Azienda Sanitaria Locale di Chieri, Carmagnola, Moncalieri e Nichelino Utilizzo della PCT in terapia intensiva Gilberto Fiore, MD Rianimazione e Terapia Intensiva Ospedale Santa Croce A.S.L. TO5 Moncalieri Savona, 15 ottobre 2009
Spectrum of disease Temp > 38 or < 36 HR > 90 bpm RR > 20 or PaCO2 < 32 SIRS WBC > 12000, < 4000 or > 10% bands Sepsis Severe sepsis Septic shock
Spectrum of disease SIRS SIRS+suspected or proven infection Positive culture White cells in sterile body fluid Perforated viscus CXR infiltrate+purulent sputum Typical syndrome (cholangitis etc) Sepsis Severe sepsis Septic shock
Spectrum of disease SIRS Sepsis Sepsis with organ dysfunction Oliguria Hypoxemia Thombocytopenia Metabolic acidosis Hypotension despite fluids Acute altered mental status Severe sepsis Septic shock
Spectrum of disease SIRS Severe sepsis+ hypotension despite adequate fluid resuscitation Vasoactive drugs required Sepsis Severe sepsis Septic shock
Crit Care Med 2004 Vol. 32, N. 3, 858-871
Categories Initial resuscitation Diagnosis Antibiotic Therapy Source control Fluid therapy Vasopressors Inotropic therapy Steroids rhapc Blood product admin. MV of ALI/ARDS Sedation, Analgesia and neuromuscolar blockade Glucose control Renal replacement Bicarbonate therapy Deep vein thombosis proph. Stress ulcer proph. Limitation of support
Initial Resuscitation 1. The resuscitation of a patient in severe sepsis or sepsis-induced induced tissue hypoperfusion (hypotension or lactic acidosis) should begin as soon as the syndrome is recognized and should not be delayed pending ICU admission. During the first 6 hours of resuscitation, the goals of initial resuscitation of sepsis-induced induced hypoperfusion should include all of the following as one part of a treatment protocol. Grade B
Initial Resuscitation Central venous pressure: 8 128 mm Hg Mean arterial pressure 65 mm Hg Urine output 0.5 ml kg -1 /hr -1 Central venous (superior vena cava) or mixed venous oxygen saturation 70% Grade B
Initial Resuscitation 2. During the first 6 hrs of resuscitation of severe sepsis or septic shock, if central venous oxygen saturation or mixed venous oxygen saturation of 70% is not achieved with fluid resuscitation to a central venous pressure of 8 128 mm Hg, then transfuse packed red blood cells to achieve a hematocrit of 30% and/or administer a dobutamine infusion (up to a maximum of 20 μg/kg -1 /min -1 ) to achieve this goal. Grade B
Suplemental oxygen ± endotracheal intubation and mecanical ventilation Central venous and arterial catheterization Sedation, paralysis (if intubated) or both 8-12 mmhg CVP < 8 mmhg Cristalloid Colloid MAP < 65 mmhg > 90 mmhg Vasoactive agents > 65 and < 90 mmhg ScvO2 < 70 mmhg Transfusion of red cells unit hematocrit > 30% < 70% No Goals achieved Yes Inotropic agents >70% Hospital admission Rivers NEJM 11-2001
Diagnosis 1. Appropriate cultures should always be obtained before antimicrobial therapy is initiated. To optimize identification of causative organisms, at least two blood cultures should be obtained with at least one drawn percutaneously and one drawn through each vascular access device unless the device was recently (<48 hrs) inserted. Grade D
Antibiotic Therapy 1. Intravenous antibiotic therapy should be started within the first hour of recognition of severe sepsis, after appropriate cultures have been obtained. Grade E
