WORKUP

Lab Studies:

• Consider the possibility of a parapneumonic effusion during the initial evaluation of every patient with bacterial pneumonia because a delay in instituting proper pleural drainage substantially increases morbidity.

• The sputum is purulent and may help with the identification of underlying bacteriology.

• Peripheral leukocytosis (15,000/mm³) usually exists.

Imaging Studies:

• Chest x-ray films

• The lateral chest x-ray film usually suggests the presence of a significant amount of pleural fluid (see Image 2).

• If either of the diaphragms is not visible throughout their entire length or the posterior costophrenic angles are blunted, obtain bilateral decubitus chest x-ray films.

• Free pleural fluid is indicated by the presence of fluid between the chest wall and the inferior part of the lung. If this distance measures more than 10 mm, perform a diagnostic thoracentesis.

• Ultrasound

• Loculated pleural effusions appear as pleural-based masses without air bronchogram on standard chest x-ray film.

• Ultrasound effectively can distinguish loculated pleural fluid from an infiltrate. Therefore, if loculated pleural effusion is suspected, perform an ultrasound examination.

• CT scan of the thorax

• CT scan of the chest with contrast enhances the pleural surface and assists in delineating the pleural fluid loculations (see Image 4).

• CT scan of the chest also may detect airway or parenchymal abnormalities such as endobronchial obstruction or the presence of lung abscesses.

Procedures:

• A thoracentesis is recommended in the workup of any undiagnosed pleural effusion (see Image 3).

• Pleural fluid may vary from a clear yellow liquid to thick foul-smelling pus. Foul-smelling fluid indicates an anaerobic infection.

• Determine pleural fluid pH. A complicated parapneumonic effusion has a pH of less than 7.2.

• Send pleural fluid for WBC count and protein, LDH, and glucose levels. Results in patients with parapneumonic effusions reveal WBC count of greater than 500 cells/mm³, elevated protein and LDH level, and decreased glucose level.

TREATMENT

Medical Care: Individualize treatment of each patient, depending on the type or stage of parapneumonic effusion.

• Initial treatment

   

  • The initial treatment of a patient with pneumonia and pleural effusion involves 2 major decisions. First, select an appropriate antibiotic. Second, decide whether to initiate tube drainage of the pleural space. The initial antibiotic selection usually is based on whether the pneumonia is community-acquired pneumonia or hospital-acquired pneumonia and the severity of the patient’s illness. For a patient with community-acquired pneumonia, the recommended agents are second-generation or third-generation cephalosporins in addition to a macrolide. For patients hospitalized with severe community-acquired pneumonia, initiate treatment with a macrolide plus a third-generation cephalosporin with antipseudomonal activity. Enteric gram-negative bacilli frequently cause pneumonia acquired in institutions (eg, hospitals, nursing homes). Therefore, initial antibiotic coverage should include an antibiotic effective against pseudomonads.

     

  • Base the decision to institute tube drainage on examination of the pleural fluid. Identify patients who need tube drainage as soon as possible because the pleural effusions will become loculated if tube thoracostomy is delayed.

     

  • Patients with pleural effusions that have a pleural fluid thickness greater than 10 mm on lateral decubitus x-ray films must have a diagnostic thoracentesis. Effusions with pleural fluid thickness less than 10 mm on decubitus chest x-ray films almost always resolve with appropriate systemic antibiotics.

     

  • If the diagnostic thoracentesis yields thick pus, the patient has an empyema. Institute tube thoracostomy immediately. If the pleural fluid is not thick pus, then the pleural fluid Gram stain and the pleural fluid glucose, pH, and LDH levels should guide the course of action.

• Uncomplicated parapneumonic effusions

   

  • If the pleural fluid pH is greater than 7.20, pleural fluid glucose is greater than 40 mg/dL, and the pleural fluid LDH is less than 1000 IU/L, the parapneumonic effusion is in the exudative stage, and no further therapeutic intervention is required. However, if the pleural effusion increases in size or the patient remains or becomes febrile, repeat the thoracentesis.

