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Presentation
of Case
This 25-year-old female patient was rushed to the emergency
department (ED) at 1 AM on a winter day. She was witnessed
having seizures followed by loss of consciousness by her
family at home. She was otherwise healthy except a history of
a traumatic injury with rupture of the right anterior cruciate
ligament about six years earlier. Despite arthroscopic repair,
she still required intermittent non-steroid anti-inflammatory
drugs (NSAID) for pain control from orthopedic outpatient
clinics. Three weeks earlier, severe right knee pain,
especially during knee flexion, developed again. She could
hardly walk due to severe knee pain and ketorolac were taken
for pain control. One hour before arriving at this hospital,
she took ketorolac and Chinese herbs including
骨碎補、補骨脂、當歸尾、白朮、川烏片、甘地、黃耆、黨參、丹森 and桃仁 for pain relief due to
break-through symptoms. One hour later, seizures and sudden
collapse were observed by the family and she was rushed to the
ED. There was no aura, palpitations, chest pain or dyspnea
reported by the patient prior to seizures.
On arriving at the ED, she was comatous with agonizing
respiration. The pulse rate was 100 beats per minute, blood
pressure 64/39 mmHg, and temperature was 36℃ and oxygen
saturation was 76% while she was breathing ambient air. She
was intubated and inotropics were administered immediately.
Profound shock and hypoxemia persisted despite initial life
support and asystole developed one hour later. Return of
spontaneous circulation was achieved after 10 min of
cardiopulmonary resuscitation and 100% oxygen and high-dose
inotropic agents were administered. Her pupil size was 2.5 mm
bilaterally with sluggish light reflex response. Chest and
cardiac examinations revealed only faint systolic murmur at
the subxyphoid region. The skin color was mottled, and both
lower limbs showed no signs of swelling or focal
indurations.
Results of laboratory tests
| Complete blood count |
Reference range |
ED lab |
| Hemoglobin (g/dl) |
12.0–16.0 |
10.2 |
| White cell count (per mm3) |
4500–11,000 |
7,690 |
| Differential count (%) |
| Neutrophils |
40–70 |
41.9 |
| Lymphocytes |
22–44 |
53.1 |
| Platelet count (per mm3) |
150,000–350,000 |
265,000 |
| Coagulation
profile |
| Partial-thromboplastin time, activated (sec) |
22.1–34.0 |
34 |
| Prothrombin time (sec) |
10.3–13.2 |
14.7 |
| D-Dimer (ng/ml) |
<324 |
>10,000 |
| Biochemistry |
| Urea nitrogen (mg/dl) |
4.5–24 |
18 |
| Creatinine (mg/dl) |
0.6–1.3 |
1.3 |
| Sodium (mmol/liter) |
135–148 |
136 |
| Potassium (mmol/liter) |
3.5–5.0 |
2.9 |
| Chloride (mmol/liter) |
98-108 |
100 |
| Aspartate aminotransferase
(U/liter) |
10–40 |
136 |
| Lactate acid (mmol/liter) |
0.5 -2.2 |
>12.0 |
| Total bilirubin (mg/dl) |
0.2-1.2 |
0.28 |
| Creatine kinase (U/liter) |
38-160 |
169 |
| Creatine kinase MB isoenzyme
(U/liter) |
<16 |
20.4 |
| Troponin I (ng/ml) |
0.6-1.5 |
0.059 |
| Arterial blood
gas |
| pH |
7.35-7.45 |
6.79 |
| pCO2, mmHg |
35-45 |
86 |
| pO2, mmHg |
83-108 |
40.6 |
| HCO3, mEq/L |
21-28 |
12.3 |
| Base excess (BE), mEq/L |
-2-3 |
-23.9 |
Course and
Treatment
Initial ECG (Figure 1 ) showed sinus
tachycardia with right bundle branch block and upslope ST
depression of the precordial leads. Chest radiography (Figure 2) after resuscitation showed mild oligemia bilaterally.
