持續(xù)性腎臟替代治療crrtnoninfectious causes of fever in icu

1、Non-infectious causes of fever in the critical care unitMarion J. Skalweit, MD PhDCase Western Reserve University School of Medicine and the Cleveland VA Medical CenterIntroductionDefining a feverPathophysiology of feverNon-infectious causes of feverClinical vignettesMarkers of infections/rapid diag

2、nosticsConclusionsReferencesLearning objectivesState several non-infectious causes of fever in ICU patientsIdentify some rapid and specific tests that might be used to detect pathogensAppreciate that non-infectious causes of fever may coexist with infectious causes of fever DisclosuresNone that are

3、relevant to todays presentationWhat 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 an

4、d the Infectious Diseases Society of America”, Crit. Care Med., (2008) Apr;36(4):1330-49.C 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, pati

5、ents with heart, liver or kidney failure, patients on antiinflammatory or antipyretic drugsPathophysiology of feverAdaptive response evolved to help host rid self of pathogensCytokines released by monocytic cells (IL-1, IL-6 and TNF-)Bind to receptors in the pre-optic region of the anterior hypothal

6、amus which activates phospholipase A releasing tissue arachadonic acid, a substrate of the cyclo-oxygenase pathwaySome 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 t

7、he ICU” Chest (2000): 117; 855-869.Marik Chest 2000“Drug fever”Malignant hyperthermiaNeuroleptic malignant syndrome (NMS)“Drug fever” with triad of fever, rash, eosinophiliaStevens-Johnsontoxic epidermal necrolysisPatel, R. A. and Gallagher, J. C. Pharmacotherapy 2010; 30(1):57-69.Drugs may cause fe

8、ver 5 ways: interference with peripheral heat dissipation, alteration of CNS temperature regulation, evoking cellular or humoral immune response, exogenous pyrogenicity and direct damage of tissueA patient recently started on ziprasadone develops fever, rhabdomyolysis and acute renal failure CAdmit

9、6 d prior for acute decompensation of schizoaffective disorder vs mania, received haloperidol x 1 dose, contd on lithium, valproic acid, ziprasadone initiatedA patient recently started on ziprasadone develops fever, rhabdomyolysis and acute renal failure Transferred to MICU, intubated, pressors, flu

10、ids and antibiotics started, activated protein C administered for presumed sepsisLabs notable for leukocytosis and markedly elevated CPK and troponin, serum Na, K and Cr; elevated Li level and mild transaminitisD3. Ziprasadone 80mg po bid + 20mg q4 IM x 3 for agitationMICUD8. P/T/V/aFVII/NSCPK 24,00

11、0WBCs 21KD9. BromocriptineThiothixene and valproic acidD33. UTI E.coli R amp/sulb, TMP-SMX, cipro, NFTN I pip/tazo rx=ceftriaxoneMICUD22. F, stridor, sloughed tracheal mucosa, aspirationA patient recently started on ziprasadone develops fever, rhabdomyolysis and acute renal failure Patient responded

12、 to supportive care and bromocriptineFinal diagnosis: NMS and diabetes insipidusNMSNeuroleptic 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 cognit

13、ive changes such as deliriumassociated 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 ou

14、tcome.Fever, Encephalopathy, Vitals (unstable), Enzymes elevated, Rigidity of muscles Caroff, Psychiatric Annals, 1991,21:130-147. NMSGenetic association studies and polymorphisms influencing susceptibility to NMSdopamine D(2) receptorserotonin receptor,cytochrome p450 2D6. While a few candidate pol

15、ymorphisms were associated with NMS, a large controlled study is needed to attain statistical power. Kawanishi, C. Am J Pharmacogenomics. 2003;3(2):89-95Rheumatologic diseases and feverGoutVasculitisHereditary feversDrug relatedPatient with painful knees, ankles, wrists, fever and leukocystosis62 y/

16、o man with prostate cancer, APA on warfarin, h/o gout and recent drainage of a scrotal abscess and treated with oral TMP/SMXReturned to ED on POD 5 with hypotension, leukocytosis, did not complete antibiotic treatment; scrotal area is normal in appearanceAdmitted to ICU for sepsis, pan-cultured, ant

17、ibiotics, 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 leukocystosisPOD 11 polyarticular pain, prednisone initiated; oral antibiotics (tmp/smx/amox/clavESR140, CRP

