Therapeutics of Clinical Drugs 臨 床 藥 物 治 療 學 橫 紋 肌 溶 解 症 案 例 探 討 衛 生 福 利 部 桃 園 醫 院 藥 劑 科 藥 師 陳 韋 璇 黃 美 鈴 張 震 鴻 摘 要 33 rhabdomyolysis hypokalemia electroyte disorders 壹 前 言 (physical) (nonphysical) ( ) 1 2 (Creatine Kinase CK) 貳 案 例 報 告 33 B aspirin 7/11 135 mg/dl AST 209 IU/L ALT 82 IU/L 116 mmol/l CPK 18091 U/L 1.5 mmol/l ( ) normal saline 0.9% 500 29 4 Dec. 31 2013 藥 學 雜 誌 第 117 冊 111
臨 床 藥 物 治 療 學 Therapeutics of Clinical Drugs ml 3 bot QD IVD (10 meq/5 ml) 6 amp QD IVD 7/12 normal saline 0.9% 500 ml 5 bot QD IVD 10 amp QD IVD [600 mg (8 meq)/tab] 2 tab TID 7/16 2.8 mmol/l 2 tab QID 7/12 (renal parenchymal disease) (bladder distension) 7/19 3.3 mmol/l CPK 5224 U/L ph 7.32 ph 7.5 7/20 B 7 potassium chloride 600 mg PO TID valsartan 80 mg PO QD ( ) 7/27 2.8 mmol/l ph 7.32 WBC Epithelial cells 14 1200 mg PO QID valsartan 80 mg PO QD sodium bicarbonate 300 mg PO TID spironolactone 25 mg PO BID 8/7 WBC Epithelial cells 28 3.8 mmol/l 600 mg PO QID ( 1 表 一 引 起 橫 紋 肌 溶 解 症 的 原 因 1. 2. 3. 4. 1. McArdle disease phosphofruktokinase deficiency 2. 3. (ethanol) (anti-psychotics) (diuretics) (drugs abuse) HMG-CoA (statins) 4. A B (influenza A and influenza B) (coxsackievirus) (falciparum malaria) (herpes viruses) (HIV) (Legionella) (Salmonella) (Streptococcus) (tularemia) 5. 5. 6. 7. 表 二 血 液 檢 驗 值 6. 7. 7/11 7/12 7/13 7/15 7/16 7/17 7/19 7/27 8/7 Glucose 74-110 mg/dl 135 148 102 BUN 7-20 mg/dl 7 4 4 4 7 7 112 THE JOURNAL OF TAIWAN PHARMACY Vol.29 No.4 Dec. 31 2013
7/11 7/12 7/13 7/15 7/16 7/17 7/19 7/27 8/7 Cr. 0.4-1.2 mg/dl 0.8 0.6 0.6 0.5 0.5 0.5 0.7 0.6 AST 12-40 IU/L 209 298 21 ALT 5-40 IU/L 82 250 225 37 CPK 25-192 U/L 18091 23534 26765 39575 39762 18922 5224 Na 136.0-144.0 mmol/l 143.0 145.0 148.0 146.0 140.0 142.0 142.0 141.0 137.0 K 3.5-5.1 mmol/l 1.5 1.6 1.9 2.0 2.8 2.8 3.3 2.8 3.8 Cl 101.0-111.0 mmol/l 116.0 117.0 121.0 116.0 120.0 118.0 110.0 Mg 1.8-2.5 mg/dl 2.4 2.4 2.2 2.1 2.2 Ca 8.9-10.3 mg/dl 9.7 8.6 8.1 8.3 8.6 9.1 9.8 P 2.4-4.7 mg/dl 1.7 2.5 3.4 2.5 2.7 1.2 2.8 ph 7.35-7.45 7.43 7.4 7.32 7.32 7.32 表 三 尿 液 檢 驗 值 7/11 7/13 7/15 7/17 7/18 7/19 7/27 8/7 ph 5.0-6.0 7.0 7.0 7.0 7.0 7.5 7.5 7.0 7.0 Protine - 1+ 1+ +/- - - - +/- - O.B - 2+ 3+ 2+ - - - - - RBC 0-2/HPF 5-10 0-2 0-2 0-2 0-2 0-2 2-5 0-2 WBC 0-2/HPF 2-5 0-2 5-10 2-5 2-5 0-2 10-25 10-25 