Computed tomography (CT) of the head (Figure 3) showed brain
swelling without intra-cranial tumors. Echocardiography
revealed dilatation of the right atrium (RA) and right
ventricle (RV) with moderate tricuspid regurgitation and the
left ventricle was normal. CT of the chest (Figure 4) showed
thrombi in bilateral pulmonary arteries and branches to
bilateral lower and upper lobes. Massive pulmonary embolism
with obstructive shock and hypoxemia was diagnosed, and
heparin infusion was begun.
However, hypoxemia progressed despite supplement of 100% O2
and traditional medical support failed to achieve stable
hemodynamics, and therefore, extracorporeal membrane
oxygenation (ECMO) was applied for hemodynamic support.
Surgery was performed for the massive pulmonary embolism.
During the operation, severe distension of RA and RV with poor
RV contractility was found. There were multiple fresh thrombi
in bilateral pulmonary arteries (Figure 5). Thromboembolectomy
over bilateral pulmonary artery was done smoothly. Her
condition improved after the surgery. Functional assays of
protein C and protein S while she was receiving
anticoagulation therapy showed relatively low levels, 38%
(reference values, 59-118) and 47% (reference value, ≧79),
respectively. Anti-nuclear antibody and anti-phospholipid
antibody were negative. Though she survived from initial
assault, sequelae of hypoxic encephalopathy developed due to
the protracted course of hypoxemia and obstructive shock.
討論:
急性肺栓塞是常見且致死率高的醫療急症，主要致病原因為，肺主動脈或其分支遭到物質栓塞，這些物質可以為血栓、空氣、脂肪或腫瘤等。急性肺栓塞又可以進一步分為massive
pulmonary embolism 與submassive pulmonary embolism。Massive
pulmonary embolism 意指大量的肺動脈栓塞造成血壓下降 (定義為收縮壓<90
mmHg，舒張壓<40 mmHg，持續時間超過15分鐘)。當發生massive pulmonary
embolism通常會造成急性右心衰竭，若沒有接受及時的治療同常會在2小時內造成死亡。
肺栓塞的危險因子:常見危險因子依分類為 (1)
環境因素，如長途航空旅行、肥胖、抽菸、高血壓、糖尿病、久臥不動；(2)先天因素，如年老；(3)女性獨特因素，如懷孕、服用避孕藥、服用女性荷爾蒙治療；(4)合併疾病，如惡性腫瘤、深層靜脈栓塞、心衰竭、服用精神科藥物、經心律調節器置入、接受中央靜脈導管植入；(5)
接受手術，特別是骨科手術、一般外科手術、婦科手術或是神經外科手術；(6)罹患血液疾病致血液凝集；或是 (7)自體免疫疾病
(autoimmune disease)，如抗磷脂症候群(anti-phospholipid syndrome)。
肺栓塞的臨床症狀與表徵:常見症狀，包括喘、胸痛、咳嗽，少部分會有抽蓄表現。臨床徵候，包括呼吸次數增加、心跳加速、頸靜脈怒張、肺囉音；嚴重者會出現血壓下降與意識障礙。
肺栓塞的診斷:
血液學檢查:
D-dimer，為纖維蛋白鍵結分解後釋放之物質，利用D-dimer正常與否作為診斷急性肺栓塞有良好的敏感度。目前建議D-dimer可運用於低度或中度可能性肺栓塞患者的檢驗，利用高敏感度ELISA檢測法，若D-dimer
<0.5
