1. Daily Awakenings Leanne Current, PharmD, BCPS January 2014

2. Reasons for a sedation vacation 1

3. Goal of sedation vacations Shorter length of time on the vent Less ICU delirium – Delirium associated with prolonged sedation – Delirium associated with benzodiazepines Prevent PTSD after hospital discharge Shorter ICU length of stay Less morbidity 2

4. Why do we need to have a sedation vacation? Tissue accumulation Change in patient needs – More tolerable ventilator settings – Better oxygenation (hypoxia=agitation) – No longer in pain – Trached and more comfortable – Delirium better managed Change in Renal or liver function Delayed response to doses and over titration Half life of medication causes overshooting of goals Reminder that drips are titratable down just as they are titratable up 3

5. 4 Days12 Goal sedation

6. Appropriateness for a sedation vacation 5

7. Reasons to Avoid Sedation Vacation Stopping agent will cause more harm than good Patient’s ventilator settings do not allow extubation in the near future Other medical reasons trump need to minimize sedation 6

8. 7 Flowsheet Outline FiO2 >60 PEEP > 7.5cm ICP >10 HR >140 MI within 24 hours Surgery scheduled ECMO Open abdomen Neurosurgical patient Active Agitation issues On NMBA Active EtOH withdrawal Active End of life Physician requested 7

9. What if the patient doesn’t seem appropriate and the MD wants a vacation anyway? An MD order trumps all items listed in the flow sheet If an MD requests a sedation vacation and the patient doesn’t meet criteria, please stop the line and clarify with the MD – “The patient’s current FiO2 is higher than the protocol allows for a sedation vacation, do you still want to do a sedation vacation?” – “The patient’s heart rate is 150bmp. Criteria for a sedation vacation indicates a heart rate less than 140bpm. How should I proceed?” 8

10. Drug Properties for pain and sedation

11. Treatment of pain OpiateIVPOIV Onset (min) Half-life (hours) Fentanyl0.1--1-22-4 Hydromorphone1.57.55-152-3 Morphine10305-103-4 10

12. Treatment of pain with IV medications OpiateIntermittent dosingIV infusion rateOther information Fentanyl 0.35-5 mcg/kg 25-100mcg 0.7-10 mcg/kg/hr 25-250mcg/hr Most lipophillic, accumulation w/ liver dysfunction Hydromorphone0.2-0.6 mg0.5-3 mg/hr May be better in patients tolerant to other agents Morphine2-4 mg2-30 mg/hr Active metabolites, histamine release 11

13. Opioid related side effects Sedation Muscle rigidity Respiratory depression Decrease GI mucus secretion and increase fluid absorption Nausea, vomiting Pruritus CONSTIPATION 12

14. Adjunctive pain agents Local and regional anesthetics Ketamine Acetaminophen NSAIDS Gabapentin or pregabalin Carbamazepine Non-pharmacological management strategies 13

15. Indications for sedation Treat agitation Promptly identify underlying causes – Delirium, pain, hypoxemia, hypoglycemia, hypotension, alcohol withdrawal Titration of sedation to light and arousable Sedation scales and protocols have reduced the amount of sedation patients receive and improve outcomes 14

16. Richmond Agitation and Sedation Scale (RASS) ScoreAgitationDescription 4CombativeViolent, dangerous to staff 3Very agitatedRemoves tubes/catheters, aggressive 2AgitatedFrequent non-purposeful movement, fights ventilator 1RestlesAnxious, not aggressive 0Alert and calm DrowsyNot fully alert, but has sustained awakening -2Light sedationBriefly awakens to voice -3Moderate sedation Movement to voice -4Deep sedationNo response to voice, but response to physical stimuli -5UnarousableNo response to voice or physical stimuli 15

17. Benzodiazepines Activate GABA-A receptors in the brain Anxiolytic, amnestic, sedating, hypnotic, and anticonvulsant effects Potency: Lorazepam > Midazolam > Diazepam Lipophilicity: Midazolam and Diazepam > Lorazepam All BDZs are metabolized hepatically Caution in elderly patients Lorazepam, oxazepam, and temazepam are renally cleared 16

18. Benzodiazepines AgentOnset (min) Half life (hours) Active metabolites IV infusion rate Midazolam2-33-11Yes1-7 mg/hr Lorazepam15-208-15No1-10 mg/hr Diazepam2-520-120YesNot used 17

19. Propofol Exact mechanism is not known Binds to GABA-A, glycine, nicotinic, and muscarinic receptors Sedative, hypnotic, anxiolytic, amnestic, antiemetic, and anticonvulsant No analgesic properties Highly lipid soluble Best for patients who need frequent awakenings Caution with egg and soybean allergies 18

20. Propofol 19 Adverse effects: hypertriglyceridemia, acute pancreatitis, myoclonus, hypotension Propofol infusion syndrome: metabolic acidosis, hypertriglyceridemia, hypotension with vasopressor use, arrhythmias, acute kidney injury, hyperkalemia, rhadbomyolysis AgentOnset (min)Half life (hours) Active metabolites IV infusion rate Propofol1-23-12No5-50 mcg/kg/min