     

  • Uncomplicated effusions resolve with antibiotics alone.

     

  • Patients with uncomplicated effusions can be monitored with serial radiographs or meticulous physical examination to document resolution of effusion.

• Complicated parapneumonic effusions

   

  • If the initial thoracentesis reveals pleural fluid with a pH less than 7.20 or a glucose level greater than 40 mg/dL, immediately perform tube thoracostomy. If the Gram stain of the pleural fluid is positive, tube thoracostomy is recommended.

     

  • Complicated effusions have a variable response to appropriate antibiotic therapy, though some patients can be treated with antibiotics alone. Patients with complicated parapneumonic effusions are treated as though they have thoracic empyema.

• Chest tubes (tube thoracostomy)

   

  • Insert chest tubes immediately after a complicated parapneumonic effusion or empyema is diagnosed because delay leads to formation of loculated pleural effusion. Position the chest tube in a dependent part of the pleural effusion. Although traditionally large-bore 38-32F tubes are recommended, smaller catheters (8.5-16F) also can be successful in draining the pleural space.

     

  • If the patient responds clinically and radiologically to closed tube drainage of the pleural space, leave the chest tubes in place until the volume of the pleural drainage is less than 50 mL/24 h and the drainage fluid becomes clear yellow.

     

  • If the patient has not demonstrated clinical or radiologic improvement, perform ultrasonic examination or CT scan of the pleural space to detect remaining loculi of pleural fluid and to ensure that the tube is in the proper place. If multiple loculi are identified, administer thrombolytic therapy intrapleurally. Closed chest tube drainage yields satisfactory results in approximately 60% of patients with aerobic infections and 25% of patients with anaerobic infections.

• Intrapleural thrombolytic agents

• Since the 1970s, several studies have reported success of thrombolytic therapy for loculated complicated parapneumonic effusions. The thrombolytic agents appeared to be more effective if they were administered early in the course of parapneumonic effusions. In a randomized trial of patients with multiloculated pleural effusions, those in the urokinase group drained significantly more pleural fluid, required less surgical intervention, and required fewer days in the hospital.

   

• With fibrinolytic therapy, success rates of 70-90% have been quoted. Streptokinase is used in a dose of 250,000 IU in 100 mL of normal saline once or twice a day. Following instillation, the chest tube is clamped for 2-4 hours before draining spontaneously. These agents may be administered daily for as many as 14 days. Both streptokinase and urokinase appear to be equally effective, though streptokinase may lead to sensitization with production of an antibody response and subsequent allergic reaction if employed for systemic thrombolysis. Multiple tubes may be inserted under CT scan guidance for multiloculated pleural space.

Surgical Care: Several surgical procedures are available to treat a patient with empyema. The definite indication for surgical therapy is persistent pleural sepsis despite antibiotics and attempts at pleural drainage with thoracoscopy.

• Thoracoscopy

• Thoracoscopy is an alternate therapy for multiloculated empyema.

   

• In patients with multiloculated parapneumonic effusion, the loculations in the pleural space can be disrupted with a thoracoscope, and the pleural space can be drained completely.

   

• If extensive adhesions are present or thick pleural peel entraps the lung, the procedure may be converted to open thoracostomy and decortication.

• Rib resection and drainage of pleural space

• Open drainage of the pleural space may be employed when closed tube drainage of the pleural infection is inadequate and the patient does not respond to intrapleural thrombolytic agents. This procedure is recommended only when the patient is too ill to tolerate a decortication. The resection of 1-3 ribs overlying the lower part of the empyema cavity is performed, a large-bore chest tube is inserted into the empyema cavity, and the tube is drained into a colostomy bag.

• When a patient is treated by open drainage, expect an open chest wound for a prolonged period. In 1 series, the median time for healing the drainage site was 142 days. With decortication, the period of convalescence is much shorter; although patients who are debilitated markedly do not tolerate decortication.

