Diapositiva 1

Caso clnicoSandra Milena Acevedo RuedaMD Residente de Segundo Ao Medicina Interna UNABOctubre 2012UNAB - FOSCAL

Temas a discutirTerapia biolgica: mecanismos de accin, indicaciones, efectos adversosCmo preparar a un paciente para inicio de terapia biolgicaTratamiento criptococosis menngea y efectos adversos del mismoCausas de hipokalemia y correccinCausas de hipocalcemia y correccin1Datos personalesEdad: 46 aosRaza: MestizaEstado civil: SeparadaEscolaridad: BachillerOcupacin: Ama de casaNatural y residente: GirnReligin: Catlica NPProcedente: Bucaramanga Informantes: Paciente, hija, hermana, sobrinoConfiabilidad: AceptableSeguridad social: Nueva EPS

Remitida de consulta externa deneurologa para hospitalizacin y estudios10 das, insidiosoNo fiebre, no sntomas respiratorios urinarios irritativosAntecedente de Criptococosis menngea el pasado Julio de 2012

Patolgicos

- Pancolitis ulcerativa severa activa en tratamientoDiagnosticada en 2002

Meningitis por CriptococoDiagnosticada en Julio 2012, recibi tratamiento con Anfotericina B (14 das) con buena respuesta clnicaELISA VIH Negativo hace 2 mesesActualmente en terapia de consolidacin con FluconazolAntecedentes personales

QuirrgicosHisterectoma por miomatosis uterina

AlrgicosNegativo

TxicosNiega cigarrillo o alcohol

Farmacolgicos

Fluconazol 400 mg da (D10)Pregabalina 75 mg cada 12 horas, Nimesulide 100mg cada 12 horas, Mesalazina 500 mg 9 tabletas al da,Infliximab por pancolitis ulcerativa Junio 2012 (2 dosis)

Antecedentes personales10 aosAzatioprinaPrednisolonaMesalazinaTraumticosNegativo

FamiliaresNegativo

SocioeconmicosAnimales en casa: conejos, gallinas, palomas, gato, ratones, murcilagos

Gineco-obsttricosG1P1A0 Citologa vaginal: Hace 2 aos normal

Antecedentes personalesPaciente ingresa a la institucin con su hija y sobrino

Alerta, orientada, colaboradora

TA 117/73, FC 82, FR 17, SAT 99%, FIO2 0.21Temp 36.5 grados Peso 52Kg Talla 1,55mts IMC 21,6 kg/m2Examen fsico

Examen fsico

Mucosa oral hmeda, conjuntivas plidas, esclerasanictricas, pupilas isocricasnormorreactivas a la luz, No lesiones en orofaringe, No ingurgitacin yugular,No adenopatas cervicales, No rigidez nucal

8Examen fsico

Ruidos cardacos rtmicos,No soplos ni galope S3Pulmones bien ventilados

9Examen fsico

AbdomenNo defendidoNo se palpan masas ni organomegalias

10Examen fsico

EutrficasNo edemas

11Examen fsico

Orientada en las 3 EBradipsiquiaParlisis bilateral VI parFuerza muscular conservadaNo alteracin sensitivaRomberg NegativoFondo de ojo: no fue realizado

12Revisin por sistemasNegativo

HemogramaLeucocitos 8.020, Neutrfilos: 62% Linfocitos: 24.4%Plaquetas 437.000Hb: 11.3 gr/dl Hto 34%VCM: 89, HCM 28, RDW 14.7%

Glucosa srica112mg/dL

Conclusinrea de hipodensidad frontal derecha

Glucometra 112mg dl

Diagnsticos de trabajo

DiagnsticosSndrome de HTEMeningitis Criptococosis menngea?SubtratadaResistencia a terapia farmacolgicaSndrome anmico (Normoctico, normocrmico, heterogneo)AntecedentesCriptococosis menngea tratada Julio/12Colitis ulcerativa en tto Infliximab y Mesalazina

Sndrome de HTE: Cefalea progresiva, Nauseas, vmito, papiledema, compromiso de pares craneanos y alteracin del estado de conciencia

Terapia biolgica

Terapia BiolgicaClulas vivas

Frmacos convencionales (sntesis qumica)

