La sedazione del paziente in UTIC Valerio Zacà U.O.C. Cardiologia Ospedaliera A.O.U. Senese

Sedazione (e analgesia) Condizione neurofisiologica complessa: Ansiolisi Amnesia Ipnosi (attività motoria minima; fisicamente sembra simile al sonno) Analgesia Riduzione o assenza della sensazione di dolore o dello stimolo nocicettivo

Continuum of depth of sedation Practice Guidelines for Sedation and Analgesia by Non-Anesthesiologists Continuum of depth of sedation Because sedation is a continuum, it is not always possible to predict how an individual patient will respond. Hence, practitioners intending to produce a given level of sedation should be able to rescue patients whose level of sedation becomes deeper than initially intended. Individuals administering Moderate Sedation/Analgesia (Conscious Sedation) should be able to rescue patients who enter a state of Deep Sedation/Analgesia, while those administering Deep Sedation/Analgesia should be able to rescue patients who enter a state of general anesthesia. Analgo-sedazione sedo-analgesia etc etc… Gross JB et al. Anesthesiology. 2002; 96:1004–17.

La sedazione in TI è evidence-based? “The most striking finding in this review was the relatively small portion of sedative agents reported as being used in surveys of both North American and European practice that have been evaluated rigorously by more than 1 or 2 randomized controlled trials.” ARGOMENTO PIUTTOSTO EMPIRICO

Altering Intensive Care Sedation Paradigms to Improve Patient Outcomes 1st ACCM Guidelines the volume of evidence available to guide ICU sedation, analgesia, and delirium has increased significantly, AMERICAN COLLEGE OF CRITICAL CARE MEDICINE Seconde linee guida ACCM 2002 Riker RR et al. Crit Care Clin. 2009;25:527-38.

In-hospital mortality Association of Intravenous Morphine Use and Outcomes in Acute Coronary Syndromes: Results from the CRUSADE Quality Improvement Initiative In-hospital mortality Retrospective registry of NSTE ACS patients at 443 US hospitals (Jan 01-Jun 03) n=57,039 Outcomes No Morphine (n=40,036) Morphine (n=17,003) Adjusted OR (95% CI) Death 4.7% 5.5% 1.48 (1.33-1.64) Death or MI 7.1% 8.5% 1.44 (1.34-1.56) Post-admission MI 3.0% 3.8% 1.34 (1.22-1.48) Cardiogenic shock 2.3% 1.71 (1.53-1.91) CHF 9.1% 10.3% 1.27 (1.19-1.36) Third, the well-described analgesic effects of IV morphine may serve to blunt the severity of angina without actually ameliorating the underlying pathophysiologic cause of chest pain (ie, coronary hypoperfusion). Finally, IV morphine may actually be deleterious to patients with NSTE ACS. Rather than simply masking the pain associated with myocardial ischemia, perhaps morphine actually exacerbates the crisis. Morphine has several well known and potentially harmful side effects. Most commonly, morphine causes hypotension, bradycardia and respiratory depression Meine TJ et al. Am Heart J. 2005;149:1043-9.

L’ambiente UTIC Cause: Patologia cardiaca Catetere Linee venose Disfunzione polmonare Cause: Patologia cardiaca Catetere Linee venose Devices Personale sanitario Immobilità Disorientamento Stress: Tachicardia Ipertensione ↑ MVO2 Ipercoagulabilità Immunosoppressione Catabolismo Dolore Ansietà Discomfort Sonno inadeguato/ deprivazione Esaustezza Agitazione

Sedazione e analgesia in UTIC Indispensabili per migliorare la qualità della vita del paziente critico: Controllo/annullamento del dolore Adattamento all’ambiente (comfort) Ottimizzazione del pattern emodinamico Possibilità di eseguire procedure invasive (ETE, CVE, pericardiocentesi) Facilitazione dell’utilizzo di devices (IABP, CVVH) Ottimizzazione delle procedure di ventilazione STORM ARITMICI

Sedativi in TI/UTIC Agenti disponibili Agente ideale Diazepam, Lorazepam, Midazolam Morfina, Meperidina, Fentanyl, Alfentanil, Sufentanil, Remifentanil Propofol Tiopentale Pentobarbital Etomidate Ketamina Aloperidolo Dexmedetomidina Effetto di rapida insorgenza Rapido recupero dopo sospensione Stabilità emodinamica Assenza di interazioni farmacologiche Facilità di titolazione Alto indice terapeutico Basso costo Senza metaboliti attivi Indipendenza dalla funzione di clearance Tanti tantissimi ma quello ideale non esiste – sedativi, analgesici, anestetici…

Uso clinico di sedativi e analgesici Ansiolisi Amnesia Ipnosi Analgesia BDZ + - Oppiodi Propofol Darrouj J et al. Am J Ther. 2009;16:339–53.