• Decortication

• In decortication, all the fibrous tissue is removed from the visceral pleural peel, and all pus is evacuated from the pleural space. Decortication is a major thoracic operation requiring full thoracotomy; therefore, do not perform decortication on patients who are markedly ill.

• Decortication is the procedure of choice for patients in whom pleural sepsis is not controlled by closed tube thoracostomy, intrapleural thrombolytic agents, and, possibly, thoracoscopy.

• Mortality rates as high as 10% have been described with this procedure.

• Do not perform decortication just to remove the thickened pleural peel because these thickened peels usually resolve spontaneously over several months. If after 6 months the pleura remains thickened and the patient's pulmonary function is reduced sufficiently to limit activities, consider decortication.

MEDICATION

The initial choice of antibiotics frequently is empiric, beginning with erythromycin, azithromycin, clindamycin, cefoxitin, penicillin, or cefuroxime. Empiric antimicrobial therapy must be comprehensive and should cover all likely pathogens in the context of the clinical setting. Base subsequent therapy upon sputum, blood culture, or pleural fluid culture results. An empyema is treated with prompt chest tube drainage in conjunction with parenteral antibiotics. For an empyema secondary to aspiration pneumonia or a parapneumonic process, choose antibiotics that are active against mouth flora. For an empyema secondary to penetrating chest trauma, administer antibiotics that have coverage for skin flora.

Drug Category: Antibiotics -- Therapy must be comprehensive and cover all likely pathogens in the context of this clinical setting.

Drug Name	Clindamycin (Cleocin) -- Lincosamide effective against aerobic and anaerobic streptococci (except enterococci). Inhibits bacterial growth, possibly by blocking dissociation of peptidyl tRNA from ribosomes, causing RNA-dependent protein synthesis to arrest.
Adult Dose	600 mg IV q6-8h
Pediatric Dose	25-40 mg/kg/d IV divided tid/qid
Contraindications	Documented hypersensitivity; regional enteritis; ulcerative colitis; hepatic impairment; antibiotic-associated colitis
Interactions	Increases duration of neuromuscular blockade induced by tubocurarine and pancuronium; erythromycin may antagonize effects of clindamycin; antidiarrheals may delay absorption of clindamycin
Pregnancy	B - Usually safe but benefits must outweigh the risks.
Precautions	Adjust dose in severe hepatic dysfunction; no adjustment necessary in renal insufficiency; associated with severe and possibly fatal colitis

Drug Name	Cefoxitin (Mefoxin) -- Second-generation cephalosporin indicated for gram-positive cocci and gram-negative rod infections. Infections caused by cephalosporin-resistant or penicillin-resistant gram-negative bacteria may respond to cefoxitin.
Adult Dose	2 g IV q6-8h
Pediatric Dose	80-160 mg/kg/d IV in 4-6 divided doses
Contraindications	Documented hypersensitivity
Interactions	Probenecid may increase effects of cefoxitin; coadministration with aminoglycosides or furosemide may increase nephrotoxicity (closely monitor renal function)
Pregnancy	B - Usually safe but benefits must outweigh the risks.
Precautions	Bacterial or fungal overgrowth of nonsusceptible organisms may occur with prolonged use or repeated treatment; caution in patients with previously diagnosed colitis

Drug Name	Penicillin G (Pfizerpen) -- Interferes with synthesis of cell wall mucopeptide during active multiplication, resulting in bactericidal activity against susceptible microorganisms.
Adult Dose	2 million U IV q4h
Pediatric Dose	150,000 U/kg/d IV q4h
Contraindications	Documented hypersensitivity
Interactions	Probenecid can increase penicillin effectiveness by decreasing its clearance; tetracyclines can decrease penicillin effectiveness
Pregnancy	B - Usually safe but benefits must outweigh the risks.
Precautions	Traditional drug for treatment of lung abscess, but spectrum of activity is narrow; use with caution in patients with impaired renal function