mg/L，幾乎可以排除肺栓塞可能。但此檢驗方式不建議運用於高度懷疑患者，因為此測量對於這類病人的陰性預測值(negative
predictive
value)較低；再者，若病患年紀大於80歲、合併惡性腫瘤或懷孕婦女，也不建議測D-dimer，因這類病患的D-dimer通常是升高的。而肺栓塞患者之Brain
natriuretic peptide (BNP) NT-pro
BNP與troponin檢驗值通常為異常，但無法直接利用於診斷急性肺栓塞，部份研究顯示其對於預後有其預測價值。
心電圖，急性肺栓塞之心電圖變化部分可見S1Q3T3, right
ventricular strain, new incomplete right bundle branch
block，當出現這些變化常暗示急性肺栓可能。但這類心電圖變化通常不太常見，反而是心跳加速與非特異性ST段變化與T波倒置(T-wave
inversion)較為常見。
胸部X光，雖大部分肺栓塞病患之胸部X光會出現異常，但通常無法單獨利用胸部X光來診斷。常見的變異，如局部肺塌陷、肋膜積水與心臟擴大等，只有約略有12%的胸部X光為正常。而Westermark
sign (局部肺實質部分血流減少) 與 Hampton’s hump
(肺部周邊出現楔形實質化)，雖對於診斷肺栓塞診斷有較高的特異性
(>90%)，但只有<2%肺栓塞患可以觀察到此變化。因此無法直接依賴胸部X光來診斷急性肺栓塞。
心臟超音波，主要檢驗肺動脈、右心室或右心房內是否有血栓，同時評估是否合併心房中膈缺損或卵圓孔未閉合等會造成有動脈系統paradoxical
emboli的危險。但大部分心臟超音波主要可看到急性肺栓塞之間接證據，如發現右心室與右心房擴大與合併右心室收縮力下降，利用Doppler所估計之右心壓力增加，與三尖辦與肺動脈瓣逆流。
Ventilation-perfusion scan
，此檢查的判讀需要合併臨床訊息與檢驗結果來判斷，整體而言，正常的ventilation-perfusion
scan可以排除肺栓塞，但其診斷準確度約為15-80%。常常會出現檢驗結果不確定的情形，因此常需要搭配其他檢查工具。
胸部電腦斷層，約略50-98%的肺動脈栓塞病人可以利用電腦斷層檢驗出。目前認為同時配合臨床表徵，與採用venous-phase的電腦斷層影像可以增加檢驗準確度。而電腦斷層的另一項優勢，乃可同時檢測主動脈、肺部、心臟腔室與縱膈腔的問題，而做為良好的鑑別診斷工具。
肺栓塞的治療:
抗凝血治療，抗凝血治療可以避免更多血栓形成，同時減少病人的死亡率，避免復發。對確定診斷或高度懷疑的病患皆應給予抗凝血治療。
血栓溶解劑，使用血栓溶解劑可以增加肺栓塞回復，但可能會增加出血危險。使用血栓溶解劑的適應症為，大量肺栓塞導致持續血壓降低、持續血氧降低、右心功能異常或合併心房心室血栓以及卵圓孔未閉合。
手術式血栓清除(Surgical
embolectomy)，部分研究顯示手術式血栓清除可以減少復發，同時避免出血併發症。手術之適應症與使用血栓溶解劑相同，主要以病患出現血液動力學不穩定為主，其餘適應症包括，對於有血栓溶解劑有使用禁忌症或是血栓溶解劑治療失敗的進階處置。
導管式血栓清除(catheter
embolectomy)，隨導管技術進步，少部分急性肺栓塞患者成功地接受導管式血栓清除治療肺栓塞。
肺栓塞預後，
急性肺栓塞若未診斷出來並接受及時治療，其死亡率約為30%。但若接受適當的治療其死亡率可以降至2-8%。特別是出現massive
pulmonary embolism時，其住院期間死亡率將提升，而這類大量肺栓塞約占所有肺栓塞4-5%。若單純出現RV
dysfunction其死亡率約為8.1%；一旦出現低血壓與休克時時，則死亡率會升高到15.2-24.5%；若發生需要急救狀況，則其死亡率則升高至64.8%。整體而言，massive
pulmonary embolism的 90天死亡率約為52.4%。
References
- Kasper W, Konstantinides S, Geibel A,
Olschewski M, Heinrich F, Grosser KD, Rauber K, Iversen S,
Redecker M, Kienast J. Management strategies and
determinants of outcome in acute major pulmonary embolism:
results of a multicenter registry. J Am Coll Cardiol.
1997;30(5):1165-1171.
- Konstantinides S. Clinical practice. Acute
pulmonary embolism. N Engl J Med. 2008;359(26):2804-2813.
- Kucher N, Rossi E, De Rosa M, Goldhaber SZ.
Massive pulmonary embolism. Circulation.
2006;113(4):577-582.
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Case Discussion
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