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Altered mental status in oncologic emergency 意識改變
Hypercalcemia, CNS metastases, raised ICP,
Medication side effects, Hyperviscosity syndrome
* Don’t forget usual, non-cancer causes
Dyspnea in oncologic emergency 喘
Lung tumor burden, SVC syndrome,
Malignant pericardial effusion, Pulmonary embolism
Malignancy-related airway compromise
(區分 Obstruction 位置在 Vocal cords 以上 or 下)
Awake fiberoptic intubation with a 5-0 or 6-0 endotracheal tube
Renal failure in oncologic emergency 腎
Pre-renal causes (Hypovolemia)
Post-renal : pelvic masses
Tumor lysis, Multiple myeloma
Infiltrating tumors, amyloidosis, Nephrotoxic drugs
Pathological fracture : Metastases from solid tumors (breast, lung, prostate)
Hypercalcemia of malignancy
骨轉移 (Breast cancer, Multiple myeloma)
Local bone destruction associated with osteoclast-activating factor
SCC (Lung, H&Neck, Skin, esophageal) paraneoplastic
Parathyroid hormone–related protein that is structurally similar to parathyroid hormone
so that calcium is mobilized from bones and its renal reabsorption is increased;
Lymphoma (Production of vitamin D analogs)
Symptoms include renal colic, bony pain, altered mental status
abdominal symptoms (anorexia, constipation, abdominal pain)
lethargy, confusion, anorexia, and nausea
Relative hypovolemia (osmotic diuresis )
疲倦無力、厭食、噁心嘔吐、腹痛
多尿、口渴、結石
甚至會引起急性胰臟炎
還有心律不整 (心電圖可見PR間距延長、QRS間距變寬、QT間距變短以及束支傳導阻滯)
ECG : Shortened QTc (< 350msec)
- Mild < 12
- Moderate : 12-14 (通常 > 12 有症狀 )
- Severe > 14
首先血清總鈣濃度必須經血清白蛋白校正
D/D 原發性副甲狀腺機能亢進 or 癌症造成
鑑別診斷重點在於血清中副甲狀腺賀爾蒙 (PTH) 及副甲狀腺類蛋白 (PTH-rP) 之濃度
ALK-P 可輔助診斷
Indication for therapy : 有症狀, 血鈣快速上升, 嚴重高血鈣
緊急治療
補充水份
給 Normal saline (4-6 L/d)
維持尿量(100-150mL/hr) 和 鈣離子排泄
IV saline will result in clinical improvement
and a modest decrease in the plasma calcium over 24 - 48 hours,
but rarely normalizes the level.
Furosemide 不建議常規使用
可以在 hydration 後
用於 heart failure or renal insufficiency 避免 Fluid overload 合併使用
Little additive effect to the use of IV saline alone in the treatment of hypercalcemia
in patients with normal cardiac and renal function.
Therefore, furosemide is not routinely recommended.
雙磷酸鹽
抑制 Osteoclast 活性, 在惡性腫瘤相關高血鈣有用
Onset 時間較慢, 效果通常要數天後才會比較明顯 (1-2days)
IV bisphosphonates : Pamidronic acid, zoledronic acid
Crcl < 35 為 contraindication, 只能用 calcitonin
Use with caution in renal insufficiency
Bisphosphonates are potent inhibitors of bone resorption
and produce a sustained decrease in calcium 12 - 48 hours after administration,
with the effect lasting for approximately 2 - 4 weeks.
Bisphosphonates are given by slow IV infusion to prevent precipitation of bisphosphonate–calcium complexes
in the kidney and subsequent renal failure
Calcitonin 短效 + 快
Calcitonin is only used when prompt reduction of calcium levels is needed.
4–8 IU/kg SC or IV every 12 h
Calcitonin lowers plasma calcium within 2 - 4 hour
使用超過 24hr 會無效 (short lived)
平均可降血鈣 1-2 mg/dL
類固醇
may be helpful with steroid-sensitive tumors,
such as lymphomas and multiple myeloma
Denosumab
humanized monoclonal antibody that inhibits osteoclast activity and function,
is approved for hypercalcemia refractory to bisphosphonate therapy.
RANKL (receptor activator of nuclear factor-κ B) 單株抗體
若給予多次雙磷酸鹽後, 仍無法有效控制
可考慮 Denosumab (抑制 Osteoclast 活性)
血液透析
非常嚴重, 症狀明顯的高血鈣, 可以考慮使用
indicated for those with profound mental status changes or renal failure or those unable to tolerate a saline load.
https://www.sem.org.tw/EJournal/Detail/267
IICP
Brain mets, hydrocephalus, bleeding, brain abscess.
