1. Dr. Alain F. Kalmar, MD, PhD Dep. Of Anaesthesia University Medical Center Groningen The Netherlands Sedation 2012

2. ASA definition of levels of sedation Copyright ® [1999] American Society of Anesthesiologists What is adequate sedation ?

3. Benefits of sedation Facilitates & expedites procedures Reduces discomfort & unpleasant memories Allows for avoidance of invasive airway intervention Cost -effective Promotes early recovery & discharge Improves overall patient satisfaction

4. Prior to sedation : Patient history Patient sensitivity to sedatives/analgesics patient risk of respiratory/cardiopulmonary complications - Cardiopulmonary disease : decreased drug dosage - Hepatic /renal disease : Altered pharmacokinetics - Medication interactions Patient allergies Alcohol / Substance abuse : may increase/decrease effects Tobacco use : increase airway irritability ; bronchospasm Prior adverse reactions difficulty in managing complications

5. Prior to sedation : Patient history Airway assessment - Airway class - Mouth opening - Thyromental distance Lam B et al. Thorax 2005;60:504-510

6. Patient education helps alleviate concerns associated with conscious sedation. Prevention of “Awareness experience” Key points :duration of sedation potential for sedation failure alternatives to sedation potential for adverse events Monitoring Informed Consent

7. Preprocedural ASA Fasting Guidelines To Minimize Aspiration Risk Substance Ingested Minimum Fasting Period (hours) Clear Liquids2 Breast Milk4 Infant Formula6 Food8

8. Required equipment Oxygen Suction Crash cart with ACLS drugs Defibrillator Bag/Valve/Mask device ; ventilator Oral & nasal airways ETT’s sizes 5.0, 6.0, 7.0, 8.0 Laryngoscopes with Mac 3, 4 and Miller 2, 3 blades Reversal agents

9. Optimal Sedation Pt maintains consciousness Independent maintenance of airway Retains protective reflexes (swallow & gag) Responds to verbal & physical commands Is not anxious & has acceptable pain control Has minimal change in baseline vital signs Remains relatively cooperative Has mild amnesia Recovers to baseline safely & promptly

10. Farmacology for Conscious Sedation propofol barbiturates benzodiazepines inhalational an. opiates Local an.

11. Pharmacology For Conscious Sedation Allows the patient to be calm, comfortable and cooperative. Mostly, a combination of hypnotics and opiates is used. Opioids  Analgesia Benzodiazepines or other sedatives  Sedation, anxiolysis, and amnesia. Sedative drugs do not provide analgesia. A drug should be allowed to exert its full effect before administering additional doses or another drug. When combining opioids and sedatives, administer the opioid first to ensure the patient receives analgesia prior to painful stimulation.

12. Conscious Sedation : Monitoring Patients must be monitored during moderate sedation. The person monitoring the patient can not have additional assignments. Heart rate and Oxygenation : continuously by Pulse Oxymetry Respiratory rate & pulmonary ventilation Clinical endpoints for conscious sedation may include a respiratory rate of 10-12 in an adult and a slurring of speech. Blood pressure and EKG Patients who receive sedatives may become disinhibited and, at times, uncooperative.

13. Does this provide safe conditions ? Observational study (University Hospital Groningen 2011). Sedation for colonoscopy : Business as usual Midazolam / Pethidine 230 patients breathing room air. Standard monitoring of ECG, NIBP, SpO 2, HR Additional recorded parameters : P et CO 2, P tc CO 2, BIS All data were recorded for subsequent analysis.

14. Main safety parameters : Oxygenation (SpO 2 ) Ventilation (P Et CO 2 / P Tc CO 2 ) Depth of sedation (BIS) – Risk of pulmonary aspiration Blood Pressure (MAP)

15. Time (min) SpO 2 < 90 : 36% (226 sec) Does this provide safe conditions ? SpO 2 Median 10 th / 90 th percentile

16. Time (min) BIS < 75 : 29% (224 sec) BIS < 70 : 17% (126 sec) Does this provide safe conditions ? BIS

17. Time (min) MAP < 70 : 36% (564 sec) Mean Arterial Pressure Does this provide safe conditions ?

18. Time (min) Does this provide safe conditions ? Incidence SpO 2 < 90 : 36% P Tc CO 2

19. Time (min) Does this provide safe conditions ? P Et CO 2

20. Does this provide safe conditions ? Hardly ! What goes wrong ? Insufficient attention of the sedation caregiver ? Insufficient knowledge on pharmacology of Midazolam / Pethidine ? “ If a combination of opioids and sedatives is used, the opioid should be given first and allowed time to become maximally effective before any sedative is added.” U.K. ACADEMY OF MEDICAL ROYAL COLLEGES Insufficient awareness of the depth of anesthesia ?

21. Conclusion : Conscious sedation should be performed by a skilled personnel with adequate knowledge of anesthesia, pharmacology and basic and advanced life support.  Anesthesiologists or Trained sedation practitioners Individual who monitors the sedated patient should do this as his/her sole task and not have other concurrent responsibilities. Choice of medication (Pethidine /Midazolam) ?

22. Conscious Sedation 2012 ? Preference to short-acting drugs A quick therapeutic response on a rapid change of peri-operative situation without “hang-over” effects. Take into account population variability Target controlled infusion (TCI) instead of mg/kg/hr Attempt to individualize dose-response relation. Careful titration with knowledge of pharmacology

23. Suitable Opiates ? Time to Peak-effect Minutes since bolus injection 02 46810 Percent of peak effect site opioid concentration 0 20 40 60 80 100 fentanyl sufentanil alfentanil remifentanil

24. Context sensitive Half-Time Time for the effect site concentration of a drug to fall 50% after a variable length infusion Egan et al. Anesthesiology 1993, 79(5) : 881-892.

25. End of procedure * Discontinuation of alfentanil infusion/no more fentanyl boluses Remifentanil Time Analgesic Effect * End of Procedure Fentanyl Alfentanil

26. Hypnotic-based procedure ? opiate-based procedure ? Propofol-Remifentanil interaction

27. Sedation for lung-reduction valve placement Patient characteristics : ASA 4 High-grade emphysema patients Often important comorbidity Requirements : Preserved hemodynamics Preserved ventilation with spontaneous ventilation Allowing bronchoscopy and intrabronchial valve placement Full-coöperative patient for diagnostic and therapeutic reasons.

28. Sedation for lung-reduction valve placement Preferred technique : Conscious sedation with Propofol/Remifentanil TCI-guided. Take into account pharmacology of agents 1. Start Remifentanil C eT 1 ng/ml 2. Wait 60 seconds until clear subjective effects 3. Start Propofol C eT 1 ug/ml 4. Wait for sedative effect to occur 5. Carefully titrate drugs depending on patients reports (anxiety /pain) Keep talking with patient (Population variability)

29. Sedation for lung-reduction valve placement Advantages : Fully-coöperative patient, good tollerance for the procedure Optimal conditions for the procedure Preserved hemodynamics Fast recovery (extremely important for these high-risk patients) High patient satisfaction (complete amnesia of the procedure) Fast patient turn-over

30. Conclusion 2012 TCI Remifentanil / Propofol - Very advantageous farmacokinetics. - Good safety profile Future … Dexmedetomidine ? Patient controlled sedation ? Similar to principles of PCA, based on patient feedback Target Controlled Sedation ? (i.e. BIS guided propofol administration)

31. Questions ?