The document discusses monitored anesthesia care (MAC), which involves administering drugs to provide anxiolytic, hypnotic, amnestic, and analgesic effects without depressing consciousness below a certain level. It provides guidelines on drug selection and dosing for MAC, including opioids like fentanyl and remifentanil, benzodiazepines like midazolam, propofol, ketamine, and dexmedetomidine. It also discusses factors that can lead to patient agitation during MAC and principles of drug administration via continuous infusion or patient-controlled methods.

1. AL JADIDI SULAIMAN MODERATOR: DR TUAN NORIZAN 14/04/2011

2. Involves administering a combination of drugs for anxiolytic , hypnotic , amnestic , and analgesic effect

3. Refers to instances in which an anaesthesiologist has been called upon to provide specific anaesthesia services to a particular patient undergoing a planned procedure, in connection with which a patient receives local anaesthesia , or in some cases, no anaesthesia at all .

4. In such a case the anaesthesiologist is providing specific services to the patient and is in control of the patient non-surgical or non-obstetrical medical care, including the responsibility of monitoring the patient’s vital sign , and is available to administer anaesthetics or provide other medical care as appropriate.

5. Conscious sedation = minimally depressed level of consciousness that retain the patient’s ability to independently and continuously maintain an airway and respond appropriately to physical stimulation and verbal command

6. MAC GRAY ZONE GENERAL ANESTHESIA Monitored Anesthesia Care

7. To maintain patient safety & sense of well-being To alleviate pain, minimise discomfort To minimise psychological response - anxiolysis, analgesia, amnesia To control behaviour To return to pre-procedural state - recognised criteria - safe discharge

8. Should be no different than for other patients Assess ability to remain motionless and cooperate, verbally communicate Important in monitoring level of sedation and cardiorespiratory function cardiorespiratory disease is often the indication for MAC over GA However, problem such as persistent cough or orthopnoea may prevent immobility

10. End points: Providing patient comfort Maintaining cardiorespiratory stability Improving operating condition Prevent recall of unpleasant perioperative event

11. MAC usually involves IV administration of drugs- alone/supplemental to LA/RA Drug should allow rapid+complete recovery, min N&V A level of sedation that allows verbal communication is optimal Increased pt agitation may be due to pain or anxiety

12. Agitation causes: pain, hypoxia, hypercarbia, impending local toxicity, cerebral hypoperfusion others: bladder distension, hypothermia, hyperthermia, pruritus, nausea, positional discomfort, IV site, tourniquet inflation, and member of the surgical team leaning on the patient

14. RESPONSIVENESS SPEECH FACIAL EXPRESSION EYES COMPOSITE SCORE LEVEL RESPOND READILY TO NAME SPOKEN IN NORMAL TONE NORMAL NORMAL CLEAR, NO PTOSIS 5 LETHARGIC RESPONSE TO NAME SPOKEN IN NORMAL TONE MILD SLOWING OR THICKENING MILD RELAXATION GLAZED OR PTOSIS (LESS THEN HALF THE EYE) 4 RESPOND ONLY AFTER NAME IS CALLED LOUDLY AND/OR REPEATEDLY SLURRING OR PROMINENT SLOWING MARKED RELAXATION GLAZED AND MARKED PTOSIS 3 RESPOND ONLY AFTER MILD PRODDING OR SHAKING FEW RECOGNISABLE WORDS 2 DOES NOT RESPOND TO MILD PRODDING OR SHAKING 1

15. Endoscopic procedures such as gastro-duodenoscopy, colonoscopy, sigmoidoscopy Minor surgical procedures performed under LA Painful diagnostic or treatment procedures such as BMA, trephine biopsy, change of burn dressing Special situation such as IV administration of X-ray contrast medium in a patient considered to be susceptible to anaphylaxis