Managing Impending Brain Herniation
- Intubate & hyperventilate to PCO2 of 30 temporarily
- Avoid hypotension
- Consider giving hypertonic 3% saline or mannitol
- Dexamethasone IV for metastases with edema
Hyperviscosity Syndrome (HVS) 血液高度黏稠症候群
Elevated WBCs or severe hyperproteinemia can cause high serum viscosity and micro-circulatory problems
in patients with Waldenstrom’s macroglobulinemia, multiple myeoma or acute leukemia.
Classic Triad
- Mucosal bleeding (epistaxis, vaginal/rectal bleeding, hematuria) <血小板功能異常>
- Visual disturbances <小血管栓塞或出血而造成視網膜或視神經病變>
- Altered LOC <因腦部灌流不足>
HSV 亦能夠影響心肺, 造成心肌梗塞、心衰竭 (high output)、肺水腫
或造成急性腎損傷, 甚至多重器官衰竭
血液的組成可分為血球及血漿
單位容積中的血球數量或是非血球成分增加皆能造成血液黏稠度上升
血球數量增加包含紅血球 (polycythemia)、白血球 (leukemia)、血小板 (thrombocytosis)、
骨髓增生不良症候群 (myelodysplastic disorders)
另外如 sickle cell disease 或 spherocytosis 等也可能因為變形的紅血球較容易凝集沉積
而導致 Hyperviscosity syndrome
非血球成分增加以蛋白質 (抗體) 為主
單株抗體 (monoclonal) 疾病如 myeloma, Waldenstrom macroglobulinemia, cryoglobulinemia
多株抗體 (polyclonal) 疾病如 rheumatoid arthritis, SLE, Sjogren syndrome, Castleman disease
HSV 最常見的原因是 Waldenstrom macroglobulinemia
主要影響 lymphoplasmacytoid cells 及 plasma cells 而產生大量的 IgM
其次是multiple myeloma, 以產生IgA及IgG3兩種型態為主
罹患Waldenstrom macroglobulinemia 的病患一生中約有三分之一的機會會產生HVS
血液黏稠度上升時, 血流流速會下降, 造成全身小血管循環不佳而使組織灌流不足
此外血液中的蛋白質 (抗體) 濃度上升也會影響血小板作用, 而使凝血功能出現異常
臨床症狀的嚴重程度會隨著血液黏稠度上升而增加
上升的血液黏稠度可以幫助診斷HSV
直接測量血液黏稠度是最理想的方式
但臨床檢驗以為血清黏稠度為主, 單位為釐泊 (centipoise, cp)
純水的黏稠度是1 cp, 正常血清黏稠度約為1.4-1.8 cp, 血清黏稠度達到 4-5 cp 以上通常會有明顯症狀
檢驗需包含全血球計數、生化、凝血功能、尿液分析
血液抹片出現 Rouleaux (aggregations of RBCs)、有globulin gap (total protein – albumin ≥ 4)、
或是血液檢驗出現異常無法被檢測
都需要懷疑有高血清黏稠度
針對蛋白質或抗體的定性可以做為疾病診斷及往後治療的依據
但並非診斷HVS的必要條件, 電解質的部分需檢驗是否有高血鈣、高血鉀、高血磷等問題
脫水是 HVS 的加重因子
治療上可以先給予1-2公升生理食鹽水, 降低血液黏稠度, 並依據臨床症狀給予相對應的支持性治療
血漿置換 (plasma exchange/plasmapheresis) 能有效降低 20-30% 的血液黏稠度, 是HVS的標準治療方式
若無法執行血漿置換, 放血 (intravenous phlebotomy) 是一個選擇, 放血約 2-3 單位並以生理食鹽水補充體液
需要注意凝血因子會一起被稀釋
治療的過程中也可能造成貧血, 可以適度補充紅血球, 降低輸血速度避免血液黏稠度大幅上升
SVC syndrome
Dyspnea in oncologic emergency :
Lung tumor burden, SVC syndrome,
malignant pericardial effusion, pulmonary embolism
May need CT to rule out PE
SVC 壓迫或阻塞 (Solid tumor or SVC thrombus)
腫瘤直接侵犯上腔靜脈, 轉移之病灶及淋巴結從外部壓迫, 或是血管內栓塞形成造成阻塞
干擾頭部及上胸部靜脈血回流到心臟 (elevated venous pressure in the upper body)
好發於縱膈腔內惡性腫瘤患者 (肺癌 70%, 淋巴瘤 20%)
癌症為主要病因 (60-85%)
肺癌佔其中 85% ( Small cell, 支氣管腫瘤 )
另外隨著血管內置入裝置應用 (中心靜脈導管、洗腎瘻管或心臟節律器) 增加
醫源性因素所造成的血管內栓塞, 佔整體比例的 30%
呼吸困難 Dyspnea, Cough
臉, 頸, 上胸部, 上肢水腫和淤血 Facial swelling, arm swelling, facial redness
胸壁和頸部靜脈曲張
結膜水腫, 周邊血管擴張充血
嚴重者伴有中樞神經系統表現 Mental status changes from raised ICP
頭痛 (前傾或躺下會加劇), 視力模糊或意識障礙
IICP that produces visual changes, dizziness, confusion, seizures, and obtundation.
