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Case Conference What Happened?

Case Conference What Happened?. October 6, 2009 Evan Schwarz. ED Presentation. 47 year old female with depression presents after overdose Witnessed by husband Called EMS Did not come to hospital Possibly hypotensive in the field Pt too somnolent to answer questions

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Case Conference What Happened?

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  1. Case ConferenceWhat Happened? October 6, 2009 Evan Schwarz

  2. ED Presentation • 47 year old female with depression presents after overdose • Witnessed by husband • Called EMS • Did not come to hospital • Possibly hypotensive in the field • Pt too somnolent to answer questions • No other information in computer aside from unknown mental disorder • No meds listed • NKDA

  3. Initial exam • VS 106/74 91 36.4 13 100% on 4 liters • Appearance: Well nourished, sedate, sleeping in bed • Head: no signs of trauma • Eye: clear, PERRL, approx 4.5 mm to 3 mm • OP: clear, moist membranes • C/V: RRR without murmur • Pulm: clear anterior fields • GI: +BS, nd, nttp, scar in RUQ • GU: foley placed and obtained 700 cc of urine

  4. Exam continued • Skin: Not flushed, abrasion to left arm • Musculoskeletal: No rigidity • Neuro: • Opens eyes to light stimulation • Mumbles in response to some questions • CN: PERRL, tongue midline, no facial droop • Reflexes: 2+, symmetric • No tremors noted • No clonus

  5. EKG

  6. Any thoughts about what she took

  7. EMS didn’t bring the bottles • But they spoke to the husband • Risperdal • Cogentin • Trazodone

  8. Labs come backDrawn at 5 am on day 1 140 109 9 12.4 141 27.1 3.4 19 0.45 1.2 TSH 1.94 AST 138 UA: trace ketones, no blood APAP < 1.2 ALT 148 UDS: +cocaine ASA < 3 Bili 0.4 ETOH 260 Ammonia 22 CT: unremarkable head CT Li < 0.1

  9. ED care • Fluids • Toxicology consult • Observation • Admit to hospital • Pt in AAPOW room and vomits • Concern for aspiration • CXR at 6:44 -? Pulm infiltrates concerning for aspiration • CXR at 7:20 – no abnormalities • Pt started on antibiotics for possible aspiration

  10. Pt goes to floor • Right upper quadrant ultrasound • Homogenous parenchyma, no focal mass • Prior cholecystectomy • Cerruloplasmin 25 • Syphilis RPR non reactive • ABG: 7.37/34/198/19

  11. And the next morning… • Pt agitated during the night and received benzos • Pt with eyes open, making picking movements at times • Mumbles in response but is incoherent, not re-directable, but not thrashing around • HR 80-90s, BP systolic < 150, no tachepnea, not febrile • CTA • RRR • Diminished bs, abd nd, nttp • No rigidity, normal reflexes • Slight diaphoresis to forehead, no flushing

  12. Agitated DeliriumAny thoughts?

  13. And then some clarity • Re-evaluation in the afternoon • Pt now pushes away noxious stimuli and says her name • Family now present • Pt is alcoholic • Drinks at least 12 beers a day • Normally stops drinking on Sundays • No infectious symptoms • Had been depressed concerning possible diagnosis of cirrhosis

  14. Delirium Tremens

  15. Alcohol • CDC – excessive use • Heavy: > 2 drinks/day • Binge: > 4 drinks/time • > ½ US population drank alcohol in last month • 79,000 deaths annually1 • 3rd leading lifestyle related cause of death2 •  Violence, child maltreatment, and risky sexual behaviors 3, 4 1. Centers for Disease Control and Prevention (CDC). Alcohol-Related Disease Impact (ARDI). Atlanta, GA: CDC. Available at http://www.cdc.gov/alcohol/ardi.htm. Accessed March 28, 2008. 2. Mokdad AH, Marks JS, Stroup DF, Gerberding JL. Actual causes of death in the United States, 2000. JAMA 2004; 291(10):1238–1245. 3. Greenfield LA. Alcohol and crime: An analysis of national data on the prevalence of alcohol involvement in crime. Report prepared for the Assistant Attorney General’s National Symposium on Alcohol Abuse and Crime. Washington, DC: U.S. Department of Justice, 1998. Available at http://www.ojp.usdoj.gov/bjs/pub/pdf/ac.pdf (PDF). Accessed March 31, 2008.

