The following cases and commentary, which involve invasive procedures and complications, are excerpted from ACP's Medical Knowledge Self-Assessment Program (MKSAP 15).
Case 1: Catheter infection
A 55-year-old man is evaluated in the hospital for a 2-day history of fever and erythema at the site of a peripherally inserted central catheter. The patient was recently diagnosed with acute myeloid leukemia for which he received chemotherapy 11 days ago. Medical history is also significant for the vancomycin IgE-mediated hypersensitivity reaction characterized by urticaria, bronchospasm, and hypotension.
On physical examination, temperature is 39.1°C (102.5°F), blood pressure is 100/70 mm Hg, pulse rate is 110/min, and respiration rate is 22/min. BMI is 25. Erythema and tenderness are noted at the catheter insertion site in the left antecubital fossa. A new grade 3/6 holosystolic murmur that increases with inspiration is heard at the left lower sternal border.
Laboratory studies show hemoglobin 7.0 g/dL (70 g/L), leukocyte count 1000/µL (1.0 × 109/L), with 5% neutrophils and platelet count 20,000 (20 × 109/L). Multiple blood cultures reveal growth of methicillin-resistant Staphylococcus aureus.
A chest radiograph and electrocardiogram are unremarkable. A transthoracic echocardiogram reveals moderate tricuspid insufficiency and a vegetation on the tricuspid valve.
In addition to catheter removal, which of the following is the most appropriate treatment?
Case 2: Chest pain during thoracentesis
A 70-year-old man is evaluated for the insidious onset of dyspnea. He does not have chest pain, cough, hemoptysis, or fever. The patient has advanced adenocarcinoma of the lung, and 1 month ago a left-sided malignant pleural effusion was diagnosed. The effusion was small, and observation was recommended.
On physical examination, the patient is thin and shows minimal increased work of breathing at rest on ambient air. The temperature is 36.9°C (98.5°F), the blood pressure is 140/75 mm Hg, the pulse rate is 96/min and regular, and the respiration rate is 22/min; oxygen saturation is 91% on ambient air. There is dullness to percussion in the left base with decreased fremitus and egophony above the level of dullness. There is digital clubbing. Chest radiograph shows left hilar and mediastinal lymphadenopathy and a moderate-sized pleural effusion occupying 50% of the hemithorax with minimal contralateral mediastinal shift. Thoracentesis was terminated because of the patient's coughing and severe anterior chest pain. The lung did not expand after thoracentesis.
Analysis of the pleural fluid shows: erythrocyte count 10,000/µL (10 × 109/L); nucleated cell count 2800/µL (2.8 × 109/L) with 7% neutrophils, 61% lymphocytes, 15% macrophages, 10% mesothelial cells, and 7% eosinophils; total protein 3.8 g/dL (38 g/L); lactate dehydrogenase 250 U/L; pH 7.18; glucose 38 mg/dL (2.1 mmol/L) and pleural fluid cytology is positive for adenocarcinoma.
Which of the following is the most appropriate management for this patient?
A. Placement of an indwelling pleural catheter
B. Radiation therapy
C. Talc pleurodesis through a small-bore catheter
D. Video-assisted thoracoscopic surgery with pleural abrasion
Case 3: Fever after placement of ventriculo-peritoneal shunt
A 40-year-old man is evaluated for the acute onset of fever, headache, nausea, and lethargy. He has a history of obstructive hydrocephalus for which he underwent ventriculo-peritoneal shunt placement approximately 6 months ago, and the shunt has been functioning well.
On physical examination, temperature is 38.0o C (100.4o F), blood pressure is 110/70 mm Hg, pulse rate is 90/min, and respiration rate is 14/min. Examination of the head reveals the presence of the shunt catheter without evidence of skin breakdown or tenderness along the site. He is oriented only to person and place and needs to be aroused to answer questions. The remainder of the physical examination, including funduscopic and neurologic examinations, is normal.
Laboratory studies indicate a leukocyte count of 11,000/µL (11 × 109/L) with a normal differential. Cerebrospinal fluid, obtained after tapping of the shunt, reveals a leukocyte count of 200/µL (200 × 106/L) with 90% neutrophils, a glucose concentration of 40 mg/dL (2.22 mmol/L), and a protein level of 100 mg/dL (1000 mg/L). Gram stain results are negative.
