A 52-year-old woman diagnosed with granulomatosis with polyangiitis (Wegener’s) 3 months ago and treated with cyclophosphamide and prednisone (40 mg daily) presents to ED due to shortness of breath and dry cough. Last time she noted bloodtinged sputum was more than 2 months ago. Her vitals on arrival are notable for temperature of 39.2°C, heart rate 110 beats/min, blood pressure 104/54, respiratory rate 25 breaths/min, and oxygen saturation 86% on room air. Chest x-ray reveals bilateral infiltrates and cystic-appearing round opacities (fig below):
She is placed on high flow nasal cannula at 55 L/min and FiO2 of 0.8, but her respiratory distress continues to worsen, and she requires endotracheal intubation. Her labs are notable for Arterial blood gas:
Lactate dehydrogenase (LDH): 664 (normal: 110-210 U/L)
Which of the following treatment regimens would MOST likely improve her condition?
Correct Answer: B
Patient has clinical symptoms and laboratory and radiographic signs consistent with pneumocystis jirovecii pneumonia (PJP), an opportunistic infection typically affecting immunocompromised hosts. These may include patients with acquired immune deficiency syndrome (AIDS), those with malignancies, stem cell and solid organ transplant recipients, and patients receiving high-dose corticosteroids and other immunosuppressants. PJP classically presents with fever, dry cough, and hypoxemic respiratory failure with exertional oxygen desaturations. Positive PJP PCR or silver stain from induced sputum or bronchoalveolar lavage (BAL) samples are confirmatory. LDH elevation is common, particularly in HIV-positive patients in whom the sensitivity is reported to be 100%; however, sensitivity is lower (∼60%) in HIV-negative individuals. Radiographic findings include bilateral patchy infiltrates with cysticappearing opacities on chest x-rays (as seen in the above chest x-ray). On high-resolution CT scans, the most common findings are ground glass opacities with cysts that are seen in approximately one third of patients. First-line treatment is intravenous trimethoprim/sulfamethoxazole (Bactrim) which should be continued for at least 7 to 10 days or until clinical improvement is seen, when transition to oral antibiotics is considered. Total duration of therapy is typically 3 weeks. PJP prophylaxis should be initiated in patients with CD4 count less than 200 cells/mm3 and those receiving high-dose steroids (>20 mg/d) for more than one month, particularly if the patient is receiving additional cytotoxic agents, as in this clinical vignette.
A 34-year-old male with recently diagnosed Hodgkin lymphoma is admitted to the hospital for induction chemotherapy with doxorubicin, bleomycin, vinblastine, and dacarbazine. On day 7 of the induction, he develops fever as high as 38.4°C and rigors. His blood pressure is 80/52 mm Hg, heart rate is 110 beats/min, respiratory rate is 22 breaths/min, and his oxygen saturation is 92% on 4 L O2 via nasal canula. He is given 2 L of lactated Ringer’s after which his blood pressure improves to 98/64. Internal jugular central line site is examined, and no erythema or purulence at the site of insertion is noted. Labs are notable for:
Which of the following interventions is MOST likely to decrease this patient’s mortality?
Correct Answer: A
This patient has neutropenic fever which is a serious complication of chemotherapy. It is defined by an isolated temperature >38.3°C (101°F) or a temperature of >38.0°C (100.4°F) lasting for >1 hour in a patient with neutropenia. If not treated promptly, sepsis and septic shock can develop. Severe neutropenia is defined as an absolute neutrophil count (ANC) of less than 500 cells/mm3 . Neutrophils prevent bacterial and fungal infections; therefore, neutropenic patients are especially prone to these types of infections.