Antibiotic Therapy 3. The antimicrobial regimen should always be reassessed after 48 72 hrs on the basis of microbiological and clinical data with the aim of using a narrow-spectrum antibiotic to prevent the development of resistance, to reduce toxicity, and to reduce costs. Grade E
Source Control 3. When a focus of infection amenable to source control has been identified, source control measures should be instituted as soon as possible following initial resuscitation. Grade E
Fluid Therapy 1. Fluid resuscitation may consist of natural or artificial colloids or cyrstalloids. There is no evidence- based support for one type of fluid over another. Grade C
Fluid Therapy 2. Fluid challenge in patients with suspected hypovolemia (suspected inadequate arterial circulation) may be given at a rate of 500 1000 ml of crystalloids or 300 500 ml of colloids over 30 mins and repeated based on response (increase in blood pressure and urine output) and tolerance (evidence of intravascular volume overload). Grade E
Vasopressors 2. Either norepinephrine or dopamine (through a central catheter as soon as available) is the first-choice vasopressor agent to correct hypotension in septic shock. Grade D
Vasopressors 3. Low-dose dopamine should not be used for renal protection as part of the treatment of severe sepsis. Grade B
Vasopressors 5. Vasopressin use may be considered in patients with refractory shock despite adequate fluid resuscitation and high- dose conventional vasopressors. Pending the outcome of ongoing trials, it is not recommended as a replacement for norepinephrine or dopamine as a first-line agent. If used in adults, it should be administered at infusion rates of 0.01 0.04 0.04 units/min. It may decrease stroke volume. Grade E
Steroids 1. Intravenous corticosteroids (hydrocortisone 200 300 mg/day, for 7 days in three or four divided doses or by continuous infusion) are recommended in patients with septic shock who, despite adequate fluid replacement require vasopressor therapy to maintain adequate blood pressure. Grade C
Steroids 1a. Some experts would use a 250-μg ACTH stimulation test to identify responders (>9 μg/dl increase in cortisol 30 60 mins post-acth administration) and discontinue therapy in these patients. Clinicians should not wait for ACTH stimulation results to administer corticosteroids. Grade E
Steroids 1b. Some experts would decrease dosage of steroids after resolution of septic shock. Grade E 1c. Some experts would consider tapering the dose of corticosteroids at the end of therapy. Grade E 1d. Some experts would add fludrocortisone (50 μg g orally four times per day) to this regimen. Grade E
Steroids 1. Doses of corticosteroids >300 mg hydrocortisone daily should not be used in severe sepsis or septic shock for the purpose of treating septic shock. Grade A
Recombinant Human Activated Protein C (rhapc) 1. rhapc is recommended in patients at high risk of death (APACHE II 25, sepsis-induced induced multiple organ failure, septic shock, or sepsis-induced induced acute respiratory distress syndrome [ARDS]) and with no absolute contraindication related to bleeding risk or relative contraindication that outweighs the potential benefit of rhapc. Grade B
Blood Product administration 1. Red blood cells (target 7.0 9.0 g/dl). Grade B 2. Erithropoietin is not recommended in sepsis Grade B 3. Routine FFP is not recommended (only for surgical procedures or presence of bleeding) Grade E 4. Antithrombin is not recommended. Grade B