17. Predict the effect of drugs Understand p/kinetic & p/dynamic properties ( context-sensitive half time, effect site equilibration time, drug interactions ) Cont infusion are superior to intermittent bolus -less-fluctuate in drug conc, prompt recovery

18. Accumulation of drugs in the poorly perfused fatty tissues during a long case can contribute to a prolonged recovery It is difficult to predict duration of action based on elimination half life alone

19. Describes the time required for the plasma drug concentration to decline by 50% after terminating an infusion of a particular duration The CSHT increases as the duration of infusion increases (particularly fentanyl & STP) -thus STP is not ideal drug for ambulatory procedures

20. There is no constant relationship between elimination half-life and context-sensitive half-time eg: fentanyl’s elimination is shorter than sufentanil (462 vs 577 minutes), its CSHT is twice that of sufentanil at 2H and 8-10x longer at 5H

21. Q: How does the CSHT relate to the time of recovery?

22. Describes the time from rapid iv admin of a drug until its clinical effect is manifest Half time of equlibration between drug concentration in the blood and drug effect = t1/2 keo Smaller values correspond with rapidity of onset

23. Drugs with shorter values: thiopental, propofol, alfentanil Drugs with longer values: midazolam (0.9-5.6 m), sufentanil, and fentanyl t1/2keo is a key factor in determining bolus spacing eg: even using the shortest value for midazolam, 2.7 minutes is required for 87.5% effect-site equlibration of a bolus dose # low cardiac output is another factor that will slow onset time

24. No one inhaled/IV can provide all the component of MAC Combination of drugs that act synergistically needed eg opiod-benzodiazepine combination to achieve the components of hypnosis, amnesia & analgesia

25. Cpss50 = plasma concentration at a steady state required to abolish purposeful movement upon skin incision in 50% of patients

26. It has a context-sensitive half-time that is short even after a prolonged infusion, and a short effect-site equlibration-time As it doesn’t posses analgesic properties, analgesia is provided by means of local infiltration or small doses of opiod. Initial bolus 0.5mg/kg then 10mg intermittent bolus as necessary

27. Alternatively, -continuous infusion at a rate 4mg/kg/h -Patient-controlled sedation (PCS) -Targer-controlled infusion, maintain target plasma concentration 0.5-1.5mcg/ml, titrating to response Ramifentanil may also be administered at rate 0.01-0.05mcg/kg/min #there is evidence that a single 10mg dose possess direct antiemetic properties

28. PROPOFOL DEXMEDETOMIDINE Pain upon injection Yes Minimal Analgesic properties with subhypnotic dose Minimal Yes Amnestic properties with subhypnotic dose Significant Insignificant Type of onset with typical administration Rapid 5-10 minutes Use by anaest provider Yes No Potential for significant bradycardia Minimal significant

29. Anxiolytic, amnestic & hypnotic properties Midazolam has many advantages over diazepam There is often significant and prolonged psychomotor impairment following conscious sedation techniques using midazolam as their main component Cpss50 decresases significantly as a function of age , reduce threefold in an 80 year-old compared to 40 year-old

30. MIDAZOLAM DIAZEPAM Water soluble Lipid soluble Painless on injection Venoirritant Thrombophlebitis is rare Thrombophlebitis is common Short elimination half time (4 hours) Long elimination half time (> 20 hours) Clearance is unaffected by H2 antagonists Clearance is reduced by H2 antagonists Inactive metabolites (1-hydroxy midazolam) Active metabolites (desmethy-diazepam, oxazepam) Resedation is unlikely Resedation is more likely

31. #Flumazenil has a very short elimination half-life ~60 minutes, shorter than that most clinically used BDZ. In one study the effect of midazolam recurred 90 minutes following administration of flumazenil

32. Initial recommended dose is 0.2mg IV If the desired level of consciousness is not achieved within 45 seconds, repeat 0.2mg IV If necessary, repeat 0.2mg IV every 60 seconds to a maximum of 1.0mg Recognise the potential for resedation

