12/12/2018

1

Altered Mental Status

Austin Smith, M.D.

Adjoint Assistant Professor of Emergency Medicine

Department of Emergency Medicine

Vanderbilt University School of Medicine

Nashville, TN

Attending Physician

Intermountain Park City Hospital and Heber Valley Hospital

Park City, Utah

Disclosures

• The views and opinions expressed in this presentation are those of the

author and solely the author and do not necessarily reflect the official

policy or position of Vanderbilt University, Vanderbilt University Medical

Center, Vanderbilt University School of Medicine, Intermountain

Healthcare, Intermountain Park City Hospital, Intermountain Heber Valley

Hospital, or any of their affiliates or agencies.

Disclosures

• Grant Support

– Supported by an educational grant from McGraw Hill Education that is

not relevant to this presentation

Disclosures

• Off label uses

Disclosures Disclosures

1 2

3 4

5 6

12/12/2018

2

Outline

• Scope of Lecture

• Definition

• Challenges

Scope

• Acute and subacute changes in mental status

Scope

• Acute and subacute changes in mental status

• Acute and subacute changes are more likely to

be precipitated by a life-threatening illness

Definition

• Any change in a patient’s baseline mental

status

Definition

• Any change in a patient’s baseline mental

status

– A VERY broad definition

Definition

• Any change in a patient’s baseline mental

status

– A VERY broad definition

– A difficult chief complaint in many ways

7 8

9 10

11 12

12/12/2018

3

Challenges

• The scope is extremely broad

Challenges

• The scope is extremely broad

• Patient is poor historian

Challenges

• The scope is extremely broad

• Patient is poor historian

• Physical exam often not helpful

Challenges

• The scope is extremely broad

• Patient is poor historian

• Physical exam often not helpful

• Labs and imaging often not helpful

Challenges

• The scope is extremely broad

• Patient is poor historian

• Physical exam often not helpful

• Labs and imaging often not helpful

• May be nothing or life threatening!

Challenges

• The scope is extremely broad

• Patient is poor historian

• Physical exam often not helpful

• Labs and imaging often not helpful

• May be nothing or life threatening!

• So many terms/scales

13 14

15 16

17 18

12/12/2018

4

Definitions

• Coma: unresponsive to any stimuli

Definitions

• Coma: unresponsive to any stimuli

• Stupor: only arouse with vigorous and

continuous stimuli

Definitions

• Coma: unresponsive to any stimuli

• Stupor: only arouse with vigorous and

continuous stimuli

• Delirium: acute disturbance of consciousness

accompanied by an acute loss of cognition

(but not better explained by dementia)

Definitions

• What is delirium and how do you assess it?

Delirium

• Hypoactive Delirium

– Appear drowsy or somnolent

– Subtle and often missed!

Delirium

• Hypoactive Delirium

– Appear drowsy or somnolent

– Subtle and often missed!

• Hyperactive Delirium

– Obvious presentation

19 20

21 22

23 24

12/12/2018

5

Delirium

• Hypoactive Delirium

– Appear drowsy or somnolent

– Subtle and often missed!

• Hyperactive Delirium

– Obvious presentation

• Mixed-Type Delirium

– Presents with both features

Delirium

Delirium

http://eddelirium.org

Delirium

Delirium Dementia

• Gradual and associated with gradual loss of

cognition

25 26

27 28

29 30

12/12/2018

6

A Stepwise Approach

Stepwise Approach

• Severity

– ”ABCs and 5 S’s”

Stepwise Approach

• Severity

– ”ABCs and 5 S’s”

– The 5 S’s:

1. Sugar

2. Stroke

3. Sepsis

4. Seizure

5. Sonorous Respirations (Opiate Intoxication)

Stepwise Approach

• Severity

– “ABCs and 5 S’s”

• Stabilize

– Address vital signs and combativeness

Agitation Stepwise Approach

• Severity

– “ABCs and 5 S’s”

• Stabilize

– Address vital signs and combativeness

31 32

33 34

35 36

12/12/2018

7

Stepwise Approach

• Severity

– “ABCs and 5 S’s”

• Stabilize

– Address vital signs and combativeness

• History and Physical

• Differential Diagnosis

• Labs/Imaging

• Disposition

Stepwise Approach

• History

Stepwise Approach

• History

– Best obtained from someone else

Stepwise Approach

• History

– Best obtained from someone else

– Timing: Acute is worse, abrupt may suggest stroke

Stepwise Approach

• History

– Best obtained from someone else

– Timing: Acute is worse, abrupt may suggest stroke

Stepwise Approach

• History

– Best obtained from someone else

– Timing

– Associated Symptoms: Recent seizures, recent

neurologic complaints, recent infectious

symptoms

37 38

39 40

41 42

12/12/2018

8

Stepwise Approach

• History

– Best obtained from someone else

– Timing

– Associated Symptoms

– Medications: Needs to be obtained first-hand,

look for recent

changes/additions/discontinuations

Stepwise Approach

Stepwise Approach

• History

– Best obtained from someone else

– Timing

– Associated Symptoms

– Medications:

• Antibiomania? Clarithromycin/Fluroquinolones

• Metronidazole encephalopathy

Stepwise Approach

• History

– Best obtained from someone else

– Timing

– Associated Symptoms

– Medications

– Social History:

• Many elderly patients are abusers of sedative hypnotics

• Also consider physical abuse

Stepwise Approach

• Physical Exam

– Complete neurologic exam

• Right parietal lobe infarcts can cause AMS without any

focal findings

• Aphasia can be confused with AMS

• Gait: Wernicke’s?

– If suspected, consider thiamine administration 500mg IV

before gluocse

Stepwise Approach

• Physical Exam

– Complete neurologic exam

• Right parietal lobe infarcts can cause AMS without any

focal findings

• Aphasia can be confused with AMS

• Gait: Wernicke’s?