Artritis reumatoide

Arthritis Res 2000, 2:337341

22

CYTOKINE PATHWAYS AND JOINT INFLAMMATION IN RHEUMATOID ARTHRITIS. N Engl J Med, Vol. 344, No. 12

VariableDiana OrigenTipo molculaX- li - S. Inmunex (i) quimrico - mab Ac. MonoclonalX- o-su Huesoz (u) humanizado - cept Prot. FusinX- tu - Tumor(m/h) u-humano - ra Antag. RcX- kin Interleukinao - ratnRi tu xi mab : Anticuerpo monoclonal quimrico antitumoral-mab Humano Quimrico Humanizado-cept-raAntiTNFaAda-li-mu-mabGo-li-mu-mabInf-li-xi-mabCertol-li-zu-mabEtaner-ceptCD20Ofa-tu-mu-mabRi-tu-xi-mabOcre-li-zu-mabAtaci-ceptIL-1Anan-ki-raIL-6Tozi-li-zu-mabRANK-LDen-osu-mabLTAbata-ceptIndicaciones Terapia biolgicaArtritis reumatoideEspondilitis anquilosanteArtritis PsoriaticaEnfermedad de ChronColitis ulcerativaLinfoma Hodgkin y No HodgkinLinfoma BurkittLinfoma SNCLinfoma MALTLeucemia linfoctica crnicaGranulomatosis WegenerPnfigo vulgarPoliangitis microscpicaPurpura trombocitopnica inmuneAnemia hemoltica autoinmuneEnfermedad injerto contra husped refractariaMacroglobulinemia de WaldestronTrastornos linfoproliferativos post-transplante

Biological drug use: US perspectives on indications andMonitoring. Ann Rheum Dis 2005;64:iv18iv23Crohns disease, ankylosing spondylitis,psoriatic arthritis, and psoriasis being either approvedindications or indications under investigation for approval.Table 4 shows that although most rheumatologists can easilyprescribe TNF inhibitors in ankylosing spondylitis, psoriaticarthritis, and psoriasis25InfliximabAdultos: 5 mg/kg 0, 2, y 6 sem, seguido de 5 mg/kg cada 8 sem

Bloqueo FNTa

InfliximabTBInfecciones fngicas invasivasInfecciones virales bacterianas oportunistasLinfoma hepatoesplnico Infliximab is a chimeric monoclonal antibody that binds to human tumor necrosis factor alpha (TNF), thereby interfering with endogenous TNF activity. Elevated TNF levels have been found in involved tissues/fluids of patients with rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, plaque psoriasis, Crohns disease and ulcerative colitis. Biological activities of TNF include the induction of proinflammatory cytokines (interleukins), enhancement of leukocyte migration, activation of neutrophils and eosinophils, and the induction of acute phase reactants and tissue degrading enzymes. Animal models have shown TNF expression causes polyarthritis, and infliximab can prevent disease as well as allow diseased joints to heal.

26

InfliximabSNCGastrointestinalesHepticosMuscularesRespiratoriosMetablicosRenalesDermatolgicos CardiovascularesHematolgicosEsquelticosInfecciososEnf. autoinmunes28

AbstractCONTEXT:Tumor necrosis factor (TNF) plays an important role in host defense and tumor growth control. Therefore, anti-TNF antibody therapies may increase the risk of serious infections and malignancies.OBJECTIVE:To assess the extent to which anti-TNF antibody therapies may increase the risk of serious infections and malignancies in patients with rheumatoid arthritis by performing a meta-analysis to derive estimates of sparse harmful events occurring in randomized trials of anti-TNF therapy.DATA SOURCES:A systematic literature search of EMBASE, MEDLINE, Cochrane Library, and electronic abstract databases of the annual scientific meetings of both the European League Against Rheumatism and the American College of Rheumatology was conducted through December 2005. This search was complemented with interviews of the manufacturers of the 2 licensed anti-TNF antibodies.STUDY SELECTION:We included randomized, placebo-controlled trials of the 2 licensed anti-TNF antibodies (infliximab and adalimumab) used for 12 weeks or more in patients with rheumatoid arthritis. Nine trials met our inclusion criteria, including 3493 patients who received anti-TNF antibody treatment and 1512 patients who received placebo.DATA EXTRACTION:Data on study characteristics to assess study quality and intention-to-treat data for serious infections and malignancies were abstracted. Published information from the trials was supplemented by direct contact between principal investigators and industry sponsors.DATA SYNTHESIS:We calculated a pooled odds ratio (Mantel-Haenszel methods with a continuity correction designed for sparse data) for malignancies and serious infections (infection that requires antimicrobial therapy and/or hospitalization) in anti-TNF-treated patients vs placebo patients. We estimated effects for high and low doses separately. The pooled odds ratio for malignancy was 3.3 (95% confidence interval [CI], 1.2-9.1) and for serious infection was 2.0 (95% CI, 1.3-3.1). Malignancies were significantly more common in patients treated with higher doses compared with patients who received lower doses of anti-TNF antibodies. For patients treated with anti-TNF antibodies in the included trials, the number needed to harm was 154 (95% CI, 91-500) for 1 additional malignancy within a treatment period of 6 to 12 months. For serious infections, the number needed to harm was 59 (95% CI, 39-125) within a treatment period of 3 to 12 months.CONCLUSIONS:There is evidence of an increased risk of serious infections and a dose-dependent increased risk of malignancies in patients with rheumatoid arthritis treated with anti-TNF antibody therapy. The formal meta-analysis with pooled sparse adverse events data from randomized controlled trials serves as a tool to assess harmful drug effects.

