Wednesday, July 16, 2008

Pulmonary Embolism


Here's an essential for management of the postoperative patient...

Where does PE originate from?

Typically after propogation and embolism of thrombi that develop in deep veins... 79% of patients with PE have evidence of calf DVT.



What are pathophysiologic sequelae of PE?
1. Anatomic obstruction of pulmonary arteries... although pulmonary infarction is typically avoided since lungs are also supplied by bronchial arteries.
2. Platelets cause the release of serotonin and vasoactive substances resulting in elevated pulmonary vascular resistance and V/Q mismatch.
3. RV afterload increases, leading to RV dilatation, ischemia, and right sided heart failure.



What are chronic sequelae of DVT and PE?
Post-thrombotic syndrome (chronic leg pain/swelling)
Chronic thromboembolic pulmonary hypertension



What are classic risk factors for DVT?
Virchow's triad - stasis, injury, and hypercoagulability

Also advanced age, obesity, pregnancy + postpartum period, malignancy, reduced mobility, polycythemia vera, smoking, central venous catheters, HITS, antiphospholipid antibodies, lupus anticoagulant
Medications - chemotherapy, oral contraceptives (3X risk), hormone-replacement therapy (2x risk), tamoxifen
Acutely-ill, hospitalized, medical patients have a risk of 15%


What specific populations are at high risk for DVT?
Total hip and knee replacement (risk of >50% without prophylaxis)
Cancer surgery
Major trauma
Spinal cord injury



What are genetic disorders that predispose to risk of venous thromboembolism?
Protein C and S deficiency
Antithrombin deficiency
Factor V Leiden
Prothrombin mutation (g20210a)
Hyperhomocyteinemia (C677T mutation)
Dysfibrinogenemia
Plasminogen deficiency



What isthe most common genetic risk factor for thrombophilia?
Factor V Leiden. This causes resistance to activated protein C



What are signs and symptoms of lower extremity DVT?
Leg pain, tenderness, warmth, or swelling

Homan's sign - calf pain with passive dorsiflexion at the ankle



What are signs and symptoms of PE?
dyspnea (73%)
tachypnea (70%)
pleuritic chest pain (66%)
rales / crackles (51%)
cough (37%)
Tachycardia (30%)
Leg swelling (28%) or pain (26%)
Fourth hearth sound (24%)
Loud P2 (23%)
Hemoptysis (13%)
Palpitations (11%)
JVD, systolic murmur, right sided gallop
syncope
hypotension
hypoxemia
PEA/cardiac arrest

Cardiogenic shock is diagnosed in 5% of acute PE.
While hypoxia and an Aa gradient is common, a normal ABG is seen in up to 20% of PE.


What are ECG findings of PE?
Tachycardia
V1-V4 T wave inversion
S1-Q3-T3 pattern
Right bundle branch block
P-wave pulmonale
Right axis deviation

These are nonspecific and are more often seen with very large PE


What are abnormal findings on CXR attributed to PE?
Westermark's sign - focal peripheral oligemia caused by PE obstruction
Hampton's hump - peripheral wedge seen above diaphragm
Palla's sign - enlarged right descending PA



How does D-dimer testing help with a diagnosis of PE?
This is a sensitive (96-98%) but very non-specific test.
It must be considered together with clinical suspicion and is better for patients presenting to the emergency room than for general surgical postop patients.
If the DDimer is negative in patients with a low-to-moderate pretest probability, imaging is not useful since PE is very unlikely.
If the patient has a high pretest probability, don't bother with checking a DDimer and go straight to imaging.



What imaging strategies are used for diagnosis of PE?

Spiral CT-angiography (90% sensitivity, 95% specificity)
Ventilation/Perfusion Scanning - limitation: frequently non-diagnostic
Pulmonary arteriogram
Venous duplex for DVT
Echocardiography for hemodynamically significant PE


Use caution when Cr>1.5 with CTA
Avoid V-Q scanning if there is associated cardiopulmonary disease noted on CXR


What are treatment stategies for DVT?
Outpatient management with low-molecular weight heparin transitioning to warfarin with a goal INR of 2-3 for 3-6 months

Pregnant patients can't take warfarin and must be kept on a LMWH...


