. Haloperidol p.r.n.   
C15. Trazodone   
C16. Zolpidem   

Decision Point D

What is the most likely predisposing factor for delirium in this patient?
D1. ____Numerous new medications starting during the hospitalization
D2. ____Any iatrogenic event
D3. ____Use of a bladder catheter
D4. ____Visual impairment
D5. ____None of the above

Decision Point E

Because antipsychotics and serotonergic agents are both used in treating delirium, the severe side effects of neuroleptic malignant syndrome, serotonin syndrome, or extrapyramidal side effects should be considered in this case. Match the following symptoms or signs with the appropriate diagnosis. (More than one answer may apply to each symptom or sign. One point is given for correct signs and symptoms. Points are taken away for incorrect responses.)
Sign or SymptomExtrapyramidal Side EffectsSerotonin SyndromeNeuroleptic Malignant Syndrome
E1. Mental status changes   
E2. Behavioral—restlessness or agitation   
E3. Autonomic dysfunction   
E4. Physical examination   
    a. Myoclonus   
    b. Hyperreflexia   
    c. Tremor   
    d. Incoordination   
    e. Muscle rigidity   
    f. Trismus   
    g. Blepharospasm   
    h. Oculogyric crisis   
    i. Dysarthria   
    j. Dysphagia   
E5. Laboratory values   
    a. Elevated creatinine phosphokinase   
    b. Leukocytosis   
    c. Myoglobinuria   
    d. Metabolic acidosis   

Decision Point F

Patients who exhibit difficulty concentrating can be misdiagnosed as having delirium, dementia, and major depression. Match the following symptoms and signs as related to delirium, dementia, or major depression. (Points are given for positive answers. Each symptom can have more than one correct answer, so mark as many as you think apply. Points are taken away for incorrect answers.)
Symptom or SignDeliriumDementiaMajor Depression
F1. Memory impairment is early sign   
F2. Aphasia, apraxia, agnosia, or disturbance in executive functioning   
F3. Acute onset   
F4. Poor judgment, poor insight   
F5. Difficulty with spatial tasks   
F6. Disturbance of consciousness   
F7. Disturbance of attention   
F8. Disturbance of cognition   
F9. Disturbance of perception   
F10. Marked fluctuation during the course of the day   

Answers: scoring, relative weights, and comments

High positive scores (+3 and above) indicate a decision that would be effective, would be required for diagnosis, and without which management would be negligent. Lower positive scores (+2) indicate a decision that is important but not immediately necessary. The lowest positive score (+1) indicates a decision that is potentially useful for diagnosis and treatment. A neutral score (0) indicates a decision that is neither clearly helpful nor harmful under the given circumstances. High negative scores (−3 and above) indicate a decision that is inappropriate and potentially harmful or life-threatening. Lower negative scores (−2) indicate a decision that is nonproductive and potentially harmful. The lowest negative score (−1) indicates a decision that is not harmful but is nonproductive, time-consuming, and not cost-effective.

Decision Point A

A1. +5 History: Determine what the patient’s baseline mental status was prior to admission. Has the patient had previous bouts of mental status changes? If so, what was done?
A2. +5 Psychiatric conditions: The patient was described as “depressed.” Does he have a preexisting psychiatric condition? Has he ever been on any psychotropic medications?
A3. +5 Medications: What medications is the patient currently taking? What medications was the patient taking prior to admission? Check for drug-drug interactions and iatrogenic causes.
A4. +5 Substances/alcohol: The patient’s urine drug screen was positive for opiates and benzodiazepines. Does the patient have a history of abuse or dependence on alcohol or other substances? Is the patient within the window of withdrawal from any of the possible offending agents?
A5. +5 Endocrine: Is the patient eating adequately while receiving treatment for diabetes? Is this renal failure or liver failure? Are endocrine abnormalities possible, such as hypo- or hyperthyroidism or hypo- or hyperparathyroidism?
A6. +5 Metabolic: Could the delirium be secondary to a thiamine or other nutritional deficiency? Is there an acid-base disturbance? Could the patient be in heart failure?
A7. +5 Vascular: The patient is hypertensive. Could he have hypertensive encephalopathy? Cerebral arteriosclerosis? Could he have cardiac emboli from atrial fibrillation? Patent foramen ovale? Endocarditic valve?
A8. +5 Infectious: Does the patient have a urinary tract infection? Obtain a urinalysis with culture and susceptibility, and also look at the urine to see if it is clear or cloudy. Given the patient’s multiple sources of infection, it is reasonable to pan-culture the patient’s infectious sources. Is he becoming septic/encephalitic/meningitic from bacteria or virus? He is less likely to have a parasitic or fungal infection, but this may need to be ruled out given the possibility of immunocompromise from multiple medical problems. The patient has multiple sources of possible infection, with a dehisced amputation wound, pneumonia or other lung infection, septic joint, sacral decubitus ulcer, and so on.
A9. +5 Brain hypoxia: Could the patient have brain hypoxia secondary to cardiac insufficiency, pulmonary infection, or chronic obstructive pulmonary disease? Could anemia be causing the delirium?