• Tone: Serotonin syndrome, malignant hyperthermia,

NMS

43 44

45 46

47 48

12/12/2018

9

Stepwise Approach

• Physical Exam

– Complete neurologic exam

– Ocular Exam

Stepwise ApproachOcular Exam

Mydriasis Sympathomimetic

Anticholinergic

Miosis Opiate

Pontine Stroke

Horizontal Nystagmus Drug Intoxication

Peripheral Nervous System Lesion[81]

Vertical Nystagmus Central Nervous System Lesion [81]

Wernicke’s encephalopathy

Rotary Nystagmus Drug Intoxication

Central Nervous System Lesion

Exophthalmos Grave’s Disease (Hyperthyroid)

Ophthalmoplegia Wernicke’s Encephalopathy

Increased Intracranial Pressure

Proptosis Retrobulbar hematoma

Orbital Cellulitis

Scleral Icterus Hepatic Failure

Gaze Deviation Seizure

Oculogyric Crisis

Visual Field Deficit Central retinal artery occlusion

Occipital Lobe Infarct

Stepwise Approach

• Physical Exam

– Complete neurologic exam

– Ocular Exam

– GU Exam

• Fournier’s Gangrene, Prostatitis, GI bleed

Stepwise Approach

• Physical Exam

– Complete neurologic exam

– Ocular Exam

– GU Exam

– Skin Exam

• Findings of liver disease, infection, drug patches

Stepwise Approach

• Differential Diagnosis

Breather

• Differential Diagnosis

49 50

51 52

53 54

12/12/2018

10

Breather Breather

Stepwise Approach

• Differential Diagnosis in 5 Categories

1. Vital Sign Abnormalities

2. Toxic/Metabolic

3. Structural

4. Infectious

5. Psychiatric

Stepwise Approach

Stepwise Approach

• Differential Diagnosis in 5 Categories

1. Vital Sign Abnormalities

2. Toxic/Metabolic

3. Structural

4. Infectious

5. Psychiatric

Stepwise Approach

• Vital Sign Abnormalities

– Should be considered life threatening as they are

causing end organ dysfunction of the brain

55 56

57 58

59 60

12/12/2018

11

Stepwise Approach

• Vital Sign Abnormalities

– Should be considered life threatening as they are

causing end organ dysfunction of the brain

– Address before moving on

Stepwise Approach

• Toxins

– Prescription AND OTC medications

– Environmental Toxins (CO, Jimson weed,

marijuana gummy bears)

– Withdrawal

Stepwise Approach

• Metabolic

– Glucose

• Hypoglycemia can mimic anything

• DKA/HHS

Stepwise Approach

• Metabolic

– Sodium

Stepwise Approach

• Metabolic

– Sodium

• The most common electrolyte disorder

Stepwise Approach

• Metabolic

– Sodium

• The most common electrolyte disorder

• Most common cause in outpatients is thiazide use

61 62

63 64

65 66

12/12/2018

12

Stepwise Approach

• Metabolic

– Sodium

• The most common electrolyte disorder

• Most common cause in outpatients is thiazide use

• Usually not the cause unless < 120 mEq/L

Stepwise Approach

• Metabolic

– Calcium

• Most common cause in outpatients is primary

hyperparathyroidism

• Most common cause in inpatients is malignancy

Stepwise Approach

• Metabolic

– BUN

• When > 100mg/dL, mental status changes may develop

and uremia is likely present

Stepwise Approach

• Metabolic

– Hyperthyroid

• Tachycardia, mania, sweating

• Thyroid Storm

Stepwise Approach

• Metabolic

– Hyperthyroid

• Tachycardia, mania

• Thyroid Storm

– Hypothyroid

• Lethargy, dry skin, enlarged thyroid, irritability, cold

sensitivity, etc.