33. α 2- adenoreceptor agonists, anxiolytic and sedatives Clonidine- good analgesia at high dose 4mcg/kg iv or 5mcg/kg orally w/out effect on respiration / PONV slow on & offset –necessitating given well before surgery and possible delay in discharge after operation

34. Dexmedetominidine provides dose-related sedation and prolongation of sensory block but cause significant haemodynamic impairemet & PONV Elimination half-life of 2H indicates a fast offset, which is the major advantages over clonidine

35. Low-dose (0.5-1mg/kg) ketamine reported to provide weak sedation but excellent analgesia Didn’t reduce propofol requirement But +ve effect on haemodynamic stability and counteract propofol-induced resp depression due to its sympatomimetic properties & CNS effects Bad dreams/hallucination were not reported at sedatives dose

36. Among opiods ramifentanil is a potent analgesic with excellent p/kinetic profile: TPE 1.5min, p/dynamic offset 5.8min, short elmination half-life & time-independent CSHT. s/e: n&v, pruritus, muscular rigidity at high dose (>1mcg/kg/min) infusion rate of 0.1mcg/kg/min suggested as optimal balance between sedatives/side-effects

37. Initial injection of LA Retrobulbar block Patient discomfort unrelated to the procedure Uncomfortable position Propofol injection Pneumatic tourniquet pain

38. In paediatric patient, chloral hydrate, paraldehyde and syrup diazepam or trimeprazine are used to provide sedation. However dose and onset of action of these drugs are often unreliable & unpredictable.

39. DRUG TYPICAL ADULT IV DOSE (TITRATED TO EFFECT IN INCREAMENT0 BDZ Midazolam Diazepam 1-2mg before propofol or ramifentanil infusion 2.5-10mg OPIODS Alfentanil Fentanyl Ramifentanil 5-20mcg/kg bolus 2 minutes before stimulus 0.5-2mcg/kg bolus 2 minutes before stimulus 0.1mcg/kg/min infusion 5 minutes before stimulus then weaned to 0.05mcg/kg/min as tolerated (adjust increment up or down in 0.025mcg/kg/min Propofol 250-500 mcg/kg bolus, 25-75 mcg/kg/min infusion Ketamine 4-6 mg/kg PO, 2-4 mg/kg IM, 0.25-1mg/kg IV Dexmedetomidine 0.5-1.0mcg/kg over 10-20min followed by 0.2-0.7mcg/kg/h

40. Increase pt satisfaction Eliminate unpredictable variability in dose requirement between patients eg: 0.5 mg midazolam and 25mcg fentanyl with 5min lockout interval Alfentanil as 5mcg/kg IV bolus with 3min lockout period

42. During normal inspiration is subatmospheric creating a tendency to collapse This tendency is opposed by upper airway muscles which contract just prior to diaphragmatic contraction This control appears sensitive to sedative-hypnotic drug administration Eg: sedatives dose of midazolam have been reported to increase upper airway resistance 3-4 fold, an effect exaggerated in elderly..

43. Protective pharyngeal and laryngeal reflexes are depressed by sedation, debilitation and advanced age Complete recovery of swallowing reflex occur ~15 minutes after the return of consciousness from propofol anaesthesia It is depressed up to 2H after midazolam

44. In an otherwise norman man whose PCO2 is increased by hypoventilation sec to opiod administration, the alveolar gas equation predicts a PAO2 ~50mmHg (SpO2 75%) If fio2 increases to 28%, the PAO2 increases to 100mmHg (Spo2 100%) Recap: PAO 2 = PIO 2 - 1.2 (PaCO 2 ) where PIO 2 = FIO 2 (P B – 47 mm Hg)

47. ASA Standards for Basic Anaesthetic monitoring -applicable to all levels of anesthesia care Communication & Observation Preparedness to recognise and treat LA toxicity