Effetti emodinamici dei principali sedativi e analgesici HR CO MAP SVR Symp Paras BDZ ↔⁄↑ ↓⁄↔ ↓ ↔ Oppiodi ↑ Propofol ↔/↓ ↓↓ Rhoney D et al. Neurol Res. 2001;23:237-59. Devlin JW et al. Crit Care Clin. 2009;25:431–49.

Caratteristiche farmacologiche - 1 Agente Meccanismo d’azione Insorgenza (min) Emivita (h) Lipofilicità Midazolam Agonista recettore GABAa/BZ 2-5 2-12 +++ Fentanyl recettore-μ <1 2-4 Propofol 1-2 1.5-12.4 Devlin JW et al. Crit Care Clin. 2009;25:431–49.

Caratteristiche farmacologiche - 2 Agente Via metabolica principale Metaboliti attivi Implicazioni Farmacogenetiche Midazolam Idrossilazione (substrato CYP3A4/5) Si Fentanyl N-dealchilazione Propofol Idrossilazione e glucoronidazione (substrato CYP2B6) No Devlin JW et al. Crit Care Clin. 2009;25:431–49.

Considerazioni specifiche Fentanyl Stabilità emodinamica (no rilascio di istamina, no ipotensione, bradicardia) Analgesia: 1-2 g/kg (fino a 20 g/kg), anestesia: 50-150 g/kg Clearance risente di età, obesità, contenuto proteico plasmatico, epatopatie, IR, accumulo gastrico e polmonare dopo lunghe infusioni Midazolam Accumulo nei tessuti periferici già dopo 1 h di infusione Prolungamento degli effetti clinici può durare h o gg Interazione con altri farmaci, età e epatopatie

Somministrazione prolungata: la principale variabile farmacologica Eventuale modificazione di PK e PD Tolleranza, dipendenza e effetti secondari ↑ carico farmacologico in pz in politerapia Interazioni ↑ tempi svezzamento ventilazione ↑ tempi degenza ↑ costi

Popolazione eterogenea in UTIC: il “peso” delle comorbidità De Luca L et al. Heart Fail Rev. 2007;12:97-104.

Use of Sedatives and Neuromuscular Blockers in a Cohort of Patients Receiving Mechanical Ventilation 68% (3,540/5,183) received a sedative 67.2% combination of drugs: 25% BDZ + opiates 6% propofol + opiates Daily use of sedatives drugs according to duration of mechanical ventilation. Of the 5,183 ICU patients admitted during the study period, 3,540 patients (68%; 95% confidence interval [CI], 67 to 69%) received a sedative at any time while receiving mechanical ventilation. For these patients, the median number of days receiving a sedative was 3 days DI QUESTI 100 ARRESTI CARDIACI Arroliga A et al. International Mechanical Ventilation Study Group. CHEST. 2005;128:496–506.

Euroheart Failure Survey II (EHFS II): a Survey on Hospitalized Acute Heart Failure Patients: Description of Population Nieminen MS et al. Eur Heart J. 2006;27:2725-36.

1397 consecutive ICCU pts Jan 1/04 – Jun 30/05 Discharge diagnosis: The Recent Evolution of Coronary Care Units into Intensive Cardiac Care Units: the Experience of a Tertiary Center in Florence 1397 consecutive ICCU pts Jan 1/04 – Jun 30/05 Discharge diagnosis: ACS 71.8% (1003/1397), AHF 3.6% (50/1397) Mechanical ventilation in 7.2% (101/1397) Valente S et al. J Cardiovasc Med. 2007;8:181-7. UTIC AOUS Senese 1/1/10 – 6/11/10 6.2% (30/478) dei pazienti ammessi trattati con ventilazione meccanica invasiva

Sedazione in pazienti sottoposti a ventilazione meccanica invasiva in UTIC Potenziali elementi da considerare: Selezione agente/associazione appropriati in base a: Scenario clinico (ACS, AHF, RCA) Età Comorbidità (alterazioni farmacocinetiche) Durata attesa Grado di sedazione desiderato Valutazione dell’efficacia Bilanciamento degli effetti Interruzione giornaliera/weaning Collaborazione con l’anestesista: pianificazione, etc… Una diapo per ogni paragrafo grosso

Valutazione dell’efficacia della sedazione: le scale a punteggio Riker Sedation Agitation Scale (SAS) 1-7 Motor Activity Assessmen Scale (MAS) 1-7 Ramsay 1-6 Punteggio Descrizione Definizione 1 Sveglio Ansioso e agitato o irrequieto o entrambe 2 Collaborante, orientato e tranquillo 3 Risponde unicamente ai comandi 4 Sedato Veloce risposta al tocco della glabella, o a stimolo uditivo potente 5 Risposta torpida al tocco della glabella, o a stimolo uditivo potente 6 Risposta pronta al tocco della glabella, o a stimolo uditivo potente Jacobi J et al. Crit Care Med. 2002;1:119–41.

