Pathway to Pain Control

Pathway to Pain Control Assessing, Preventing, and Managing Pain in the Intensive Care Unit Caitlin S. Brown, PharmD Brianne M. Ritchie, PharmD, MBA, BCCCP, BCPS Pharmacy Grand Rounds November 21, 2017 2015 MFMER slide-1

Disclosures The presenters have nothing to disclose 2015 MFMER slide-2

Objectives Discuss valid and reliable pain assessment tools in the ICU Recognize common ICU procedures that cause pain, necessitating interventions to prevent pain Describe important strategies to integrate into everyday clinical practice to prevent and manage pain ICU intensive care unit 2015 MFMER slide-3

Unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage. Pain. 1979;6:249. 2015 MFMER slide-4

Background Incidence of significant pain is 50% in ICU patients Approximately 50% of patients have pain at rest Untreated pain is associated with increased morbidities and cost In surgical patients, post-operative pain has been associated with chronic pain ICU intensive care unit Macrae WA. Br J Anaesth. 2008:101:77-86. Sinatra R. Pain Med. 2010;11:1859-1871. Barr J. Crit Care Med. 2013;41: 263-306. 2015 MFMER slide-5

Caring for ICU Patients Survival Comfort & Preventing Long Term Complications 2015 MFMER slide-6

Stressors in the ICU: Patients Evaluation Rank Description Mean Standard Deviation 1 Have pain 3.36 1.01 2 Not being able to sleep 3.34 0.98 3 Have tubes in your nose and mouth 3.26 1.01 4 Not being in control of yourself 3.10 1.11 ICU intensive care unit Novaes MA. Intensive Care Med. 1997;23:1282-1285. 2015 MFMER slide-7

Sources of Pain Invasive Procedures Daily Care Disease Process Pain Exacerbating Factors Sigakis M. Crit Care Med. 2015. 2015 MFMER slide-8

What Do We Care About Untreated Pain? Consequences of Pain Physiological Psychological Social/Economic Sigakis M. Crit Care Med. 2015. 2015 MFMER slide-9

Physiological Increased catecholamines Vasoconstriction Impaired tissue perfusion Catabolic hypermetabolism Hyperglycemia Lipolysis Breakdown of muscle Suppression of natural killer cells Sigakis M. Crit Care Med. 2015. Barr J. Crit Care Med. 2013;41: 263-306. 2015 MFMER slide-10

Psychological Insufficient sleep Most traumatic ICU memory Posttraumatic stress disorder Chronic pain ICU intensive care unit Sigakis M. Crit Care Med. 2015. Barr J. Crit Care Med. 2013;41: 263-306. 2015 MFMER slide-11

Socioeconomic Increased duration of mechanical ventilation Increased length of stay Increased mortality Increased cost Decreased quality of life Sigakis M. Crit Care Med. 2015. Barr J. Crit Care Med. 2013;41:263-306. 2015 MFMER slide-12

Barriers to Treatment of Pain Provider Healthcare System Patient Sigakis M. Crit Care Med. 2015. 2015 MFMER slide-13

Objectives Discuss valid and reliable pain assessment tools in the ICU Recognize common ICU procedures that cause pain, necessitating interventions to prevent pain Describe important strategies to integrate into everyday clinical practice to prevent and manage pain ICU intensive care unit 2015 MFMER slide-14

Assessing Pain in the ICU Patient s self-report Patient proxy report Clinician s assessment Barr. Crit Care Med. 2013; 41: 263-306. 2015 MFMER slide-15

Assessing Pain in the ICU Patient s self-report 1 Search for potential causes of pain 2 Observe patient behavior 3 Patient s proxy report 4 Attempt an analgesic trial 5 ASA. Anesthesiology. 2012; 116: 248-273. Barr. Crit Care Med. 2013; 41: 263-306. Chanques. Pain. 2010; 151: 711-721. Herr. Pain Manag Nurs. 2011; 12: 230-250. 2015 MFMER slide-16