• Myxedema coma: most severe complication-

multisystem organ failure

Stepwise Approach

• Metabolic

– Adrenal Insufficiency

• Often missed early

• Dark Skin Pigmentation

• Hyponatremia with Hyperkalemia

• Cardiovascular Collapse

• Sepsis not responding to treatment

67 68

69 70

71 72

12/12/2018

13

Stepwise Approach

• Metabolic

– Hepatic

• Hepatic encephalopathy

• Cerebral Edema

• High risk of ICH

Stepwise Approach

• Infectious

– Systemic

• SOFA score has shown that AMS is an independent

predictor of ICU stay and hospital mortality

Stepwise Approach

• Infectious

– Systemic

• SOFA score has shown that AMS is an independent

predictor of ICU stay and hospital mortality

– Neurologic

• Meningitis, Encephalitis

• Anti-NMDA Encephalitis

Stepwise Approach

• Neurologic

– Intracranial hemorrhage

– Traumatic hemorrhage

– Locked-in Syndrome

– Non-Convulsive Status Epilepticus

Stepwise Approach

• Psychiatric

– A diagnosis of exclusion

Stepwise Approach

• Psychiatric

– A diagnosis of exclusion

– 20% have a medical problem causing or

exacerbating their psychiatric condition

73 74

75 76

77 78

12/12/2018

14

Stepwise Approach

• Psychiatric

– A diagnosis of exclusion

– 20% have a medical problem causing or

exacerbating their psychiatric condition

– Psychiatric patients have a high rate of medical

comorbidities

• Largely undiagnosed and untreated

Stepwise Approach

• Psychiatric

– Atypical presentations of common medical

problems are common

– Changes in vision appear to be most predictive of

a medical illness causing, or at least contributing

to, their symptoms

Stepwise Approach Stepwise Approach

• Labs

Stepwise Approach

• Labs

– Most should have a CBC/BMP

Stepwise Approach

• Labs

– Most should have a CBC/BMP

– Urinalysis

• Yes, but be careful

79 80

81 82

83 84

12/12/2018

15

Stepwise Approach

• Labs

– Most should have a CBC/BMP

– Urinalysis

• Yes, but be careful

• Asymptomatic bacteriuria is common and overtreated

Stepwise Approach

• Labs

– Most should have a CBC/BMP

– Urinalysis

• Yes, but be careful

• Asymptomatic bacteriuria is common and overtreated

• Bacteria can be in the urine with a systemic infection

Stepwise Approach

• Labs

– Toxicologic Screen

• Serum ETOH/APAP/ASA levels

Stepwise Approach

• Labs

– Toxicologic Screen

• Serum ETOH/APAP/ASA levels

• Consider serum osmolality too

Stepwise Approach

• Labs

– Toxicologic Screen

• Serum ETOH/APAP/ASA levels

• Consider serum osmolality too

• Urine Drug Screen?

– Prone to false positives, not particularly sensitive, and rely on

multiple factors for detection

Stepwise Approach

• Labs

– LP?

• If you think about it, you should probably do it

• Save CSF

85 86

87 88

89 90

12/12/2018

16

Stepwise Approach

• Imaging

Stepwise Approach

• Imaging

– CXR

• Hypoxia, fever, cough, respiratory symptoms

• Free air?

Stepwise Approach

• Imaging

– EEG

1. No cause

2. Any history of seizure or seizing before arrival

Stepwise Approach

• Imaging

– EEG

1. No cause

2. Any history of seizure or seizing before arrival

– Incidence in patients with AMS is 8-30%

Stepwise Approach

• Imaging

– Noncontrast Head CT

• Routine in AMS?

– Controversial, but if impaired level of consciousness, consider

– Always if concerned or trauma, deficit, anticoagulants

Stepwise Approach

• Imaging

– CT Angiography

• Excellent for stenosis, aneurysms, dissections

91 92

93 94

95 96

12/12/2018

17

Stepwise Approach

• Imaging

– MRI

• If no cause is found, MRI can be helpful, particularly for

strokes and tumor

Stepwise Approach

• Disposition

– Stuporous/Comatose = ICU

Stepwise Approach

• Disposition

– Stuporous/Comatose = ICU

– Stroke = Stroke unit (improved mortality and

outcomes)

Stepwise Approach

• Disposition

– Stuporous/Comatose = ICU

– Stroke = Stroke unit (improved mortality and

outcomes)

– Poisoning = Discuss with toxicologist

Stepwise Approach

• Disposition

– No cause, but resolved = observation vs discharge

home (but great followup/supervision plan

needed)

• However, missed delirium in elderly patients carries a

higher mortality rate

References• 1. Morandi A, Pandharipande P, Trabucchi M, Rozzini R, Mistraletti G, Trompeo AC, et al. Understanding international differences in terminology for delirium and other types of acute

brain dysfunction in critically ill patients. Intensive care medicine. 2008;34(10):1907-15.

• 2. Kanich W, Brady WJ, Huff JS, Perron AD, Holstege C, Lindbeck G, et al. Altered mental status: evaluation and etiology in the ED. The American journal of emergency medicine.

2002;20(7):613-7.

• 3. Erkinjuntti T, Wikström J, Palo J, Autio L. Dementia among medical inpatients: Evaluation of 2000 consecutive admissions. Archives of Internal Medicine. 1986;146(10):1923-6.

• 4. Wofford JL, Loehr LR, Schwartz E. Acute cognitive impairment in elderly ED patients: Etiologies and outcomes. The American journal of emergency medicine. 1996;14(7):649-53.

• 5. Naughton BJ, Moran MB, Kadah H, Heman-Ackah Y, Longano J. Delirium and other cognitive impairment in older adults in an emergency department. Annals of emergency medicine.

1995;25(6):751-5.

• 6. Han JH, Schnelle JF, Ely EW. The relationship between a chief complaint of "altered mental status" and delirium in older emergency department patients. Acad Emerg Med.

2014;21(8):937-40.

• 7. Clarfield AM. The decreasing prevalence of reversible dementias: an updated meta-analysis. Archives of internal medicine. 2003;163(18):2219-29.

• 8. Posner JB, Plum F. Plum and Posner's diagnosis of stupor and coma. 4th ed. Oxford ; New York: Oxford University Press; 2007. xiv, 401 p. p.

• 9. Douglas VC, Josephson SA. Altered mental status. Continuum (Minneapolis, Minn). 2011;17(5 Neurologic Consultation in the Hospital):967-83.

• 10. American Psychiatric Association., American Psychiatric Association. DSM-5 Task Force. Diagnostic and statistical manual of mental disorders : DSM-5. 5th ed. Washington,

D.C.: American Psychiatric Association; 2013. xliv, 947 p. p.

• 11. Meagher DJ, Trzepacz PT. Motoric subtypes of delirium. Seminars in clinical neuropsychiatry. 2000;5(2):75-85.

• 12. Nicholas LM, Lindsey BA. Delirium presenting with symptoms of depression. Psychosomatics. 1995;36(5):471-9.

• 13. Farrell KR, Ganzini L. Misdiagnosing delirium as depression in medically ill elderly patients. Archives of internal medicine. 1995;155(22):2459-64.

• 14. Inouye SK, Foreman MD, Mion LC, Katz KH, Cooney LM, Jr. Nurses' recognition of delirium and its symptoms: comparison of nurse and researcher ratings. Archives of

internal medicine. 2001;161(20):2467-73.

• 15. Han JH, Zimmerman EE, Cutler N, Schnelle J, Morandi A, Dittus RS, et al. Delirium in older emergency department patients: recognition, risk factors, and psychomotor

subtypes. Acad Emerg Med. 2009;16(3):193-200.