Current Practices in Sedation and Analgesia for Mechanically Ventilated Critically Ill Patients 1,381 adult pts included in a prospective, observational study in 44 ICUs in France Payen JF et al. for the DOLOREA Investigators. Anesthesiology. 2007;106:687–95.

Qualità e “quantità” della sedazione Qualità della sedazione = Target >85% “Quantità” H di adeguata sedazione H totali di sedazione x100 Insufficiente Eccessiva ↑ stress Coma farmacologico Agitazione Prolungata ventilazione meccanica Ipertensione e tachicardia Rigidità, TVP Ridotto adattamento al ventilatore Mancato riconoscimento di danni cerebrali Estubazione accidentale Tolleranza, sindrome da astinenza Ischemia miocardica ↑ costi Alterazione ritmo sonno-veglia ↑ degenza REF DA SIIARTI!!! Mattia C, et al. Linee Guida SIIARTI Minerva Anestesiol. 2006;72:769-805.

(Target Ramsay score 3-4 for both) Daily Interruption of Sedative Infusions in Critically Ill Patients Undergoing Mechanical Ventilation 128 pts randomized to: Daily interruption of sedatives 48 hrs after enrollment (intervention) Or Continuous infusion of sedatives with interruption only at the discretion of the intensive care unit team (control) (Target Ramsay score 3-4 for both) The exclusion criteria were pregnancy, transfer from an outside institution where sedatives had already been administered, and admission after resuscitation from cardiac arrest. Within each group, the patients were then randomly assigned to receive either midazolam or propofol. Kress JP et al. N Engl J Med. 2000;342:1471-7.

Daily Interruption of Sedative Infusions in Critically Ill Patients Undergoing Mechanical Ventilation Median duration of MV 4.9 Vs. 7.4 days (P=0.004) Median length of stay 6.4 Vs. 9.9 days (P=0.02) The exclusion criteria were pregnancy, transfer from an outside institution where sedatives had already been administered, and admission after resuscitation from cardiac arrest. Within each group, the patients were then randomly assigned to receive either midazolam or propofol + morfina. Kress JP et al. N Engl J Med. 2000;342:1471-7.

Sedation and Weaning from Mechanical Ventilation: Linking Spontaneous AwakeningTrials and Spontaneous Breathing Trials to Improve Patient Outcomes Just as spontaneous breathing trials are used to determine when a patient is ready for unassisted breathing, spontaneous awakening trials are used to determine a patient’s need for sedation by a careful assessment conducted when the patient’s pharmacologic sedation has been discontinued. The spontaneous awakening trial—originally referred to as daily interruption of sedatives—was first introduced into the literature by Kress and colleagues13 in a single-center trial that enrolled 128 mechanically ventilated patients receiving continuous IV sedation. In this randomized trial, compared with usual care, a sedation strategy involving daily interruption of sedative infusions (until patients were awake) significantly reduced duration of mechanical ventilation and ICU length of stay. Hooper MH et al. Crit Care Clin. 2009:515–25.

Awakening and Breathing Controlled trial HR for death, 0.68 95% CI, 0.50–0.92; P=0.01 Girard TD et al. Lancet. 2008;371:126–34.

Nonsolofarmaci… Modulazione degli stimoli ambientali (luci, rumori) Rilassamento Musicoterapia Massaggi Presenza di familiari White JM. Effects of relaxing music on cardiac autonomic balance and anxiety after acute myocardial infarction. Am J Crit Care. 1999; 8:220–30.

UTIC Unità di Tuttologia Incredibilmente Complessa […] Senza rinunciare all’originaria vocazione cardiologica e senza aspirare ad un improbabile ruolo polispecialistico, per il cardiologo dell’UTIC si rende quindi necessario un impegnativo allargamento delle proprie competenze

24 Novembre 1859 It is not the strongest of the species that survive, nor the most intelligent, but the one most responsive to change.

Dosaggi e costi Devlin JW et al. Crit Care Clin. 2009;25:431–49.

Delirio 20-80% dei pazienti delle TI Diagnosi se presenti 1-2 o 3-4 CAM-ICU: Alterazioni dello stato mentale ad insorgenza acuta o fluttuanti Disattenzione Disorganizzazione del pensiero Alterazioni del livello di coscienza Trattamento: neurolettici (clorpromazina, aloperidolo, quetiapina). Jacobi J et al. Crit Care Med. 2002;1:119–41.