Assessing Pain in the ICU Patient s Self-Report Pain assessment tools Numeric Rating Scale Visual Analog Scale Verbal Descriptor Scale ASA. Anesthesiology. 2012; 116: 248-273. Barr. Crit Care Med. 2013; 41: 263-306. 2015 MFMER slide-17

Assessing Pain in the ICU Patient s Self-Report Not all pain is avoidable Individualized and goal-oriented analgesia is essential ASA. Anesthesiology. 2012; 116: 248-273. Barr. Crit Care Med. 2013; 41: 263-306. Chanques. Pain. 2010; 151: 711-721. 2015 MFMER slide-18

Assessing Pain in the ICU Patient s Self-Report Pain assessment tools Numeric Rating Scale Visual Analog Scale Verbal Descriptor Scale Limitations Unable to self-report ASA. Anesthesiology. 2012; 116: 248-273. Barr. Crit Care Med. 2013; 41: 263-306. 2015 MFMER slide-19

Assessing Pain in the ICU Clinician s Assessment Pain assessment tools Facial expressions Body movements Ventilator interaction Consensus Guideline recommended scales Behavioral Pain Scale Critical Care Pain Observation Tool ASA. Anesthesiology. 2012; 116: 248-273. Barr. Crit Care Med. 2013; 41: 263-306. Puntillo. Chest. 2009; 135: 1069-1074. Li. J Pain. 2008; 9: 2-10. Arbour. J Trauma Nurs. 2011; 2015 MFMER 18: 52-60. slide-20

Assessing Pain in the ICU Behavioral Pain Scale Item Description Score Facial expression Upper limbs Compliance with mechanical ventilation Relaxed Partially tightened Fully tightened Grimacing No movement Partially bent Fully bent with finger flexion Permanently retracted BPS > 5 = Pain Tolerating movement Coughing but mostly tolerating ventilation Fighting ventilator Unable to control ventilation Total Score 3-12 1 2 3 4 1 2 3 4 1 2 3 4 ASA. Anesthesiology. 2012; 116: 248-273. Barr. Crit Care Med. 2013; 41: 263-306. Puntillo. Chest. 2009; 135: 1069-1074. Li. J Pain. 2008; 9: 2-10. Arbour. J Trauma Nurs. 2011; 18: 52-60. 2015 MFMER slide-21

Assessing Pain in the ICU Critical Care Pain Observation Tool Item Description Score Facial expression Body movements Relaxed, neutral: no muscular tension observed Tense: presence of frowning, brow lowering, orbit tightening, and levator contraction Grimacing: all of the above facial movements plus eyelids tightly closed Absent: doesn t move at all Protection: slow, cautious movements, toughing or rubbing the pain site, seeking attention Restlessness: pulling tube, attempting to sit up, moving limbs/thrashing, not following commands, striking at staff, trying to climb out of bed Muscle tension CPOT Relaxed: no resistance to passive > movements 2 = Pain Passive flexion/extension of Tense or rigid: esistance to passive movements upper extremities Very tense or rigid: trong resistance to passive movements, inability to complete them Ventilator compliance Tolerating ventilator or movement: alarms not activated, easy ventilation Coughing but tolerating: alarms spontaneously Fighting ventilator: asynchrony, blocking ventilation, alarms frequently activated OR Talking in normal tone or no sound Vocalization Sighing, moaning Crying out, sobbing Total Score 0 8 0 1 2 0 1 2 0 1 2 0 1 2 0 1 2 ASA. Anesthesiology. 2012; 116: 248-273. Barr. Crit Care Med. 2013; 41: 263-306. Puntillo. Chest. 2009; 135: 1069-1074. Li. J Pain. 2008; 9: 2-10. Arbour. J Trauma Nurs. 2011; 18: 52-60. 2015 MFMER slide-22