EP. CELL 0-2/HPF 2-5 0-2 2-5 2-5 2-5 0-2 5-10 2-5 表 四 逐 日 用 藥 記 錄 表 7/11 7/12 7/13 7/14 7/15 7/16 7/17 7/18 7/19 (KCL 10 meq/5 ml) AMP 6 QD IVD (KCL 10 meq/5 ml) AMP 10 QD IVD normal Saline 0.9% (N.S. 0.9% 500 ml) BOT 3 QD IVD normal Saline 0.9% (N.S. 0.9% 500 ml) BOT 5 QD IVD (Slow-K 600 mg) TAB 2 TID PO (Slow-K 600 mg) TAB 2 QID PO 表 五 出 院 帶 藥 及 回 診 用 藥 7/20-7/26 7/27-8/06 8/07-9/03 Slow-K 600 mg 1 TAB TID PO Slow-K 600 mg 2 TAB QID PO Slow-K 600 mg 1 TAB QID PO Diovan valsartan 160 mg 0.5 TAB QD PO Soda sodium bicarbonate 300 mg 1 TAB TID PO Spirotone spironolactone 25 mg 1 TAB BID PO 29 4 Dec. 31 2013 藥 學 雜 誌 第 117 冊 113
臨 床 藥 物 治 療 學 Therapeutics of Clinical Drugs 參 討 論 一 橫 紋 肌 溶 解 症 ( 一 ) 與 鉀 離 子 的 相 關 性 ( ) 3-5 3.5 5.0 meq/l 3.5 meq/l (> 15 meq/ 6 1 圖 一 低 血 鉀 引 起 橫 紋 肌 溶 解 ( 二 ) 橫 紋 肌 溶 解 症 之 治 療 1. 40 mmhg 2 2. NaCl 0.9% 300 ml 1,2,7 3. sodium bicarbonate (NaHCO3) (myoglobin) NaHCO3 ph 6.5 ph 7.40-7.45 1,2,7 4. mannitol ( ) Henle's loop diuretics furosemide bumetanide furosemide ph mannitol NaCl 0.9% NaHCO3 NaCl 0.9% mannitol NaCl 0.9% 1,2,7 ( 三 ) 併 發 症 6.0 meq/l glucose insulin solution (12-14 IU insulin 1000 ml dextrose 5%) NaHCO3 (50-100 nmol/day) disodium polysterene sulphonate calcium chloride calcium gluconate 114 THE JOURNAL OF TAIWAN PHARMACY Vol.29 No.4 Dec. 31 2013
橫紋肌溶解症案例探討 碳酸鹽濃度低於15 nmol/l 或血液 ph 值低於 期治療 表現症狀主要是患者感覺肌肉痛 7.2時才建議給予治療 靜脈輸注 NaHCO3並 虛弱 尿液呈現紅棕色 檢驗 CK 值上升 注意監測避免高血容積 代謝性鹼中毒 低 但也有大半數患者沒有肌肉痛的症狀 治療 血鈣 低血鉀等併發症 當前面幾種治療對 策略首先應先排除潛在原因 避免肌肉細胞 於嚴重代謝性酸中毒或高血鉀都無效時 才 繼續損壞 並儘早給予大量體液輸注 並給 7 考慮使用血液透析 二 本案例用藥探討 本案例因低血鉀入院後以 potassium chloride 10 meq/5 ml 針劑和 potassium chloride 600 mg/tab 口服治療低血鉀症 並給 予大量 NaCl 0.9%靜脈輸注避免併發急性腎 衰竭 出院帶藥每日給予 1800 mg 和 valsartan 80 mg 併用治療低血 鉀 因 valsartan 屬血管張力素受體阻斷劑 予 sodium bicarbonate 以維持尿液偏鹼性 配合使用利尿劑減少肌球蛋白蓄積 降低腎 傷害 且注意維持電解質平衡 降低嚴重併 發症發生的機會 當症狀表現伴隨有發燒或 疲勞時 就要特別注意避免併發症的發生 尤其是急性腎衰竭和高血鉀為主要影響橫紋 肌溶解症預後良好與否的關鍵 參考資料 1. (angiotensin II receptor blockers ARB) 與鉀 離子補充劑 同時使用會增 2. 加鉀離子的滯留 使得血鉀值上升 門診回 3. 診追蹤因血中 ph 7.32 故新增用藥 sodium bicarbonate 300 mg TID 用以矯正體內酸毒 症 促進鉀離子進入細胞 並加入保鉀性利 尿劑 spironolactone 改善低血鉀 且定期追蹤 血鉀值 但須注意的是 若發生肌肉無力或 4. 5. 6. 