Drug Name	Azithromycin (Zithromax) -- These agents are replacing erythromycin as therapy for community-acquired pneumonia. They cover most potential etiologic agents, including Mycoplasma species. The newer macrolides offer decreased GI upset and the potential for improved compliance through reduced dosing frequency. They also afford more improved action against Haemophilus influenzae than erythromycin.
Adult Dose	Day 1: 500 mg PO Days 2-5: 250 mg/d PO; alternatively, 500 mg/d IV
Pediatric Dose	Day 1: 10 mg/kg PO Days 2-5: 5 mg/kg PO
Contraindications	Documented hypersensitivity; hepatic impairment; do not administer with pimozide
Interactions	May increase toxicity of theophylline, warfarin, and digoxin; effects are reduced with coadministration of aluminum and/or magnesium antacids; nephrotoxicity and neurotoxicity may occur when coadministered with cyclosporine
Pregnancy	B - Usually safe but benefits must outweigh the risks.
Precautions	Site reactions can occur with IV route; bacterial or fungal overgrowth may result with prolonged antibiotic use; may increase hepatic enzymes and cholestatic jaundice; caution in patients with impaired hepatic function, prolonged QT intervals, or pneumonia; caution in patients who are hospitalized, geriatric, or debilitated

Drug Name	Clarithromycin (Biaxin) -- Another antibiotic used during initial therapy in otherwise uncomplicated pneumonia. More GI symptoms appear to occur than with azithromycin (eg, gastric upset, metallic taste). Inhibits bacterial growth, possibly by blocking dissociation of peptidyl tRNA from ribosomes, causing RNA-dependent protein synthesis to arrest.
Adult Dose	500 mg PO bid for 10 d
Pediatric Dose	<6 months: Not recommended >6 months: 7.5 mg/kg PO bid for 10 d; not to exceed 1 g/d
Contraindications	Documented hypersensitivity; coadministration with pimozide
Interactions	Toxicity increases with coadministration of fluconazole, astemizole, and pimozide; clarithromycin effects decrease and GI adverse effects may increase with coadministration of rifabutin or rifampin; may increase toxicity of anticoagulants, cyclosporine, tacrolimus, digoxin, omeprazole, carbamazepine, ergot alkaloids, triazolam, and HMG CoA-reductase inhibitors; serious cardiac arrhythmias may occur with coadministration of cisapride; plasma levels of certain benzodiazepines may increase, prolonging CNS depression; arrhythmias and increase in QTc intervals occur with disopyramide; coadministration with omeprazole may increase plasma levels of both agents
Pregnancy	B - Usually safe but benefits must outweigh the risks.
Precautions	Coadministration with ranitidine or bismuth citrate is not recommended with CrCl <25 mL/min; administer one-half dose or increase dosing interval if CrCl <30 mL/min; diarrhea may be a sign of pseudomembranous colitis; superinfections may occur with prolonged or repeated antibiotic therapies

Drug Name	Erythromycin (E.E.S., Erythrocin, Ery-Tab) -- Recommended dosing schedule of erythromycin may result in GI upset, causing one to prescribe an alternative macrolide or change to tid dosing. Covers most potential etiologic agents, including Mycoplasma species. Oral dosing regimen may be insufficient to adequately treat Legionella species. Erythromycin is less active against H influenzae. Although 10 d seems to be a standard course of treatment, treating until the patient has been afebrile for 3-5 d seems a more rational approach. Inhibits bacterial growth, possibly by blocking dissociation of peptidyl tRNA from ribosomes, causing RNA-dependent protein synthesis to arrest. For treatment of staphylococcal and streptococcal infections.
Adult Dose	250 mg stearate/base (or 400 mg ethylsuccinate) PO q6h 1 h ac or 500 mg q12h; alternatively, use 333 mg q8h and increase up to 4 g/d depending on severity of infection Hospitalized with severe pneumonia: 1 g IV q6h; alternatively, administer 15-20 mg/kg/d IV in divided doses q6h
Pediatric Dose	In children, age, weight, and severity of infection determine proper dosage; when bid dosing is desired, one-half total daily dose may be taken q12h; for more severe infections, double the dose 7.5 mg/kg/d PO divided bid; alternatively, 20-40 mg/kg/d IV divided q6h or by constant infusion; not to exceed 4 g/d
Contraindications	Documented hypersensitivity; hepatic impairment
Interactions	Coadministration may increase toxicity of theophylline, digoxin, carbamazepine, and cyclosporine; may potentiate anticoagulant effects of warfarin; coadministration with lovastatin and simvastatin increases risk of rhabdomyolysis
Pregnancy	B - Usually safe but benefits must outweigh the risks.
Precautions	Caution in liver disease; estolate formulation may cause cholestatic jaundice; GI adverse effects are common (administer doses pc); discontinue use if nausea, vomiting, malaise, abdominal colic, or fever occurs