29Curr Gastroenterol Rep (2010) 12:502506

Candidato a terapiaEsteroidesActualizar estadovacunasInmunomoduladoresBiolgicosCalcioVitamina DDEXATBInfeccionesHemogramaFuncin hepticaTPMTConsideraciones a tener en cuenta antes de iniciar terapia inmunosupresoraIt is important to inquire about childhood or previous infections for which vaccines are now available todetermine whether live vaccines are indicated. A history of varicella infection precludes a varicella vaccination, butan unknown history may require checking titers. An adult patient whose vaccination history is unknown should havetheir measles, mumps, and rubella titers determined to ascertain whether vaccination may be warranted. If a livevirus needs to be administered, then IS therapy should be delayed about 6 weeks. A nice review of this topic waspublished recently by Wasan et al.

It is important to either perform a skin survey or refer to a dermatologist to screen for skin cancer or suspicious moles before initiating IS therapy. Basal cell and squamous cell cancer are easily managed with resection, but melanomamay present in a more advanced stage with a higher potential for metastasis or recurrence. Data suggest that therisk for skin cancers of all types is higher in patients with IBD than in other patients

HIV, tuberculosis (TB), and hepatitis should all be ruled out prior to starting any IS therapy

Women should have documentation of an up-to-date Pap smear to rule out active human papilloma virus (HPV)infection or abnormal cervical cytology prior to initiating IS therapy. Two studies have suggested a higher prevalence ofabnormal Pap smears in women with IBD, and the risk appears to be associated with immunomodulator use [17,18]. If appropriate for the patients age, vaccination for HPV is warranted, and counseling regarding more frequentscreening is also important.

When the anticipated length of steroid exposure will be longer than 6 weeks, the potential for bone loss has to beconsidered. [20]. Patients should be supplemented with at least 1,000 mg of calcium and 800 IU of vitamin D daily,with consideration for further treatment with a bisphosphonate to prevent steroid-induced osteoporosis in the patientwith appropriate risk factors such as age, sex, and family history

(TPMT) thiopurine methyltransferase30Paciente InmunosuprimidoEnfermedad heptica, pulmonar cardacaVigilar/excluir neoplasia slida hematolgicaInicio de esteroidesReacciones transfusionalesEmbarazo y lactanciaPreparing the Patient for Immunosuppressive TherapyCurr Gastroenterol Rep (2010) 12:502506Consideraciones a tener en cuenta antes de iniciar terapia inmunosupresoraThe definition of immunosuppressed in this context is the use of corticosteroids at doses greater than 20 mg for longer than 2 weeks, effective doses of immunomodulators, methotrexate, or biologics, and significant protein-calorie malnutrition

If a patient already on a biologic and an IS drug then requires steroids, prophylaxis for Pneumocystis carinii pneumonia (PCP) is indicated (some would advocate that treatment with steroids and either a biologic or immunomodulator requires PCP Prophylaxis)

31Consideraciones a tener en cuenta antes de iniciar terapia inmunosupresoraVacunacin / Virus vivos atenuados Rx de trax, Mantoux, BoosterVHB, VHCHIVCMV ?Clostridium difficile ?Papiloma virus ?Enfermedades desmielinizantes neuritis pticaPreparing the Patient for Immunosuppressive TherapyCurr Gastroenterol Rep (2010) 12:502506 SCREENING FOR LATENT TUBERCULOSIS INFECTION (LTBI) PRIOR TO USE OF BIOLOGICAL AGENTS IN AUSTRALIA. April 2010 . www.rheumatology.org.auALTO RIESGOAcquired immunodeficiency syndrome (AIDS)110-1701,2Human immunodeficiency virus infection (HIV)50-1103,4Transplantation (related to immune-suppressant therapy)20-745-8Silicosis309,10Chronic renal failure requiring hemodialysis10-2511-14Carcinoma of head and neck16.015Recent TB infection (2 years)15.016,17Abnormal chest x-ray with apical fibronodular changes typical of healed TB (not granuloma)6-1918-20Tumor necrosis factor (TNF)-alpha inhibitors

MODERADO RIESGOTreatment with glucocorticoids4.923Diabetes mellitus (all types)2-3.624-27Young age when infected (4 years)

