藥物中毒之臨床藥事照顧經驗 4
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分享毛地黃(digoxin)中毒和warfarin中毒的解毒
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藥物中毒之臨床藥事照顧經驗 4
- 2. 案例五 • 67歲男性，有心衰竭病史，長期使用ramipril 10 mg po qd，digoxin 0.125 mg po qd，因為呼吸 窘迫入院，digoxin 濃度是7.2 ng/ml (正 常值0.8-2.0 ng/ml) ，伴隨有心跳過慢的症狀(每 分鐘40-50下) • 醫師詢問藥師 ▫ 本院是否有digoxin的解毒劑呢? 2
- 3. Digoxin (毛地黃) 3 因其強心作用，神經賀爾蒙和電生理的作用 可用於治療 因收縮性不全的心衰竭和 上心室心律快速 Ref: Michael L, MD Digitalis poisoning. In: UpToDate, Jonathan G, MD(Ed), UpToDate, Waltham, MA, 2015.
- 4. 治療區間(therapeutic index)狹窄 4 TI=LD50/ED50 LD50 為使50%使用者死亡所需劑量 ED50 為使50%使用者產生療效所需劑量 TI越高，該藥物越安全。 反之，越危險。
- 5. Digoxin臨床上會有甚麼毒性呢? • 噁心嘔吐，腹瀉，黃綠色視覺非特異性 • 房室阻斷(AV block)，心搏過緩 (bradycardia)特異性 • 停藥，症狀治療，若危及生命可 用解毒劑Digibind處理 5 Ref: Michael L, MD Digitalis poisoning. In: UpToDate, Jonathan G, MD(Ed), UpToDate, Waltham, MA, 2015.
- 6. 解毒劑 • Digoxin-specific antibody ▫ 毛地黃抗體 Fab fragment • 適應症 ▫ 毛地黃中毒導致 可能致命之心血管毒性症狀：如ventricular arrhythmias 、 progressive bradyarrhythmias 、 second or third degree AV block等；合併生命徵象不穩定者(unrefractory hypotension)。 嚴重高血鉀(K+ ＞5.5 mmol/L) 潛在導致心跳停止之危險因素存在時，如成人服用超過10 mg之digoxin、兒童服用超過4 mg之digoxin、血液digoxin 濃度在服用後6－8小時大於10 ng/ml。 6 Ref: http://www.pcc.vghtpe.gov.tw/antidote/p4new.asp
- 7. 劑型 • Digibind ▫ 可結合 0.5 mg digoxin/38 mg digoxin specific Fab/vial • Digitalis antidote BM ▫ 可結合1 mg digoxin//80 mg digoxin specific Fab/vial ▫ 用法同Digibind，但所需瓶數減半 7 Ref: http://www.pcc.vghtpe.gov.tw/antidote/p4new.asp
- 8. Digibind(可結合 0.5 mg digoxin/vial) 建 議劑量 • 中毒劑量未知或緊急狀況下 ▫ 急性中毒建議給 Digibind 10 vial，慢性中毒成人建議給 2－ 6 vial （兒童1 vial） IV 30 min。而後依臨床反應決定是否 繼續治療。 • 依服用藥量，決定劑量 ▫ 服用digoxin總量（mg） X 0.8÷0.5 mg=所需Digibind瓶數 ▫ 每服用25 顆含 0.25 mg之digoxin，所需劑量為Digibind 10 vial • 慢性中毒時，可依穩定態之血液濃度，決定劑量 ▫ Serum digoxin level (ng/ml) X 體重(kg) ÷100＝所需Digibind 支數 ▫ 此法可能低估所需劑量；如反應不佳，可增加1/2劑量。 8 Ref: http://www.pcc.vghtpe.gov.tw/antidote/p4new.asp
- 10. 洗胃呢? • 活性碳或cholestyramine洗胃可當做輔助治療 • 若剛大量服用digoxin 1-2小時內是有幫助的 • 要小心病人是否清醒或有插管 10 Ref: Michael L, MD Digitalis poisoning. In: UpToDate, Jonathan G, MD(Ed), UpToDate, Waltham, MA, 2015.
- 11. 小心電解質異常 • 常見高血鉀 • 和中毒嚴重度與死亡率有關 • 一旦給與Digoxin-specific antibody解毒劑後 ▫ 鉀離子就會降下來 ▫ 給與降鉀的藥，反而可能出現低血鉀 • 若出現低血鉀 ▫ 要補充鉀離子，因為低血鉀會惡化digoxin中毒 11 Ref: Michael L, MD Digitalis poisoning. In: UpToDate, Jonathan G, MD(Ed), UpToDate, Waltham, MA, 2015.
- 12. 洗腎洗的出來嗎? • 因為digoxin的分怖體積大，分子量大 • 所以洗腎洗不出來 12 Ref: Michael L, MD Digitalis poisoning. In: UpToDate, Jonathan G, MD(Ed), UpToDate, Waltham, MA, 2015.
- 13. 那怎麼辦? • 若病人症狀穩定且腎功能正常 • 可監測病人心律並且六小時後監測濃度 • 若無繼續上升 • 則可持續觀察至恢復正常 • 臨床經驗: 在本院多數的digoxin中毒，皆停藥後， 症狀治療並觀察心律，大部份病人約1星期 digoxin濃度可恢復正常。 13 Ref: Michael L, MD Digitalis poisoning. In: UpToDate, Jonathan G, MD(Ed), UpToDate, Waltham, MA, 2015.