Drug Name	Amoxicillin-clavulanate (Augmentin) -- An alternative antibiotic for patients allergic or intolerant to the macrolide class. Usually is well tolerated and provides good coverage to most infectious agents. Not effective against Mycoplasma and Legionella species. Cost is a major problem. Drug combination treats bacteria resistant to beta-lactam antibiotics.
Adult Dose	500 mg PO bid or 875 mg PO bid for 10 d or until afebrile for 3-5 d
Pediatric Dose	<3 months: Base dosing protocol on amoxicillin content <40 kg: 20-40 mg/kg/d (based on amoxicillin content) divided bid; do not use 250-mg tab until child weighs >40 kg >40 kg: Administer as in adults
Contraindications	Documented hypersensitivity
Interactions	Coadministration with warfarin or heparin increases risk of bleeding
Pregnancy	B - Usually safe but benefits must outweigh the risks.
Precautions	Administer for a minimum of 10 d to eliminate organism and prevent sequelae (eg, endocarditis, rheumatic fever); following treatment, perform cultures to confirm eradication of streptococci

Drug Name	Levofloxacin (Levaquin) -- Rapidly becoming a popular choice in pneumonia. A good monotherapy for pseudomonal infections and infections due to multidrug-resistant gram-negative organisms.
Adult Dose	500 mg/d PO/IV for 7-14 d
Pediatric Dose	<18 years: Not recommended >18 years: Administer as in adults
Contraindications	Documented hypersensitivity
Interactions	Antacids, iron salts, and zinc salts may reduce serum levels; administer antacids 2-4 h before or after taking fluoroquinolones; cimetidine may interfere with metabolism of fluoroquinolones; levofloxacin reduces therapeutic effects of phenytoin; probenecid may increase levofloxacin serum concentrations; may increase toxicity of theophylline, caffeine, cyclosporine, and digoxin (monitor digoxin levels); may increase effects of anticoagulants (monitor PT)
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	In prolonged therapy, perform periodic evaluations of organ system functions (eg, renal, hepatic, hematopoietic); adjust dose in renal function impairment; superinfections may occur with prolonged or repeated antibiotic therapy

Drug Name	Cefaclor (Ceclor) -- Second-generation cephalosporin that binds to one or more of the penicillin-binding proteins, which in turn inhibits cell wall synthesis and results in bactericidal activity. Has gram-positive activity that first-generation cephalosporins have and adds activity against Proteus mirabilis, H influenzae, Escherichia coli, Klebsiella pneumoniae, and Moraxella catarrhalis. The condition of the patient, severity of the infection, and susceptibility of the microorganism should determine the proper dose and route of administration.
Adult Dose	500 mg PO q8h for 10 d
Pediatric Dose	20-40 mg/kg/d PO divided q8-12h; not to exceed 2 g/d
Contraindications	Documented hypersensitivity
Interactions	Alcoholic beverages consumed <72 h after taking cefaclor may produce disulfiramlike reactions; may increase hypoprothrombinemic effects of anticoagulants; coadministration with potent diuretics and aminoglycosides (eg, loop diuretics) may increase nephrotoxicity
Pregnancy	B - Usually safe but benefits must outweigh the risks.
Precautions	Reduce dosage by one half if CrCl is 10-30 mL/min and by one fourth if <10 mL/min; bacterial or fungal overgrowth of nonsusceptible organisms may occur with prolonged or repeated therapy

