Morning Report Don’t forget to swipe in!

1. Morning ReportDon’t forget to swipe in! Adam Cifu, MD Bhakti Patel, MD Liz Retzer, MD August 11th, 2010

2. MKSAP • A 53 year-old woman is evaluated in the office for a 4-month history of tremor. The tremor affects both upper extremities and is present “most of the time.” She has a 15-year history of type 2 diabetes mellitus; she also has a history of hypertension, gastroparesis, and chronic kidney disease. Medications are insulin glargine, insulin lispro, lisinopril, hydrochlorothiazide, and metoclopramide.

3. MKSAP • On examination, she has diminished pedal pulses. Speech, language, and mental status are normal, although a paucity of facial expression is noted. Movements are slow, and there is mild bilateral upper and lower extremity rigidity. Deep tendon reflexes are normal, as are results of manual muscle strength testing. Sensory examination reveals distal sensory loss. She had a mildly stooped posture but no postural instability. A 4-Hz resting tremor in both upper extremities is noted, as is a prominent postural tremor.

4. MKSAP • Which of the following is the most likely diagnosis? • A) Dementia with Lewy bodies • B) Drug-induced parkinsonism • C) Multiple system atrophy • D) Parkinson disease

5. MKSAP • Which of the following is the most likely diagnosis? • A) Dementia with Lewy bodies • B) Drug-induced parkinsonism • C) Multiple system atrophy • D) Parkinson disease

6. MKSAP Teaching points • Objective: To diagnose drug-induced parkinsonism • Associated drugs are neuroleptic medications and dopamine-blocking medications such as metoclopramide. • Metoclopramide causes drug-induced parkonsonism in 1/3 of all patients using it • Treatment is stopping the medication • Features that suggest alternative condition to Parkinsonism • Symmetric signs and symptoms (tremor and rigidity) • Postural tremor • Early falls, rapid progression, poor or waning levodopa response, dementia, early autonomic failure, and ataxia • Multiple systems atrophy would be a consideration in this case • Can start off with Parkinsonian signs and symptoms • Bilateral Parkinsonian signs • Lack significant tremor • Would also have cerebellar and autonomic signs

7. Chief Complaint • 62 yo F brought to ER by CFD, found at home, minimally responsive on sofa, covered in vomitus over mouth and chest.

8. First Steps?

9. First Steps • ABC’s • Airway: (+) Gag, controlling secretions • Breathing: Bilateral Air Movement • Cardiac: (+) Pulse, strong throughout all extrmities

10. Differential ?

11. Additonal History • ROS: • Per sister: (+) for increased suicidal ideation over past 2-3 weeks (more serious) • Otherwise unremarkable • Social Hx: • Per sister: increased stress  1) works @ school w/ threat of closing, 2) recent apt move – lease more expensive than the patient can pay for • PMHx: • Depression/Bipolar D/O • DM • Hypothyroidism • HTN • PSHx: • Colonic resection

12. Medications • MEDS: (NKDA) • Prozac • Synthroid • HCTZ • Seroquel • Lunesta • Prandin • Tylenol #3 • Clonazepam • Acetaminophen • Provigil • Singular

13. Differential: AMS • Metabolic: • Hypoglycemia • Hypoxia • Hypercapnia • Hypo/Hypernatremia • Hypo/Hyperkalemia • Hypo/Hypermagnesimia • Hypo/Hypercalcemia • Thiamine - Vit B1 Def. • Rapid Osmolar Shifts • Uremia • Hepatic Encephalopathy • Hypo/Hyperthermia • Acidosis • Endocrine: • Hypo/Hyperthyroidism • DKA • Hyperosmoticnonketotic coma • Infectious: • Meningitis • Encephalitis • Sepsis • Pneumonia • Aspiration • Neuro/CNS: • Trauma (subdural/ • epidural hematoma) • Tumor/Mass • Seizure/Post-ictal State • CVA • Increased ICP • SAH • Psych: • Dementia • Delerium/Sun-downing • Psychosis • Catatonia • Cardiovascular: • MI • Hypotension • PE • Hypertensive • Encephalopathy • Medications • Withdrawal • Toxins/Ingestions

