【持续性肾脏替代治疗crrt，non-infectious causes of fever in icu课件

Non-infectious causes of fever in the critical care unit,Marion J. Skalweit, MD PhD Case Western Reserve University School of Medicine and the Cleveland VA Medical Center,Introduction,Defining a fever Pathophysiology of fever Non-infectious causes of fever Clinical vignettes Markers of infections/rapid diagnostics Conclusions References,Learning objectives,State several non-infectious causes of fever in ICU patients Identify some rapid and specific tests that might be used to detect pathogens Appreciate that non-infectious causes of fever may coexist with infectious causes of fever,Disclosures,None that are relevant to todays presentation,What is a fever?,“The definition of fever is arbitrary and depends on the purpose for which it is defined.” OGrady, N. P. et al., “Guidelines for evaluation of new fever in critically ill adult patients: 2008 update from the American College of Critical Care Medicine and the Infectious Diseases Society of America”, Crit. Care Med., (2008) Apr;36(4):1330-49. “As a broad generalization, it is reasonable in many ICUs to consider everyone with a temperature of 38.3C to be febrile and to warrant special attention.” OGrady, ibid. Exceptions to the rule: immunocompromised patients, elderly patients, patients with large abdominal wounds or burns, patients on ECMO or CRRT, patients with heart, liver or kidney failure, patients on antiinflammatory or antipyretic drugs,Pathophysiology of fever,Adaptive response evolved to help host rid self of pathogens Cytokines released by monocytic cells (IL-1, IL-6 and TNF-) Bind to receptors in the pre-optic region of the anterior hypothalamus which activates phospholipase A releasing tissue arachadonic acid, a substrate of the cyclo-oxygenase pathway Some cytokines cause direct liberation of Prostaglandin E2, a small molecule that crosses the blood brain barrier and causes the firing of warm sensitive neurons Marik, P. E. “Fever in the ICU” Chest (2000): 117; 855-869.,Marik Chest 2000,“Drug fever”,Malignant hyperthermia Neuroleptic malignant syndrome (NMS) “Drug fever” with triad of fever, rash, eosinophilia Stevens-Johnsontoxic epidermal necrolysis,Patel, R. A. and Gallagher, J. C. Pharmacotherapy 2010; 30(1):57-69.,Drugs may cause fever 5 ways: interference with peripheral heat dissipation, alteration of CNS temperature regulation, evoking cellular or humoral immune response, exogenous pyrogenicity and direct damage of tissue,A patient recently started on ziprasadone develops fever, rhabdomyolysis and acute renal failure,47 y/o male found down, somnolent, unable to follow simple commands or walk, BP 68/40, T 39.4C Admit 6 d prior for acute decompensation of schizoaffective disorder vs mania, received haloperidol x 1 dose, contd on lithium, valproic acid, ziprasadone initiated,A patient recently started on ziprasadone develops fever, rhabdomyolysis and acute renal failure,Transferred to MICU, intubated, pressors, fluids and antibiotics started, activated protein C administered for presumed sepsis Labs notable for leukocytosis and markedly elevated CPK and troponin, serum Na, K and Cr; elevated Li level and mild transaminitis,D3. Ziprasadone 80mg po bid + 20mg q4 IM x 3 for agitation,MICU,D8. P/T/V/aFVII/NS,CPK 24,000 WBCs 21K,D9. Bromocriptine,Thiothixene and valproic acid,D33. UTI E.coli R amp/sulb, TMP-SMX, cipro, NFTN I pip/tazo rx=ceftriaxone,MICU,D22. F, stridor, sloughed tracheal mucosa, aspiration,A patient recently started on ziprasadone develops fever, rhabdomyolysis and acute renal failure,Patient responded to supportive care and bromocriptine Final diagnosis: NMS and diabetes