Decision Point B

B1. −5 You do not know how much haloperidol the patient has received to this point. Moreover, the patient’s symptoms sound like acute dystonic reaction, an extrapyramidal side effect. You do not wish to worsen these symptoms, so it makes sense to back off the haloperidol and give a trial of 50 mg i.v. of diphenhydramine or 1–2 mg i.v. of benztropine to see if the symptoms abate. If the symptoms continue unchanged or worsen, then other causes must be explored, especially a CNS infection.
B2. −3 First, perform a bedside neurological exam and a Mini-Mental State Examination to establish a current baseline. Data are limited on the efficacy of benzodiazepines for the treatment of delirium, except in the case of alcohol or benzodiazepine withdrawal. Although there are reports of successful use of a combination of a benzodiazepine and an antipsychotic in treating delirium, these reports are inconclusive and did not use standardized assessment tools. Benzodiazepines can increase sedation and cause behavioral inhibition, amnesia, ataxia, respiratory depression, physical dependence, rebound insomnia, withdrawal reactions, and delirium. Lorazepam, oxazepam, and temazepam are primarily metabolized by glucuronidation, not oxidated, and clonazepam is acetylated. Thus, all are relatively unaffected until parenchymal liver disease is quite severe; they are subsequently relatively safer in the context of liver failure if a benzodiazepine is necessary to treat withdrawal symptoms, to raise seizure threshold, or to counteract anticholinergic side effects or akathisia associated with concurrent use of antipsychotics. For this patient, whose medical history includes extensive lung disease, obstructive sleep apnea, chronic renal insufficiency, and hepatic encephalopathy, benzodiazepines are relatively contraindicated.
B3. +3 Because this seems a likely cause of the current classical manifestation of an extrapyramidal acute dystonic reaction (thickened tongue, stiffening, torticollis, and facial grimacing), a small trial of an anticholinergic is reasonable. Anticholinergics, antiparkinsonian agents, and antihistamines such as trihexyphenidyl, benztropine, biperiden, procyclidine, and diphenhydramine are all commonly used for the treatment of neuroleptic-induced parkinsonism and acute dystonic reactions. Diphenhydramine can be given up to a total of 400 mg/day. Keep in mind that you have not yet seen the patient and may be surprised when you get to the bedside. Typically in these circumstances the patient must be reevaluated frequently, and physical restraints should be removed once the patient is considered safe from harm to himself or others.
B4. +2 A CNS infection is lower on the differential diagnosis but must still be considered, especially if the more likely scenario of acute dystonic reaction secondary to antipsychotic use is ruled out. If suspicion of a CNS infection rises, computed tomography of the head and a lumbar puncture are indicated, in which case the patient will likely require sedation to lie still through the procedures.
B5. −5 This response is inappropriate in a hospital. Patients’ comfort and safety must be maintained, and this patient’s condition is very likely treatable and not something to “ride out.”

Decision Point C

Assign +1 point for each correct answer, and −1 point for each incorrect answer. Explanation follows the table.
MedicationNo ConcernPossibly DangerousDefinitely Dangerous
C1. Glyburide  X
C2. Metformin  X
C3. Insulin sliding scale with Humalog  X
C4. Aspirin X 
C5. Furosemide X 
C6. Piperacillin/tazobactam  X
C7. Gentamycin X 
C8. AtenololX  
C9. Lisinopril X 
C10. Clonidine X 
C11. Fluoxetine X 
C12. Fluticasone/salmeterol X 
C13. AlbuterolX  
C14. Haloperidol p.r.n.  X
C15. Trazodone  X
C16. Zolpidem X 

Explanation for Decision Point C

1.
Drug-drug interactions
a.a.
Fluoxetine-trazodone: May result in toxic levels of either fluoxetine (serotonin syndrome, including hypertension, hyperthermia, myoclonus, and mental status changes) or trazodone (sedation, dry mouth, urinary retention)
a.b.
Haloperidol-fluoxetine: May exacerbate the side effects of the antipsychotic, including pseudoparkinsonism, akathisia, tongue stiffness, increased risk of cardiotoxicity (QT interval prolongation, torsade de pointes, and cardiac arrest)
2.
Disease contraindications
b.a.
Hydrochlorothiazide/lisinopril: Hyperglycemia, hyperuricemia
b.b.
Furosemide: Hyperglycemia, hyperuricemia
b.c.
Clonidine: Hyperglycemia, hyperuricemia
3.
General
c.a.
Piperacillin/tazobactam must be renally calculated given the patient’s poor kidney function.
c.b.
Zolpidem: This drug is known to cause worsening mental status in certain people, especially the elderly.
c.c.
The inhalers are helping the patient breathe and do not have any drug-drug interactions or contraindications in this patient.
c.d.
Insulin Sliding Scale: This should be carefully monitored according to the patient’s appetite, blood glucose chemsticks, and testing. If the patient will not be eating, either for testing or because of lack of appetite, the insulin scale must be carefully monitored so as not to allow him to become hypo- or hyperglycemic, which could result in a change in mental status.

