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Interesting case

  1. 1. Case Conference December 15, 2007
  2. 2. <ul><li>Patient profile </li></ul>Case Conference • Chief complaint : ซึมลง 10 นาทีก่อนมาโรงพยาบาล : ผู้ป่วยหญิงไทยอายุ 25 ปี , กทม . ประวัติจากมารดา ผู้ป่วย
  3. 3. Present illness <ul><li>1-2 ชั่วโมง PTA ผู้ป่วยมีอาการเครียด ปวดศีรษะมาก จึงเอายาของพี่สาวมาทาน ไม่ทราบว่าเป็นยาอะไร หลังทานยาประมาณ 1 ชั่วโมง มีอาการคลื่นไส้อาเจียน ประมาณ 10 ครั้ง ญาติพบว่าผู้ป่วยดูซึม และอ่อนเพลียมากจึงพามาโรงพยาบาล </li></ul>
  4. 4. Past illness <ul><li>1 yr PTA เคยไปตรวจที่โรงพยาบาลเอกชน แพทย์บอกว่าเป็นไมเกรน ไม่ได้ทานยาใดเป็นประจำ </li></ul><ul><li>ไม่มีโรคประจำตัว ไม่แพ้ยา </li></ul><ul><li>1 wk PTA มีปัญหาเครียดเรื่องงาน ปวดศีรษะ ไม่ได้ทานยาใด </li></ul>
  5. 5. Physical examination <ul><li>GA : A Thai woman, appear to her staged age look drowsiness </li></ul><ul><li>V/S : BP 130/81 mmHg ,BT 36 °c, </li></ul><ul><li> PR 89 bpm , RR 18 pm </li></ul><ul><li>HEENT : not pale, no jaundice , normal mucosa Heart : normal S1S2 , no murmur , PMI at </li></ul><ul><li>5 ICS , MCL </li></ul><ul><li>Lung : clear , no adventitious sound </li></ul>
  6. 6. Physical examination <ul><li>Abdomen : soft , not tender , </li></ul><ul><li> no hepato-splenomegaly </li></ul><ul><li>normoactive bowel sound </li></ul><ul><li>Ext : no edema </li></ul><ul><li>Neurological Examination : </li></ul><ul><li>E3 V5 M6 , drowsiness , not well corporate </li></ul><ul><li>pupil 4 mm RTL both eyes </li></ul><ul><li>No stiff neck , no facial palsy </li></ul><ul><li>motor power at least grade III+ all , equal </li></ul><ul><li>DTR all 2+ BKK :absent both sides </li></ul>
  7. 7. Problem list & differential diagnosis
  8. 9. Investigation
  9. 10. 23/9/50 20.06
  10. 11. EKG
  11. 12. Medication <ul><li>Chloroquine(250) </li></ul><ul><li>Nortryptyline(10) </li></ul><ul><li>Prednisolone </li></ul><ul><li>MTV </li></ul><ul><li>CaCO3 </li></ul><ul><li>Cereblex </li></ul><ul><li>Bromhexine </li></ul>
  12. 13. Investigation <ul><li>CBC: </li></ul><ul><ul><li>Hb 10.3 g/dL Hct 30.6 % </li></ul></ul><ul><ul><ul><li>Aniso 2+ poikilo 1+ micro 2+ hypo 2+ </li></ul></ul></ul><ul><ul><li>WBC 11,600 cells/mcl N 86 % L 9 % M 5 % </li></ul></ul><ul><ul><li>Platelet 191,000 cells/mcL </li></ul></ul>
  13. 14. <ul><li>Blood chemistry </li></ul><ul><ul><li>Blood sugar : 114 mg/dL </li></ul></ul><ul><ul><li>BUN 9 mg/dL Cr 0.7 mg/dL </li></ul></ul><ul><ul><li>Electrolytes : </li></ul></ul><ul><ul><li>Na 143 mEq/L K 2.65 mEq/L </li></ul></ul><ul><ul><li>Cl 105 mEq/L HCO3 21.8 mEq/L </li></ul></ul><ul><ul><li>Ca 8.3 mg/dL Mg 1.6 mg/dL </li></ul></ul><ul><ul><li>PO4 2.7 mg/dL </li></ul></ul>Investigation
  14. 15. <ul><li>Serum for common drug screening </li></ul><ul><li>: negative </li></ul><ul><li>Gastric content for common drug screening </li></ul><ul><li>: negative </li></ul>Investigation
  15. 16. At ER <ul><li>Problem list </li></ul><ul><ul><li>Alteration of consciousness </li></ul></ul><ul><ul><li>imp </li></ul></ul><ul><ul><li>Side Effect from Na channel blocker </li></ul></ul><ul><ul><li>ddx </li></ul></ul><ul><ul><li>:TCA  wide QRS complex ,tall R in aVR(>3mm) </li></ul></ul><ul><ul><li>:Chloroquine  prolong QT, hypokalemia </li></ul></ul>