insipidus,NMS,Neuroleptic malignant syndrome (NMS) life threatening rare neurological disorder caused by adverse reaction to neuroleptic or anti-psychotic drugs. presents with muscle rigidity,fever, autonomic instability and cognitive changes such as delirium associated with elevated CPK Incidence has declined since discovery (due to proactive prescription habits ) still dangerous to patients treated with antipsychotics. generally, removal of the antipsychotic drug treatment, along with medical management, lead to a positive outcome. Fever, Encephalopathy, Vitals (unstable), Enzymes elevated, Rigidity of muscles Caroff, Psychiatric Annals, 1991,21:130-147. ,NMS,Genetic association studies and polymorphisms influencing susceptibility to NMS dopamine D(2) receptor serotonin receptor, cytochrome p450 2D6. While a few candidate polymorphisms were associated with NMS, a large controlled study is needed to attain statistical power. Kawanishi, C. Am J Pharmacogenomics. 2003;3(2):89-95,Rheumatologic diseases and fever,Gout Vasculitis Hereditary fevers Drug related,Patient with painful knees, ankles, wrists, fever and leukocystosis,62 y/o man with prostate cancer, APA on warfarin, h/o gout and recent drainage of a scrotal abscess and treated with oral TMP/SMX Returned to ED on POD 5 with hypotension, leukocytosis, did not complete antibiotic treatment; scrotal area is normal in appearance Admitted to ICU for sepsis, pan-cultured, antibiotics, vanco/zosyn; all cx are negative. Patient noted to have very high ESR and CRP values. No obvious etiology on exam. TTE negative.,Patient with painful knees, ankles, wrists, fever and leukocystosis,POD 11 polyarticular pain, prednisone initiated; oral antibiotics (tmp/smx/amox/clav ESR140, CRP 12,POD 15 pancultured for fever, leukocytosis, IV antibiotics resumed; TEE done and is negative,POD 19 All cx negative, ESR downtrending, ID and Rheum recommend stopping all antibiotics; pt remains afebrile and is d/cd home,Patient with painful knees, ankles, wrists, fever and leukocystosis,Patient continues to do well off antibiotics, tapered from steroids and is continued on his allopurinol and colchicine. Diagnosis: scrotal abscess resolved, gout flare,Autoinflammatory diseases and fever,Church, LD, Cook GP and McDermott MF, Nature Clinical Practice Rheumatology (2008): 4; 34-42.,Malignancy and fever,“Tumor fever” “Neutropenic fever” “Drug fever”,A patient with MDS/AML, fever, resp distress and nodular infiltrates,60 y/o male with MDS admitted for Broviac placement cytarabine and idarubicin chemotherapy Developed neutropenia on day 12 of hospitalization followed by diarrhea, abd pain, fever and found to have Gram negative bacteremia (C. freundii); Develops SOB, nodular infiltrates ?septic emboli, transfer to ICU,A patient with MDS/AML, fever, resp distress and nodular infiltrates,A patient with MDS/AML, fever, resp distress and nodular infiltrates,presumed source is Broviac which is removed on day 19; shows no growth Patient is intubated, voriconazole and then TMP/SMX are added; serum galactomannan is sent BAL is negative for bacteria, mycobacteria, fungi, P. jirovecii, viruses Post chemo BMBx still shows blasts Initially worsens with MOSF but eventually is off pressors, extubated and is sent to ward to await decision re further chemotx, complete antibiotics Serum galactomannan returnsnegative. On day 29, has diarrhea, oral vanco started; C. diff antigen is negative but is continued. Day 35 respiratory distress, worsening of nodular process, receives pip/tazo/vanco/acyclovir/voriconazole,A patient with MDS/AML, fever, resp distress and nodular infiltrates,A patient with MDS/AML, fever, resp