Adequate antibiotic therapy is the key intervention to decrease mortality of this patient. The initial empiric antibiotic therapy for febrile neutropenia is a beta-lactam with pseudomonas coverage (such as ceftazidime, cefepime, piperacillin-tazobactam) or a carbapenem (meropenem, imipenem). While vancomycin is not typically a part of the empiric antibiotic regimen, it should be added in patients with evidence of hemodynamic instability (such as in this patient), pneumonia, skin or soft tissue infection, or catheter-related infection. Vancomycin or alternative gram-positive coverage may be discontinued at 48 hours if there is no confirmation of gram-positive pathogens. Antibiotic therapy should be further tailored to resistance patterns of bacteria previously isolated from a patient and colonization with resistant organisms such as methicillinresistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococcus (VRE), extended-spectrum β-lactamase (ESBL) gram-negative organisms, or carbapenemase-producing organisms.
Patients should be evaluated for the presence of indwelling lines both as a source of infection and for removal depending on the isolated pathogen. In this clinical scenario, immediate removal of central line is not indicated. In patients that are considered to be high risk for infectious complications (hospitalized at the time of fever, age >65 years, expected protracted neutropenia lasting >10 days, or ANC <100/µL, sepsis, pneumonia, or invasive fungal infections), administration of granulocyte colonystimulating factor should be considered. Neutropenic precautions alone would not be sufficient to decrease this patient’s mortality.
A 53-year-old man with celiac disease is admitted to hospital from primary physician’s office for a workup of weakness and anemia. His hemoglobin is 6.0 g/dL and is suspected to be a result of a slow GI bleed. His vitals are notable for:
Two units of cross-matched packed red blood cells are ordered. Ten minutes into the blood transfusion, patient becomes febrile (38.6°C), but other vitals remain unchanged. Transfusion is continued. Fifteen minutes later the patient develops worsening hypotension to 75/40 mm Hg, urticarial rash, and wheezing.
Which of the following is the MOST likely etiology of the patient’s decompensation?
Correct Answer: C
This patient developed anaphylactic reaction to blood product. Anaphylactic reactions to blood products occur in about 1 out of 1.3 million transfusions. These reactions occur most commonly either during or within 4 hours of a transfusion. Anaphylactic reactions should be treated by immediately stopping the blood transfusion, administration of intramuscular epinephrine, intravenous H1 blocker antihistamines (eg, diphenhydramine), H2 blocker antihistamines (eg, ranitidine), intravenous methylprednisolone, and beta-agonists (eg, albuterol) as needed. Adequate respiratory support including supplemental oxygen and/or mechanical ventilatory support should be provided based on the clinical status of the patient.
Isolated IgA deficiency is the most common immunoglobulin deficiency with the prevalence estimated to be between 1 in 200 and 1 in 500. AntiIgA–mediated anaphylactic reactions occur when patients with IgA deficiency have developed anti-IgA antibodies that can react with IgA in red blood cell products. Sensitization to IgA may occur during prior blood transfusions, pregnancy, or intravenous immunoglobulin infusions. However, some patients do not have a history that suggests prior sensitization. In these cases, it is postulated the anti-IgA antibodies may either occur spontaneously or as a consequence of sensitization either in utero or via breast milk. IgA deficiency is common in patients with celiac disease, such as the patient in this vignette.
Hemolytic blood transfusion reactions occur when there is ABO incompatibility. This is exceptionally rare in the setting of rigorous crossmatching protocols. Symptoms of a hemolytic transfusion reaction include temperature increase >1 or <1°C with associated fevers, chills, hypotension, nausea or vomiting, and evidence of hemolysis. Acute airway compromise and wheezing are not classic signs of hemolytic transfusion reactions.
A diagnosis of septic transfusion is made when bacteria are isolated from both the blood product and the patient. A presumptive diagnosis can be made when bacteria are isolated solely from the blood product in a patient with a clinical syndrome of sepsis. Urticarial rash and respiratory distress would not be consistent with bacterial contamination. Guidelines recommend starting empiric antibiotics (β-lactam or aminoglycoside) with pseudomonas coverage. While a sudden GI bleed could present with worsening hypotension, an urticarial rash and respiratory distress would be atypical.