Pending culture results, which of the following antimicrobial regimens should be initiated in this patient?
B. Trimethoprim-sulfamethoxazole plus rifampin
D. Vancomycin, ampicillin, plus ceftriaxone
E. Vancomycin plus cefepime
Case 4: Severe sepsis
A 71-year-old woman is brought to the emergency department from a nursing home because of confusion, fever, and flank pain. Her temperature is 38.5°C (101.3°F), blood pressure is 82/48 mm Hg, pulse rate is 123/min, and respiration rate is 27/min. Mucous membranes are dry, and there is costovertebral angle tenderness, poor skin turgor, and no edema. Hemoglobin concentration is 10.5 g/dL (105 g/L), leukocyte count is 15,600/µL (15.6 × 109/L); urinalysis reveals 50 to 100 leukocytes/hpf and many bacteria/hpf. The patient has an anion gap metabolic acidosis. A central venous catheter is placed, and antibiotic therapy is started.
Which of the following additional interventions is most likely to improve survival for this patient?
A. Aggressive fluid resuscitation
B. Hemodynamic monitoring with a pulmonary artery catheter
C. Maintaining hemoglobin concentration above 12 g/dL (120 g/L)
D. Maintaining PCO2 below 50 mm Hg
Case 5: Pleural infection
A 60-year-old man is evaluated in the emergency department for a 3-hour history of shaking chills and cough productive of purulent sputum. He has a 35-pack-year history of cigarette smoking but has no other significant medical history.
On physical examination, the temperature is 38.5°C (101.4°F), the blood pressure is 150/90 mm Hg, the pulse rate is 115/min and regular, and the respiration rate is 28/min. There is increased dullness to percussion at the right base, crackles in the right mid-lung field, and anterior wheezes. Chest radiograph shows a right lower lobe posterior infiltrate and a moderate-sized pleural effusion; diagnostic thoracentesis reveals a turbid pleural fluid.
Analysis of the fluid shows: erythrocyte count 750/µL; nucleated cell count 18,000/µL (18 × 109/L) with 87% neutrophils, 5% lymphocytes, 4% macrophages, and 4% mesothelial cells; total protein 4.5 g/dL (45 g/L); lactate dehydrogenase 1000 U/L; pH 7.20; glucose 50 mg/dL (2.8 mmol/L). Ultrasonography at the time of thoracentesis showed complex septations in the pleural fluid. Cytology is pending. Therapy with ceftriaxone, azithromycin, and inhaled bronchodilators is started.
Which of the following is the most appropriate management for this patient?
A. Admit to the hospital and perform pleural cavity drainage
B. Admit to the hospital and repeat chest radiograph in 2 days
C. Admit to the hospital for video-assisted thoracoscopic surgery
D. Treat as an outpatient
Case 6: Pneumococcal pneumonia
A 70-year-old woman is hospitalized for pneumococcal pneumonia. She was ambulatory until the day of admission but is now unable to leave her bed. She has a permanent venous catheter through her left subclavian vein. The patient has a history of stage IIIB non–small cell lung cancer.
On physical examination, the temperature is 37.8°C (100.0°F), the blood pressure is 110/70 mm Hg, the pulse rate is 110/min, and the respiration rate is 22/min. On admission, the patient's serum creatinine level was 3.0 mg/dL (265.2 µmol/L); it was 0.7 mg/dL (61.9 µmol/L) 1 month ago.
Which of the following is the best management to prevent venous thromboembolism in this patient?
B. Low-dose unfractionated heparin, subcutaneously
C. Low-molecular-weight heparin, subcutaneously
D. Periodic lower extremity ultrasonography
E. Warfarin to maintain the INR at 2.0 to 3.0
Answers and commentary
Correct answer: C. Daptomycin.
This patient has nosocomially acquired methicillin-resistant Staphylococcus aureus (MRSA)–associated cellulitis, bacteremia, and tricuspid valve infective endocarditis secondary to a peripherally inserted central catheter. In addition to catheter removal, this patient requires a 6-week course of intravenous antibiotics. Daptomycin is a lipopeptide agent with very broad bactericidal activity against gram-positive pathogens, including those resistant to other drug classes, such as MRSA and vancomycin-resistant enterococci. It has a novel mechanism of action in that it binds to the bacterial membrane and, in a calcium-dependent manner, causes electrical depolarization of the cell resulting in leakage of potassium and rapid cell death. Resistance is rare, and cross-resistance between daptomycin and other agents that are active against gram-positive organisms is absent. Daptomycin is currently approved for treatment for bacteremia and right-sided endocarditis. Daptomycin may cause muscle toxicity when given twice daily, but changing to once-daily administration appears to reduce this risk.