RIESGO MENORUnderweight (95 percent for diagnosis of latent TB infection [1,2]. The sensitivity for T-SPOT.TB appears to be higher than for QFT-GIT or TST (approximately 90, 80, and 80 percent, respectively) [2]. The higher sensitivity of T-SPOT.TB may be useful for evaluating individuals with immunosuppressive conditions.TST specificity is high in populations not vaccinated with BCG (97 percent). Among populations where BCG is administered, it is much lower although variable (approximately 60 percent) [2].IGRA sensitivity is diminished by HIV infection [9]. Lower CD4 counts have been associated with higher rates of indeterminate IGRA results; this is especially the case with QFT-GIT [9]. TSPOT appeared to be less affected by immunosuppression than QFT-GIT, likely because the testing procedure requires that an adequate number of peripheral blood mononuclear cells are placed in each test well, even if the overall peripheral blood lymphocyte count is low [9].For the diagnosis of active TB, IGRA sensitivity and specificity are poor, particularly in high TB incidence settings [12,13]. Specificity is poor because these populations will have high prevalence of LTBI, and the immune based tests cannot distinguish between active disease and latent infection [12]. Sensitivity is reduced because of the temporary anergy of the acute illness. Therefore, IGRAs should not be used for diagnosis of active TB.

United States guidelinesThe United States Centers for Disease Control (CDC) 2010 guidelines addresses both T-SPOT.TB and QFT-GIT [5]. The guidelines indicate that IGRAs can be used in place of (but not in addition to) TST in all situations in which CDC recommends TST as an aid in diagnosing Mycobacterium tuberculosis infection. This includes contact investigations, testing during pregnancy, and screening of health care workers and others undergoing serial evaluation for M. tuberculosis infection.Populations in which IGRAs are preferred over TST include individuals who have received BCG (either as a vaccine or for cancer therapy) and individuals from groups that historically have poor rates of return for TST reading. TST is preferred over IGRAs for testing children less than five years of age. Despite the preferences noted, use of either TST or IGRA is acceptable in these groups; each institution should evaluate the availability and benefits of IGRAs in prioritizing their use.Routine testing with both TST and IGRA isnotrecommended. However, results from both tests might be useful in the following situations:When the initial test (whichever test was used first) isnegativeand the risk for infection, progression to disease, and/or poor outcome is high (eg, HIV-infected individuals or children under five years of age who are exposed to a person with infectious TB).When the initial test ispositiveand:Additional evidence of infection would be helpful to encourage adherence to latent tuberculosis infection (LTBI) treatment (for example, in the setting of foreign-born healthcare workers (HCWs) who believe their positive TST is due to BCG).The person has a low risk of infection and progression from infection to TB disease. A positive result from the second test increases the likelihood that the test reflects infection. An alternative is to assume, without additional testing, that the initial result is a false positive or that the risk for disease does not warrant additional evaluation or treatment, regardless of test results.Repeating an IGRA or performing a TST might be useful when the initial IGRA result is indeterminate and there is a persistent reason for testing. Multiple negative results from any combination of these tests cannot exclude M. tuberculosis infection. Selection of the most suitable test or combination of tests for detection of M. tuberculosis infection should be based on the reasons and the context for testing, test availability, and cost of testing

335 mm 10 mm 15 mm

HIV Inmigrantes Sin riesgo* Contacto TB activa Condiciones alto riesgoRx anormal Usuarios drogas IV Inmunosupresin Nios < 4 aos Trabajadores salud Residentes crceles, asilos, hospitales

*stas personas no deberan ser estudiadas en ausenciade indicacinTB Latente

SCREENING FOR LATENT TUBERCULOSIS INFECTION (LTBI) PRIOR TO USE OF BIOLOGICAL AGENTS IN AUSTRALIA. April 2010 . www.rheumatology.org.au

+ - + - Tumour Necrosis Factor- (TNF-)antagonists and Tuberculosis Workshop. August 2007Irish Society for RheumatologyREPEAT TST INTERPRETATIONThe interpretation of serial or repeated TST depends on the context [15]. (See'Repeat and serial testing'above.)BoosterresponseBoosterresponse refers to a positive TST performed one to four weeks after an initial negative TST in the absence of exposure (such as pre-employment screening of healthcare workers). Theboosterresponse is less specific for diagnosis of LTBI than the initial TST since theboosterresponse may be caused by prior BCG vaccination, sensitization to nontuberculous mycobacteria, or remote TB infection. Therefore, the risk of developing active TB among individuals with aboosterresponse is lower than the risk of developing active TB among individuals with an initial positive TST [8,28].ConversionSkin test conversion refers to one of the following:A positive TST up to eight weeks after an initial negative TST in the setting of recent exposure. (See'Risk of new infection'above.)A positive TST detected as part of serial testing with ongoing risk of exposure (such as healthcare workers), in the setting of baseline negative TST.The risk of developing active TB is much higher in the setting of skin test conversion thanboosterresponse.DefinitionFor both boosting and conversion, the second TST is defined as positive if the induration measures 10 mm or greater and has increased by 6 mm since the previous test [15]. This definition is used because test variability may cause increases in induration of up to 6 mm.Criteria for boosting and conversion of 12 mm, 15 mm, or even 18 mm have been suggested; these may be more specific but are much less sensitive. Individuals with reactions of 10 mm should be referred for medical evaluation to exclude active TB prior to initiation of LTBI therapy. The reaction should be documented, and no further tuberculin testing should be done.INTERFERON GAMMA RELEASE ASSAYSIssues related to interferon-gamma release assays (IGRAs) and their use are

