Analgesia, Sedation and Neuromuscular block in the ICU

1. Analgesia, Sedation and Neuromuscular block in the ICU Gau-Jun Tang, MD, MHS I-Lan Hospital affiliated with Taipei Veterans General Hospital National Yang-Ming University Taipei, Taiwan

2. SEDATION • The process of reducing the level of stress and anxiety to produce a calm mental and physical state • Mental support • Analgesics • Hypnotics • Sedatives

3. Tie the patient

4. ANESTHESIA • Analgesia 麻 • Amnesia 醉

5. ANALGESIA麻 • Regional anesthesia • Nerve block • Spinal anesthesia • Epidural anesthesia

10. NSAID • Block cycloocygenase • Prevent the production of Leukotrine and Prostagladin • Advantage: • No respiratory depression • Inhibit platelet aggregation • Attenuate inflammatory response • Disadvantage: • Weak analgesics • Nephrotoxicity

11. Opioid Anesthetics • opiate n adj 鴉片劑 : • Opium 鴉片 Opium puppy 罌粟花 • Opioids • bind to any opioid receptors • Narcotic : opioid & nonopioid

12. Opioid Potency ratio Safety margin • Morphine 1 32 • Demerol 1/3 2 • Fentanyl 124 500 • Afentanyl 31 125 • Sufentanyl 1240 1000

13. Characteristics of Opioids Receptors

14. CNS Action of Narcotics • Analgesia • Mood change, Euphoria • Sedation, Mental clouding • Nausea and vomiting • Respiratory depression • Cough suppression

15. Peripheral Action of Narcotics • Decrease gastrointestinal motility • Increase bile duct pressure • Pruritis • Urinary retention

16. Effect on respiration • Dose-dependent depression of respiration • Direct action on the brain stem respiratory center • Apneic threshold is increased by opioid • Resting end-tidal PC02 increased by opioids. • Decrease Hypoxic Ventilatory Drive.

17. Opioid on Respiratory Rhythm • Decreased respiratory rate • Increased pauses, delay in expiration • Irregular and/or periodic breathing • Tidal volume may decrease, normal, or increase

18. Opioids • Cardiovascular • Reduce sympathetic outflow • morphine • Histamine, severe hypotension (SVR) • bradycardia : all except Meperidine (atropine-like) • direct myocardial depression • Meperidine • Muscle rigidity (Truncal rigidity) • chest & abd. M. • Tx : m. Relaxant, narcotic antagonist

19. Morphine in the ICU • 24 critically ill patients on ventilator • Morphine 0.5 mg/kg • Decrease in HR, CO, BP, • Oxygen consumption Decrease • No change in oxygen extraction • Rouby, circulation, 1981

20. Opioids Antagonists • Naloxone • reserve respiratory or CNS depression • 0.04 mg q2-3 min, onset 2 min • t½α:1 hr; t½β:1-4 hrs; by liver • renarcotization • Adverse effects • Pain • Hypertension • Tachycardia • cardiac arrest • pulmonary Edema • MI

21. ANESTHESIA • Analgesia 麻 • Amnesia 醉

22. Different level of sedation醉for specific clinical situations • Conscious sedation • patient's ability to maintain the airway • respond appropriately to physical stimulation and verbal command • Deep sedation • partial loss of protective reflexes • respond purposefully to verbal command • General anesthesia • complete loss of protective reflexes • inability to maintain an airway independently Be careful

23. DOSE continuum Sedatives Stimulus Level of Sedation Movement, Hemodynamics, Sleep, Respiratory suppress

24. Sedative agents • All intravenous agents used for general anesthesia • Ideal sedative agent • No effect on the respiratory or cardiovascular system • High therapeutic index • Rapid metabolized • Goal of therapy • Analgesia • Sedation • anxiolysis

25. Multiple drug approach • Narcotics • Hypnotics • Sedatives

26. Barbiturate (巴比妥鹽) Loss of conscious in one circulation time • dissociation of GABA receptor & direct effect : chloride conductance

28. Thiopentone Pharmacodynamics • ◆Respiratory system • central respiratory depression • respiratory acidosis • low therapeutic index

29. Thiopentone Pharmacodynamics ◆Vascular injury not due to pH (moderate alkalinity, pH 10-11) due to chemical nature of drug venous 5% of patients thickening of vein wall resolves after several weeks arterial severe pain and thrombosis ischaemic injury

30. Thiopentone Pharmacodynamics ◆Contraindications Absolute respiratory obstruction previous immune reaction acute intermittent porphyria Relative hypovolaemia septicaemia severe CVS disease

32. Benzodiazepine • Receptor occupancy • Anxiolytic: < 20% • Sedation: 30-50% • Unconsciousness: >60% Benzodiazepine Receptor GABA Receptor

33. Diazepam • long-acting lipophilic benzodiazepine • rapidly penetrates the blood brain barrier • sedative effect within 2 to 3 min • last 15 to 30 min • drug redistributes to peripheral tissue • Metabolic half life: 24 hr • No longer recommended for ICU sedation • excessive sedation by delayed metabolism • pain and thrombophlebitis during peripheral vein injection.

34. Benzodiazepines

35. Midazolam • compatibility with intravenous solutions • cardiovascular suppression is minimal in therapeutic doses • rapid onset and short duration • continuous infusion at variable infusion rate • titrate to the desired clinical level of sedation

36. Lorazepam • Lorazepam is an intermediate acting benzodiazepine • less lipophilic than diazepam, • potential for peripheral accumulation. • for the prolonged treatment of anxiety in ICU

37. Reversal of Benzodiazepenes • rapidly reverse the respiratory and central depression effects of benzodiazepenes in up to 80% of patients. • Flumazenil, anexete

38. Etomidate • 1972 launched • hemodynamic stable • Safety (LD50/TD50) 26.4 vs. thiopental 4.6 • CV : < 10 % in MAP, MPAP, PCWP, CVP, SV, CI • Decrease PVR 18%, 50% in myocardium O2 cons. • Water insoluble, pain on injection • Side effects • 10-30% myoclonic movement, seizure • 10-70% hiccuping • 30-40% thrombophlebitis • Increase mortality in ICU (1983) • Adrenal insufficiency

39. Ketamine • 1965 • Stable BP for hypotensive patients

40. Ketamine ◆’dissociative anaesthetic’ related to phencyclidine (‘angel dust’) cataleptic state profound analgesia

41. Ketamine • Good • CV : increase BP, HR, CO • PVR > SVR • Sympathetic outflow & release of NE • Myocardial depression • Contraindications • IICP, IIOP, • ischemic heart disease • vascular aneurysm • Schizophrenia • delirium

42. Propofol

43. PROPOFOL • Ultra-short acting hypnotics • Onset in one circulating time • Wake up in 15 min • Not influenced by hepatic and renal failure • Ideal for ICU sedation except patients in shock

44. ICU nurses usually addict to it

45. Drawbacks of Propofol • Cardiovascular suppression • Not to use during shock and hypotension • Respiratory depression • Cost

46. Sedation for ICU nurses • ICU nurse and staff • 10% believe pancuronium possess analgesic effect • 70% believe pancuronium possess anxiolytic effect • Pain: 37, 1989

47. Is Paralysis enough? • Terror in the ICU • Paralyzed with pain • Anesth Anal, 1989 • Pain and anxiety induce stress response

48. Let patients sleep before muscle relaxant • Control pain: Analgesics • Sedate the patients: hypnotic, sedation • Paralyze the patient

49. Muscle relaxant • South America India • Arrow tip to paralyze the animal • Extract from Calabash (葫蘆) Curare