  16. 17. Management at ER <ul><li>Investigation </li></ul><ul><li>Serum + GC  common drug screen </li></ul><ul><li>EKG , CXR portable </li></ul><ul><li>NG larvage </li></ul><ul><li>Activated charcoal 50 gm </li></ul><ul><li>7.5% NaHCO3 50 ml IV push then 7.5 % NaHCO3 100 ml +5%D/W 1000 cc IV drip 100 ml/hr </li></ul><ul><li>ABG, EKG ( หลังให้ NaHCO3 30 min) </li></ul>
  17. 18. <ul><li>Arterial blood gas (post NaHCO3) </li></ul><ul><ul><li>pH 7.503 </li></ul></ul><ul><ul><li>pCO2 42.8 mmHg </li></ul></ul><ul><ul><li>pO2 131.1 mmHg </li></ul></ul><ul><ul><li>HCO3 33.8 mEq/L </li></ul></ul><ul><ul><li>BE 10.2 </li></ul></ul><ul><ul><li>O2sat 100% </li></ul></ul>Investigation
  18. 19. 23/9/50 20.33 ( after injection of NaHCO3)
  19. 20. 23/9/50 21.22
  20. 21. 23/9/50 22.39
  21. 22. 24/9/50 08.56
  22. 24. Sodium channel blocking agent <ul><li>inhibit the fast sodium channel in the His-Purkinje system, atrial and ventricular myocardium. This decreases conduction velocity, increases the duration of repolarization, and prolongs absolute refractory periods </li></ul>
  23. 26. Drug with Na channel blockade property (membrane stabilizing effect) Amantadine Amitryptyline Amoxapine Carbamazepime Chloroquine Cocaine Imipramine Loxapine Maproyiline Nortryptyline Orphenadrine Phenothaizine Desipramine Diltiazem Diophenhydramine Encainide Flecainide Hygroxychloroquine Procainamide Propanolol Thioridazine Quinidine Quinine Verapamil Note; Many Na channels blocking agents also bind to K channels and prevent efflux: Phenothiazine, antihistamines, and type A antidysrhythmics (7)
  24. 27. Indication for NaHCO 3 in Na channel blocking agent toxicity <ul><li>Tintinalli(TCA): ORS > 100 mSEC, hypotension refractory to fluid hydration,terminal RAD inavr> 3 mm or a dysrhythmia or if acidemic </li></ul><ul><li>Goldfrank_s_Toxicologic_Emergencies__8e_2006 </li></ul><ul><li>: If the QRS complex > 100 msec, R in avr >3mm, wide complextachycardia, VTwidth is increased, sodium bicarbonate should be administered </li></ul><ul><li>3 Rosen’s emergency medicine vol.3, chapter 149,page 2355(TCA ) </li></ul><ul><li>: ORS > 100 mSEC with symptomatic hypotension or a dysrhythmia or if acidemic </li></ul>
  25. 28. Indication for NaHCO 3 in Na channel blocking agent toxicity <ul><li>Ramathibodi poison and drug information Bullitin,Oct-December 2006 Vol 14, No4 (TCA ) </li></ul><ul><li>1: Hypotension ที่ไม่สามารถแก้ได้ด้วยการให้สารน้ ำ </li></ul><ul><li>2. Ventricular dysrhythmia </li></ul><ul><li>3. QRS prolongation </li></ul><ul><li>• มากกว่า 140 msec หรือ </li></ul><ul><li>• 110-140 msec ร่วมกับมีภาวะความดันโลหิตต่ำ </li></ul><ul><li>• การเริ่มให้รักษาด้วย sodium bicarbonate กับ </li></ul><ul><li>ผู้ป่วยที่มี QRS มากว่า 100 msec ยังไม่เป็นข้อสรุปที่แน่ชัด เพราะ </li></ul><ul><li>อาจทำให้ผู้ป่วยมีโอกาสได้รับ sodium bicarbornate ในปริมาณที่มาก </li></ul><ul><li>เกินไป ซึ่งจะเสี่ยงต่อภาวะน้ำเกิน hypernatremia หรือ มีภาวะเป็นด่าง </li></ul><ul><li>มากเกินไปได้ </li></ul><ul><li>4. Terminal RAD in aVR มากกว่า 3 mm </li></ul>
  26. 29. Role of NaHCO3 <ul><li>1. Sodium load </li></ul><ul><li>2. Increase pH  increased sodium conductance through myocardial sodium channel </li></ul>
  27. 30. Role of hypertonic saline <ul><li>Reverse cardiotoxic in several animal studies </li></ul><ul><li>No controlled human study but but numerous reports and experience support its efficacy </li></ul><ul><li>Considered in refractory hypotension, widecomplex tachycardia, </li></ul><ul><li>Potential risk: fluid overload, sodium overload, hyperchloremic metabolic acidosis </li></ul>