35Hepatitis BLet the fog be lifted: screening for hepatitis B virus beforebiological therapy . Ann Rheum Dis October 2011 Vol 70 No 10

Hepatitis B lab nomenclatureHbsAg Hepatitis B surface antigen is a marker of infectivity in acute or chronic HBV infection.HbsAb Antibody to surface antigen is a marker of immunity and most often found in isolation in HBVimmunised patients. It is also found in conjunction with HBcAb in resolved infection and rarely inisolation in naturally infected individuals.HbcAb Antibody to core antigen is a marker of acute (IgM), chronic (IgG) or resolved HBV infection. Inthe absence of HBsAg, HBcAb is generally found in conjunction with HBsAb and is a markerof resolved infection. In isolation it may represent a false positive test or indicate occult HBVinfection.HbeAg HB e antigen is a marker of a high degree of HBV infectivity, correlating with a high level of HBVreplication. HB e antigen is absent in patients with core and pre-core mutants.HbeAb Antibody to hepatitis B e antigen may be present in infected or immune individuals. In personswith chronic HBV, the presence of HBeAb suggests a low level of infectivity.HBV DNA HBV DNA is a direct marker of HBV replication and correlates with disease activity. In blood it isused to monitor treatment. HBV may be detected in the absence of HBsAg with or without anti-HBc and when present represents active HBV infectionHBV, hepatitis B virus; IgG, immunoglobulin G; IgM, immunoglobulin M.36NeurologaHTE secundaria a criptococosis menngea (reactivacin?)Se solicita valoracin por medicina interna

Medicina InternaSSN 0.9% a 60 cc/hDAD 5% 20 cc/hAlizapride amp x 50mg, 1 amp ev c/8 horasDexametasona amp x 8mg, 1 amp ev c/8 horasAcetaminofen tab x 500mg, 1 tab vo c/6 horasDipirona amp x 2,5gr, 1 amp c/6 horas segn dolorPregabalina cap x 75 mg, 1 capsula vo c/12 horasHaloperidol frasco, 2 gotas (6 am-2 pm) y 4 gotas 10 pmFluconazol tab x 200mg , 4 tabs vo dia HBPM amp x 40mg , 1 amp sc diaOmeprazol cap x 20mg , 1 cap c/12 horasNimesulide tab x 100mg, 1 tab c/12 horasValoracin por infectologa

MICROBIOLOGA

Examen en fresco Muestra LCRColoracin de GRAMReaccin Leucocitaria 1-5 x campo 100xNo se observan bacterias

CULTIVOReporte final Negativo las 72 horas de incubacin

CRIPTOCOCO, Exmen Directo (Tinta china) POSITIVO

Antgeno para Criptococcus neoformans prueba Latex 1:16

BaciloscopiaResultado (-) No se encuentran BAAR en cien campos microscpicos observados, ni en diez minutos de observacin39InfectologaAnfotericina B amp x 50 mg, diluir 50mg en 500cc de DAD 5% para pasar en 4 horas (CVC)Flucitosina tab x 500 mg, tomar 3 tab VO cada 6 horas 14 dasSS/ Susceptiblidad para antimicticos en el cultivo de LCR para hongos, antifungigrama, BUN, Creatinina, Sodio, Potasio, CloroSS K, BUN, Creatinina cada 72 horasSS CH 2 veces por semana

Creat 0.56 BUN 14.8 Sodio 138.5 Potasio 3.1 Cloro 99.8Magnesio 1.62Calcio 6,3 (6,9)Albumina 3,3

EKG

VIH negativos

Induccin: AnfoB 0.7-1 mg/kg/d (ms flucitosina 100 mg/kg/d) 2 sem (bajo riesgo)

4 sem (sin complicacin neurolgica, inmunosupresin, comorbilidad, cultivo LCR negativo 2 sem)

