Pulmonary Circulation Disorders Flashcards
An obstruction of the pulmonary artery or one of its branches by an embolus
what is this term?
Pulmonary Embolism (PE)
3rd leading cause of mortality in hospitalized pts
3rd MC CV cause of death in the US
what condition?
Pulmonary embolism
8 types of PE
- Thrombus - arising from any area of the venous circulation or the heart
- MC - Deep veins of the lower extremities (LE) - Air - during neurosurgery, central venous catheters
- Amniotic fluid - during active labor
- Fat - long bone fractures
- Foreign bodies - talc in injection drug users, cement emboli (joint replacement)
- Parasite eggs - schistosomiasis
- Septic emboli - acute infective endocarditis
- Tumor cells - renal cell carcinoma
Pathophysiological response from pulmonary vascular obstruction
-
Infarction
- Most often occurs when small emboli lodge distally where there is little collateral blood flow -
Impaired gas exchange = hypoxia
- Altered ventilation to perfusion ratio
- Inflammation → Surfactant dysfunction → Atelectasis → Functional intrapulmonary shunting
- Stimulation of the respiratory drive → hypocapnia and respiratory alkalosis -
CV compromise
- Obstruction of vascular bed → Increased pulmonary vascular resistance → Right heart and intraventricular septal strain
- Less blood returning to the left ventricle → Reduced CO→ Hypotension
risk factor of PE
virchow’s triad
-
venous stasis
- Immobility - obesity, stroke, bed rest, post-op
- Hyperviscosity - polycythemia
- Increased central venous pressures - low CO states, pregnancy - injury to vessel wall - Prior episodes of thrombosis, orthopedic surgery, or trauma
-
hypercoagulability
- Meds - OCs, hormonal replacement
- Disease - malignancy, surgery
- Inherited gene defects - Factor V Leiden (MC)
— Deficiency of dysfunction of protein C, protein S, and antithrombin
— Prothrombin gene mutation
— Hyperhomocysteinemia
— Antiphospholipid antibodies
- Sudden onset dyspnea, pleuritic chest pain, cough
- Tachypnea
- Sx of DVT may precede
- Lower leg pain / “charley horse”
- Associated sx: swelling, warmth and/or erythema
this presentation is associated with which dx?
PE - “The Great Masquerader”
- significant pain is associated with small PE’s that result in infarction
- Tachypnea - most reliable exam finding
how to approach “pre-test” probability with PE dx?
- Wells Criteria
- If Well’s is low = PERC Rules
- Low risk + no PERC rules criteria → No testing
-
Low risk + at least 1 positive PERC/ Intermediate risk → high-sensitivity plasma D-dimer
— Normal → no imaging
— Elevated d-dimer → imaging - High risk → Imaging (not D-dimer)
scoring system of Wells Criteria
- > 6 = high risk (78.4%)
- 2–6 = moderate risk (27.8%)
- <2 = low risk (3.4%)
what are the PERC rules?
- low probability (<15% prob. of PE based on gestalt assessment)
- <50 y/o
- HR <100 bpm during entire stay in ED
- pulse ox >94% at near sea level
- >92% for altitudes near 5000ft above sea level - no hemoptysis
- no prior venous thromboembolism hx
- no surgery/trauma requiring endotracheal or epidural anesthesia within last 4 wk
- no estrogen
- no unilateral leg swelling
- asymmetrical calves on visual inspection w/ pt’s heels raised off bed
diagnostics for PE
- D-dimer (sensitivity 95–97%; specificity 45%)
- CTA (chest/pulmonary artery) - first line imaging
- Ventilation–perfusion (V̇/Q̇) scanning
-
Pulmonary Angiography - gold standard for making dx
- Safe but invasive requiring interventional radiology and contrast dye - EKG
- Chest radiograph - to r/o other etiologies
- skipped in mod-high probability - additional labs (not necessary to make dx):
- CBC - 20K
- ABG - low pO2, rsp alkalosis w/ hypocapnia, more likely to be abnormal in other pulmonary conditions than PE
- troponin & BNP - related to size of PE causing acute right ventricular myocardial stretch
how to interpret results of D-dimer? what could cause false positives?
A protein fragment from a broken down blood clot
(sensitivity 95–97%; specificity 45%)
- Normal: < 500 ng/mL
- Adults >50 w/ low or intermediate probability use age-adjusted threshold (age × 10 ng/mL) -
Elevations are not diagnostic
- false positives: age >50 years, recent surgery or trauma, acute illness, pregnancy or postpartum state, rheumatologic disease, renal dysfunction and sickle cell disease
CTA requires IV contrast, therefore what is needed to do before doing this imaging?
pre-tesing BUN/Cr
there is a (+) filling defect in the CTA, what does this indicate?