14. Physical Exam • EXAM: • VSS: T: 37.8, HR 102, BP: 160/90, RR: 22, Px 96% on RA • NEURO: Altered, responsive to voice but not following commands, moving all extremities but hypertonic (lower>upper), mild rigidity, hyperreflexic (lower>upper), inducible clonus • PULM: Crackles @ bases, coarse BS B/L • CARDS: Tachy, regular, no murmurs, capillary refill < 3 secs. • ABD: (↑) BS, NT/ND, soft, (-) HSM

15. New Differential • Can’t Miss Diagnoses? • Top Three Diagnoses?

16. Differential: AMS • Metabolic: • Hypoglycemia • Hypoxia • Hypercapnia • Hypo/Hypernatremia • Hypo/Hyperkalemia • Hypo/Hypermagnesimia • Hypo/Hypercalcemia • Thiamine - Vit B1 Def. • Rapid Osmolar Shifts • Uremia • Hepatic Encephalopathy • Hypo/Hyperthermia • Acidosis • Endocrine: • Hypo/Hyperthyroidism • DKA • Hyperosmoticnonketotic coma • Infectious: • Meningitis • Encephalitis • Sepsis • Pneumonia • Aspiration • Neuro/CNS: • Trauma (subdural/ • epidural hematoma) • Tumor/Mass • Seizure/Post-ictal State • CVA • Increased ICP • SAH • Psych: • Dementia • Delerium/Sun-downing • Psychosis • Catatonia • Cardiovascular: • MI • Hypotension • PE • Hypertensive • Encephalopathy • Medications • Withdrawal • Toxins/Ingestions

17. Work Up?

18. Work Up: Initial Labs 15.6 143 102 16 195 9.9 165 2.6 26 1.3 45.8 7.6 4.3 9.6 0.8/1.8 2.6 2.2 2.6 27 35 77

19. Work Up: Initial Labs 15.6 143 102 16 195 9.9 165 2.6 26 1.3 45.8 7.6 4.3 9.6 0.8/1.8 2.6 2.2 2.6 27 35 77 Anion Gap (AG) = ? Affect of Albumin = ?

20. Work Up: Initial Labs 15.6 143 102 16 195 9.9 165 2.6 26 1.3 45.8 7.6 4.3 9.6 0.8/1.8 2.6 2.2 2.6 27 35 77 AG = Na – (Cl + HCO3) AG = 143 – (102 + 26) AG = 15 Albumin = wnl (no change in anion gap)

21. Work Up: Initial Labs • Ammonia 93 • TSH 0.53 • CK 148 • CKMB 2.6 • Troponin <0.03 • ABG: 7.4/44/249/97 • BCx X2 drawn • UA/UCx collected • Ketones 0.33 • Lactate 2.3

22. EKG

23. Chest X-Ray

24. Work Up Continued • CXR: (-) Acute Process • EKG: Prolonged QTc • Head CT: no acute intracranial abnormality • LP: Clear, Glucose 108, Protein 85, 2 WBC  4N, 72L, 24M

25. Additonal History • Hx of Depression/Bipolar D/O w/ previous suicide attempts by overdose • Last time seen/talked with family = Friday • Monday  no show for work (unusual behavior for pt.)  sister notified  CFD

26. Further Workup?

27. Ingestion W/U • Call Poison Control! • Consider Additional Ingestions! • Pill Counts!

28. Ingestion W/U • Acetaminophen < 3 • Salicatyes <3 • Valproic Acid < 13 • Urine Myoglobin (+) • Urine Osms 430 • Serum Osms 300 • Utox (-) • ETOH (-)

29. Calculating Osmolar Gaps • The osmolality gap (OG) is an indication of unmeasured solute in the blood. • OG = MO – CO (where MO = measured OSMs, & CO = Calculated OSMs) • CO = 2 x [Na(mM/L)] + [glucose(mg/dL)/18] + [urea(mg/dL)/2.8]