Assessing Pain in the ICU Clinician s Assessment Pain assessment tools Facial expressions Body movements Ventilator interaction Consensus Guideline recommended scales Behavioral Pain Scale Critical Care Pain Observation Tool Limitations Validation in diverse patient populations Unable to assess behaviors ASA. Anesthesiology. 2012; 116: 248-273. Barr. Crit Care Med. 2013; 41: 263-306. Puntillo. Chest. 2009; 135: 1069-1074. Li. J Pain. 2008; 9: 2-10. Arbour. J Trauma Nurs. 2011; 18: 52-60. 2015 MFMER slide-23

Assessing Pain in the ICU 70% 60% 50% 40% 30% Incidence of Pain Pain Unassessed Pain Assessed 63% P<0.01 P<0.01 42% 36% Medication Usage and Patient Outcomes Opioid Duration, hours Sedative Duration, hours Mechanical ventilation, hours Pre Post p 47% 96 54% 84 46% 60 55% 48 NS 0.02 NS 0.03 120 65 0.01 20% 10% 0% 16% Nosocomial infection 17% 8% 0.05 ICU LOS, days 8.5 7.0 NS Mortality 12% 15% NS Pain Severe Pain More escalation and de-escalation of analgesics and sedatives post-implementation Barr. Crit Care Med. 2013; 41: 263-306.. Chanques. Crit Care Med. 2006; 34: 1691-1699. 2015 MFMER slide-24

Assessing Pain in the ICU Medication Usage Pre Post p Opioids 95% 92% NS Nonopioids 29% 42% 0.01 Multimodal analgesia 24% 35% 0.01 Sedatives 86% 75% 0.01 Neuromuscular blockade 13% 7% 0.01 Days 20 18 16 14 12 10 8 6 4 2 0 Patient Outcomes Pain Unassessed 11 8 Mechanical Ventilation Pain Assessed 18 13 P=0.05 P=0.04 ICU Duration Barr. Crit Care Med. 2013; 41: 263-306. Payen. Anesthes. 2009; 111: 1187-1188. 2015 MFMER slide-25

Assessing Pain in the ICU Impact of Assessing Pain Pain assessment with a validated tool improves patient care Improved pain scores Improved utilization of multimodal analgesics No difference in opioid-related adverse events Decreased utilization of sedatives Decreased utilization of neuromuscular blockade Decreased duration of mechanical ventilation Decreased ICU length of stay Decreased mortality Improved utilization of chronic opioids Payen. Anesthesiology. 2007; 106: 687-695. Payen. Anesthesiology. 2009; 111: 1308-1316. van Gulik. Eur J Anaesthesiol. 2010; 27: 900-905. ASA. Anesthesiology. 2012; 116: 248-273. Barr. Crit Care Med. 2013; 41: 263-306. Gelinas. Int J Nurs Stud. 2011; 48: 1495-1504. Erdek. Int J Qual Health Care. 2004; 16: 59-64. 2015 MFMER slide-26

Assessing Pain in the ICU Key Concepts from Consensus Guidelines SCCM/ACCM Pain, Agitation, Delirium Guidelines Pain should be routinely monitored in all adult ICU patients Use of validated pain assessment tools Patient s self-report vs. behavioral pain scales Vital signs should never be used alone for pain assessment in adult ICU patients, but may trigger further assessment of pain ASA Perioperative Pain Guidelines Use standardized, validated instruments to facilitate the regular evaluation and documentation of pain intensity, effects of pain therapy, and side effects caused by therapy ASA. Anesthesiology. 2012; 116: 248-273. Barr. Crit Care Med 2013; 41: 263-306. 2015 MFMER slide-27

Assessing Pain in the ICU Key Concepts from Consensus Guidelines Pain should be routinely assessed and documented with validated pain assessment tools Self-reporting and behavioral pain scales are essential Therapeutic goals of analgesia should be individualized and patient-specific Pain assessment tools have limitations Analgesic trials may be an effective form of assessment ASA. Anesthesiology. 2012; 116: 248-273. Barr. Crit Care Med. 2013; 41: 263-306. 2015 MFMER slide-28