PE
cautions with CTA
Pregnancy
Metformin
Allergy to contrast dye
indications for VQ scanning
- pregnancy
- renal insufficiency
- severe prior adverse reaction to contrast material
after a VQ scanning, it shows normal perfusion. What does this indicate?
r/o PE
PE = reduced perfusion w/ normal ventilation
(+) Intraluminal filling defect is found in a pulmonary angiography, what does this indicate?
PE
indication for pulmonary angiography
when there is high pre-test probability and inconclusive CTA result
EKG findings of PE
1. sinus tach
2. non-specific ST segment and T-wave changes affecting R precordial leads V1-3 +/- V4
3. S1Q3T3 pattern
4. right ventricular strain - R axis deviation
5. new incomplete RBBB
what are the chest radiograph findings of a PE
-
Westermark’s sign (14% sensitivity, 92% specificity)
- an area of lung oligemia - from complete lobar artery obstruction -
Hampton’s hump (22% sensitivity, 82% specificity)
- dome-shaped dense opacification in the periphery of the lung - indicative of pulmonary infarction - Nonspecific findings are common - cardiomegaly, basilar atelectasis, infiltrate, or pleural effusion
Performed to look for evidence/location of DVT
helps to determine the etiology of the PE and affects disposition
Lower Extremity Venous Doppler
70% of patients with PE with have a DVT evident on evaluation
risk stratifications of PE
-
high risk (massive) Hemodynamic instability
(any of the following)
- hypotension (SBP < 90 mmHg x >15 min)
- drop in SBP >40 mmHg below baseline
- hypotension requiring vasopressors
- causing a cardiac arrest -
Intermediate-risk PE (Submassive)
- Hemodynamic stability with signs of R sided heart strain/dysfunction via CTA, echo, elevated troponin or BNP. -
Low-risk PE (Less severe)
- Normotension without signs of right ventricular dysfunction
Initial management for all PE patients:
- supplemental oxygen
- ventilatory support
- hemodynamic support
- avoid excessive IV fluids → increased risk of RHF
Three primary forms of PE therapy
- Anticoagulation - mainstay
- Fibrinolysis
- Thrombectomy
Anticoagulation will reduce mortality from PE to < 5%
Anticoagulation Management options for PE
- Unfractionated heparin (UFH)
- Low-molecular weight heparin (LMWH)
- Direct-acting oral anticoagulants (DOAC’s)
- Factor Xa Inhibitors - rivaroxaban (Xarelto) and apixaban (Eliquis)
- Direct thrombin inhibitor - dabigatran (Pradaxa) - fondaparinux
- Warfarin
Binds to and accelerates the activity of antithrombin, preventing additional thrombus formation
Reserved for unstable patients, severe renal insufficiency
which anticoag is this
UFH
dosing with UFH
- 80 units/kg/dose IV x 1 (or 5000 U) followed by 18 units/kg/hour (max 2000 u/hr)
- Monitoring required: obtain aPTT every 6 hours during tx; goal - 60-80 seconds
- Normal PTT - 25-30 seconds
In high risk patients, which anticoagulation may be give before imaging confirms dx
UFH
risks with UFH?
reversal?
- hemorrhage
-
Protamine sulfate - reverses effects of heparin
— Indicated for life-threatening or intracranial hemorrhage
enoxaparin (Lovenox)
LMWH
which anticoag is Preferred over other injectable agents in those who can not take oral anticoagulants
why?
enoxaparin (Lovenox)
Greater bioavailability, more predictable dose response, longer half-life compared to UFH
monitoring of enoxaparin (Lovenox) in who?
Monitoring only in obese, underweight (<45 kg) or renal impairment
risk with enoxaparin
reversal?
Risk of hemorrhage
Protamine sulfate - reverses effects of heparin
Indicated for life-threatening or intracranial hemorrhage
rivaroxaban (Xarelto)
Factor Xa Inhibitors - DOAC
apixaban (Eliquis)
Factor Xa inhibitors - DOAC
dosing for DOACs
Xarelto: initiate BID then QD after 21 days
Eliquis: BID dosing
which anticoag is safe in pregnancy
enoxaparin (Lovenox) - LMWH
which DOAC does not require bridging therapy with LMWH?
Factor Xa Inhibitors - rivaroxaban and apixaban
No lab monitoring, few drug-drug or drug-food interactions
reversal agent of Factor Xa inhibitors?
AndexXa - reversal agent for life-threatening or uncontrolled bleeding
dabigatran (Pradaxa)
Direct thrombin inhibitor
which DOAC requires bridging with UFH/LMWH? for how long?