Drug Name	Cefprozil (Cefzil) -- Second-generation cephalosporin that binds to one or more of the penicillin-binding proteins, which in turn inhibits cell wall synthesis and results in bactericidal activity. Has gram-positive activity that first-generation cephalosporins have and adds activity against P mirabilis, H influenzae, E coli, K pneumoniae, and M catarrhalis. The condition of the patient, severity of the infection, and susceptibility of the microorganism should determine the proper dose and route of administration.
Adult Dose	500 mg/d PO for 10 d
Pediatric Dose	<12 years: 30 mg/kg/d PO divided q12h for 10 d >12 years: Administer as in adults
Contraindications	Documented hypersensitivity
Interactions	Probenecid increases effect of cefprozil; coadministration with furosemide and aminoglycosides increases nephrotoxic effects of cefprozil
Pregnancy	B - Usually safe but benefits must outweigh the risks.
Precautions	Adjust dosage in renal impairment

Drug Name	Cefuroxime (Ceftin) -- Second-generation cephalosporin that binds to one or more of the penicillin-binding proteins, which in turn inhibits cell wall synthesis and results in bactericidal activity. Has gram-positive activity that first-generation cephalosporins have and adds activity against P mirabilis, H influenzae, E coli, K pneumoniae, and M catarrhalis. The condition of the patient, severity of the infection, and susceptibility of the microorganism should determine the proper dose and route of administration.
Adult Dose	250 mg PO bid for 10 d
Pediatric Dose	Neonates: 20-50 mg/kg/d IV divided q12h Infants and children: 75-150 mg/kg/d IV divided q8h; not to exceed 6 g/d <13 years: 250 mg PO bid for 20 d >13 years: Administer as in adults
Contraindications	Documented hypersensitivity
Interactions	Disulfiramlike reactions may occur when alcohol is consumed within 72 h after taking cefuroxime; may increase hypoprothrombinemic effects of anticoagulants; may increase nephrotoxicity in patients receiving potent diuretics such as loop diuretics; coadministration with aminoglycosides increases nephrotoxic potential
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Administer one-half dose if CrCl is 10-30 mL/min and one-fourth dose if <10 mL/min; fungal and microorganism overgrowth may occur with prolonged therapy

Drug Name	Ceftriaxone (Rocephin) -- Third-generation cephalosporin with broad-spectrum, gram-negative activity; lower efficacy against gram-positive organisms; higher efficacy against resistant organisms. Arrests bacterial growth by binding to one or more penicillin-binding proteins. The condition of the patient, severity of the infection, and susceptibility of the microorganism should determine the proper dose and route of administration.
Adult Dose	500-1000 mg IV q12h; not to exceed 4 g/d
Pediatric Dose	Neonates >7 d: 25-50 mg/kg/d IV/IM; not to exceed 125 mg/d Infants and children: 50-75 mg/kg/d IV/IM divided q12h; not to exceed 2 g/d
Contraindications	Documented hypersensitivity
Interactions	Probenecid may increase ceftriaxone levels; coadministration with ethacrynic acid, furosemide, and aminoglycosides may increase nephrotoxicity
Pregnancy	B - Usually safe but benefits must outweigh the risks.
Precautions	Adjust dose in renal impairment; caution in women who are breastfeeding and persons with allergy to penicillin

Drug Name	Ceftazidime (Fortaz) -- Third-generation cephalosporin with broad-spectrum, gram-negative activity; lower efficacy against gram-positive organisms; higher efficacy against resistant organisms. Arrests bacterial growth by binding to one or more penicillin-binding proteins. The condition of the patient, severity of the infection, and susceptibility of the microorganism should determine the proper dose and route of administration.
Adult Dose	1-2 g IV/IM q8-12h
Pediatric Dose	Neonates: 30 mg/kg IV q12h Infants and children: 30-50 mg/kg/dose IV q8h; not to exceed 6 g/d Adolescents: Administer as in adults
Contraindications	Documented hypersensitivity
Interactions	Nephrotoxicity may increase with aminoglycosides, furosemide, and ethacrynic acid; probenecid may increase ceftazidime levels
Pregnancy	B - Usually safe but benefits must outweigh the risks.
Precautions	Adjust dose in renal impairment

Drug Category: Fibrinolytic agents -- Restore circulation through a previously occluded vessel by the rapid and complete removal of a pathologic intraluminal thrombus or embolus that has not been dissolved by the endogenous fibrinolytic system.