Assessing Pain in the ICU Assessment Question JT is a 70M admitted to the MICU for respiratory failure secondary to pneumonia. He arrives to your unit from the ED intubated with RASS +3. His past medical history and home medication list reveals diagnoses and medications for COPD and chronic pain. Which of the following do you recommend to obtain to improve JT s agitation? A. Vital signs B. Behavioral Pain Scale C. Urine toxicology screen D. Confusion Assessment Method for the ICU 2015 MFMER slide-29

Assessing Pain in the ICU Assessment Question JT is a 70M admitted to the MICU for respiratory failure secondary to pneumonia. He arrives to your unit from the ED intubated with RASS +3. His past medical history and home medication list reveals diagnoses and medications for COPD and chronic pain. Which of the following do you recommend to obtain to improve JT s agitation? A. Vital signs B. Behavioral Pain Scale C. Urine toxicology screen D. Confusion Assessment Method for the ICU 2015 MFMER slide-30

Objectives Discuss valid and reliable pain assessment tools in the ICU Recognize common ICU procedures that cause pain, necessitating interventions to prevent pain Describe important strategies to integrate into everyday clinical practice to prevent and manage pain ICU intensive care unit 2015 MFMER slide-31

Preventing Pain in the ICU Procedural Pain Procedural pain is common in adult ICU patients Pain Score 6 5 4 3 2 1 4.93 Thunder II: Procedural Pain Intensity 4.67 4.42 3.94 2.72 2.65 0 Turning Wound Drain Removal Wound Care Tracheal Suctioning Central Line Placement Femoral Sheath Removal ICU intensive care unit Barr. Crit Care Med. 2013; 41: 263-306. Puntillo. Am J Crit Care. 2001; 10: 238-251. 2015 MFMER slide-32

Preventing Pain in the ICU Procedural Pain Procedural pain is common in adult ICU patients 70% 60% 50% 40% 30% 20% 10% 0% 58% Turning Thunder II: Patients Reporting Increased Procedural Pain Intensity 65% Wound Drain Removal 53% 55% Wound Care Tracheal Suctioning 52% Central Line Placement 47% Femoral Sheath Removal ICU intensive care unit Barr J. Crit Care Med. 2013; 41: 263-306. Puntillo. Am J Crit Care. 2001; 10: 238-251. Puntillo. Am J Crit Care. 2002; 11: 415-431. 2015 MFMER slide-33

Preventing Pain in the ICU Procedural Pain Procedural pain is common in adult ICU patients Pain Score 7.0 6.0 5.0 4.0 3.0 2.0 1.0 0.0 4.1 Increased Procedural Pain Intensity 1.9 1.7 Pre-Procedure 6.5 2.4 4.4 Turning Drain Removal Tracheal Suctioning Post-Procedure P<0.05 2.4 1.6 1.9 Line Removal 5.5 Deep Breathing & Coughing ICU intensive care unit Barr. Crit Care Med. 2013; 41: 263-306. Siffleet. J Clin Nurs. 2007; 16: 2142-2148. 2015 MFMER slide-34

Preventing Pain in the ICU Procedural Pain but procedural pain is not commonly prevented! Sharp Tiring Shooting Exhausting Stabbing Awful Less than 20% of all patients received opioids before undergoing routine procedures Barr. Crit Care Med. 2013; 41: 263-306. Puntillo. Am J Crit Care. 2001; 238-251. 201510: MFMER slide-35

Preventing Pain in the ICU Procedural Pain but procedural pain is not commonly prevented! 100% Thunder II Untreated Treated Opiates Local Anesthetics 80% 60% 40% 20% 0% Turning Wound Drain Removal Wound Care Tracheal Suctioning Central Line Placement Femoral Sheath Removal Barr. Crit Care Med. 2013; 41: 263-306. Puntillo. Am J Crit Care. 2001; 10: 238-251. Puntillo. Am J Crit Care. 2002; 11: 415-431. 2015 MFMER slide-36