• 16. Ross CA, Peyser CE, Shapiro I, Folstein MF. Delirium: phenomenologic and etiologic subtypes. International psychogeriatrics / IPA. 1991;3(2):135-47.

• 17. Voyer P, Cole MG, McCusker J, Belzile E. Prevalence and symptoms of delirium superimposed on dementia. Clinical nursing research. 2006;15(1):46-66.

• 18. Boller F, Verny M, Hugonot-Diener L, Saxton J. Clinical features and assessment of severe dementia. A review. Eur J Neurol. 2002;9(2):125-36.

• 19. McKeith IG, Galasko D, Kosaka K, Perry EK, Dickson DW, Hansen LA, et al. Consensus guidelines for the clinical and pathologic diagnosis of dementia with Lewy bodies (DLB):

report of the consortium on DLB international workshop. Neurology. 1996;47(5):1113-24.

• 20. Healey C, Osler TM, Rogers FB, Healey MA, Glance LG, Kilgo PD, et al. Improving the Glasgow Coma Scale score: motor score alone is a better predictor. The Journal of

trauma. 2003;54(4):671-8; discussion 8-80.

97 98

99 100

101 102

12/12/2018

18

References• 21. Gill MR, Reiley DG, Green SM. Interrater reliability of Glasgow Coma Scale scores in the emergency department. Annals of emergency medicine. 2004;43(2):215-23.

• 22. McNarry AF, Goldhill DR. Simple bedside assessment of level of consciousness: comparison of two simple assessment scales with the Glasgow Coma scale. Anaesthesia.

2004;59(1):34-7.

• 23. Sessler CN, Gosnell MS, Grap MJ, Brophy GM, O'Neal PV, Keane KA, et al. The Richmond Agitation-Sedation Scale: validity and reliability in adult intensive care unit patients.

American journal of respiratory and critical care medicine. 2002;166(10):1338-44.

• 24. Ely EW, Truman B, Shintani A, Thomason JW, Wheeler AP, Gordon S, et al. Monitoring sedation status over time in ICU patients: reliability and validity of the Richmond

Agitation-Sedation Scale (RASS). JAMA. 2003;289(22):2983-91.

• 25. Fabbri RM, Moreira MA, Garrido R, Almeida OP. Validity and reliability of the Portuguese version of the Confusion Assessment Method (CAM) for the detection of delirium

in the elderly. Arq Neuropsiquiatr. 2001;59(2-A):175-9.

• 26. Wong CL, Holroyd-Leduc J, Simel DL, Straus SE. Does this patient have delirium?: value of bedside instruments. Jama. 2010;304(7):779-86.

• 27. Han JH, Wilson A, Vasilevskis EE, Shintani A, Schnelle JF, Dittus RS, et al. Diagnosing delirium in older emergency department patients: validity and reliability of the delirium

triage screen and the brief confusion assessment method. Annals of emergency medicine. 2013;62(5):457-65.

• 28. Han JH, Wilson A, Graves AJ, Shintani A, Schnelle JF, Dittus RS, et al. Validation of the Confusion Assessment Method for the Intensive Care Unit in older emergency

department patients. Acad Emerg Med. 2014;21(2):180-7.

• 29. Hustey FM, Meldon SW. The prevalence and documentation of impaired mental status in elderly emergency department patients. Annals of emergency medicine.

2002;39(3):248-53.

• 30. Han JH, Shintani A, Eden S, Morandi A, Solberg LM, Schnelle J, et al. Delirium in the emergency department: an independent predictor of death within 6 months. Annals of

emergency medicine. 2010;56(3):244-52.

• 31. Han JH, Eden S, Shintani A, Morandi A, Schnelle J, Dittus RS, et al. Delirium in older emergency department patients is an independent predictor of hospital length of stay.

Acad Emerg Med. 2011;18(5):451-7.

• 32. Pandharipande PP, Girard TD, Jackson JC, Morandi A, Thompson JL, Pun BT, et al. Long-term cognitive impairment after critical illness. The New England journal of medicine.

2013;369(14):1306-16.

• 33. Gross AL, Jones RN, Habtemariam DA, Fong TG, Tommet D, Quach L, et al. Delirium and long-term cognitive trajectory among persons with dementia. Archives of internal

medicine. 2012 172(17):1-8.

• 34. McCusker J, Cole M, Abrahamowicz M, Primeau F, Belzile E. Delirium predicts 12-month mortality. Archives of internal medicine. 2002;162(4):457-63.

• 35. McCusker J, Cole M, Dendukuri N, Belzile E, Primeau F. Delirium in older medical inpatients and subsequent cognitive and functional status: a prospective study. CMAJ.

2001;165(5):575-83.

• 36. Inouye SK. Delirium in hospitalized elderly patients: recognition, evaluation, and management. Connecticut medicine. 1993;57(5):309-15.

• 37. Elie M, Cole MG, Primeau FJ, Bellavance F. Delirium risk factors in elderly hospitalized patients. J Gen Intern Med. 1998;13(3):204-12.

• 38. Schor JD, Levkoff SE, Lipsitz LA, Reilly CH, Cleary PD, Rowe JW, et al. Risk factors for delirium in hospitalized elderly. JAMA. 1992;267(6):827-31.

• 39. Marcantonio ER, Goldman L, Mangione CM, Ludwig LE, Muraca B, Haslauer CM, et al. A clinical prediction rule for delirium after elective noncardiac surgery. JAMA.

1994;271(2):134-9.

• 40. Gustafson Y, Berggren D, Brannstrom B, Bucht G, Norberg A, Hansson LI, et al. Acute confusional states in elderly patients treated for femoral neck fracture. Journal of the

American Geriatrics Society. 1988;36(6):525-30.