Decision Point D

D2. 0 An iatrogenic event does not necessarily put the patient at risk for a delirium.
D3. +1 An indwelling catheter puts patients at risk of developing a bladder infection and subsequent sepsis. In elderly patients the first sign of sepsis may be a change in mental status.
D4. +2 Impairment of vision and/or hearing places patients at risk of developing a delirium.
Other risk factors that should, if present, cause the clinician to assume delirium is present until proven otherwise include:
1.
Advanced age (especially over 80 years)
2.
Severe illness (especially cancer)
3.
Dehydration
4.
Dementia
5.
Fever or hypothermia
6.
Substance abuse
7.
Azotemia
8.
Hypoalbuminemia
9.
Abnormal sodium levels

Decision Point E

More than one answer may apply to each symptom or sign. One point is given for necessary signs or symptoms, and 2 points if the sign or symptom is a necessary criterion for diagnosis (these are indicated by two X’s). Points are taken away for incorrect responses.
Sign or SymptomExtrapyramidal Side EffectsSerotonin SyndromeNeuroleptic Malignant Syndrome
E1. Mental status changes XX
E2. Behavioral—restlessness or agitationXXX
E3 Autonomic dysfunction  X X
E4. Physical examination   
    a. MyoclonusXXX
    b. HyperreflexiaXXX
    c. TremorXXX
    d. Incoordination X 
    e. Muscle rigidityXXX X
    f. TrismusX  
    g. BlepharospasmX  
    h. Oculogyric crisisX  
    i. DysarthriaX  
    j. DysphagiaX  
E5. Laboratory values   
    a. Elevated creatinine phosphokinase  X
    b. Leukocytosis  X
    c. Myoglobinuria  X
    d. Metabolic acidosis  X

Decision Point F

Patients who exhibit difficulty concentrating can be misdiagnosed as having delirium, dementia, and major depression. Match the following symptoms and signs as related to delirium, dementia, or major depression. (Points are given for positive answers. Each symptom can have more than one correct answer, so mark as many as you think apply. Points are taken away for incorrect answers.)
Symptom or SignDeliriumDementiaMajor Depression
F1. Memory impairment is early signXX 
F2. Aphasia, apraxia, agnosia, or disturbance in executive functioningXX 
F3. Acute onsetX  
F4. Poor judgment, poor insightXX 
F5. Difficulty with spatial tasksXX 
F6. Disturbance of consciousnessX  
F7. Disturbance of attentionXXX
F8. Disturbance of cognitionXXX
F9. Disturbance of perceptionXX 
F10. Marked fluctuation during the course of the dayX  
YOUR TOTAL
Decision PointYour ScoreIdeal Best Score
A 25
B 5
C 16
D 7
E 30
F 19
Total 102

Footnotes

CME Financial Disclosure B. Harrison Levine, M.D., M.P.H., Department of Psychiatry, University of Michigan Health System.
No affiliations with commercial supporters.
Ronald C. Albucher, M.D., Clinical Assistant Professor of Psychiatry, University of Michigan Medical School, and Assistant Chief, Psychiatry Service, Ann Arbor VA Health System.
No affiliations with commercial supporters.
Disclosure of Unapproved, Off-label or Investigational Use of a Product
APA policy requires disclosure by CME authors of unapproved or investigational use of products discussed in CME programs. Off-label use of medications by individual physicians is permitted and common. Decisions about off-label use can be guided by the scientific literature and clinical experience.

References

American Psychiatric Association: Practice Guidelines for the Treatment of Psychiatric Disorders, Compendium 2004. Arlington, Va, American Psychiatric Publishing, 2004
Inouye SK: A practical program for preventing delirium in hospitalized elderly patients. Cleve Clin J Med 2004; 71:890–896
Sadock BJ, Sadock VA: Synopsis of Psychiatry, 9th ed. Philadelphia, Lippincott Williams & Wilkins, 2003
Schatzberg AF, Nemeroff CB: Essentials of Clinical Psychopharmacology. Washington, DC, American Psychiatric Publishing, 2001
Wyszynski AA, Wyszynski B: Manual of Psychiatric Care for the Medically Ill. Arlington, Va, American Psychiatric Publishing, 2005

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Published online: 1 April 2005
Published in print: April 2005

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B. Harrison Levine, M.D., M.P.H.
Ronald C. Albucher, M.D.

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