Drug Name	Streptokinase (Kabikinase, Streptase) -- Acts with plasminogen to convert plasminogen to plasmin. Plasmin degrades fibrin clots as well as fibrinogen and other plasma proteins. Increase in fibrinolytic activity that degrades fibrinogen levels for 24-36 h takes place with intravenous infusion of streptokinase. Absorbed from the pleural space.
Adult Dose	250,000 IU IV in 100 mL of normal saline qd or bid is instilled into pleural space for 3-5 d
Pediatric Dose	Not established
Contraindications	Documented hypersensitivity; active internal bleeding; intracranial neoplasm; aneurysm; diathesis; severe uncontrolled arterial hypertension
Interactions	Antifibrinolytic agents may decrease effects of streptokinase; heparin, warfarin, and aspirin may increase risk of bleeding
Pregnancy	B - Usually safe but benefits must outweigh the risks.
Precautions	Caution in severe hypertension, intramuscular administration of medications, trauma, or surgery in the previous 10 days; measure hematocrit, platelet count, aPTT, TT, PT, or fibrinogen levels before therapy is implemented; either TT or aPTT should be less than twice the normal control value following infusion of streptokinase and before instituting or re-instituting heparin; do not take blood pressure in the lower extremities because it may dislodge a possible deep vein thrombi; PT, aPTT, TT, or fibrinogen should be monitored 4 hours after the initiation of therapy

Drug Name	Urokinase (Abbokinase) -- Direct plasminogen activator that acts on the endogenous fibrinolytic system and converts plasminogen to the enzyme plasmin, which in turn degrades fibrin clots, fibrinogen, and other plasma proteins. Most often used for local fibrinolysis of thrombosed catheters and superficial vessels. Advantage is that agent is nonantigenic; however, more expensive than streptokinase and, thus, limits use. When used for local fibrinolysis, urokinase is administered as local infusion directly into area of thrombus and with no bolus administered. Dose of medication should be adjusted to achieve clot lysis or patency of affected vessel.
Adult Dose	100,000 IU IV in 100 mL of normal saline once or twice a day is instilled into pleural space for 3-5 d
Pediatric Dose	Not established
Contraindications	Documented hypersensitivity; internal bleeding; recent trauma; history of intracranial or intraspinal surgery or trauma; cerebrovascular accident; intracranial neoplasm
Interactions	Thrombolytic enzymes, alone or in combination with anticoagulants and antiplatelets, may increase risk of bleeding complications
Pregnancy	B - Usually safe but benefits must outweigh the risks.
Precautions	Caution in patients receiving intramuscular administration of medications, severe hypertension, trauma, or surgery in previous 10 days; avoid dislodging a possible deep vein thrombi; do not measure blood pressure in lower extremities; monitor therapy by performing PT, aPTT, TT, or fibrinogen approximately 4 h after initiation of therapy; monitor therapy by performing PT, aPTT, TT, or fibrinogen approximately 4 h after initiation of therapy

FOLLOW-UP

Further Inpatient Care:

• Patients require admission to a hospital for aggressive antibiotic therapy, drainage of pleural space, thrombolytic therapy (possibly), and surgery (in patients in whom medical therapy fails).

Further Outpatient Care:

• Often, prolonged antibiotic therapy is required, particularly in patients who have anaerobic infection. The length of antibiotic therapy generally is dictated by response to antibiotics and clinical and radiologic resolution.