References• 41. Jitapunkul S, Pillay I, Ebrahim S. Delirium in newly admitted elderly patients: a prospective study. The Quarterly journal of medicine. 1992;83(300):307-14.

• 42. Kolbeinsson H, Jonsson A. Delirium and dementia in acute medical admissions of elderly patients in Iceland. Acta psychiatrica Scandinavica. 1993;87(2):123-7.

• 43. Rockwood K. Acute confusion in elderly medical patients. Journal of the American Geriatrics Society. 1989;37(2):150-4.

• 44. Pompei P, Foreman M, Rudberg MA, Inouye SK, Braund V, Cassel CK. Delirium in hospitalized older persons: outcomes and predictors. Journal of the American Geriatrics

Society. 1994;42(8):809-15.

• 45. Francis J, Martin D, Kapoor WN. A prospective study of delirium in hospitalized elderly. JAMA. 1990;263(8):1097-101.

• 46. Smith AT, Wrenn KD, Barrett TW, Jones ID, Rohde JP, Slovis CM, et al. Delayed intracranial hemorrhage after head trauma in patients on direct-acting oral anticoagulants.

The American journal of emergency medicine. 2017;35(2):377.e1-.e2.

• 47. Zehtabchi S, Abdel Baki SG, Malhotra S, Grant AC. Nonconvulsive seizures in patients presenting with altered mental status: an evidence-based review. Epilepsy Behav.

2011;22(2):139-43.

• 48. van de Beek D, de Gans J, Spanjaard L, Weisfelt M, Reitsma JB, Vermeulen M. Clinical features and prognostic factors in adults with bacterial meningitis. The New England

journal of medicine. 2004;351(18):1849-59.

• 49. Dougherty MJ, Smith AT. Acute streptococcal meningitis presenting as bilateral conductive hearing loss. The American journal of emergency medicine. 2018.

• 50. Martin PR, Singleton CK, Hiller-Sturmhofel S. The role of thiamine deficiency in alcoholic brain disease. Alcohol research & health : the journal of the National Institute on

Alcohol Abuse and Alcoholism. 2003;27(2):134-42.

• 51. Tang L, Alsulaim HA, Canner JK, Prokopowicz GP, Steele KE. Prevalence and predictors of postoperative thiamine deficiency after vertical sleeve gastrectomy. Surgery for

obesity and related diseases : official journal of the American Society for Bariatric Surgery. 2018.

• 52. Stoner GD. Hyperosmolar Hyperglycemic State. Am Fam Physician. 2017;96(11):729-36.

• 53. Upadhyay A JB, Madias NE. Incidence and prevalence of hyponatremia. The American journal of medicine. 2006;119 (7 Suppl 1):S30-S5.

• 54. Tasdemir V OA, Sayin I, Ergun I. Hyponatremia in the outpatient setting: clinical characteristics, risk factors, and outcome. Int Urol Nephrology. 2015;47(12):1977-83.

• 55. Adrogue HJ, Madias NE. The challenge of hyponatremia. Journal of the American Society of Nephrology : JASN. 2012;23(7):1140-8.

• 56. Adrogue HJ, Madias NE. Hyponatremia. The New England journal of medicine. 2000;342(21):1581-9.

• 57. Sterns RH, Hix JK, Silver S. Treatment of hyponatremia. Current opinion in nephrology and hypertension. 2010;19(5):493-8.

• 58. Sterns RH, Nigwekar SU, Hix JK. The treatment of hyponatremia. Seminars in nephrology. 2009;29(3):282-99.

• 59. Berl T. Treating hyponatremia: damned if we do and damned if we don't. Kidney international. 1990;37(3):1006-18.

• 60. Norenberg MD. Central pontine myelinolysis: historical and mechanistic considerations. Metabolic brain disease. 2010;25(1):97-106.

• 61. Barri YM KJ. Hypercalcemia and electrolyte disturbacnes in malingnancy. Hematol Oncol Clin North Am. 1996;10:775-90.

• 62. Hurley K BD. Hypocalcemic cardiac failure in the emergency department. The Journal of emergency medicine. 2005;28(2):155-9.•

References• 63. Chavan CB SK, Rao HB, Narsimhan C. Hypocalcemia as a cause of reversible cardiomyopathy with ventricular tachycardia. Ann Intern Med. 2007;146(7):541-2.

• 64. Waika SS BJ. Acute Kidney Injury. In: J KDFAHSLDJJL, editor. Harrison's Principles of Internal Medicine. 19e ed. New York, NY: McGraw-Hill; 2015.

• 65. Notice. Kidney International Supplements. 2012;2(1):1.

• 66. Mackenzie J, Chacko B. An isolated elevation in blood urea level is not 'uraemia' and not an indication for renal replacement therapy in the ICU. Crit Care. 2017;21(1):275.

• 67. Rehman SU CD, Senseney AD, Brezezinski W. Thyroid Disorders in Elderly Patients. South Med J. 2005;98(5):543-9.

• 68. Pun BT, Ely EW. The importance of diagnosing and managing ICU delirium. Chest. 2007;132(2):624-36.

• 69. Fearing MA, Inouye SK. Delirium. In: Blazer DG, Steffens DC, editors. The American Psychiatric Publishing textbook of geriatric psychiatry. 4th ed. Washington, DC: American

Psychiatric Pub.; 2009. p. 229 - 42.

• 70. Jones AE, Trzeciak S, Kline JA. The Sequential Organ Failure Assessment score for predicting outcome in patients with severe sepsis and evidence of hypoperfusion at the

time of emergency department presentation. Crit Care Med. 2009;37(5):1649-54.