Preventing Pain in the ICU Procedural Pain but procedural pain is not commonly prevented! 100% 80% 63.6% of patients receive NO analgesics before undergoing or during procedure Thunder II Untreated Treated Opiates Local Anesthetics 94% 83% 82% 77% 60% 40% 42% 20% 7% 0% Turning Wound Drain Removal Wound Care Tracheal Suctioning Central Line Placement Femoral Sheath Removal Barr. Crit Care Med. 2013; 41: 263-306. Puntillo. Am J Crit Care. 2001; 10: 238-251. Puntillo. Am J Crit Care. 2002; 11: 415-431. 2015 MFMER slide-37

Preventing Pain in the ICU Procedural Pain but procedural pain is not commonly prevented! 100% 80% 63.6% of patients receive NO analgesics before undergoing or during procedure Thunder II Untreated Treated Opiates Local Anesthetics 90% 60% 40% 20% 0% 14% 15% 20% 0% 0% 2% 4% 0% Turning Wound Drain Removal Wound Care Tracheal Suctioning 16% Central Line Placement 34% 29% Femoral Sheath Removal Barr. Crit Care Med. 2013; 41: 263-306. Puntillo. Am J Crit Care. 2001; 10: 238-251. Puntillo. Am J Crit Care. 2002; 11: 415-431. 2015 MFMER slide-38

Preventing Pain in the ICU Procedural Pain but procedural pain is not commonly prevented! 80% 70% 60% 50% 40% 30% 20% 10% 0% 39% 33% Procedural Pain Management Opioid Non-opioid Post-Procedure Opioid 50% 50% 13% 38% 16% 53% 39% 39% Turning Drain Removal Tracheal Suctioning Line Removal Deep Breathing & Coughing Barr. Crit Care Med. 2013; 41: 263-306. Siffleet. J Clin Nurs. 2007; 16: 2142-2148. 2015 MFMER slide-39

Preventing Pain in the ICU Procedural Pain but procedural pain is not commonly prevented! 80% 70% 60% 50% 40% 30% 20% 10% 0% 15% Procedural Pain Management Opioid Non-opioid Post-Procedure Opioid 67% 6% 13% 31% Turning Drain Removal Tracheal Suctioning Line Removal Deep Breathing & Coughing Barr. Crit Care Med. 2013; 41: 263-306. Siffleet. J Clin Nurs. 2007; 16: 2142-2148. 2015 MFMER slide-40

Preventing Pain in the ICU Procedural Pain 100% Administration of Pre-emptive Fentanyl for Procedural Pain Associated with Turning Mechanically Ventilated Patients No Pretreatment 94% Procedural Pretreatment 80% 60% 74% 64% 49% 40% 20% 0% P=0.03 Pain P=0.25 Severe Pain Barr. Crit Care Med. 2013; 41: 263-306. Robleda. Intensive Care Med. 2016; 42: 183-191. 2015 MFMER slide-41

Preventing Pain in the ICU Procedural Pain 80% 70% Hospital Day 2 68% 80% 70% Hospital Day 6 68% 60% 50% 40% 30% 20% 60% P<0.01 P<0.01 50% P<0.01 P<0.01 40% 26% 30% 30% 17% 20% 18% 10% 0% 4% Procedural Pain Assessment Procedural Pain Treatment 10% 0% 3% Procedural Pain Assessment Procedural Pain Treatment Barr. Crit Care Med. 2013; 41: 263-306. Payen. Anesthes. 2009; 111: 1187-1188. 2015 MFMER slide-42

Preventing Pain in the ICU Key Concepts from Consensus Guidelines Procedural pain management technique is as important as agent selection Initiate pre-emptive analgesia before procedures, ensuring it is operational during procedures, in order to reduce procedural pain Pre-emptive analgesia is more effective than the same treatment administered during or after the procedure to reduce pain and subsequent analgesics Consider both non-pharmacologic and pharmacologic options ASA. Anesthesiology. 2012; 116: 248-273. Barr. Crit Care Med 2013; 41: 263-306. Pogatzki-Zahn. Curr Opin Anaesthesiol. 2006; 19: 551-555. 2015 MFMER slide-43