  16. Alcohol http://www.cdc.gov/alcohol/

  17. 2007 National Youth Risk Behavior survey http://www.cdc.gov/HealthyYouth/yrbs/

  18. Some more fun facts • Alcohol dependence (USA) • 6% men • 2% women • Estimated cost of $185 billion • 200,000 die annually • Leading cause of mortality in 15-45 year olds Goldfrank’s Toxicologic Emergencies, eighth edition

  19. DSM IV Criteria for Alcohol Withdrawal • Cessation/Reduction of heavy/prolonged drinking • Two or more of the following • Autonomic hyperactivity • Hand tremor • Insomnia • Nausea/vomiting • Hallucinations/illusions • Pyschomotor agitation • Anxiety • Grand mal seizures • Must cause clinical distress or some impairment • Symptoms not due to other disorder

  20. Ethanol Withdrawal • Early uncomplicated withdrawal • Develop as early as 6 hours after last drink • Autonomic hyperactivity • Uncomfortable but generally not dangerous • Alcoholic Hallucinosis • 25% of AWS develop hallucinations • Subset of these develop alcoholic hallucinosis • Classically visual or tactile • Formication • Clear sensorium • Not a predictor of DTs • Alcohol withdrawal seizures • Approx. 10% of patients with AWS • 3% develop status • If occur in presence of ETOH, may be poor prognostic sign

  21. Delirium Tremens • Generally manifests between 48-96 hours after cessation of drinking • 1/3 have seizure as precipitating event • Many manifestations similar to uncomplicated AWS • Per DSM IV criteria • Disturbance of consciousness with reduced ability to focus • Change in cognition • Development of perceptual disturbance • Can last for up to 2 weeks

  22. Predictors • Multiple have been evaluated • ALT > 50 U/L • Chloride < 96 mEq/L • Potassium < 3.6 mEq/L • Blood ETOH concentrations • Homocysteine levels • We’ll look at a few more in a little bit

  23. Resistance • GABA • NMDA • Kindling phenomena • Increasing severity of events

  24. Biochemistry and Alcohol • NAD+:NADH ratio • Pyruvate to lactate (not glucose • Acetyl-Co-A + Acetate to Acetacetate • Along with thiamine deficiciency • TCA cycle

  25. Clinical Institute Withdrawal Assessment of Alcohol Scale, Revised

  26. Suggested that scores > 15 correspond to severe AWS and an increased risk of DTS and seizures (Bayard et al., 2004)

  27. Looking for Markers

  28. ANP study • Background • Changes in volume and electrolyte homeostasis during alcohol withdrawal • Natriuretic peptide produced by the heart • Multiples experimental studies with inconclusive results • Relied on information from 2 studies • 60% of patients had symptoms of DTs • Compared study patients to age matched controls • Study patients were in a state of severe alcohol withdrawal • ANP level was higher and remained higher at day 10 of hospitalization

  29. Levels 50% higher on day of admission

  30. Patients who developed DTs

  31. ANP Study • ? Study quality • Hypothesized about mechanism • BNP? • Rat study with injection of ANP and antibody to ANP centrally

  32. Platelet Study

  33. Platelets • Retrospective cohort study • All patients > 20 years old • Consecutively admitted to an alcohol treatment center from 1997-1998 • DC Dx of alcohol dependence and alcohol withdrawal syndrome • Blood samples taken the morning after admission • Records obtained from previous alcohol related stays

  34. Platelets • 334 patients included • Female 17% • Male 83% • 7% history of DTs • 9% history of previous seizure • During treatment • 3% (10/334) developed DTs • 2% (8/333) developed seizures • No one had both