Blood Product administration 5. In patients with severe sepsis, platelets should be administered when counts are <5000/mm 3 (5 10 9 /L) regardless of apparent bleeding. Platelet transfusion may be considered when counts are 5000 30,000/mm 3 (5 30 10 9 /L) and there is a significant risk of bleeding. Higher platelet counts ( 50,000/mm( 3 [50 10 9 /L]) are typically required for surgery or invasive procedures. Grade E
Mechanical Ventilation of Sepsis- Induced ALI/ARDS 1. High tidal volumes that are coupled with high plateau pressures should be avoided in ALI/ARDS. Clinicians should use as a starting point a reduction in tidal volumes over 1 21 2 hrs to a low tidal volume (6 ml/kg predicted body weight) as a goal in conjunction with the goal of maintaining end-inspiratory plateau pressures <30 cm H 2 O. Grade B
Mechanical Ventilation of Sepsis- Induced ALI/ARDS 2. Hypercapnia. Grade C 3. PEEP. Grade E 4. Prone positioning. Grade E
Mechanical Ventilation of Sepsis- Induced ALI/ARDS 5. Unless contraindicated, mechanically ventilated patients should be maintained semirecumbent, with the head of the bed raised to 45 to prevent the development of ventilator-associated associated pneumonia. Grade C
Mechanical Ventilation of Sepsis- Induced ALI/ARDS Weaning Protocol & Spontaneous Breathing Trials
Sedation, Analgesia, and Neuromuscular Blockade in Sepsis 1. Protocols should be used when sedation of critically ill mechanically ventilated patients is required. The protocol should include the use of a sedation goal, measured by a standardized subjective sedation scale. Grade B
Sedation, Analgesia, and Neuromuscular Blockade in Sepsis 2. Either intermittent bolus sedation or continuous infusion sedation to predetermined end points (e.g., sedation scales) with daily interruption/lightening or continuous infusion sedation with awakening and retitration, if necessary, are recommended methods for sedation administration. Grade B
Glucose Control 1. Following initial stabilization of patients with severe sepsis, maintain blood glucose <150 mg/dl (8.3 mmol/l). Studies supporting the role of glycemic control have used continuous infusion of insulin and glucose. With this protocol, glucose should be monitored frequently after initiation of the protocol (every 30 60 mins) and on a regular basis (every 4 hrs) once the blood glucose concentration has stabilized. Grade D
Renal Replacement Continuous renal replacement therapies and intermittent hemodialysis are equivalent in patients with severe sepsis and acute renal failure Grade 2B Continuous therapies facilitate management of fluid balance in haemodynamically unstable septic patients Grade 2B
Bicarbonate Therapy 1. Bicarbonate therapy for the purpose of improving hemodynamics or reducing vasopressor requirements is not recommended for treatment of hypoperfusion-induced induced lactic acidemia with ph 7.15. The effect of bicarbonate administration on hemodynamics and vasopressor requirement at lower ph as well as the effect on clinical outcome at any ph has not been studied. Grade C
Prophylaxis 1. Deep Vein Thrombosis. a. heparin: Grade 1A b. LMWH: Grade 1A c. mechanical prophylactic device: Grade 1A 2. Stress Ulcers. a. H2 blockers: Grade 1A b. proton pomp inhibitor: Grade 1B 3. Selective Digestive Tract Decontamination (SDD).
Consideration for Limitation of Support 1. Advance care planning, including the communication of likely outcomes and realistic goals of treatment, should be discussed with patients and families. Decisions for less aggressive support or withdrawal of support may be in the patient s s best interest. Grade E