A 52-year-old male with history of end-stage renal disease on hemodialysis is recovering in PACU following deceased donor renal transplant. He is receiving infusion of rabbit antithymocyte globulin (ATG) which was started intraoperatively. On a regular nursing check, he is found to have fever of 38.5°C. His heart rate is 90 beats/min, blood pressure is 110/60 mm Hg (baseline 150/80 mm Hg), CVP is 8, and oxygen saturation is 98% on room air. He is anuric. He has no specific complaints, and his surgical site appears normal.
Which of the following is the next BEST step in management of his condition?
Antithymocyte globulin (ATG) consists of polyclonal antibodies directed against lymphocytes, therefore depleting them. It is used for induction of immunosuppression and for treatment of acute rejection. ATG use spares early use of nephrotoxic calcineurin inhibitors and also allows for decreased steroid exposure. Common side effects of ATG include fever, hypotension, rash, leukopenia, and thrombocytopenia. Serum sickness and acute respiratory distress syndrome (ARDS) have also been described in the literature.
The patient developed new-onset fever and hypotension in the PACU which could be caused by ATG. The ATG infusion rate should be decreased to see if there is improvement in hypotension, and additional workup should be pursued. Workup of new hypotension in the postoperative period includes repeat laboratory testing (blood counts), culture data (blood culture, urine culture, chest x-ray, sputum culture if available). Should hypotension and fever not improve with decreased rate of ATG infusion, empiric antimicrobials would be reasonable. Administration of volume (crystalloids, blood products) in an anuric patient with a CVP of 8 cm may be harmful by causing volume overload and potentially respiratory failure. Vasopressors may cause arterial constriction and result in ischemic injury of the delicate new renal graft.
A 62-year-old man with refractory non-Hodgkin lymphoma is admitted to hospital for infusion of chimeric antigen receptor T cells (CAR T). On day 3 following the infusion of CAR T cells, he becomes febrile to 38.9°C, hypotensive, and somnolent. Neurological examination is nonfocal. His blood pressure remains 75/40 mm Hg despite quick administration of 2 L lactated Ringer’s, and he is transferred to the ICU for further management. The infusion of norepinephrine is initiated. He now requires 6 L/min O2 via nasal cannula to maintain oxygen saturation >90%.
Which of the following is the next BEST step in management?
This patient most likely has cytokine release syndrome or sepsis, which are difficult to distinguish clinically.
Cytokine release syndrome (CRS) is a known complication of CAR T cell therapy. This syndrome is a result of the release of proinflammatory cytokines (interleukins 6 and 10 and interferon gamma) during the interaction between genetically engineered CAR T cells and target tumor cells. CRS is reported to occur in up to 50% to 100% of patients receiving CAR T therapy. CRS has many clinical manifestations ranging from minor (fever, fatigue, rash) to severe (hypotension, respiratory failure, coagulopathy, multisystem organ failure, death). Interleukin 6 (IL-6) is thought to be the main inflammatory cytokine in the pathophysiology of CRS. Elevated IL-6 levels are associated with increased vascular leakage, activation of complement, and coagulation cascade as well as myocardial dysfunction. Administration of tocilizumab (IL-6 receptor monoclonal antibody) should be considered in patients with high-grade CRS (requiring vasopressors, FiO2 > 40%).
Distinguishing CRS from other syndromes with similar presentations, such as septic shock, is challenging. Therefore, broad-spectrum antibiotics should be the first-line therapy administered to each CAR T patients with new-onset hemodynamic or respiratory instability. Delaying antibiotic treatment while awaiting the clinical benefit of tocilizumab or confirming infection results in high mortality rates. Corticosteroids are the mainstay of treatment for high-grade CAR T neurotoxicity. In this patient, somnolence is likely related to hypotension, fever, and CRS, and if improved with fluid, vasopressors, and antibiotics, treatment with corticosteroids is not indicated.
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