21. Dexmedetomidine Selective alpha 2 receptor agonist Sedative, sympatholytic, and questionable analgesic properties Generally patients are more easily arousable with minimal respiratory depression Hepatically cleared Adverse effects: hypotension, bradycardia 20 AgentOnset (min) Half life (hours) Active metabolites IV infusion rate Dexmedetomidine5-101-3No0.2-0.7 mcg/kg/min

22. Awakening time Would you expect the patient to wake up fairly quickly based on its drug properties? And what confounding factors may slow clearance causing delayed awakening? – Propofol – Ativan – Versed – Fentanyl – Dilaudid – Morphine – Dexmedetomidine 21

23. Expectations of Daily awakenings 22

24. What does a sedation vacation mean? To stop intravenous pain and sedative agents that are currently causing the patient to not be as alert as baseline – Propofol, Ativan, Versed – Fentanyl, Dilaudid 23

25. What should I do to prepare for a sedation vacation? Evaluate your flowsheet checklist If patient doesn’t meet requirement, ask for clarification on multidisciplinary rounds The most important tool you can have for a sedation vacation is PRN pain and sedative agents. Why??? – If a patient fails vacation and patient isn’t going to be extubated you will need PRN agents to get them under control and to prevent dose titrations beyond their requirements. 24

26. Utilizing boluses to prevent over sedation 25 Days Goal Sedation 12

27. What about precedex? This agent is typically ordered when preparing for extubation Purpose of precedex is to allow the pt to remain calm and compliant with the ventilator without lowering respiratory drive Allow the patient to prove that he/she needs the agent when the other sedatives are stopped 26

28. How do I handle a sedation vacation when the patient is already on precedex? 90 percent of the time, it is appropriate to keep this agent going If the patient is only on precedex and they are overly drowsy, they may not require this agent to remain calm for extubation, consider stopping It is not wrong to pause this agent, in fact, the ideal patient would remain calm with no agent on board. If patient has had a h/o agitation and this was the reason for starting the agent, another appropriate method would be to titrate down to minimal requirements during the “sedation vacation” Once the patient is extubated, stop the agent. If agitation occurs after extubation, clarify with MD what agent to use. In general we will use other agents after extubation to assist the patient in remaining calm 27

29. The patient failed the trial, how do I proceed Is the patient acutely in pain? – Give PRN Pain agent (fentanyl, dilaudid, morphine, norco, etc) Is the patient acutely agitated? – Give PRN Sedative agent (ativan, versed) – If patient was on propofol gtt What rate to I set my drips at? – Regardless of agitation or not, restart at half the rate! – Utilize PRN pushes to support the patient through the agitation/pain period – If more than one push is required, then titrate up the agent – Let the patient prove they need more agent – Always titrate to calmness, while trying to maintain the highest level of alertness unless MD order specifies otherwise 28

30. Difficult patient scenarios

31. What if my patient is fully alert on their sedation? Stop the agent and do a sedation vacation. Let them prove they need the agent to remain calm The agent may be frivolous at that point…why give something they do not need? It is never wrong to ask for clarification, but the majority of the time your answer will be to stop the agent Remember, the ideal patient is the one tolerating the ventilator without any continuous infusion on board. Ideally we would have no gtts and utilize PRN agents to support them through acute pain and agitation 30

32. What if my patient is complaining of pain, should I stop the agent? If your pt is alert and complaining of pain, then get a clarification from the MD. We do not want to cause pain that would increase respirations and thus negatively impact their ability to be extubated. The patient may qualify for a transition to longer acting oral agents to control pain If they aren’t alert and unable to verbalize their pain, then stop the agent. – Let them prove to you they need the pain medication 31

33. Patient specific scenarios

34. HF is a 60 yoF on a ventilator now for 3 days. Her current regimen is Fentanyl 3mcg/kg/hour and Versed 5mg/hour. She qualifies for a sedation vacation so Sally stops the Versed. Has she done the correct thing? What recommendations would you make? 33

35. HF is a 60 yoF on a ventilator now for 3 days. Her current regimen is Fentanyl 3mcg/kg/hour and Versed 5mg/hour. She qualifies for a sedation vacation. After your brilliant education, Sally stops both the fentanyl and versed. However an hour later the patient starts fighting the ventilator and requires reinitiating the patient’s pain and sedation regimen. How should she proceed with reinitiating the pain and sedation on this patient? 34

36. MM is a 50 yoM on a ventilator for 7 days. He was initiated on precedex 0.5mcg/kg/hour yesterday after his propofol was stopped and he became agitated. He is also on fentanyl at 1mcg/kg/hr. He meets requirements for a sedation vacation. What other information do you need before deciding how to proceed? If he is in pain how would you proceed? If he is drowsy how would you proceed? 35

37. Questions?? Can you come up with difficult patient scenarios we can address in this session? 36