Other Therapies in pediatric patients Steroids: recommended for children with catecholamine resistance and suspected or proven adrenal insufficiency. Activated protein C not studied adequately in children yet. GM-CSF shown to be of benefit in neonates with sepsis and neutropenia. ECMO may be considered in children with refractory shock or respiratory failure.
PCT Application in Diagnostics Is the best infection and sepsis-marker available today, PCT reacts sensitive and specific to bacterial infections and sepsis Is the best marker to differentiate between bacterial and sterile inflammation reactions Correlates closely with the severity of the inflammatory response Differentiates between a bacterial and viral infection
Clinical Utility of PCT in the ICU Is useful for the diagnosis and monitoring of therapy of bacterial infections and sepsis Recognizes early a beginning infection in patients with increased risks (major surgery, poly-traumatized or immunosuppressed patients, long-stay or ventilated patients) Allows to check on the successful surgical revision of focus of infection
How to interpret PCT-values Normal values: PCT < 0,05 ng/ml when measured with a sensitive PCT-Assay (PCT sensitive KRYPTOR PCT sensitive LIA) PCT < 0,3 ng/ml when measured in a classical PCT assays (PCT LIA) Exception: Neonates <3 days of age PCT < 0,5 ng/ml Severe bacterial infection or sepsis is unlikely, localized infection possible PCT 0,5-2 ng/ml Moderate systemic inflammation reaction (SIRS), infection possible, induction also through trauma, surgery, cardiogenic shock PCT 2 10 ng/ml Severe systemic inflammation reaction (SIRS), most likely through infection/sepsis, with or without organ dysfunction (MODS) PCT > 10 ng/ml Severe systemic inflammation reaction (SIRS), in most cases entirely due to a severe bacterial sepsis or septic shock
30 25 28,4 ng/ml (110 1.1) PROCALCITONINA Procalcitonin ng/ml 20 15 10 9,1 ng/ml (26,9 0.4) 5 1,9 ng/ml (9 0,1) < 0,1 ng/ml 0 Documented Severe sepsis/ septic shock Severe infections Infection excluded No infection
PROCALCITONINA 25 Procalcitonin ng/ml 20 15 10 5 Vivi Deceduti 0 Sepsi severa /shock Sepsi Colonizzazione settico
Caso clinico 1
C.F. 69 aa Pz ricoverato in medicina con diagnosi di polmonite medioascellare dx in quadro di fibrotorace postattinico. APR: Cardiopatia Ipertensiva BPCO severa in O 2 terapia domiciliare Ca bronchiale a grandi cellule parailare dx infiltrante trattato con radioterapia, attualmente in fase di remissione S. depressiva in trattamento polifarmacologico IRC lieve Ulcera peptica Diabete tipo II insulinotrattato
Terapia domiciliare Insulina pronta 8 UI + 17 UI + 12 UI Insulina lenta 6 UI Broncodilatatori inalatori Prednisone 12,5 mg / die Omeprazolo 20 mg /die Allopurinolo 300 mg/die Canrenone 100 mg/die Nortriptilina 10 mg/die Alprazolam 0,5 mg/die Dotiepina 75 mg/die
III giornata GCS = 2 + 4 + 1 Dispnea, tachipnea, FR 35/m PA 140/ 70 con DA 15 y/kg/m Oligo-anuria T = 39.8 Ematochimici: Wbc: 19.200 N%: 93.5 PCR: 54.8 Procalcit. 62.6 ph 7.187 pco 2 87.7 po 2 79.6 HCO 3 32.5 BE 2.0 S a O 2 92.7 P a O 2 / F i O 2 EGA 79 Reservoir 12 lit/m Creat: 2.4 Az: 191 Glicemia: 210
Ipotesi dgn:shock settico in polmonite dx Trasferimento in ICU IOT e VAM a bassi Vt ATB terapia largo spettro EGDT secondo Rivers Piperacillina/tazobactam 16 g/die Levofloxacina 500 mg x 2 Fluconazolo 400 mg /die Noradrenalina Terapia cortisonica sec. Annane Controllo intensivo glicemia (90 110 mg/dl)