  28. 31. Chloroquine Intoxication
  29. 32. Chloroquine <ul><li>Used in the treatment or prevention of Malaria. </li></ul>Goldfrank_s_Toxicologic_Emergencies__8e_2006 Anti-inflammatory agent
  30. 33. Phamacokinetics <ul><li>Oral :rapidly and completely absorbed </li></ul><ul><li>highly bound to many different tissues, particularly kidney, liver, </li></ul><ul><li>and lung, and to erythrocytes. </li></ul>Goldfrank_s_Toxicologic_Emergencies__8e_2006 About half of the ingested chloroquine is eliminated in the urine
  31. 34. Pathophysiology Severe chloroquine poisoning is usually associated with ingestions of 5 g or more in adults, or with serum concentrations exceeding 5 mg/L. Goldfrank_s_Toxicologic_Emergencies__8e_2006
  32. 35. The cardiovascular effects QRS prolongation: block fast Na channel of perkinje fiber and his bundle  delay depolarization, QTc interval prolongation, increased U wave: in inhibit K efflux  delay repolarization Goldfrank_s_Toxicologic_Emergencies__8e_2006 Pathophysiology VT : delayed depolarization ที่ไม่พร้อมกันของเซลล์กล้ามเนื้อหัวใจที่ ventricle ทำให้เกิด reentry circuit และเกิดเป็น VT ตามมา Torsades depointes: prolong QT
  33. 36. Related Dose Effect <ul><li>20 mg/Kg is a toxic dose, </li></ul><ul><li>30 mg/Kg may be lethal </li></ul><ul><li>40 mg/Kg is usually lethal without early intensive therapy </li></ul>
  34. 37. Clinical Manifestations Symptoms usually occur within 1- 3 hours of ingestion Respiratory depression Hypotension Cardiovascular compromise Significant hypokalemia results from direct chloroquine-induced intracellular shifts . Goldfrank_s_Toxicologic_Emergencies__8e_2006
  35. 38. The neurologic manifestations include CNS depression, dizziness, headache, and convulsions. Rarely. Clinical Manifestations Red blood cell (RBC) oxidant stress from chloroquine may result in hemolysis in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency Goldfrank_s_Toxicologic_Emergencies__8e_2006
  36. 39. Summary of clinical effects <ul><li>rapidly onset within one to three hours after ingestion </li></ul><ul><li>Cardiac disturbances: </li></ul><ul><ul><li>circulatory arrest, shock, conduction disturbances, ventricular arrhythmias. </li></ul></ul><ul><li>Neurological symptoms: </li></ul><ul><ul><li>drowsiness, coma and sometimes convulsions. Visual disturbances not uncommon. </li></ul></ul><ul><li>Respiratory symptoms: </li></ul><ul><ul><li>apnea. </li></ul></ul><ul><li>Gastrointestinal symptoms: </li></ul><ul><ul><li>nausea, vomiting, cramps, diarrhea. </li></ul></ul>
  37. 40. Management Patients should receive early endotracheal intubation and mechanical ventilation : if arrhythmias, hypotension, seizures or significant CNS depression are present Inotropes may also be necessary : for hypotension unresponsive to a fluid challenge ( 1) thiopental was used to facilitate intubation, its use immediately preceded sudden cardiac arrest in 7 of 25 patients after chloroquine overdose.(1) 1. ABC epinephrine (0.25 mcg/kg/min) should be given IV with D 5 W, and adjusted incrementally until a systolic blood pressure greater than 100 mm Hg (1)