By definition, methicillin resistance means that this organism is resistant to oxacillin; nafcillin; and other β-lactam agents, including cefazolin.
Clindamycin, a bacteriostatic agent, is not included in the consensus guidelines for treatment of MRSA-associated infective endocarditis. Clindamycin monotherapy has been associated with treatment failure and relapse when used to treat methicillin-susceptible S. aureus bacteremia and infective endocarditis.
- Daptomycin is appropriate treatment of methicillin-resistant Staphylococcus aureus–associated bacteremia and right-sided infective endocarditis; regular assessment for signs of myopathy is indicated with this agent.
Correct answer: A. Placement of an indwelling pleural catheter.
The development of severe, anterior chest pain during therapeutic thoracentesis is virtually diagnostic of an unexpandable lung with the development of significant negative intrapleural pressure. The anterior chest pain is quickly relieved by allowing air entry into the pleural space through the thoracentesis needle or catheter. In this situation, the patient is best managed with an indwelling catheter. The patient and his family are instructed to drain the pleural fluid when breathlessness ensues and to discontinue drainage immediately when anterior chest pain develops.
This patient has two distinct pathophysiologic causes of his pleural effusion: (1) fluid produced by the malignant involvement of the pleura primarily due to increased levels of vascular endothelial growth factor and (2) an unexpandable lung due to tumor involvement of the visceral pleura. Therefore, an indwelling catheter removes the “malignant fluid,” and when this volume of fluid has been removed, further fluid removal (due to the unexpandable lung) results in a significant decrease in pleural pressure causing anterior chest pain. Talc pleurodesis will not be completely effective because all of the lung cannot expand to the chest wall to promote pleurodesis. A surgical procedure in a patient with advanced malignancy would not be the appropriate initial treatment, and furthermore, pleural abrasion would not promote effective pleurodesis with an unexpandable lung, which would require a decortication that would not be appropriate for this patient. Outpatient thoracentesis could be appropriate; however, it requires frequent trips to the hospital or clinic, which might be problematic for some patients. Radiation therapy is not indicated for lung entrapment from adenocarcinoma.
- The development of severe, anterior chest pain during therapeutic thoracentesis is virtually diagnostic of an unexpandable lung with the development of significant negative intrapleural pressure.
Correct answer: E. Vancomycin plus cefepime.
This patient has a cerebrospinal fluid (CSF) shunt infection. Ventriculo-peritoneal shunt infections can be difficult to diagnose owing to the variability of the clinical presentation. Symptoms may reflect increased intracranial pressure (headache, nausea, vomiting, lethargy, or altered mental status) as the result of shunt obstruction or even signs of peritonitis. Classic meningeal irritative symptoms may be absent, and fever may or may not be present. This patient has fever and signs of increased intracranial pressure and laboratory findings confirming the diagnosis of shunt infection. The most likely causative microorganisms are coagulase-negative staphylococci (especially Staphylococcus epidermidis), S. aureus, diphtheroids (including Propionibacterium acnes), and gram-negative bacilli (including Pseudomonas aeruginosa).
Empiric therapy with vancomycin to cover staphylococci and diphtheroids and ceftazidime, cefepime, or meropenem to treat the gram-negative bacilli, is appropriate pending culture results. Trimethoprim-sulfamethoxazole; trimethoprim-sulfamethoxazole plus rifampin; vancomycin; and vancomycin, ampicillin, plus ceftriaxone do not provide a broad enough spectrum of in vitro activity for the possible infectious pathogens in this patient.
- Empiric treatment for cerebrospinal fluid shunt infection should include agents with activity against staphylococci, diphtheroids, and aerobic gram-negative bacilli.
Correct answer: A. Aggressive fluid resuscitation.