Preventing Pain in the ICU Assessment Question MK is a 65F who remains intubated in the cardiac surgery ICU overnight following CABG. As MK s assigned nurse, you note she is due for tracheal suctioning and wound cares, and her daughter tells you she believes MK would be more comfortable if she were repositioned. Which of the following procedures do you choose to provide pre-emptive procedural pain treatment with a fentanyl bolus to improve MK s pain intensity? A. Tracheal suctioning B. Wound cares C. Turning D. All of the above 2015 MFMER slide-44

Preventing Pain in the ICU Assessment Question MK is a 65F who remains intubated in the cardiac surgery ICU overnight following CABG. As MK s assigned nurse, you note she is due for tracheal suctioning and wound cares, and her daughter tells you she believes MK would be more comfortable if she were repositioned. Which of the following procedures do you choose to provide pre-emptive procedural pain treatment with a fentanyl bolus to improve MK s pain intensity? A. Tracheal suctioning B. Wound cares C. Turning D. All of the above 2015 MFMER slide-45

Objectives Discuss valid and reliable pain assessment tools in the ICU Recognize common ICU procedures that cause pain, necessitating interventions to prevent pain Describe important strategies to integrate into everyday clinical practice to prevent and manage pain ICU intensive care unit 2015 MFMER slide-46

Patient-Centered Multidisciplinary Approach Patient assessments improve outcomes Treat pain as a preventable adverse event Assess pain daily on rounds Analgesia-first sedation is recommend by the PAD guidelines PAD pain, agitation, delirium Barr J. Crit Care Med. 2013; 41: 263-306. Sessler C. Chest. 2009;135: 894-896. 2015 MFMER slide-47

Sedation Analgesia 2015 MFMER slide-48

Analgosedation Analgesia-based sedation Agitation is commonly secondary to pain Optimize pain management add sedation as needed Not recommended in certain patient populations Devabhakthuni S. Ann Pharmacotherapy. 2012;46:530-540. 2015 MFMER slide-49

Analgosedation Disadvantages Advantages Devabhakthuni S. Ann Pharmacotherapy. 2012;46:530-540. 2015 MFMER slide-50

A Protocol of No Sedation Study Design Population Intervention Primary Endpoint Secondary Endpoints Randomized, unblinded prospective study in Denmark Critically ill patients expected to need mechanical ventilation for > 24 hours admitted to medical and surgical ICU No sedation: Morphine and haloperidol as needed Sedation: Propofol (Ramsay 3-4) and morphine as needed x 48 hours then midazolam and morphine as needed with daily sedation interruption Number of days without mechanical ventilation in a 28-day period -Length of ICU stay -Length of hospital stay Strom S. Lancet. 2010;375:475-480. 2015 MFMER slide-51

Outcomes Days Without Mechanical Ventilation (From Intubation to Day 28) 16 14 14 Days (mean) 12 10 8 6 4 2 0 No Sedation p=0.0191 Study Group 10 Sedation Length of ICU and hospital stay were shorter in the no sedation group Morphine doses were similar between groups ICU intensive care unit Strom S. Lancet. 2010;375:475-480. 2015 MFMER slide-52

Impact of an Analgesia-Based Sedation Protocol Study Design Retrospective before and after cohort study Population Patients admitted to the medical ICU Intervention New & old sedation/analgesia protocols Primary Endpoint Secondary Endpoints Duration of mechanical ventilation -Medical ICU LOS -RASS scores during mechanical ventilation -CPOT scores -Sedative and analgesic medication use ICU intensive care unit LOS length of stay RASS Richmond Agitation Sedation Scale CPOT Critical Care Pain Observation Tool Faust A. Anesth Analg. 2016; 123: 903-909. 2015 MFMER slide-53