• 71. Cardenas-Turanzas M, Ensor J, Wakefield C, Zhang K, Wallace SK, Price KJ, et al. Cross-validation of a Sequential Organ Failure Assessment score-based model to predict

mortality in patients with cancer admitted to the intensive care unit. Journal of critical care. 2012;27(6):673-80.

• 72. Felker B, Yazel JJ, Short D. Mortality and medical comorbidity among psychiatric patients: a review. Psychiatr Serv. 1996;47(12):1356-63.

• 73. Isenberg-Grzeda E, Kutner HE, Nicolson SE. Wernicke-Korsakoff-syndrome: under-recognized and under-treated. Psychosomatics. 2012;53(6):507-16.

• 74. Zimitat C, Nixon PF. Glucose loading precipitates acute encephalopathy in thiamin-deficient rats. Metabolic brain disease. 1999;14(1):1-20.

• 75. Ropper AH. 'Convulsions' in basilar artery occlusion. Neurology. 1988;38(9):1500-1.

• 76. Gadoth A, Hallevi H. Basilar artery occlusion presenting as a tonic-clonic seizure. The Israel Medical Association journal : IMAJ. 2011;13(5):314-5.

• 77. Demel SL, Broderick JP. Basilar Occlusion Syndromes: An Update. The Neurohospitalist. 2015;5(3):142-50.

• 78. Johnson TM, Romero CS, Smith AT. Locked-in syndrome responding to thrombolytic therapy. The American journal of emergency medicine. 2018.

• 79. Mesulam MM, Waxman SG, Geschwind N, Sabin TD. Acute confusional states with right middle cerebral artery infarctions. Journal of neurology, neurosurgery, and

psychiatry. 1976;39(1):84-9.

• 80. Campaign SS. SSC Hour-1 Bundle: Society of Critical Care Medicine; 2016 [

• 81. Seymour CW, Gesten F, Prescott HC, Friedrich ME, Iwashyna TJ, Phillips GS, et al. Time to Treatment and Mortality during Mandated Emergency Care for Sepsis. The New

England journal of medicine. 2017;376(23):2235-44.

• 82. Seymour CW, Liu VX, Iwashyna TJ, et al. Assessment of clinical criteria for sepsis: For the third international consensus definitions for sepsis and septic shock (sepsis-3).

Jama. 2016;315(8):762-74.

• 83. Freund Y, Lemachatti N, Krastinova E, et al. Prognostic accuracy of sepsis-3 criteria for in-hospital mortality among patients with suspected infection presenting to the

emergency department. Jama. 2017;317(3):301-8.

• 84. Brophy GM, Bell R, Claassen J, Alldredge B, Bleck TP, Glauser T, et al. Guidelines for the evaluation and management of status epilepticus. Neurocritical care. 2012;17(1):

References• 85. Silbergleit R, Durkalski V, Lowenstein D, Conwit R, Pancioli A, Palesch Y, et al. Intramuscular versus intravenous therapy for prehospital status epilepticus. The New England

journal of medicine. 2012;366(7):591-600.

• 86. Alshehri A, Abulaban A, Bokhari R, Kojan S, Alsalamah M, Ferwana M, et al. Intravenous Versus Nonintravenous Benzodiazepines for the Cessation of Seizures: A Systematic

Review and Meta-analysis of Randomized Controlled Trials. Academic emergency medicine : official journal of the Society for Academic Emergency Medicine. 2017;24(7):875-83.

• 87. Singh TD, Fugate JE, Rabinstein AA. Central pontine and extrapontine myelinolysis: a systematic review. European journal of neurology. 2014;21(12):1443-50.

• 88. Lheureux P, Penaloza A, Gris M. Pyridoxine in clinical toxicology: a review. European journal of emergency medicine : official journal of the European Society for Emergency

Medicine. 2005;12(2):78-85.

• 89. de' Clari F. The paradoxical anticonvulsive and awakening effect of high-dose pyridoxine treatment for isoniazid intoxication. Arch Intern Med. 1992;152(11):2346-7.

• 90. Howland MA. Goldfrank's Toxicologic Emergencies. In: Hoffman RS, Howland MA, Lewin NA, Nelson LS, Goldfrank LR, editors. Pyridoxine. 10th Edition ed. China: McGraw-

Hill Education; 2015.

• 91. A Cook I. Practice Guideline for the Treatment of Patients With Delirium: Guideline Watch Update1999.

• 92. Inouye SK, Bogardus ST, Jr., Williams CS, Leo-Summers L, Agostini JV. The role of adherence on the effectiveness of nonpharmacologic interventions: evidence from the

delirium prevention trial. Arch Intern Med. 2003;163(8):958-64.

• 93. Chan TC, Vilke GM, Neuman T. Restraint position and positional asphyxia. The American journal of forensic medicine and pathology. 2000;21(1):93.

• 94. Nunno MA, Holden MJ, Tollar A. Learning from tragedy: a survey of child and adolescent restraint fatalities. Child abuse & neglect. 2006;30(12):1333-42.

• 95. Takeuchi A, Ahern TL, Henderson SO. Excited delirium. The western journal of emergency medicine. 2011;12(1):77-83.

• 96. Marsden CD, Jenner P. The pathophysiology of extrapyramidal side-effects of neuroleptic drugs. Psychological medicine. 1980;10(1):55-72.

• 97. Knott JC, Taylor DM, Castle DJ. Randomized clinical trial comparing intravenous midazolam and droperidol for sedation of the acutely agitated patient in the emergency

department. Ann Emerg Med. 2006;47(1):61-7.

• 98. Spain D, Crilly J, Whyte I, Jenner L, Carr V, Baker A. Safety and effectiveness of high-dose midazolam for severe behavioural disturbance in an emergency department with

suspected psychostimulant-affected patients. Emerg Med Australas. 2008;20(2):112-20.