  38. 41. Management <ul><li>High dose : diazepam has been reported to have a specific cardioprotective action in severe chloroquine (2) poisoning. </li></ul><ul><li>During decontamination, 2 mg/kg IV diazepam is given over 30 minutes, and then 2 mg/kg/d for 2-4 days. </li></ul><ul><li>Continuous and aggressive cardiorespiratory support </li></ul><ul><li>appears to be the most critical factor in survival. </li></ul>Overdrive pacing: is the treatment of choice for ventricular tachycardia or torsade de pointes.(2)
  39. 42. 2. GI decontamination Management Orogastric lavage: within 1 hour after ingestion Activated charcoal : 1 g/kg Goldfrank_s_Toxicologic_Emergencies__8e_2006
  40. 43. Management <ul><li>Plasma potassium should be monitored, although </li></ul><ul><li>hypokalaemia may have a protective effect </li></ul><ul><li>and should not be aggressively corrected in the early stages of poisoning as there is no total body deficit of potassium </li></ul><ul><li>and attempted early correction can worsen cardiotoxicity. </li></ul><ul><li>If hypokalaemia persists beyond eight hours, </li></ul><ul><li>potassium should be replaced cautiously.(4) </li></ul>3. Hypokalemia
  41. 44. If the QRS complex width is increased, sodium bicarbonate should be administered Management Goldfrank_s_Toxicologic_Emergencies__8e_2006 Chloroquine significant protein binding, and long terminal elimination half-lives, enhanced elimination procedures are not beneficial
  42. 45. Review <ul><li>B Riou et al. </li></ul><ul><ul><li>Retrospective </li></ul></ul><ul><ul><li>51 case </li></ul></ul><ul><ul><li>Ingested > 5 gm </li></ul></ul><ul><ul><li>Blood level >25 mmol/L : all death </li></ul></ul>B Riou (1988), NEJ volume 318:1-6
  43. 46. Results <ul><li>Drowsiness appears early within 10 to 30 minutes of ingestion . </li></ul><ul><li>Severe cardiovascular symptoms appear within 1 to 3 hours of ingestion . </li></ul><ul><li>Fatal outcome usually occur within 2 to 3 hours . </li></ul><ul><li>Cardiovascular symptoms may last for 48 hours . After the 48th hour patients usually recover . </li></ul>
  44. 47. <ul><li>B Riou et al. </li></ul><ul><ul><li>Retrospective </li></ul></ul><ul><ul><li>51 case </li></ul></ul><ul><ul><li>Combinating early machanical ventilation with diazepam & adrenaline maybe effective </li></ul></ul>B Riou (1988), NEJ volume 318:1-6 Review
  45. 48. <ul><li>K.Marquardt </li></ul><ul><ul><li>(1) diazepam for seizures and sedation; </li></ul></ul><ul><ul><li>(2) early intubation and mechanical ventilation; </li></ul></ul><ul><ul><li>(3) epinephrine for treatment of vasodilation and myocardial depression; </li></ul></ul><ul><ul><li>(4) potassium replacement with close monitoring of levels; </li></ul></ul><ul><ul><li>(5) charcoal for gastrointestinal decontamination if ingestion occurred within an hour; </li></ul></ul><ul><ul><li>(6) high dose diazepam for life-threatening symptoms </li></ul></ul>K.Marquardt (2001) AJEM , volume 19,issue 5 Pages 420-424 Review
  46. 49. Revue / Journal Title Intensive care medicine  (Intensive care med.)  