Tto Criptococosis menngeaInduccin: 0.7-1 mg/kg/day (plus flucytosine 100 mg/kg/day) for 2 weeks (low-risk patients), 4 weeks (non-low-risk, but without neurologic complication, immunosuppression, underlying disease, and negative CSF culture at 2 weeks), >6 weeks (neurologic complication or patients intolerant of flucytosine) Follow with azole consolidation/maintenance treatment43Tto Criptococosis menngeaVIH negativos

>6 sem (complicacin neurolgica intolerancia a la flucitosina)

Seguido de consolidacin con azoles/tratamiento de mantenimiento

Induccin: 0.7-1 mg/kg/day (plus flucytosine 100 mg/kg/day) for 2 weeks (low-risk patients), 4 weeks (non-low-risk, but without neurologic complication, immunosuppression, underlying disease, and negative CSF culture at 2 weeks), >6 weeks (neurologic complication or patients intolerant of flucytosine) Follow with azole consolidation/maintenance treatment44Anfotericina BAdultos: 0.3-1.5 mg/kg/d; 1-1.5 mg/kg en 4-6 horas cada da por medio

Unin al ergosterol - permeabilidad membrana

Estimulacin de macrfagos dependiente reacciones de oxidacin (Lyman, 1992)

Efectos Adversos Anfotericina B

Cardiovasculares: HipotensinSNC: Fiebre, cefalea, malestar, delirium, aracnoiditisMetablicos: Hipomagnesemia, HipokalemiaHematolgicos: Trombocitopenia, Anemia, LeucocitosisNeuromusculares: Dolor artcularGastrointestinales: Vmito, nusea, diarreaRenales y GU: Acidosis tubular renal, retencin U

Binds to ergosterol altering cell membrane permeability in susceptible fungi and causing leakage of cell components with subsequent cell death. Proposed mechanism suggests that amphotericin causes an oxidation-dependent stimulation of macrophages (Lyman, 1992)

>10%:Cardiovascular: Hypotension, tachypneaCentral nervous system: Fever, chills, headache (less frequent with I.T.), malaiseEndocrine & metabolic: Hypokalemia, hypomagnesemiaGastrointestinal: Anorexia, nausea (less frequent with I.T.), vomiting (less frequent with I.T.), diarrhea, heartburn, cramping epigastric painHematologic: Normochromic-normocytic anemiaLocal: Pain at injection site with or without phlebitis or thrombophlebitis (incidence may increase with peripheral infusion of admixtures)Neuromuscular & skeletal: Generalized pain, including muscle and joint pains (less frequent with I.T.)Renal: Decreased renal function and renal function abnormalities including azotemia, renal tubular acidosis, nephrocalcinosis (>0.1 mg/mL)1% to 10%:Cardiovascular: Hypertension, flushingCentral nervous system: Delirium, arachnoiditis, pain along lumbar nerves (especially I.T. therapy)Genitourinary: Urinary retentionHematologic: LeukocytosisNeuromuscular & skeletal: Paresthesia (especially with I.T. therapy)20 mEq al da Na+ >100 mEq al da (Si Na+ 100 mEq per day)

Hipertensin arterialRenina en plasmaTA normalHCO3Mayo Clinic Internal Medicine Board Review. Eight Edition. Mayo Foundation for Medical Education and Research. 2008

alteraciones ECG tales como aplanamiento e inversin de las ondas T,onda U prominente, descensos del ST, prolongacin del QT y PR. Todo ello predisponea latidos ectpicos aurculo-ventriculares y se potencia la toxicidad digitlica,pudiendo producirse arritmias mortales.

Por falta de aporte

Anorexia nerviosa. Alcoholismo. LEV libre de potasio

Por redistribucin (extracelular intracelular)

Alcalosis Aporte de insulina Catecolaminas en situaciones de estrs Betadrenrgicos. Hipotermia Parlisis peridica hipokalmica tirotxica Tto anemia megaloblstica con B12 y cido flico.

Por prdidas extrarrenales (K + en orina < 20 mEq/l)

Si acidosis metablica diarrea, laxantes, fstulas.