30. Calculating Osmolar Gaps • CO = 2 x [Na(mM/L)] + [glucose(mg/dL)/18] + [urea(mg/dL)/2.8] • CO = 2 x 143 + [195/18] + [16/2.8] • CO ≈ 302 • OG = MO – CO • OG = 300 – 302 • OG = -2

31. Why it’s Important • 97% of patients will have osmolar gaps in the range +10 to -10. • ≥ 14 = a critical value; ↓ pH, ↑ AG & ↑ ↑ OG = Medical Emergency. • Things that cause elevated osmolar gaps: • Decreased serum water: Hyperproteinemia, Hypertriglyceridemia • Presence of unmeasured Osms: Mannitol (diuretics), Isopropyl Alcohol (acetone detected), Ethanol, Methanol (↓ pH), Ethylene Glycol (↓ pH), Propylene Glycol (lorazepam), Sorbitol, Glycerol, Acetone, Paraldehyde, Ether Trichloroethane

32. Meanwhile ... • EXAM: • VSS: T: 38.9, HR 120, BP: 190/80, RR: 26 • PULM/CARDS: unchanged • NEURO: no longer responsive to voice, minimally responsive to sternal rub, ? Gag, remains with neuromuscular rigidity, hyper-reflexia & inducible clonus

33. So ... • COURSE: • Intubated for airway protection • IV abx, steroids (LP results not back by now) • Transferred to ICU

34. What Happened ?

35. Serotonin Syndrome • Classic Triad: • 1) AMS • 2) Autonomic Hyperactivity • 3) Neuromuscular Abnormalities* • Net effect: ↑ Serotonergic Neurotransmission

36. Serotonin Syndrome • Spectrum of clinical symptoms • Easily overlooked • No single receptor responsible • Combination vs Sensitivity vs Overdose* • No lab test confirmation

37. Serotonin • Actions in body: • CNS: Modulates Thermoregulation, Behavior, Attention • PNS: GI Motility, Vasoconstriction, Broncho-constriction, Uterine Contraction • Promotion of platelet aggregation

38. Physical Findings VS abnormalities; hyperthermia, agitation, ocular clonus, tremor, akathisia, deep tendon hyperreflexia, clonus, muscle rigidity, dilated pupils, dry MM, ↑ bowel sounds, diaphoresis, flushed skin.

39. Responsible Meds

40. Hunter Criteria for Dx • Spontaneous Clonus • Inducible clonus + agitation or diaphoresis • Ocular clonus + agitation or diaphoresis • Tremor and Hyperreflexia • Hypertonia • Temp > 38 + ocular or inducible clonus Serotonergic agent +1 84% sensitive, 97% specific gold standard = dx by toxocologist

41. Differential • NMS = Neuroleptic Malignant Syndrome • Anticholinergic Toxicity • Malignant Hyperthermia • Encephalitis/Meningitis • Sympathomimetic Intoxication

42. Differential

43. Differential * * * *

44. Treatment • Discontinue Serotonergic Meds • Cyproheptadine (Antidotes) • Supportive Care • Sedation w/ benzos • Monitoring

45. Usual Course • Quick Onset (<24 hours) • Quick Recovery (<24 hours) • Recovery may be prolonged depending on source of serotonin

46. Day 2 • Remained Intubated, (-) gag • Agitated  tx = Ativan • Tachy & HTN  tx = Esmolol • CK 2440, Trop nl, Phos 1  tx = Fluids

47. Day 3 • MS improved, Extubated • VSS normalized • Labs normalizing • Once awake, pt admits to intentional Seroquel overdose. • Once deemed medically cleared  transferred to inpatient psych unit.

48. Key points • Reglan (metoclopramide) can cause drug-induced Parkinsonism in up to 1/3 of patients. • AMS is a broad differential, but one that needs to be thorough. • Serotonin Syndrome is easily missed, especially in the outpatient setting where we use many of these meds regularly. • Easily confused w/ similar syndromes. • Differentiate with exam of pupils, skin, reflexes, muscle tone

49. References • Boyer et al, The Serotonin Syndrome, NEJM (2005) • Dunkley et al, The Hunter Serotonin Toxicity Criteria: simple and accurate diagnostic decision rules for serotonin toxicity, QJM (2003)