Direct thrombin inhibitor - dabigatran (Pradaxa)
5-10 d of bridging
reversal for dabigatran
praxbind
reversal agent for life-threatening or uncontrolled bleeding
Injectable factor Xa inhibitor
Preferred if hx of heparin-induced thrombocytopenia (HIT)
Less preferred to LMWH
which anticoag?
fondaparinux (Arixtra)
Vitamin K antagonist prevents activation of coagulation factors II, VII, IX, and X
Many interactions with food and other drugs
which anticoag?
warfarin
PK of warfarin?
- Takes 5 days to reach full effects
- requires bridging with LMWH until INR 2-3 - Start dose at 5 mg/d
- Monitoring required: keep INR 2-3
- requires variable dosing regimens that changes frequently
Alteplase
Tissue Plasminogen Activator (tPA) - fibrinolysis
Anticoags started after fibrinolytic
indications for alteplase
Tissue Plasminogen Activator (tPA)
- High risk PE patients
- Intermediate risk PE with elevated troponin or BNP, or persistent hypoxemia with distress
CI of alteplase
- intracranial disease (active tumor or hx of bleed)
- uncontrolled HTN (>220 or >110) at presentation
- recent major surgery or trauma (<3 wks)
- ischemic CVA in last 3 months
- metastatic cancer
Manual removal of the emboli surgically or with a catheter
what is this PE management called?
Embolectomy
Catheter-directed procedure offers the benefit of locally injecting tPA at a lower dose decreasing bleeding risk
indications of Embolectomy
Hemodynamically unstable patients with a contraindication or failure to respond to tPA
prevention of PE
IVC filter
- Indications:
— active bleeding that prevent anticoagulation
— recurrent VTE despite intensive anticoagulation
indications for inpatient PE tx?
- Severe illness or presence of comorbidities
- Associated DVT
- Educational needs (eg, lack of knowledge about PE and its management)
- Problematic social situations (eg, prior noncompliance with follow-up care)
The presence of any of these factors places patient at high risk and requires admission:
(pulmonary embolism)
- Age > 80
- Hx of CA
- Hx of chronic cardiopulmonary dz
- HR ≥ 110
- SBP <110
- O2 Sat <90%
management for PE: how long should pts be on anticoagulants? (considerations?)
- 3-6 months minimum vs indefinite
- found risk of recurrence in all pts (provoked or unprovoked) was decreased with prolonged anticoagulation therapy - Considerations when determining length of therapy:
- provoked or unprovoked
- presence of risk factors (eg, transient or persistent)
- estimated risk of bleeding and recurrence
— intensity and duration of the anticoag; concomitant administration of meds, such as aspirin, increased age, previous GI hemorrhage, and coexistent CKD
- pt preferences and values (eg, occupation, life expectancy, burden of therapy)
Hypercoagulation evaluation of these certain disorders if no obvious cause for VTE is identified
consult hem:
- AT III def
- Protein C and protein S def
- Lupus anticoagulant
- Homocystinuria
- Occult neoplasm
- CTD
physiology of pulmonary circulation
- Low pressure, low resistance system
- Able to accommodate significant increase in blood flow during exercise
Mean pulmonary arterial pressure (mPAP) should be between ?
10-18 mmHg
pathophys of pulm HTN
Increase in pulmonary vascular resistance, typically due to vasoconstriction, remodeling, and thrombosis of the small pulmonary arteries and arterioles leading to hyperplasia and hypertrophy of the vessels.
value of mPAP to be pulm HTN?
(mPAP) >20 mmHg
Pulmonary Hypertension: WHO Classifications
presentation of pulm HTN
Non-specific symptoms
- Malaise and fatigue - MC
-
Dyspnea - most common
- starts with exertion but progresses to resting - Anginal pain
- Nonproductive cough
- Hemoptysis
- rare - life threatening - results from rupture of pulmonary artery
- Exertional syncope
- more severe cases where CO affected - Often normal early in disease
- Late disease - RHF
- JVD
- Accentuated P2
- 3rd heart sound (“Kentucky”)
results from a dysfunctional right ventricular
wall
- Tricuspid regurg murmur
- Hepatomegaly
- Lower extremity edema
- Cyanosis - if an open PFO leading to R→L shunt
initial work-up for pulm HTN? findings?