心律不整的症狀時 可能有血鉀值過高的風 險 ( 7.0 meq/l) 應緊急檢測血鉀值 肆 結論 橫紋肌溶解症的治療著重於早期診斷早 7. Ana L Huerta-Alardín, Joseph Varon and Paul E Marik Review Bench-to-bedside review: Rhabdomyolysis - an overview for clinicians. Critical Care 2005, 9:158-169. Efstratiadis G, Voulgaridou A, Nikiforou D, et al: Rhabdomyolysis updated. Hippokratia 2007; 11 (3): 129-137. James P. Knochel and Edward M. Schlein On the Mechanism of Rhabdomyolysis in Potassium Depletion. The Journal of Clinical Investigation 1972 Jul; 51(7):1750-8. Muthukrishnan J, Harikumar K, Jha R, et al: Pregnancy predisposes to rhabdomyolysis due to hypokalemia. Saudi J Kidney Dis Transpl 2010;21:1127-8. Ghacha R, Sinha AK Acute Renal Failure due to Rhabdomyolysis Caused by Hypokalemia. Saudi J Kidney Dis Transpl 2001;12:187-90. Hirofumi Yasue, Teruhiko Itoh, Yuji Mizuno, et al: Severe Hypokalemia, Rhabdomyolysis, Muscle Paralysis, and Respiratory Impairment in a Hypertensive Patient Taking Herbal Medicines Containing Licorice. DOI: 10.2169/ internalmedicine.46.6316. Yiannis S. Chatzizisis, Gesthimani Misirli, et al: Review article The syndrome of rhabdomyolysis: Complications and treatment. European Journal of Internal Medicine 19 (2008) 568-574. 第 29 卷第 4 期 Dec. 31 2013 藥學雜誌 第117冊 115
臨床藥物治療學 Therapeutics of Clinical Drugs Rhabdomyolysis Case Study Wei-Shein Chen, Mei-Lin Huang, Chen-Hung Chang Department of Pharmacy, Tao-Yuan General Hospital, Ministry of Health and Welfare Abstract Non-trauma induced rhabdomyolysis is more frequent than that caused by traumatic conditions. Severe rhabdomyolysis may lead to a potentially life-threatening condition such as cardiac arrhythmia and acute renal failure. The deficiency of potassium will bring muscle to relative ischemia; severe hypokalemia even results in muscle necrosis and rhabdomyolysis. This case is a 33-year-old healthy woman who felt severe general weakness and moderate nausea, the diagnosis for her is hypokalemia and rhabdomyolysis. Massive hydration with appropriate supplement was given after admission, few days later the symptoms were improved gradually and the patient was follow-up at OPD. We want to discuss the etiology and treatment of rhabdomyolysis and its complications by this case. The treatment of rhabdomyolysis includes aggressive hydration, urine alkalization, diuresis to reduce renal injury, to correct electrolyte imbalance, and to avoid severe complications. 116 THE JOURNAL OF TAIWAN PHARMACY Vol.29 No.4 Dec. 31 2013