distress and nodular infiltrates,ABX: Vanco (2/12-2/25, 3/9-now) Pip-tazo (2/12-2/15, 3/9-now) Voriconazole (2/21-2/28, 3/9-now) Acyclovir 400mg PO BID (2/2-now) Fluconazole 400mg PO daily (2/3-2/22; 2/28-now) Metronidazole (3/9-now) Cefepime (2/24-3/5) Bactrim (2/22-2/24) Meropenem (2/19-2/24) Gentamicin (2/19-2/22) Cipro (2/12-2/21) Imipenem (2/15-2/19),GRAM STAIN: MODERATE WBCS FEW EPITHELIAL CELLS MANY GRAM NEGATIVE RODS MODERATE GRAM POSITIVE COCCI CULTURE RESULTS: MODERATE PSEUDOMONAS AERUGINOSA ANTIBIOTIC SUSCEPTIBILITY TEST RESULTS: PSEUDOMONAS AERUGINOSA : SUSC INTP AMIKACN 4 S MCG/ML CIPROFLOXACIN =4 R MCG/ML GENTAMICIN =16 R MCG/ML IMIPENEM. 8 I CEFEPIME 8 S PIP/TAZO 32 S MCG/ML,A patient with MDS/AML, fever, resp distress and nodular infiltrates,D 2 Broviac D 3 idarubicin/ cytarabine,D11 Diarrhea, F/C D12 GNR bacteremia Pip/tazo/vanco/cipro,D19 Broviac removed,D21 intubated,D20 BAL negative, voriconazole added; serum galactomannan sent; D22 Bactrim added,D23 negative smears BAL, pressors D24 renal insuff D26 off pressors, extubated D27 negative galactomannan,D35 resp failure, MICU D38 death,A patient with MDS/AML, fever, resp distress and nodular infiltrates,Non-infectious etiologies: Acute leukemia Pulm infarcts, emboli Pneumonitis without infection Untreated infection?,Galactomannan vs -1,3-D-glucan,Galactomannan vs -1,3-D-glucan,Blood and fever,Transfusions Transfusion reactions Blood where it doesnt belong Thrombosis and fever CVA and fever MI and fever,A patient 19 days post-op from wedge biopsy of right lower lobe,79 y/o male with CAD, severe AS, a. fib on warfarin developed hemoptysis CT scan showed RLL infiltrate vs mass,A patient 19 days post-op from wedge biopsy of right lower lobe,A patient 19 days post-op from wedge biopsy of right lower lobe,Underwent bronchoscopy which showed chronic inflammation and bleeding from medial basilar segment of rll Washings were negative for afb, cytology Needed 2v CABG and AVR but CT surgery service felt patient was not safe to put on CPB given the degree of hemoptysis so underwent RLL lobectomy; path showed bronchiolitis, focal organizing pneumonia,A patient 19 days post-op from wedge biopsy of right lower lobe,POD#14 patient has a new RML infiltrate and is intubated for respiratory failure. He is afebrile and has a normal WBC count. Has a fever spike to 38.5C,A patient 19 days post-op from wedge biopsy of right lower lobe,A patient 19 days post-op from wedge biopsy of right lower lobe,Afebrile throughout post-op courseintubated for resp distress, new R infiltrate POD 14,A patient 19 days post-op from wedge biopsy of right lower lobe,Dressler syndrome Fever and CVA Fever and DVT,Examples of rapid and direct pathogen specific tests that are useful for detecting pathogens that cause fever,Clostridium difficile antigen test HIV rapid test Rapid antigen panels for respiratory viruses DFA for HSV Urine antigen for legionella and histoplasma Serum cryptococcal antigen Serum urine pneumococcal antigen Serum galactomannan B-1,3-D-glucan PCR methods,Direct PCR detection of pathogens,Malhotra-Kumar, S., et al., J. Clin. Micro. (2008):46;1577-1587,TIGER BIOSENSOR IBIS,Biomarkers of infection,Procalcitonin ESR, CRP, ferritin,Procalcitonin,Christ-Crain M and Muller B, Eur. Respir. J (2007): 30; 556-573.,Christ-Crain M and Mller B, Eur. Respir. J (2007): 30; 556-573.,Conclusions,Not all fever is infectious Careful clinical evaluation and chart review are imperative in determining sources of fever Always consider non-infectious etiologies in the differential and evaluate accordingly; diagnosis of exclusion or inclusion. “A man can have as many diseases as