• 99. Battaglia J. Pharmacological management of acute agitation. Drugs. 2005;65(9):1207-22.

• 100. Alexander J, Tharyan P, Adams C, John T, Mol C, Philip J. Rapid tranquillisation of violent or agitated patients in a psychiatric emergency setting. Pragmatic randomised trial

of intramuscular lorazepam v. haloperidol plus promethazine. Br J Psychiatry. 2004;185:63-9.

• 101. Breitbart W, Marotta R, Platt MM, Weisman H, Derevenco M, Grau C, et al. A double-blind trial of haloperidol, chlorpromazine, and lorazepam in the treatment of delirium

in hospitalized AIDS patients. The American journal of psychiatry. 1996;153(2):231-7.

• 102. Practice guideline for the treatment of patients with delirium. American Psychiatric Association. The American journal of psychiatry. 1999;156(5 Suppl):1-20.

• 103. Gottlieb M, Long B, Koyfman A. Approach to the Agitated Emergency Department Patient. The Journal of emergency medicine. 2018;54(4):447-57.

• 104. Linder LM, Ross CA, Weant KA. Ketamine for the Acute Management of Excited Delirium and Agitation in the Prehospital Setting. Pharmacotherapy. 2018;38(1):139-51.

• 105. Green SM, Rothrock SG, Lynch EL, Ho M, Harris T, Hestdalen R, et al. Intramuscular ketamine for pediatric sedation in the emergency department: safety profile in 1,022

cases. Annals of emergency medicine. 1998;31(6):688-97.

References• 106. Scheppke KA, Braghiroli J, Shalaby M, Chait R. Prehospital use of i.m. ketamine for sedation of violent and agitated patients. The western journal of emergency medicine.

2014;15(7):736-41.

• 107. Hopper AB, Vilke GM, Castillo EM, Campillo A, Davie T, Wilson MP. Ketamine use for acute agitation in the emergency department. The Journal of emergency medicine.

2015;48(6):712-9.

• 108. Sleigh J, Harvey M, Voss L, Denny B. Ketamine &#x2013; More mechanisms of action than just NMDA blockade. Trends in Anaesthesia and Critical Care. 2014;4(2):76-81.

• 109. Mion G, Villevieille T. Ketamine pharmacology: an update (pharmacodynamics and molecular aspects, recent findings). CNS neuroscience & therapeutics. 2013;19(6):370-80.

• 110. Cai YC, Ma L, Fan GH, Zhao J, Jiang LZ, Pei G. Activation of N-methyl-D-aspartate receptor attenuates acute responsiveness of delta-opioid receptors. Molecular

pharmacology. 1997;51(4):583-7.

• 111. Sutton CD, Carvalho B. Optimal Pain Management After Cesarean Delivery. Anesthesiology clinics. 2017;35(1):107-24.

• 112. Han JH, Bryce SN, Ely EW, Kripalani S, Morandi A, Shintani A, et al. The effect of cognitive impairment on the accuracy of the presenting complaint and discharge instruction

comprehension in older emergency department patients. Annals of emergency medicine. 2011;57(6):662-71.

• 113. Pendlebury ST, Rothwell PM. Risk of recurrent stroke, other vascular events and dementia after transient ischaemic attack and stroke. Cerebrovascular diseases (Basel,

Switzerland). 2009;27 Suppl 3:1-11.

• 114. Li L, Yiin GS, Geraghty OC, Schulz UG, Kuker W, Mehta Z, et al. Incidence, outcome, risk factors, and long-term prognosis of cryptogenic transient ischaemic attack and

ischaemic stroke: a population-based study. The Lancet Neurology. 2015;14(9):903-13.

• 115. Mazer M, Deroos F, Hollander JE, McCusker C, Peacock N, Perrone J. Medication history taking in emergency department triage is inaccurate and incomplete. Acad Emerg

Med. 2011;18(1):102-4.

• 116. Staroselsky M, Volk LA, Tsurikova R, Newmark LP, Lippincott M, Litvak I, et al. An effort to improve electronic health record medication list accuracy between visits: patients'

and physicians' response. Int J Med Inform. 2008;77(3):153-60.

• 117. American Geriatrics Society 2015 Updated Beers Criteria for Potentially Inappropriate Medication Use in Older Adults. Journal of the American Geriatrics Society.

2015;63(11):2227-46.

• 118. Abouesh A, Stone C, Hobbs WR. Antimicrobial-induced mania (antibiomania): a review of spontaneous reports. Journal of clinical psychopharmacology. 2002;22(1):71-81.

• 119. Lambrichts S, Van Oudenhove L, Sienaert P. Antibiotics and mania: A systematic review. Journal of affective disorders. 2017;219:149-56.

• 120. Vitturi BK, da Silva Junior RG, da Rocha AJ, Narimatsu K. Metronidazole-induced encephalopathy. Revue neurologique. 2018;174(5):342-3.

• 121. Finlayson RE, Davis LJ, Jr. Prescription drug dependence in the elderly population: demographic and clinical features of 100 inpatients. Mayo Clin Proc. 1994;69(12):1137-45.

•

References• 122. Blazer DG, Wu LT. The epidemiology of substance use and disorders among middle aged and elderly community adults: national survey on drug use and health. Am J Geriatr

Psychiatry. 2009;17(3):237-45.

• 123. Baugnon KL, Hudgins PA. Skull base fractures and their complications. Neuroimaging clinics of North America. 2014;24(3):439-65, vii-viii.

• 124. Calvi LM BD. When is it appropriate to order an ionized calcium? Journal of the American Society of Nephrology : JASN. 2008;19(7):1257-60.

• 125. Stahl J. Studies of the blood ammonia in liver disease. Its diagnostic, prognostic, and therapeutic significance. Annals of internal medicine. 1963;58:1-24.