- CXR/CT
- may be normal
- enlargement of the pulmonary arteries may be found incidentally - EKG
- Signs of RVH may be seen - 2D Transthoracic Echocardiogram with Doppler
- Signs of PH
— Elevated estimated pulmonary artery systolic pressure (ePASP)
— Tricuspid regurgitation, RV enlargement, wall thickness or dysfunction may be seen
- Normal echo doesn’t r/o PH
diagnostics of pulm HTN
Right-sided heart catheterization (aka Swan-Ganz catheter) - Gold standard
Labs: to look for less common causes
- CBC; CMP; Coags -pT, apTT; ABG; HIV testing; Hepatitis panel; Urine toxicology
what reading in a right-sided heart cath (swan-ganz) is diagnostic for PH?
mPAP ≥ 20 mmHg
what diagnostic approach assesses left sided heart disease
Pulmonary capillary wedge pressure (PCWP)
scoring for PCWP
- ≤15 mm Hg = no left sided heart disease
- Elevated PCWP = L sided heart dz and should be confirmed with a L heart cath
Collagen-vascular disease screening has what findings?
antinuclear ab (ANA), rheumatoid factor (RF), antineutrophil cytoplasmic ab (ANCA),
Scleroderma: anti-Scl-70, anticentromere, and anti-U1-RNP antibodies
general measures in management for PH
- Exercise and pulmonary rehabilitation
- Oxygen therapy
- resting, exercise-induced, or nocturnal use - Age appropriate vaccinations
- Smoking cessation (if applicable)
- Maintain healthy body weight
- Psychosocial support
- Birth control (non-estrogen)
- PAH is associated with increased maternal and fetal risks, including high risk of death.
refer PH to who
Pulmonology or specialist in PH management
Cardiology if WHO II
how to classify severity of PH?
New York Heart Association (NYHA) System
- NYHA I: No sx, no limitation of activity
- NYHA II: Slight limitation of activity. sx with ordinary activity
- NYHA III: Marked limitation of activity. sx with < ordinary activity
- NYHA IV: Unable to perform any activity without sx. Evidence of right heart failure. Dyspnea and fatigue at rest that worsens on exertion
what are the NYHA sx?
dyspnea, fatigue, chest pain, or near syncope with exertion.
approach management of PH
Step1 : Treat any underlying condition
- Treat underlying conditions or any condition that may worsen PH
- WHO II - treat left sided heart failure
- WHO III - treat lung disease and/or hypoxia
Step 2: Is there vasoreactive disease?
- Vasoreactive disease
- CCB used for NYHA class I-III - High dose diltiazem and nifedipine most commonly used - Non-vasoreactive disease
- Based upon NYHA Classification
— Only WHO PH 1 and 4 have FDA approved meds for PH
pharm management of PH
- Endothelin receptor antagonists - ambrisentan, bosentan, macitentan,
- MOA: reduces endothelin release leading to vasodilation - PDE 5 inhibitors (oral) - sildenafil, tadalafil
- MOA: inhibition of PDE5 leads to vasodilation
— PDE5 is abundantly expressed in the lungs and causes vasoconstriction - Soluble guanylate cyclase stimulators - riociguat
- MOA: stimulates the activity of guanylate cyclase - Prostanoid agents - epoprostenol, treprostinil, iloprost
- MOA: potent pulmonary vasodilation by acting on prostaglandin receptors with an additional benefit of inhibiting platelet aggregation - Prostacyclin receptor agonists - Selexipag
- MOA: attaches to and activates prostacyclin receptors in the lung resulting in vasodilation
what is produced in the cells that line the heart and lungs; when released results in vasoconstriction
endothelin
what is produced in the lungs as a response to nitric oxide. Cyclic GMP causes the arteries to relax and widen (vasodilation).
Guanylate cyclase produces cyclic guanosine monophosphate (cyclic GMP)
Selexipag (Uptravi) is more selective for what receptor than the prostanoid agents?
prostacyclin receptor than the prostanoid agents
which Prostanoid agents are continuous IV pump, inhalation, and has multiple delivery methods?
- epoprostenol (Flolan) - continuous IV pump
- treprostinil - 3 delivery methods - oral, inhalation, continuous IV infusion via pump
- iloprost (Ventavis) - inhalation
difference between IV and PO Selexipag/prostacyclin receptor agonist
IV only for short term if unable to take PO
Management: Non-vasoreactive disease
based on (NYHA) System
- NYHA I - consider monotherapy
- NYHA II/III - combo therapy
- Endothelin antagonists + PDE5 inhibitors
- Add guanylate cyclase stimulators / oral prostacyclin receptor agonists if uncontrolled - NYHA IV
- Add on parenteral prostanoid to oral combination therapy
additional managements for PH
- Long-term anticoag - WHO 4 (some WHO 1)
- warfarin (Coumadin)
- dabigatran (Pradaxa), rivaroxaban (Xarelto), and apixaban (Eliquis) - Thromboendarterectomy - if no response to meds in WHO 4
- Diuretics for symptomatic RHF
- watch for hypovolemia as pts are preload dependant - Lung transplant reserved for those unresponsive to medical management
- Double (preferred) or single can be effective