What are treatment strategies for PE?
PE should be managed by inpatient hospitalization.
Parenteral unfractionated heparin (therapeutic PTT), low-molecular weight heparin, or fondaparinux for at least 5 days while starting warfarin - bridging therapeutic INR of 2-3 for 2 consecutive days, continuing treatment for 3-6 months.

Factor VII - measured by the INR - has a half life of 6hrs... however thrombin (factor II) depletion takes 5 days...


How is unfractionated heparin administered?
It is bolused 60-80 U/kg, followed by a continuous infusion of 18 U/kg/hr. The infusion is titrated to a therapeutic PTT (60-80 seconds) by checking the PTT level every 6 hrs.



What are benefits of LMWH?
These have more predictible pharmacokinetics and greater bioavailability than unfractionated heparins, allowing subcutaneous administration once or twice per day.

Therapeutic dosing for enoxaparin is 1mg/kg SC BID or 1.5mg/kg SC QD


How can you monitor if levels of LMWH are therapeutic?
Check anti-factor Xa levels

This is not as convenient as a PTT, but consider this in morbidly obese or pregnant patients, or if there have been issues with renal function.


What is fondaparinux?
A synthetic pentasaccharide that inhibits Factor Xa
Structurally, it looks like the antithrombin-binding portion of heparin. It is administered once daily, subcutaneously.

This should not be used in patients with severe renal insufficiency.


What if the patient has heparin-induced thrombocytopenia with thombosis?
The patient should be treated with direct thrombin inhibitors (argatroban or lepirudin). Warfarin treatment should be held until the disease process is controlled and the platelet count has normalized to avoid thrombotic complitcations and warfarin-induced skin necrosis.

Lepirudin is excreted by the kidneys and argatroban is metabolized by liver.


What is the risk of death from recurrent thromboembolism in patients treated for DVT?
0.4%



What is the risk of death from recurrent thromboembolism in patients treated for PE?
1.5%



What are indications for a vena caval filter?
Contraindications to anticoagulation
Major bleeding complications during anticoagulation
Recurrent DVT or PE while receiving adequate therapy

Retrievable filters can often be inserted... although often times they are forgotten to be removed!
The tide is beginning to turn against prophylactically placing IVC filters, but they may be recommended in select trauma patients.


When is thrombolytic therapy considered for management of PE?
If the PE is severe enough to cause cardiogenic shock or right ventricular dysfunction

There is no hard data to answer this question... surgical embolectomy may also be considered in certain cases of massive PE when conservative measures fail.


What is the overall mortality rate for PE?
15% at 3 months



What is the optimal duration of therapy for a DVT or PE
If it is secondary to a reversible risk factor, including the postoperative state, 3-6 months should be sufficient.
If it is idiopathic or secondary to a documented hypercoagulable state, 6-12 months can be considered.
Patients with a DVT/PE secondary to cancer should be treated until their cancer has resolved, with a LMWH for whe first 3-6 months.
Patients with recurrent thromboembolisms may require indefinite therapy.





Late... SG

References:
Goldhaber SZ. Pulmonary Embolism. NEJM 339; 1998: 93-104.
Tapson VF. Acute Pulmonary Embolism. NEJM 358; 2008: 1037-1052.
Cameron's Current Surgical Therapy (9th ed.)

Wednesday, July 9, 2008

Acute Calculous Cholecystitis


A recent edition of NEJM has a nice review on this common surgical topic...

What proportion of patients with gallstones become symptomatic?

1-4% per year


What proportion of patients with symptomatic cholelithiasis develop cholecystitis?
20%


What is gangrenous cholecystitis?
When the gallbladder wall undergoes necrosis and gangrene.


What is emphysematous cholecystitis?
When gas is visible on imaging in the wall or lumen of the gallbladder... this is indicative of superinfection with gas-forming organisms and may lead to perforation without urgent intervention.


What is Mirizzi's Syndrome?
Obstruction of the common bile duct as a result of extrinsic compression of a stone within the gallbladder or cystic duct.


What is Murphy's Sign?
Arrest of inspiration while palpating the gallbladder during a deep breath.