Si alcalosis metablica aspiracin nasogstrica, vmitos, adenoma velloso de colon

Por prdidas renales (K + en orina > 20mEq/l)

a) Si acidosis metablica, calcular el anin GAP [Na-( Cl + CO3H)]Normal (10-14) acidosis tubular renal.Alto cetoacidosis diabtica.

b) Si alcalosis metablicaTA elevada hiperaldosteronismo, HTA maligna, estenosisarteria renal, corticoides, Sind. Cushing.TA normal diurticos, sndrome de Bartter

47Prdidas renales K+Renina plasmatica elevada HT maligna Enfermedad Renovascular Tumor secretor de reninaAltaHiperaldosteronismo Hiperplasia Bilateral

Hipertensin arterialRenina en plasma

Renina plasmatica bajaBaja Ingesta de mineralocorticoides Hiperplasia congenita Sindrome CushingTA normalHCO3

Bajo HCO3Acidosis tubularrenalAlto HCO310 mEq al da S. Bartter Diureticos Deficit MgAldosterona

Mayo Clinic Internal Medicine Board Review. Eight Edition. Mayo Foundation for Medical Education and Research. 2008

Potassium is predominantly an intracellular cation. Total body potassiumis approximately equal to 4,200 mEq, with only 60 mEq in thetotal volume of extracellular fluid. Gastric fluid contains 5 to 10 mEqof potassium/L and diarrheal fluid, 10 to 100 mEq/L. The intracellularbalance of potassium is regulated by endogenous factors suchas acidemia, sodium, adenosine triphosphatase, insulin, catecholamines,and aldosterone. The extracellular balance is regulated primarily bypotassium excretion, which is regulated by urinary flow rate, aldosterone,vasopressin, and sodium delivery to the distal tubule48Hipokalemia Central PerifricaMedicin cada 4 horas10meq/hPrdidas renales GIT: 10-20 meq/hHipokalemia amenaza la vida: mx. 40meq/h

Efficacy and safety of potassium infusion therapy in hypokalemic critically ill patients.Hamill RJ, Robinson LM, Wexler HR, Moote CCrit Care Med. 1991;19(5):694.1000 mL: se sugiere un mximo de 60 meq de K

100-200 mL por vena perifrica: se sugiere 10 meq de K

100 mL va central central: se sugiere 40 meq de K

Dficit3-3,5 Leve 5%3-2,5 Moderado 10%2,5-2 Severo 15%2 Muy severo 20%Potassium : Vegetables SpinachTomatoesBroccoliWinter squashBeetsCarrotsCauliflowerPotatoes FruitsBananasCantaloupeKiwisOrangesMangos MeatsGround beefSteakPorkVealLambDried fruits (dates, prunes)Nuts Avocados Bran cereals Wheat germ Lima beansHighest content: Dried figs Molasses Seaweed496,98,28,88,78,48,68,7Kelley's Textbook of Internal Medicine 4th edition ,2000. Lippincott Williams & Wilkins PublishersHipocalcemiaExamen fsicoCalcio ionizadoFosforo, magnesio25-Vitamina DPTH intactaPte crticamente enfermoAlcalosis respiratoria SepsisPancreatitisQuemaduras extensas y severas RabdomiolisisSx Lisis tumoralTratar causa subyacente y considerar Ca IV en sintomticosCalcio corregido = Calcio srico medido +0.8 (4.0 albumina srica)AltaCreatinina normal Fosforo normal altoAlbumina bajaHipoalbuminemia(pseudohipocalcemia)Creatinina alta Fosforo N altoMg normalEnfermedad renal pseudo-hipoparatiroidismoCreatinina normal Fosforo N o bajoMg normalVitD, 25 hidroxivit DBajaDeficit Vitamina DMagnesio normalHipoparatiroidismoMagnesio bajoDeficit MgBajaCreatinina normal Fosforo bajo normalMg normalNormalFsforo 2,8PTH 6,7151Hipocalcemia Gluconato de calcio (10% - 10mL, 94mg Ca elemental)Inicio: 100-200mg Ca elementalInfusin: 0,5 2 mg k hora

Goldmans Cecil Medicine. 25 . Chapter 253. Edition, Elsevier, Inc. 201252Medicina Interna

Mltiples picos febriles cuantificados por lo que se decide realizacin dehemocultivos y continuar igual manejo

HEMOCULTIVO 1 MSDNegativo a los 5 das de incubacin

HEMOCULTIVO 2 MSDNegativo a los 5 das de incubacin

HEMOCULTIVO 3 MSDNegativo a los 5 das de incubacin

Infectologa

Criptococosis menngea en esquema de primera lnea Da 14 de anfoB y flucitosina Persisten picos febriles Mejora de parmetros del LCRCultivos negativos para hongos

Fiebre asociada a anfoB? Cambiar a Fluconazol 800mg IV al da

Resuelve la fiebreInfectologa

Criptococosis menngeaProbable resistencia a Fluconazol pues huborecada mientras lo estaba tomando

SUSPENDER FluconazolREINICIAR AnfoB Luego continuar con Voriconazol

Reinicia fiebreSi fiebre no relacionada con paso de AnfoB, realizar hemocultivosPaciente con criptocococis meningea quien presenta nueva recaida de su enfermedad posterior al inicio con fluconazol por lo que se considera que existe la alta probabilidad de resistencia al fluconazol, indicando nuevo ciclo de tratamiento con anfotrecina B y continuar posteirorment con voriconazol ya que la resistencia no es de clase de grupo. Solicito igualmente estudios para descartar otras fuentes de infecciones como el cateter o bacteremia primaria. Se realizan nuevamente estudios de liquido cefalorraquideo y se solicita concepto a neurologia sobre el uso de acetazolamida con el fin de disminuir la presion intracerebral.