Esegue: Ecocardio: Vsx lievemente ipertrofico ed ipercinetico. V dx ed atri non dilatati. Minima falda di versamento pericardico RX torace: Addensamento polmonare medioascellare dx invariato. TC torace: Atelettasia completa del lobo superiore dx con broncogramma aereo da ostruzione completa del bronco tributario. Limitata falda di versamento pleurico bilaterale. Fibrotorace post attinico Colturali: Broncoscopia con BAL Emocolture Ag urinari pneumococco e legionella pneumofila
IV giornata Quadro clinico grave ma stazionario ANTIBIOGRAMMA PCR 45.3 (=) Procalcitonina: 63.87 (=) Nel tardo pomeriggio: COLTURALE BAL: Pseudomonas aeruginosa MDR 10 6 UFC Terapia antibiotica: Amikacina 1 g x 1 Cefepime 2 g x 3 Amikacina Aztreonam Cefepime Ceftazidim Ciprofloxa Imipenem Pip/Taz Gentamicina Meropenem S R I R R R R R R
Dalla V giornata Parametri infiammatori 100 90 80 70 60 50 40 30 20 10 0 N% Tracheostomia secondo Fantoni Miglioramento degli scambi respiratori Procalcitonina (ng/ml) Risoluzione del focolaio broncopneumonico PCR (mg/dl) WBC (n x 10 3 ) Sospensione del supporto aminico Ripristino della funzione renale III IV V VI VII VIII Giornata degenza
Caso clinico 2
R.D. 81 aa BPCO Vasculopatia cerebrale Iperuricemia, Anemia emolitica cronica AdenoCa prostata con catetere a permanenza Pregressa IVU da Pseudomonas aeruginosa Sostituzione valvolare mitro aortica (protesi meccanica) nel 1993 Reintervento per insuff. mitralica acuta periprotesica nel 1996 Nel 02/2004 distacco parziale valvola mitrale con nuova sostituzione. Nel post operatorio episodio di TPSV per cui ha iniziato terapia con amiodarone
R.D. 81 aa Terapia domiciliare: Amiodarone 200 mg 1 cp Acediur 1 cp / die Furosemide 1cp x 2 Coumadin sec INR Clenil 2 puff x 2
R.D. 81 aa Giunge in PS in seguito ad improvviso episodio di dispnea All ingresso: GCS = 15 EOP: Tachipnea, dispnea. MV ridotto alla base dx; Crepitii bibasali. EOC: Toni aritmici, bradicardici; soffio sistolico 2/6 apicale. FC = 50/m PA 90/60 Edemi arti inferiori T=38.9
R.D. 81 aa Esami strumentali: ECG: Ritmo giunzionale 48/m; QT alllungato Rx torace: stasi piccolo circolo Ecocardiogramma: doppio jet mitralico e paraprotesico EF: 50%
R.D. 81 aa Ematochimici: WBC: 20.050 N%: 78.4 PCR: 9.7 Hb: 10 PLT: 162.000 INR: 3.48 APTTr: 2.24 Glicemia: 111 Creat 1.3 LDH: 501 Enzimi cardiaci neg.
R.D. 81 aa Ricovero in cardiologia con dgn di scompenso cardiaco in cardiopatia valvolare e sindrome del QT lungo di natura iatrogena Posizionato PM temporaneo R/ emocoltura, urocoltura Inizia terapia diuretica Terapia ATB con Amikacina 500 mg ogni 12 h
R.D. 81 aa All ingresso in ICU: GCS : 15 EOP: Grave tachipnea FR = 50/m. Sibili bilateralmente. Non stasi. EOC: Soffio sistolico 1/6 eiettivo. PA 90/60 FC 90/r Diuresi conservata T = 35.7
R.D. 81 aa EGA Ematochimici: WBC: 44.160 N%: 95% PCR: 16 Hb: 9.2 Hct: 27.5 PLT: 139.000 Creat: 2.2 glic: 270 Lattati: 2 INR: 3.23 APTTr: 2.11 Bil tot: 1.5 ph 7.49 pco 2 22.6 po 2 138 HCO 3 16.2 BE -5 SaO 2 99.2 pao 2 /FiO 2 150 Procalcit: 44.2 Colturali: negativi ScVO 2 : 65%
R.D. 81 aa Esami strumentali: ECG: RS 90/min. Possibile ischemia anteriore Rx torace: Versamento pleurico dx. Stasi piccolo circolo. Ombra cardiaca ingrandita. Ecocardio: EF conservata. Vsx lievemente dilato. Vdx ipocinetico e dilatato. Dilatazione biatriale. Protesi valvolari normofunzionanti.
