Sufentanile4. Fentanile. Remi fentanile. Alfentanile1

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1 Nicoletta Barzaghi Anestesia e Terapia Intensiva Cardiovascolare ASO Santa Croce e Carle - Cuneo

2 CPK 2004; 43:577 BOLO IV

3 Sufentanile4 DOSE: A x 200 = μg/kg 720 Fentanile 3 60 DOSE: A x 10 = 3 μg/kg Remi fentanile 2 40 DOSE: A x 20 = μg/kg Alfentanile1 1 DOSE: 30 μg/kg POTENZA: 1/X

4 Compartimento centrale Compartimento periferico a equilibrio rapido Compartimento periferico a lento equilibrio Log

5 FARMACO T ½ (min) Fentanil Sufentanil 164 Alfentanil Remifentanil 10-12

6 CPK 2004; 43:577 FARMACO CSHL a 50 (min) CSHL a 100 (min) CSHL a 300 (min) CS Fentanile ~ 30 ~ 70 SI Alfentanile ~ 30 ~ 45 ~ 60 SI Sufentanile ~ 10 ~ 20 ~ 35 SI Remifentanile ~ 3; offset: 5 ~ 3; offset: 5 ~ 3; offset: 5 NO

7 Using the Time of Maximum Effect Site Concentration to Combine Pharmacokinetics and Pharmacodynamics Propofol Reduces Perioeprative Remifentanil Requirements in a Synergistic Manner The response surface models reveal the tremendous synergy between remifentanil and propofol. The surface morphologic features give some indication of the relative contributions of sedation and analgesia to blunting subject response.

8 Clinical practice guidelines for the sustained use of sedatives and analgesics in the critically ill adult. The challange to bedside clinicians is to find the balance between agitation and coma the comfort zone. 1. Use validated assessment tools within protocols to guide sedation and analgesic therapy in order to avoid under-treatment 2. Allow daily evaluations of the need for continued sedative and analgesic therapy (titration of dose) in order to avoid over-treatment 3. Recognize the clinical importance of delirium. 4. Consider pain or discomfort as the primary cause of agitation, with opiate therapy as the initial mainstay of treatment. Curr Opin Anesthesiol 2007; 20: 119

9 Algorithm for the sedation and analgesia of mechanically ventilated patients CCM 2002; 30: 119

10 PAIN SCALES VAS, NRS, VRS Visual Analogue Scale (VAS) Number Rating Scale (NRS) 0 : absent 1-2 : mild 3-4 : moderate 5-7 : severe 8-10: worst possible Verbal Rating Scale (VRS) Target of analgesic therapy: 3

11 PAIN SCALES Behavioral Pain Scale Payen JF et al. Assessing pain in critically ill sedated patient by using a behavioral pain scale. Crit Care Med 2001; 29: Target of analgesic therapy : 4 Behavioral Pain Scale Aissaoui Y et al. Validation of a behavioral pain scale in critically ill, sedated, and mechaniclly ventilated patients. Anesth Analg 2005; 101: The BPS was internally reliable (Cronbach = 0.72). The intraclass correlation coefficient to evaluate inter-rater reliability was high (0.95). Validity was demonstrated by the change in BPS scores, which were significantly higher during painful procedures, with an average 3.9 ± 1.1 at rest and 6.8 ± 1.9 during procedures (P<0.001).

12 CONFORT SCALES RAMSAY SEDATION SCALE T A R G E T

13 CONFORT SCALES RICHMOND AGITATION-SEDATION SCALE Quality of Sedation = Adeguate sedation (hrs) X 100 Sedation (hrs) TARGET: >85%

14 DELIRIUM ASSESSMENT CAM-ICU CONFUSION ASSESSMENT METHOD IN ICU (CAM-ICU) Feature 1: Acute onset of mental status changes or a fluctuating course AND Feature 2: Inattention AND Ely et al. JAM MA 2001;286: Feature 3: Disorganized thinking OR Feature 4: Altered level of consciousness = DELIRIUM

15 DELIRIUM ASSESSMENT ICDSC INTENSIVE CARE DELIRIUM SCREENING CHECKLIST ICDSC includes 8 items based on the Diagnostic and Statistical Manual of Mental Disorders. Total score: from 0 to 8 points. Manifestation of a item = 1 point Delirium: 4 points.

16 Daily interruption of sedative infusions in critically ill patients undergoing mechanical ventilation Kress et al. N Engl J Med 2000;342:1471 P =.002 Length of stay in ICU Mechanical ventilation (days): Intervention group = 4.9 ( ) Control group = 7.3 ( ) Dosage of drugs: P =.004 In the intervention group a significant decrease in total dose and in the average rate of infusion of both midazolam and morphine was detected.

17 A comparison of hypnotic and analgesic based sedation in a general intensive care unit British Journal of Anesthesia 98 (1): (2007) Midazolam & morphine Remifentanil PROTOCOL Hypnotic-based (n=111) Analgesia-based (n=96) P No use of hypnotic agents 37 % pts Percentage of time at a satisfactory sedation level (median [IQ range]) SIMV: 19 [2, 55] PSB: 88 [45,100] SIMV: 50 [14,83] PSB: 100 [92, 100] <.001 <.01 Time (hrs) on PSB as a % of the total 22 [5,40] 9 [0, 35] <.01 time on MV (median [IQ range]) Time on propofol during MV (hrs) (median [IQ range]) 20 [12,54] 4 [3,8] <.001 Pts requiring propofol by infusion <.01 during MV (%) Pts requiring additional analgesia (%) 26 6 <.001. analgesic-based approach using remifentanil achieved a satisfactory level of sedation in significantly more patients than the hypnotic- based approach.

18 With modifications Mechanically ventilated ICU patient TARGET RASS: -1 0 VAS 3 or BPS 4 RASS 1 VAS 4 BPS >4 Start Remifentanile [R], 75 ng/kg/min [D1, t0] No dosage adjustement in patients with renal impairment No dosage adjustement in patients aged < 65 years Patients in spo ontaneous breathing: R 50 ng/kg/min (25-75) R, 50 ng/kg/min [D2] RASS 1 VAS < 4 BPS 4 RASS 1 VAS < 4 BPS 4 T2 = 20 R, 25 ng/kg/min [D3] T1 = 10 RASS 1 VAS 4 BPS >4 RASS 1 VAS 4 BPS >4 R, 100 ng/kg/min [D2] R, 125 ng/kg/min [D3] T2 = 20 T 50 R, 200 ng/kg/min [D6] RASS 1 VAS 4 BPS >4 At 10 intervals R dosage =200 ng/kg/min + Sedatives: Remifentanil infusion rate can be increased 5 minutes before a stimulating and /or painful procedure to provide additional analgesia Propofol: 15 μg/kg/min (Range: ) Midazolam: 0.5 μg/kg/min (up to 5) Clonidine: 3 ng/kg/min (up to 9) Ketamine Dexmetedominine