更嚴重者甚至會因腦水腫, 咽喉水腫
導致呼吸窘迫、意識不清、癲癇甚至死亡
症狀一般發生在幾天至幾週內
PE :
Dilated superficial veins above the neck
Pemberton’s sign for SVC syndrome : facial redness caused by elevating the arms.
CXR : 常見縱隔變寬, 以及上縱隔, 右肺門, 肺門周遭或右肺上葉腫塊
Chest CT + C
治療 : 目前缺乏 Evidence based guideline
- Sit the patient upright & provide oxygen
- 類固醇可能對 Lymphoma 有幫助, 短期高劑量類固醇可改善嚴重水腫造成氣道阻塞的情況
Corticosteroids and loop diuretics are commonly used,
but there is no evidence that they contribute to clinical improvement,
with the exception that corticosteroids would be expected to be helpful to lymphoma.
- Airway edema and altered LOC from cerebral edema can occur
- 利尿劑亦可作為改善水腫斟酌使用
- 特殊治療：
Urgent stenting and radiotherapy 置放血管內支架, Intravascular stents with or without angioplasty
如有栓塞產生建議使用抗凝血劑打通栓塞, Catheter-directed fibrinolytics, Postfibrinolytic anticoagulation
Combination chemotherapy：Small cell, 惡性淋巴瘤
RT：NSCLC, Meta (Many patents experience a reduction in symptoms within 3 days after the start of radiation treatment)
手術 : 胸骨後甲狀腺腫 (retrosternal goiter), 主動脈血管瘤
Tumor lysis syndrome
- 高尿酸 (nucleic acids metabolize to uric acid)
高血鉀, 高血磷, 低血鈣
腎衰竭 (Urate Nephropathy) (Crystal induced Nephropathy)
- ALL, 淋巴瘤 (Burkitt lymphoma), non-Hodgkin’s lymphoma 較常見, AML 偶而也會出現
大 or 快速生長的腫瘤
(Rapid cell turnover and growth rates, bulky tumor mass, and high sensitivity to antineoplastic agents)
- Spontaneous tumor lysis syndrome : uncommon with solid tumors or without prior therapy
大多在治療前或開始治療後一至五天內發生
症狀不特異 : 噁心嘔吐, 腹痛, 抽筋, 意識變差, 尿量變少, 甚至心律不整
Dysrhythmias, seizures, and acute renal failure.
(Acute kidney injury, seizure, cardiac dysrhythmia, or arrest)
Intracellular potassium can produce acute hyperkalemia
and provoke or contribute to cardiac dysrhythmias or cardiac arrest.
and provoke or contribute to cardiac dysrhythmias or cardiac arrest.
Hypocalcemia may induce tetany and seizures and contribute to dysrhythmias
事先給予大量水份 + 鹼化尿液是最好的預防方法
腫瘤溶解症候群的處理原則 :
1. Aggressive IV hydration, 給予水份 3000ml/m2/day
2. Lower the K !
Be cautious about giving calcium, as these patients have high phosphate !
Supplemental calcium can lead to calcium phosphate crystalluria
Avoid calcium administration unless there is cardiovascular instability !
(Ventricular dysrhythmias or wide QRS complexes or seizures)
in case dialysis is needed.
3. Allopurinol 500mg/m2/day PO
當尿酸濃度穩定時, 降至 200mg/m2/day
allopurinol 只能夠預防尿酸的新合成
並不能降低之前原本就已經存在的尿酸
因此尿酸的降低可能需要 2-3 天或更久的時間
Rasburicase 可在腎衰竭情況下降低尿酸
Rasburicase is contraindicated in G6PD due to its potential
to precipitate hemolytic anemia or methemoglobinemia
to precipitate hemolytic anemia or methemoglobinemia
4. NaHCO3 150-200 meq/m2/day 將尿酸鹼化, 維持PH值在7-7.5
Tintinalli : Urinary alkalinization is no longer recommended.
5. 化學藥物暫停直到代謝狀況穩定
6. Q6-8H 監測電解質, 血液尿素氯, 肌酸酐, 鈣, 尿酸, 磷酸鹽, 鎂
Q3-4H 監測攝取及排出量, 矯治電解質不平衡
7. 若由於腎功能降低而導致鉀及尿酸升高時, 考慮 H/D
8. 給予 aluminium-based 制酸劑, 以促進磷酸鹽的結合
9. A loop diuretic could be considered in volume replete patients,
because volume depletion worsens acute kidney injury
Avoid calcium administration unless there is cardiovascular instability
(ventricular dysrhythmias or wide QRS complexes) or neuromuscular irritability (seizures)
because supplemental calcium may cause metastatic precipitation of calcium phosphate.
https://emergencymedicinecases.com/episode-33-oncologic-emergencies/
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