48. Visual, tactile and Auditory assessment -rate, depth & pattern of breathing -palpation of arterial pulse -peripheral perfusion, Cap refill -diaphoresis -pallor -shivering -cyanosis -acute change in neurological status

49. Auscultation -heart & breath sounds (precordial stethoscope) Pulse oximetry (an ASA standard) Capnography Electrocardiography Temperature Bispectral index (value <80 minimise recall)

51. This study was designed to determine the optimal infusion rates of propofol and alfentanil when administering during LA Randomised, double-blind study effect of different propofol infusion rates on the alfentanil requirement, level of sedation, intraoperative recall, respiratory and cardiovascular variables, and recovery evaluated. 72 ASA I or II female outpatients undergoing breast biopsy procedures with local anesthesia were randomly assigned to 1 of 4 treatment groups

52. All patients received IV midazolam 2mg for premedication Propofol was infused at 0, 25, 50 or 75 mcg/kg/min Sedation was evaluated using OAA/S scale at 5 min intervals by blinded observer 2 minutes before infiltration of LA, bolus of alfentanil 2.5mcg/kg IV given, folllowed by infusion 0.5mcg/kg/min Alfentanil infusion titrated varied to patient comfort and stable cardiovascular and respiratory fx.

53. Results: Propofol produced dose-dependant increases in the level of sedation (with median OAA/S scores of 2-4, P<0.05. Higher infusion rates of propofol (50-75mcg/kg/min) produced significant amnesia, opiod-sparing effect (alfentanil 0.3±0.2 vs 0.6±0.2 mcg/kg/min) and less PONV. Thus in healthy outpatients premedicated with IV midazolam 2mg, a propofol infusion 25-50mcg/kg/min in combination with an alfentanil infusion 0.2-0.4mcg/kg/min is recommended for sedation and analgesia during MAC in the ambulatory setting.

55. Study found that 13 of 98 (12%) patients with an UL block without sedation for hand surgery would like to be sedated for future similar surgery Sedatives can help to decrease the requirement of opiod analgesics, reduce PONV Sedation allows the choice of shorter anaesthetic method (local or RA vs spinal or GA) Sedation does involve risks especially respiratory depression, haemodynamic instability or uncontrolled movement

56. Patient factors: Dose requirement for sedative agents are decreased in elderly patients Risk of desaturation/haemodynamic instability is increased I patients >70 yr Similar in ASA III/IV or ASA I/II Elderly people are expected to be less anxious Thus sedation should be more restricted in the elderly

57. Factors influencing the level of sedation.. Several studies have shown that spinal and epidural can reduce anaesthetic requirement and induce sedation The peak sedation effect is usually detected 30-45 minutes after starting the block Enhance sedation by adding adrenaline Listen to music..

58. Ideal pharmacokinetic & pharmacodynamic properties Rapid onset, easy titration and high clearance p/dynamic dep on actions w/in the effect-site compartment = constant k Time to peak effect (TPE) seems to be a better measure as it is independent of the p/kinetic model, and the time course is predictable Elimination half life is of limited use

59. A short Context-sensitive half-time and a high clearance are essential for rapid offset of sedation and fast recovery The ideal sedative agent should also have minimal side effect

61. 326 patients were randomised to DEX 0.5, DEX 1 mcg/kg or saline placebo as initial loading dose Followed by maintenance 0.2-1.0 mcg/kg/h, titrate until <4 on OAA/S Midazolam given for OAA/S >4, and fentanyl for pain Primary end point - % of patients not requiring rescue midazolam

62. Results: Significantly fewer pts in the 0.5 and 1.0mcg/kg DEX group required supplemental midazolam compared with placebo (59%,45.7% vs 96.8%), at a lower dose to achieve OAA/S <4 before and during surgery Both DEX group required significantly less fentanyl 84.8&83.6mcg vs 144.4mcg Patient satisfaction was higher

63. Common adverse events ie bradycardia and hypotension were predominately mild to moderate in severity

64. Thank you for listening…