- 14. 案例六 • 68歲女性，因心律不整服用warfarin預防血栓，5 mg qd po，於門診追蹤時，INR皆控制在1.5(目 標值 2-3) 。 • 本次因肺炎感染，入住加護病房，因持續服用 warfarin 5 mg qd，一星期後監測發現INR上升至 9.02。 • 藥師立即建議停藥，並且依文獻建議是否給與 vitamin k1 14 INR: international normalized ratio
- 16. 危險因子 • 藥物交互作用 • 其它共病症 ▫ 肝臟疾病 ▫ 營養不良 ▫ 維它命K缺乏 • 病人服用多少的劑量 • 病人順服性好嗎? • 假性上升，檢查數據異常 16
- 17. 治療建議 INR 是否出血 建議 >治療目標 to 5.0 否 降低warfarin劑量 或停一個劑量，等INR回到治療區間後改 用較低的劑量 或INR僅短暫延長，不需降低劑量 5.0 to 9.0 否 停用warfarin一兩個劑量，等INR回到治 療區間後改用較低的劑量 或停一個劑量並給與1-2.5 mg口服維它 命K1 > 9.0 否 停用warfarin並給與2.5-5 mg口服維它命 K1，密切監測INR，視情況再給與K1， 等INR回到治療區間後改用較低的劑量 任何 嚴重出血 停用warfarin並給與10 mg靜脈注射維它 命K1，並依臨床情況給與冷凍血漿等 17
- 18. 回到病人 • 給與病人vitamin K1靜脈注射(因本院只有針劑) • 停用warfarin兩天後，INR回到2.3 • 再改用低劑量warfarin重新給藥 • 檢討: ▫ 病人順服性不好? ▫ 藥物交互作用 類固醇? 抗生素? 18
Hinweis der Redaktion
- Digoxin intoxication SUMMARY AND RECOMMENDATIONS ●Arrhythmia is the most dangerous manifestation of digitalis (cardiac glycoside) poisoning. Arrhythmias occur through several mechanisms, which are described in the text. (See 'Pharmacology and cellular toxicology' above and 'Kinetics' above.) ●The cardiac manifestations of digitalis toxicity can include virtually any type of arrhythmia with the exception of rapidly conducted atrial arrhythmias. Gastrointestinal (anorexia, nausea, vomiting, and abdominal pain) and neurologic signs (confusion and weakness) may be present. Chronic toxicity is more difficult to diagnose, as symptom onset tends to be more insidious. In addition to gastrointestinal symptoms, visual changes may occur, including alterations in color vision, the development of scotomas, or blindness. (See 'Clinical features and diagnosis' above.) ●The differential diagnosis for digitalis intoxication includes poisoning with beta blockers, calcium channel blockers, or alpha agonists (eg, clonidine), as well as nontoxicologic etiologies such as sick-sinus syndrome, hypothermia, hypothyroidism, myocardial infarction, and hyperkalemia unrelated to digitalis. (See 'Differential diagnosis' above.) ●In the patient with suspected digoxin toxicity, a serum digoxin concentration, serum potassium concentration, creatinine and BUN, and serial electrocardiograms should be obtained. (See 'Laboratory and ECG evaluation' above.) ●A quantitative serum digoxin concentration is readily determined in most hospital laboratories. The therapeutic range is 0.8 to 2 ng/mL (1 to 2.6 nmol/L). The serum digoxin concentration does notnecessarily correlate with toxicity. (See 'Serum digoxin concentration' above.) ●We recommend that any patient with clinically significant manifestations of digitalis poisoning be treated with digoxin-specific antibody (Fab) fragments (Grade 1B). Significant findings include: •Life-threatening arrhythmia (eg, ventricular tachycardia; ventricular fibrillation; asystole; complete heart block; Mobitz II heart block; symptomatic bradycardia) •Evidence of end-organ dysfunction (eg, renal failure, altered mental status) •Hyperkalemia (serum potassium >5 to 5.5 meq/L [>5 to 5.5 mmol/L]) (see 'Antidotal therapy with antibody (Fab) fragments' above). ●As temporizing measures or if Fab fragments are not immediately available, bradycardia can be treated with atropine (0.5 mg IV in adults; 0.02 mg/kg IV in children, minimum dose 0.1 mg) and hypotension with IV boluses of isotonic crystalloid. (See 'Basic measures and arrhythmias' above.) ●Hyperkalemia is common in acute digitalis intoxication and accurately reflects the degree of toxicity and risk of death. However, hyperkalemia itself does not cause death and treatment of hyperkalemia does notreduce mortality but does increase the risk of hypokalemia following treatment with Fab fragments. Therefore, we treat hyperkalemia with Fab fragments as described above; we suggest not treating hyperkalemia in patients with digitalis poisoning with anything other than Fab fragments (Grade 2C). (See'Electrolyte abnormalities' above.) ●Patients suspected of having acute digitalis intoxication who present to the emergency department within one to two hours of ingestion may benefit from the administration of activated charcoal. The standard dose is 1 g/kg (maximum 50 g). The decision to administer activated charcoal should be made after ensuring that the patient is alert and adequately protecting their airway. (See 'GI decontamination' above.)
- four-factor prothrombin complex concentrate(4-factor PCC) or fresh frozen plasma