• 126. Reynolds BM, Dargan EL. Acute obstructive cholangitis; a distinct clinical syndrome. Annals of surgery. 1959;150(2):299-303.

• 127. Zhang XP, Tian H. Pathogenesis of pancreatic encephalopathy in severe acute pancreatitis. Hepatobiliary Pancreat Dis Int. 2007;6(2):134-40.

• 128. Schulz L, Hoffman RJ, Pothof J, Fox B. Top Ten Myths Regarding the Diagnosis and Treatment of Urinary Tract Infections. The Journal of emergency medicine. 2016.

• 129. Moeller KE, Lee KC, Kissack JC. Urine drug screening: practical guide for clinicians. Mayo Clinic proceedings. 2008;83(1):66-76.

• 130. Hasbun R, Abrahams J, Jekel J, Quagliarello VJ. Computed tomography of the head before lumbar puncture in adults with suspected meningitis. The New England journal of

medicine. 2001;345(24):1727-33.

• 131. Broder J. Imaging the Head and Brain. in: Broder J, editor. Diagnostic Imaging for the Emergency Physician. Philadelphia, PA: Elsevier Saunders; 2011 2011.

• 132. Thacker PJ, Sethi M, Sternlieb J, Schneider D, Naglak M, Patel RR. Rapid Response: To Scan or Not to Scan? The Utility of Noncontrast CT Head for Altered Mental Status.

Journal of patient safety. 2018.

• 133. Naughton BJ, Moran M, Ghaly Y, Michalakes C. Computed tomography scanning and delirium in elder patients. Acad Emerg Med. 1997;4(12):1107-10.

• 134. Fiebach JB, Schellinger PD, Jansen O, Meyer M, Wilde P, Bender J, et al. CT and diffusion-weighted MR imaging in randomized order: diffusion-weighted imaging results in

higher accuracy and lower interrater variability in the diagnosis of hyperacute ischemic stroke. Stroke. 2002;33(9):2206-10.

• 135. Teasdale GM, Hadley DM, Lawrence A, Bone I, Burton H, Grant R, et al. Comparison of magnetic resonance imaging and computed tomography in suspected lesions in the

posterior cranial fossa. BMJ (Clinical research ed). 1989;299(6695):349-55.

• 136. Merwick A, Werring D. Posterior circulation ischaemic stroke. BMJ (Clinical research ed). 2014;348:g3175.

• 137. Oppenheim C, Stanescu R, Dormont D, Crozier S, Marro B, Samson Y, et al. False-negative diffusion-weighted MR findings in acute ischemic stroke. AJNR American journal of

neuroradiology. 2000;21(8):1434-40.

• 138. Zehtabchi S, Abdel Baki SG, Grant AC. Electroencephalographic findings in consecutive emergency department patients with altered mental status: a preliminary report. Eur

J Emerg Med. 2012.

• 139. Jorgensen HS, Nakayama H, Raaschou HO, Larsen K, Hubbe P, Olsen TS. The effect of a stroke unit: reductions in mortality, discharge rate to nursing home, length of hospital

stay, and cost. A community-based study. Stroke. 1995;26(7):1178-82.

• 140. Jovin TG, Nogueira RG. Thrombectomy 6 to 24 Hours after Stroke. The New England journal of medicine. 2018;378(12):1161-2.

• 141. Kakuma R, du Fort GG, Arsenault L, Perrault A, Platt RW, Monette J, et al. Delirium in older emergency department patients discharged home: effect on survival. Journal of

the American Geriatrics Society. 2003;51(4):443-50.

103 104

105 106

107 108

12/12/2018

19

References• 142. Marcantonio ER, Ngo LH, O'Connor M, Jones RN, Crane PK, Metzger ED, et al. 3D-CAM: Derivation and Validation of a 3-Minute Diagnostic Interview for CAM-Defined

Delirium: A Cross-sectional Diagnostic Test Study. Annals of internal medicine. 2014;161(8):554-61.

• 143. Bellelli G, Morandi A, Davis DH, Mazzola P, Turco R, Gentile S, et al. Validation of the 4AT, a new instrument for rapid delirium screening: a study in 234 hospitalised older

people. Age Ageing. 2014;43(4):496-502.

• 144. Kean J, Trzepacz PT, Murray LL, Abell M, Trexler L. Initial validation of a brief provisional diagnostic scale for delirium. Brain Inj. 2010;24(10):1222-30.

• 145. Sands MB, Dantoc BP, Hartshorn A, Ryan CJ, Lujic S. Single Question in Delirium (SQiD): testing its efficacy against psychiatrist interview, the Confusion Assessment Method

and the Memorial Delirium Assessment Scale. Palliative medicine. 2010;24(6):561-5.

• 146. Han JH, Vasilevskis EE, Schnelle JF, Shintani A, Dittus RS, Wilson A, et al. The Diagnostic Performance of the Richmond Agitation Sedation Scale for Detecting Delirium in

Older Emergency Department Patients. Acad Emerg Med. 2015;22(7):878-82.

• 147. Vilke GM, Bozeman WP, Dawes DM, Demers G, Wilson MP. Excited delirium syndrome (ExDS): treatment options and considerations. Journal of forensic and legal medicine.

2012;19(3):117-21.

• 148. Wilson MP, Pepper D, Currier GW, Holloman GH, Jr., Feifel D. The psychopharmacology of agitation: consensus statement of the american association for emergency

psychiatry project Beta psychopharmacology workgroup. The western journal of emergency medicine. 2012;13(1):26-34.

• 149. Kerber KA. Vertigo and Dizziness in the Emergency Department. Emergency medicine clinics of North America. 2009;27(1):39-viii.

109