55

Glucometra 93mg/dLParaclnicos

MICROBIOLOGAFROTIS/GRAMMuestra LCRColoracin GRAM Reaccin leucocitaria 0-1 leucos x campo No se observan bacterias

BACILOSCOPIANo se observan BAAR

Criptococo, Prueba de LatexAntgeno para Criptococo Neoformans prueba LatexEstudio semicuantitativo 1: 16Infectologa

PCR 223.09Hemocultivo perifrico (1/10/12): (2/2) Positivo para BGNUroanlisis Normal

Suspender AnfoB y retirar CVCIniciar VoriconazolIniciar Piperazilina tazobactam

Infectologa Bacteremia asoc. CVCE. coli BLEE negativo Resistente a pip/taz

Suspender pip/tazIniciar Ertapenem 1gr IV cada 24 horas 10 dasContinuar Voriconazol

CVC 16:08 horasMSD 17: 38 horasMSI 18:58 horaspor menor dao colateral que cefaloporinas de tercera generacion se decide manejo con ertapneme 1gr IV cada 24 horas 10 dias59Presenta intolerancia a la voEdema miembros inferioresPersiste fiebre, taquicardiaDolor en hipocondrio derecho

Eco dupplex miembros inferiores (Neg)

Se solicita TAC de Abdomen

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Neumona nosocomial

Suspender ErtapenemIniciar Meropenem

Fiebre persistenteLinezolidReiniciar AnfotericinaB

Paciente con criptococisis meningea en recaida tratada con anfoB (34d) y actulamente con voriconazol, evolucion torpida con fiebre presistente y aparicion de foco pulmonar (neumonia, nodulos, derrame pleural derecho) qu ebien podrian ser por criptococo o por otro oportunista (TBC?), o neumonia nosocomial (P. aeruginosa, S. aureus, Enterobacterias), se esperaria que el cubirmianto con meropenem resolviera la neumonia nosocomial por gramnegativos pero persiste febril, hemocultivos negativos, decido adicionar linezolid para SAMR, no inuicio vancomicina pues tambien voy a reiniciar anfotericina B y el riesgo de neftrotoxicidad seria alto.Hoy pendiente nueva PL, ademas debe studiarse el derame pleural (que se ve claramente en la RX y la TAC, derecho).Pasar nuevo CVC para re`posicion de potasio y adicionar anfoB ante sospecha de recidiva de la cirptocoosis con oco pulmonar.

65Deposiciones diarreicasNo sangreNo moco

Coprocultivo, coproparasitoscpicoNegativos

SueroGlucosa 83mg/dLProt totales 4.1 gLDH 191 U/l

MICROBIOLOGIAMuestra LIQUIDO PLEURAL

CULTIVO PARA HONGOSKOH No se observan estructuras micticas

ADA , TEST 10.20 U/L a 37cValor compatible con TBC:LCR: >5.0 U/L a 37cLiquido pleural: > 32 U/L a 37cLquido pericrdico: >96 U/L a 37cLquido peritoneal: >36 U/L a 37c

Lavado bronquialGRAMMas de 10 Leu x campo 10xMenos de 10 cel epit por campoMas de 25 PMN por campo 10xCocos gram positivos Moderada cantidadPseudomicelios Abundante cantidadBlastoconidias Abundante cantidadCULTIVO Cndida famata 2000 UFCMuestra LAVADO BRONQUIALCultivo para mycobacteriasPneumocystis jiroveciiNegativosINMUNOLOGA

HIV 1+2, PRUEBA PRESUNTIVALectura del paciente 0,165Interpretacin: NO REACTIVOPersiste fiebre

Bx heptica guiada por eco (histoqumica, coloracin para hongos y micobacterias)

Quantifern (test de liberacin de interfern)

Plan

Suspender linezolid y meropenem

Iniciar isoniazida, rifampicina, pirazinamida, ethambutol tab x 75 + 150 + 400 + 275mg

Dar 3 y 1/2 tableta al da

Se llena ficha de notificacin obligatoria

Luego de 4 das sin fiebre, sta reaparece. Persisten deposiciones diarreicas (blandas), aumenta derrame pleural.

Persiste hipokalemia, hipoalbuminemia, persiste anemia que requiri transfusin y persiste hipocalcemia

Gracias!