What are ultrasonographic findings of acute calculous cholecystitis?
Gallstones
Gallbladder wall thickening, greater than 5mm
Pericholecystic fluid
Positive ultrasonographic Murphy's sign

It's also important to assess for choledocholithiasis by evaluating for a common bile duct dilated greater than 7mm or frank CBD stones.


The PPV of stones + Murphy's sign is 92%.
The PPV of stones + GBW thickening is 95%.
The NPV of no stones, and a normal GBW and no Murphy's sign is 95%.



What does a HIDA scan involve?
Hepatic scintigraphy uses an IV injection of technetium-labelled iminodiacetic acid analogues. These are excreted by the liver into bile, and allows visualization of the gallbladder within 30 minutes. An absence of filling of the gallbladder after 60 minutes indicates cystic duct obstruction and is 80-90% sensitive for cholecystitis.

Morphine can improve the specificity of the test by increasing resistance at the sphincter of Oddi. Overall, HIDA has greater specificity and accuracy in comparison to ultrasound, but is usually reserved when the diagnosis of cholecystitis is uncertain.



What is a 'rim sign' on HIDA?
A pericholecystic blush that is seen in 30% of patients with acute cholecystitis and 60% of patients with gangrenous cholecystitis.


What are the Tokyo guidelines?
Diagnostic criteria for Acute Cholecystitis:
Presence of one local sign/symptom, one systemic sign, and any confirmatory finding on an imaging test...
Local signs and symptoms: Murphy's sign, RUQ pain or tenderness, RUQ mass
Systemic signs: Fever, leukocytosis, elevated CRP

According to the Tokyo guidelines, acute cholecystitis can be subdivided into three grades of severity...



What are criteria for Grade 1 - Mild Cholecystitis?
No organ dysfunction
Does not meet criteria for a more severe grade

Early laparoscopic cholecystectomy is recommended.



What are criteria for Grade 2 - Moderate Cholecystitis?
The presence of any of the following:
WBC greater than 18,000
Palpable, tender RUQ mass
Duration greater than 72hrs
Marked local inflammation including pericholecystic abscess, hepatic abscess, gangrenous or emphysematous cholecystitis, or biliary peritonitis

Early or delayed laparoscopic cholecystectomy may be considered depending on the scenario and the surgeon's expertise.



What are criteria for Grade 3 - Severe Cholecystitis?
Organ system dysfunction - hypotension requiring pressors, mental status changes, respiratory insufficiency with PaO2/FiO2 less than 300, oliguria, Cr greater than 2.0, INR greater than 1.5, platelet count less than 100k

Management with antibiotics and percutaneous cholecystostomy tube may be considered, reserving surgery for treatment failures.



What is the optimal timing of cholecystectomy?
For most patients, early cholecystectomy may be favored. 15-20% who had their procedures delayed after the initial attack subsided require intervention before their planned lap chole.

In several studies/meta-analyses, there were no differences in operative time or conversion rates between early and delayed lap chole. However, bile duct injuries in general may be more common in the setting of acute cholecystitis. Postoperative bile duct leaks were more common with early intervention (3%) compared to delayed (0%).



What are the rates of conversion from laparoscopic to open during cholecystectomy for acute cholecystitis?
5-30%

These are greater in acute cholecystitis compared to uncomplicated cholelithiasis, but there is no difference between early and delayed intervention.



When should antibiotics be administered in the setting of cholecystitis?
Per the IDSA, a second-generation cephalosporin or a fluoroquinolone and metronidazole shold be administered in the following scenarios:
WBC greater than 12,500 or Temperature greater than 38.5C AND
Radiographic findings of cholecystitis
Also in elderly, diabetics, or immunocompromised

Patients undergoing cholecystectomy will also get a prophylactic perioperative dose, even if they don't require empiric treatment.



When should percutanous cholecystostomy tubes be used?
Patients with Grade 3/Severe cholecystitis
Septic shock
Poor surgical candidates

Delayed cholecystectomy may be considered at a later time.



Late... SG

References:
Strasberg SM. Acute Calculous Cholecystitis. NEJM 2008; 358: 2804-2811.