ISSN 0342-4642   CODEN ICMED9  <ul><li>Objective : Acute chloroquine intoxication is responsible for a membrane-stabilising effect </li></ul><ul><li>. Diazepam is used in acute chloroquine intoxication on the basis of clinical and experimental observations, but its utility alone, in man, remains unproven. The goal of this study was to verify whether diazepam alone has an effect on the membrane-stabilizing effect observed in moderately severe chloroquine intoxications. </li></ul><ul><li>Design : Prospective, multi-center, double-blind, placebo-controlled study. </li></ul><ul><li>a suspected ingested dose of 2 or more but less than 4 g, systolic blood pressure (SBP) higher than 80 mmHg, QRS duration less than 0.12 s and the absence of dysrhythmia at inclusion. Interventions : </li></ul><ul><li>Patients received either a loading dose of 0.5 mg/kg diazepam followed by an infusion of I mg/kg over 24 h or an equivalent volume of placebo. Measurements and results : Outcome was measured by serial assessments of SBP, ECG (QRS and QT segments) and clinical deterioration. There were no significant differences observed in the initial or serial ECG or SBP measurements. </li></ul><ul><li>Conclusions : Diazepam, at the dose studied, does not appear to reverse the chloroquine-induced membrane-stabilising effect in acute moderately severe chloroquine intoxication. Supportive intensive care of these intoxications appears to be all that is necessary . </li></ul>
  47. 50. Take home message <ul><li>Sodium bicarbonate and hypertonic saline have been shown effectively to treat the cardiac conduction abnormalities that can occur form Na channel blocking agent </li></ul><ul><li>ECG highlights in Na channel blocking agent: QRS complex widening, QT interval prolongation, Ventricular dysrhythmia, Bradydysrhythmia( rarely with omnious prognostic implication) </li></ul><ul><li>The ECG can neither ruled in nor ruled out toxicity from Na channel blocking agent. </li></ul><ul><li>In chloroquine toxicity: hypokalaemia may have a protective effect and should not be aggressively corrected in the early stages of poisoning as there is no total body deficit of potassium </li></ul><ul><li>การเริ่มให้รักษาด้วย sodium bicarbonate กับ </li></ul><ul><li>ผู้ป่วยที่มี QRS มากว่า 100 msec ยังไม่เป็นข้อสรุปที่แน่ชัด เพราะ </li></ul><ul><li>อาจทำให้ผู้ป่วยมีโอกาสได้รับ sodium bicarbornate ในปริมาณที่มาก </li></ul><ul><li>เกินไป ซึ่งจะเสี่ยงต่อภาวะน้ำเกิน hypernatremia หรือ มีภาวะเป็นด่าง </li></ul><ul><li>มากเกินไปได้ </li></ul>
  48. 51. Take home messages <ul><li>High dose : diazepam has been reported to have a specific cardioprotective action in severe chloroquine (2) poisoning. igh </li></ul>
  49. 52. Reference <ul><li>(1)Goldfrank_s_Toxicologic_Emergencies__8e_2006 </li></ul><ul><li>(2) Jaeger A, Sauder P, Kopferschmitt J et al . Clinical features </li></ul><ul><li>and management of poisoning due to antimalarialdrugs. </li></ul><ul><li>Med Tox 1987; 2: 242–73. </li></ul><ul><li>(3) Clemessy JL, Favier C, Borron SW et al . Hypokalaemia </li></ul><ul><li>related to acute chloroquine ingestion. Lancet 1995; </li></ul><ul><li>346: 877–80. </li></ul><ul><li>(4) Bouvier AM, Bertrand D, Timsit JF et al . Intoxications </li></ul><ul><li>massives et prolongees par la nivaquine: effets du </li></ul><ul><li>diazepam. Reanimation Soins Intensifs, Medicine d’Urgence </li></ul><ul><li>1986; 2: 265. </li></ul><ul><li>(5) Riou B, Barriot P, Rimailho A et al . Treatment of severe </li></ul><ul><li>chloroquine poisoning. New Engl J Med 1988; 318: 1–6. </li></ul><ul><li>(6) A.Rajah (1990) anesthesia 45(11) 955-957 </li></ul><ul><li>(7) ECG in emergency and acute care, ELSEVIER/MOSBY </li></ul>
  50. 53. Thank you For your attention Merry Christmas and Happy New Year 2008

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