The patient has severe sepsis presumptively from pyelonephritis. Aggressive fluid resuscitation with resolution of lactic acidosis within 6 hours would have a beneficial effect on this patient's survival. Resuscitation of the circulation should target a central venous oxygen saturation (SCVO2) or mixed venous oxygen saturation (SVO2) of at least 70%. Other reasonable goals include a central venous pressure of 8 to 12 mm Hg, a mean arterial pressure of at least 65 mm Hg, and a urine output of at least 0.5 mL/kg/h. In patients such as the one presented, this often translates into administration of 5 to 6 L of fluid. Timing of resuscitation matters to survival. In a landmark study by Rivers and colleagues, early goal-directed therapy that included interventions within the first 6 hours to maintain a SCVO2 of greater than 70% and to resolve lactic acidosis resulted in higher survival rates than more delayed resuscitation attempts. Over the first 72 hours, patients in the control arm received the same quantity of fluid for resuscitation, but they had a significantly higher likelihood of dying by discharge or at 60 days.
Crystalloid is given much more frequently than colloid, and there are no data to support routinely using colloid in lieu of crystalloid. Blood transfusion may be part of resuscitation for anemic patients in shock, but maintaining hemoglobin levels above 12 g/dL (120 g/L) is not supported by evidence. In stable patients who are not in shock, a transfusion threshold of 7 g/dL (70 g/L) is an acceptable conservative approach. There are no data to support that maintaining a lower PCO2 or using a pulmonary artery catheter would help to increase survival in this patient.
- In patients with severe sepsis, early goal-directed therapy within the first 6 hours to maintain a central venous or mixed venous oxygen saturation of greater than 70% and to resolve lactic acidosis improves survival compared with more delayed resuscitation attempts.
Correct answer: A. Admit to the hospital and perform pleural cavity drainage.
Pleural infections often resolve with antibiotic therapy alone, but fibrinous organization and lung entrapment require invasive treatment in about 10% of parapneumonic effusions. Effusions at risk for loculation are called complicated parapneumonic effusions. Because clinical prediction is unreliable, thoracentesis should be done to assess the need for invasive treatment provided that the effusion can be clearly visualized on ultrasonography. This patient with presumed underlying chronic obstructive pulmonary disease had typical symptoms of an acute bacterial pneumonia with development of a parapneumonic effusion with septations, low pleural fluid pH, low glucose, and elevated lactate dehydrogenase level. All of these factors suggest that the patient will have a poor outcome without immediate pleural space drainage with either thoracostomy tube placement or a radiologically guided small-bore catheter. The evidence for use of fibrinolytic agents is still unclear, but in this situation, pleural space drainage is imperative and, with the ultrasonographic findings, a trial of a fibrinolytic agent is warranted before performing video-assisted thoracoscopic surgery (VATS). Intrapleural administration of fibrinolytic agents does not cause systemic thrombolysis. Early VATS or thoracotomy is the generally preferred approach for patients who are candidates for surgery and who have persistent sepsis and loculation.
The patient should not be discharged; he needs close follow-up for possible escalation of therapy. He should not be sent for surgery immediately without a trial of chest tube drainage with or without fibrinolytic therapy. If clinical improvement is not obvious by 3 days, surgical consultation should be initiated.
- Immediate pleural space drainage, with or without fibrinolytic therapy, is indicated in a patient with acute bacterial pneumonia and a parapneumonic effusion with septations.
Correct answer: B. Low-dose unfractionated heparin, subcutaneously.
This patient is at substantial risk for venous thromboembolism because of her malignancy and her acute medical illness. Unfractionated heparin and low-molecular-weight heparins have been shown to reduce the risk of venous thromboembolism and are highly recommended for patients at moderate or high risk. Unfractionated heparin does not rely on normal renal function for clearance and would be an appropriate option in this patient.
Aspirin is not commonly recommended for the prevention of venous thromboembolism and has not been demonstrated by clinical trials to reduce the incidence of thromboembolism in most populations at risk. Low-molecular-weight heparins are renally cleared and would accumulate unpredictably in this patient with acutely worsening renal function. The same limitation is applicable to fondaparinux. Ultrasonographic surveillance for deep venous thrombosis and subsequent treatment has not been shown to improve outcomes. Warfarin, especially at therapeutic doses, is not recommended as a first choice for prophylactic use in medical patients. Its long duration of action may be especially detrimental in medical inpatients who may need invasive procedures. In addition, it would take several days before the INR reached the therapeutic target.
- Unfractionated heparin does not depend on normal renal function for clearance and is appropriate for prophylaxis of venous thromboembolism for patients with renal insufficiency.