Protocol Old Protocol New Protocol Propofol titrated to RASS 0 to -2 Fentanyl titrated to RASS 0 to -2 PRN pain medications for CPOT score RASS +1 to +4 IV morphine initiated Acute agitation treated with fentanyl and midazolam IV push RASS +1 to +4 propofol or dexmedetomidine initiated Daily sedation awakening Faust A. Anesth Analg. 2016; 2015 123: MFMER 903-909. slide-54

Hours 160 140 120 100 Outcomes 80 60 40 20 0 Duration of Mechanical Ventilation 138.3 p=0.01 92.9 Sedation Protocol Analgosedation Protocol Sedation Protocol Deeper RASS scores during the sedation protocol Improved CPOT scores during analgosedation protocol ICU length of stay was shorter in the analgosedation group Only 38% of patients in the analgosedation group required continuous infusions of sedatives Faust A. Anesth Analg. 2016; 123: 903-909. 2015 MFMER slide-55

Opioid Review Fentanyl Hydromorphone Remifentanil Onset 1 2 minutes 5 15 minutes 1 3 minutes Elimination Half Life 2 4 hours* 2 3 hours 3 10 minutes Metabolism CYP3A4 Glucuronidation Active Metabolites *Context sensitive half life Hydrolysis by plasma esterases None None None Barr J. Crit Care Med. 2013;41:263-306. 2015 MFMER slide-56

Administration Techniques Supratherapeutic Steady state Therapeutic Range Subtherapeutic Bolus + Infusion Infusion Infusion (blind titration) 1 2 3 4 5 6 7 Half Lives 2015 MFMER slide-57

Population Pharmacokinetics of Fentanyl in the Critically Ill Study Design Population Primary Endpoint Prospective cohort study Patients admitted to the medical and surgical ICU receiving 48 hours of continuous infusion or 2 intermittent doses in 24 hours Duration of infusion: 58 hours Dose: 130 mcg/hr Fentanyl clearance Fentanyl pharmacokinetics in critically ill were affected by severe liver disease, congestive heart failure, and weight Chronic kidney disease did not affect fentanyl clearance Choi L. Crit Care Med. 2016; 44: 64-72. 2015 MFMER slide-58

Transitioning to Oral Agents Methadone NMDA receptor antagonist QTc prolongation Long half life titrate cautiously Enteral methadone decreased weaning time from mechanical ventilation Oxycodone Schedule doses to wean from sedation and analgesia for weaning from mechanical ventilation Wanzuita R. Crit Care. 2012;16:R49. 2015 MFMER slide-59

Multimodal Pain Agents Acetaminophen Enteral absorption in critically illness? Cost of IV acetaminophen Gabapentin Pregabalin Neuropathic pain Limited literature in critically ill patients Guillain-Barré and post-cabg patients Ketamine NMDA receptor antagonist Option for analgosedation NSAIDS Bleeding risk Kidney injury Dexmedetomidine Clonidine α2 adrenergic receptor agonist Provides sedation and analgesia Patanwala AE. J Intensiv Care Medicine. 2017;31:124. Borde DP. J Cardiothorac Vasc Anesth. 2017;31:124. Pandey CK. Anesh Analg. 2002;95:1719-1723. Barr J. Crit Care Med. 2013; 41: 263-306. 2015 MFMER slide-60

What About the Opioid Epidemic? 2015 MFMER slide-61

Strategies to Treat and Prevent Pain Assess pain BPS and/or RASS at goal No Yes Fentanyl 50-100 mcg IV push OR Hydromorphone 0.5-2mg IV push Continue to reassess Yes At RASS and BPS goal with 2-3 boluses No Fentanyl 25 200 mcg/hr OR Hydromorphone 0.5 5 mg/hr with PRN bolus doses for BPS not at goal Yes Undersedated Propofol, dexmedetomidine, midazolam RASS at goal No Oversedated Reduce dose of analgesic