R.D. 81 aa Sospetto clinico: shock settico: EGDT secondo Rivers ATB terapia ad ampio spettro Vancomicina 2 g/die in inf continua Amikacina 1 g x 1 Meropenem 1 g x 3 Fluconazolo 400 mg x 1 Vasopressori: Noradrenalina e dobutamina Idrocortisone 100 mg x 3 Infusione di plasma e emazie Controllo intensivo glicemia (90 110 mg/dl) Richiesti: TC torace: negativa per focolai broncopolmonari Ecotomografia addome: negativa Ecocardiogramma transesofageo (non eseguito) Colturali
R.D. 81 aa II giornata: Progressivo peggioramento degli scambi respiratori: IOT e VAM WBC 58.640 N% 96 procalcit: 56.2 PLT 107.000 Creat 2.2
R.D. 81 aa III giornata: Progressivo peggioramento degli scambi respiratori Emodinamica instabile con NA 2y/kg/min e dobutamina 10 y/kg/min Soffio Sistolico 5/6 su tutti focolai Diuresi valida con furosemide 1 g/die Ematochimici: WBC: 55.680 N%:98% PCR: 11.5 Procalcit: 21.1 Hb: 9.5 Hct: 28.3 PLT: 68.000 Creat: 2.6 Bil tot 2.7 INR e APTTr in range ScVO 2 : 67%
R.D. 81 aa Ecocardiogramma transesofageo: Insuff. Paraprotesica mitralica severa con evidenza di vegetazioni endocarditiche Il paziente viene trasferito presso la cardiorianimazione di un vicino ospedale in attesa di intervento chirurgico
CASO CLINICO 3
S.P. 78 aa Inviata in PS dal medico curante per riscontro incidentale di grave anemia (Hb: 4,4 g/dl) La settimana precedente episodio diarroico con feci ipercromiche. Da qualche giorno comparsa di artromialgie diffuse, profonda astenia, edemi diffusi e cianosi periferica.
- APR: ipertensione arteriosa ipercolesterolemia vasculopatia carotidea sindrome ansioso-depressiva diverticolosi intestinale - Terapia domiciliare: alprazolam 0,5 mg x 3 zoloft 1 cp/die atenololo ½ cp/die cardioasa 1 cp/die ipocolesterolemizzanti
All ingresso: vigile, cosciente MV bilateralmente, SpO 2 : 95% in AA PA: 105/65, tachicardia sinusale: 120/m Edemi declivi addome trattabile Non retto enterorragia Ematochimici: Hb: 4,7 Hct: 15.2 wbc 13.770 N%: 79,8 PCR: 2,1
Esami strumentali: Rx torace: addensamento ombre ilari per stasi piccolo circolo. Ombra cardiaca di dimensioni aumentate. Terapia impostata in PS: EC 2 sacche Ferlixit 1 f/die Omeprazolo 20 mg x 2
In II giornata: Soporosa, risvegliabile Dispnea improvvisa con tachipnea Broncospasmo diffuso PA 70/40 FC 150/r Cute fredda e marezzata Oligo-anuria T = 35.5 Ematochimici: wbc: 21.680 N%: 88 PCR: 2,2 EGA ph 7,17 pco 2 33 po 2 74 HCO 3 11.9 B.E. - 15.2 Sao2 89 O 2 4 l/m Hb 6,4 Hct 19,8 T-T 0,977 Enzimi cardiaci negativi
Esami strumentali: TC torace/addome: Incremento volumetrico cardiaco con falda di versamento pleurico e fegato da stasi. ECOcardio: Vsx non dilatato con EF 30%. Non alterazioni segmentarie. Dilatazione biatriale. IM ++ IT ++ PAP = 40 mm Hg. VCI dilatata.
Ipotesi diagnostica: Scompenso cardiaco acuto in grave anemizzazione di ndd? Shock settico con focolaio infettivo occulto?
Ricovero in ICU: IOT e VAM protettiva EGDT + trasfusione emazie Noradrenalina 0,5 y/kg/m Dobutamina 15 y/kg/m Controllo intensivo glicemia Amoxi/clav 4,4 g x 3 Richiesti: Coltuali Procalcitonina e ProBNP Hb feci
In III giornata: Condizioni generali sempre gravi Emodinamica instabile nonostante supporto aminico Procalcitonina: 1,55 ng/ml ProBNP: 21.915 Colturali negativi Hb feci positiva
Conferma quadro di scompenso cardiaco acuto: Sospensione terapia ATB Supporto aminico e aggressiva terapia diuretica sino a normalizzazione del quadro clinico e recupero della normale cinesi cardiaca. Normalizzazione Hb. Dopo la dimissione dalla TI la paz. è stata studiata mediante EGDS che ha evidenziato ulcera sanguinante della porzione anteriore del bulbo duodenale che è stata trattata con infiltrazione sclerosante.
Azienda Sanitaria Locale di Chieri, Carmagnola, Moncalieri e Nichelino Grazie per l attenzione