Prognosis:

• Prognosis is quite favorable in patients who have been started on appropriate antibiotic therapy and in patients who are assessed for the need of pleural space drainage if fever recurs or if chest x-ray films show an effusion. Early chest tube drainage has been shown to be beneficial. Patients in whom medical and conservative therapies fail require pleural decortication or open drainage, which has increased mortality and morbidity.

MISCELLANEOUS

Medical/Legal Pitfalls:

• The indication for thoracentesis in pleural effusions is to differentiate between an exudate and a transudate pleural effusion and to differentiate between an uncomplicated and a complicated pleural effusion.

• Measure the pH each time a parapneumonic effusion is suspected.

• In the treatment of parapneumonic pleural effusions, indications for fibrinolytic treatment are unclear. Furthermore, the best timing for surgical decortication in empyema and fibrothorax is still unclear.

Special Concerns:

• For an empyema associated with bronchopleural fistula, adequate pleural drainage is crucial. Pleural fluid may drain internally, and overwhelming pneumonia may result. If a patient is raising large amounts of sputum when lying in a particular position, bronchopleural fistula is strongly suspected.

• Radiologically, a bronchopleural fistula is manifested by the presence of an air-fluid level in the pleural space. To differentiate the air-fluid level from the lung abscess, an ultrasound or CT scan may be helpful.

• The presence of bronchopleural fistula in conjunction with infected pleural fluid is a medical emergency. Immediately institute drainage, and start appropriate antibiotics promptly.

• An empyema distal to an obstructed bronchus should not be drained with a chest tube because the underlying lung does not expand, and the patient remains with a chest tube or open chest wound for the remainder of life. In patients with an empyema distal to an obstructed bronchus, administer appropriate antibiotics along with radiotherapy or laser therapy to the affected bronchus. Only institute tube thoracostomy if radiotherapy relieves the obstruction. Otherwise, patients should remain on long-term oral antibiotics.

• A postpneumonectomy empyema accounts for approximately 25% of empyemas. Incidence of postpneumonectomy empyema is 2-10%, and approximately one half of these patients have bronchopleural or esophagopleural fistula.

• After a pneumonectomy, characteristic evolution of radiologic findings exists. Deviations from this suggest the possibility of postpneumonectomy empyema. In the postoperative period, if the volume of air increases or the mediastinum shifts toward the mid line or contralateral side, strongly consider postpneumonectomy empyema. Diagnosis is further established by a thoracentesis, demonstrating bacteria on the Gram stain of the pleural fluid. The usual bacteria responsible for infection are gram-negative organisms or S aureus.

• Treat all patients with postpneumonectomy empyema with a chest tube and appropriate antibiotics. If no bronchopleural fistula exists, antibiotic irrigation of the pleural space also appears to be effective in most patients.

• An alternate approach to postpneumonectomy empyema is the creation of a large opening in the chest, where the empyema cavity is irrigated with antibiotics and slowly is allowed to close over time. If a bronchopleural fistula is present, one of several different procedures described can be used to attempt closure of the fistula. These procedures involve transposition of extrathoracic skeletal muscle to facilitate closure. Multiple operations may be required. Closure of small fistulas may be attempted with instillation of tissue adhesive via a bronchoscope.

PICTURES

Caption: Picture 1. Left pleural effusion developed 4 days after antibiotic treatment for pneumococcal pneumonia. Patient developed fever, left-sided chest pain, and increasing dyspnea. During thoracentesis, purulent pleural fluid was removed, and the Gram stain showed gram-positive diplococci. The culture confirmed this to be Streptococcus pneumoniae.
Picture Type: X-RAY

Caption: Picture 2. Left lateral chest radiograph shows a large, left pleural effusion.
Picture Type: X-RAY

Caption: Picture 3. A right lateral decubitus chest radiograph shows a free-flowing pleural effusion, which should be sampled with thoracentesis for pH determination, Gram stain, and culture.
Picture Type: X-RAY

Caption: Picture 4. CT scan of thorax shows loculated pleural effusion on left and contrast enhancement of visceral pleura, indicating the etiology is likely an empyema.
Picture Type: CT