  35. Thrombocytopenia

  36. Statistics • Development of DTs • Sensitivity 70% • Specificity 69% • PPV 65% • NPV 99% • Development of Seizures • Sensitivity 75% • Specificity 69% • PPV 6% • NPV 99% • Normal Hgb, WBC • ?Parallel phenomena

  37. Overlap • Incidence

  38. Treatment Possibilities

  39. Dexmedetomidine: a case report • 30 year old patient • Last alcohol intake approximately 30 hours before admission • Had multiple admissions for AWS • Serum ETOH < 10 mg/dL • Admitted with AMS/agitation • Meds: • Dilantin 20 mg/kg • Oxazepam 30 bid • Thiamine Chemical structures from Wikipedia clonidine

  40. Dexmedetomidine • Day 2 patient becomes agitated, disoriented, combative with severe tremors and tachycardia • Treatment: • Lorazepam 10 mg IM • Total of midazolam 35 mg IV • Infusion at 0.16 mg/kg/hr for 3 hours • Tremors less severe but agitation severe • 31 hours after ED admission IV dexmedetomidine started at 0.2 mcg/kg/hr with titration to 0.7 mcg/kg/hr (to patient comfort) • Improved tremor, confusion, and less severe agitation • Midazolam tapered to 1 mg/hr over next 3 hours • Within 5 hours of midazolam taper, mental status and behavior improve

  41. Continued • Midazolam stopped • Dexmedetomidine kept at 0.7 mcg/kg/hr as only sedation • Titrated down and stopped 24 hours later • Infusion time of 39 hours • FDA approval for ventilated patients for 24 hours • Does not inhibit respiratory drive or depress neurologic status

  42. Dexmedetomidine • Decreases hyperarousal state • Clonidine has not been shown to reduce the incidence of seizures or delirium • Second case of patient treated with dex. For DTs • Monotherapy?

  43. Other possibilities • Magnesium • Carbamezapine • Used in Europe • Increases CNS GABA concentrations • Gabapentin • Valproic Acid

  44. References • 1. Centers for Disease Control and Prevention (CDC). Alcohol-Related Disease Impact (ARDI). Atlanta, GA: CDC. Available at http://www.cdc.gov/alcohol/ardi.htm. Accessed March 28, 2008. • 2. Mokdad AH, Marks JS, Stroup DF, Gerberding JL. Actual causes of death in the United States, 2000. JAMA 2004; 291(10):1238–1245. • 3. Greenfield LA. Alcohol and crime: An analysis of national data on the prevalence of alcohol involvement in crime. Report prepared for the Assistant Attorney General’s National Symposium on Alcohol Abuse and Crime. Washington, DC: U.S. Department of Justice, 1998. Available at http://www.ojp.usdoj.gov/bjs/pub/pdf/ac.pdf (PDF). Accessed March 31, 2008. • 4. The National Center on Addition and Substance Abuse at Columbia University, 1999. No safe haven: Children of substance-abusing parents. Available at http://www.casacolumbia.org/Absolutenm/articlefiles/No_Safe_Haven_1_11_99.pdf* (PDF). Accessed March 31, 2008. • 5. Kovacs GL. The role fo atrial natriuretic peptide in alcohol withdrawal: a preipheral indicator and central modulator. European Jounral of Pharmacology 405(2000) 103-112. • 6. Berggren U, Fahlke C, Berglund KJ, et al. Thrombocytopenia in Early Alcohol Withdrawal is Associated with Development of Delirium Tremens or seizures. Alcohol and Alcoholism 2009; 44 (4)382-6. • 7. Darrouj, Puri N, Prince E, et al. Dexmedetomidine infusion as adjunctive therapy to benzodiazepines for acute alcohol withdrawal. Ann Pharmacother 2008;42:1703-5. • 8. Goldfrank’s Toxicologic Emergencies, eighth edition, chapter 75 and 76. • 9. Wikipedia (chemical structures of dexmedetomidine and clonidine

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