18、 12POD 15 pancultured for fever, leukocytosis, IV antibiotics resumed; TEE done and is negativePOD 19 All cx negative, ESR downtrending, ID and Rheum recommend stopping all antibiotics; pt remains afebrile and is d/cd homePatient with painful knees, ankles, wrists, fever and leukocystosisPatient con

19、tinues 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 feverChurch, LD, Cook GP and McDermott MF, Nature Clinical Practice Rheumatology (2008): 4; 34-42.Malignancy and f

20、ever“Tumor fever”“Neutropenic fever”“Drug fever”A patient with MDS/AML, fever, resp distress and nodular infiltrates60 y/o male with MDS admitted for Broviac placement cytarabine and idarubicin chemotherapyDeveloped neutropenia on day 12 of hospitalization followed by diarrhea, abd pain, fever and f

21、ound to have Gram negative bacteremia (C. freundii);Develops SOB, nodular infiltrates ?septic emboli, transfer to ICUA patient with MDS/AML, fever, resp distress and nodular infiltratesA patient with MDS/AML, fever, resp distress and nodular infiltrates presumed source is Broviac which is removed on

22、 day 19; shows no growthPatient is intubated, voriconazole and then TMP/SMX are added; serum galactomannan is sent BAL is negative for bacteria, mycobacteria, fungi, P. jirovecii, virusesPost chemo BMBx still shows blastsInitially worsens with MOSF but eventually is off pressors, extubated and is se

23、nt to ward to await decision re further chemotx, complete antibioticsSerum 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

24、A patient with MDS/AML, fever, resp distress and nodular infiltratesA patient with MDS/AML, fever, resp distress and nodular infiltratesABX: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/

25、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 AN

26、TIBIOTIC 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 infiltratesD 2 Broviac D 3 idarubicin/cytarabineD11 D

27、iarrhea, F/C D12 GNR bacteremiaPip/tazo/vanco/ciproD19 Broviac removedD21 intubatedD20 BAL negative, voriconazole added; serum galactomannan sent; D22 Bactrim addedD23 negative smears BAL, pressorsD24 renal insuff D26 off pressors, extubated D27 negative galactomannanD35 resp failure, MICUD38 deathA

28、 patient with MDS/AML, fever, resp distress and nodular infiltratesNon-infectious etiologies: Acute leukemiaPulm infarcts, emboliPneumonitis without infectionUntreated infection?Galactomannan vs -1,3-D-glucanGalactomannan vs -1,3-D-glucanBlood and feverTransfusions Transfusion reactionsBlood where i

29、t doesnt belongThrombosis and feverCVA and feverMI and feverA 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 hemoptysisCT scan showed RLL infiltrate vs mass A patient 19 days post-op from wedge biopsy of right lower lobe A

30、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 rllWashings were negative for afb, cytologyNeeded 2v CABG and AVR but CT surgery service felt patient was not safe to put on CPB given th

31、e degree of hemoptysis so underwent RLL lobectomy; path showed bronchiolitis, focal organizing pneumoniaA 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. CA pati

32、ent 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 14A patient 19 days post-op from wedge biopsy of right lower lobe Dressler syndromeFever and C

33、VAFever and DVTExamples of rapid and direct pathogen specific tests that are useful for detecting pathogens that cause feverClostridium difficile antigen testHIV rapid testRapid antigen panels for respiratory virusesDFA for HSVUrine antigen for legionella and histoplasmaSerum cryptococcal antigenSer

34、um urine pneumococcal antigenSerum galactomannanB-1,3-D-glucanPCR methodsDirect PCR detection of pathogensMalhotra-Kumar, S., et al., J. Clin. Micro. (2008):46;1577-1587TIGER BIOSENSOR IBISBiomarkers of infectionProcalcitoninESR, CRP, ferritinProcalcitoninChrist-Crain M and Muller B, Eur. Respir. J

35、(2007): 30; 556-573.Christ-Crain M and Mller B, Eur. Respir. J (2007): 30; 556-573.ConclusionsNot all fever is infectious Careful clinical evaluation and chart review are imperative in determining sources of feverAlways consider non-infectious etiologies in the differential and evaluate accordingly; diagnosis of exclusion or inclusion.“A man can have as many diseases as he damn well pleases