Roles in Treating & Preventing Pain Optimal drug selection Ensure BPS and RASS monitoring Pain Treatment & Prevention Education Multidisciplinary collaboration on hospital protocols Assess pain on rounds daily 2015 MFMER slide-63

EO is a 83 year old male admitted to the medical ICU with septic shock and respiratory failure. He is on day 2 of mechanical ventilation. He is currently on propofol 50 mcg/kg/min and fentanyl 25 mcg/hr. His BPS score is a 6 and his RASS score is a +1. He is being treated with antibiotics for a pneumonia and he is currently on a norepinephrine infusion at 0.4 mcg/kg/min and a vasopressin infusion at 0.04 units/min. Which of the following options would be best to improve EO s pain management? A. Add acetaminophen 1000mg Q6H via Gtube B. Increase propofol to 70 mcg/kg/min C. Switch propofol to midazolam D. Increase fentanyl to 100 mcg/hr ICU intensive care unit BPS Behavioral Pain Scale RASS Richmond Agitation Sedation Scale 2015 MFMER slide-64

Unanswered Questions Difficult patient populations Opioid addiction after ICU admission Patient recollection and reconstructed memories 2015 MFMER slide-65

Summary There are deleterious effects of untreated pain Pain should be routinely assessed and documented with reliable and validated tools Routine ICU procedures and cares cause patients pain, and pre-emptive treatment should be considered and provided Analgosedation should be the foundation of pain and agitation management in the ICU Multidisciplinary approach for individualized pain management 2015 MFMER slide-66

Questions & Discussion 2015 MFMER slide-67

Pathway to Pain Control Assessing, Preventing, and Managing Pain in the Intensive Care Unit Caitlin S. Brown, PharmD Brianne M. Ritchie, PharmD, MBA, BCCCP, BCPS Pharmacy Grand Rounds November 21, 2017 2015 MFMER slide-68

Assessing Pain in the ICU Etiology of Agitation Gas exchange Hypoxemia Hypercarbia Metabolic Hypoglycemia Acidosis Ventilator-related Endotracheal tube malposition Tension pneumothorax Patient-ventilator dysynchrony Inadequate flow rates High or low tidal volumes Ventilator I/E times Pain Surgical/trauma/procedural Baseline pain Routine care/mobilization Infection Central nervous system Sepsis Ischemia Myocardial Intestinal Cerebral Drug and alcohol-related Intoxication Withdrawal Patient positioning in bed Fear and Anxiety Inability to communicate Sleep deprivation Full bladder or colon Drug side effects Anticholinergic Paradoxical response to benzos 2015 MFMER slide-69

Managing Pain in the ICU Difficult patient populations Patient population Chronic opioid users ECMO Severe burns Severe brain injury Obesity Obstructive sleep apnea Dementia or cognitive impairment Pediatrics Barriers to management Intrathecal pumps Buprenorphine requires switch to full agonist Tolerance, sensitization, and hyperalgesia Altered pharmacokinetics Mobilization requirements for lung transplant Altered pharmacokinetics Complex pain physiology Assessment of pain symptoms Altered pharmacokinetics Respiratory depression susceptibility Assessment of pain symptoms Altered pharmacokinetics Assessment of pain symptoms 2015 MFMER slide-70

Causes of Pain, Agitation, and Delirium 2015 MFMER slide-71

Pathophysiology of and Agents for Pain 2015 MFMER slide-72

Context-Sensitive Half Life Kim YS. J Neurocrit Care 2015;8:53-65. 2015 MFMER slide-73

Opioid Rotation A change in opioid drug or route of administration with the goal of improving outcomes Literature in cancer and chronic pain patients Mechanism not fully understood Synthetic vs. semi-synthetic Genetic polymorphisms Affinity for different opioid receptors Smith HS. J Pain Research. 2014;7:589-608. Fine PG. J Pain Symptom Manag. 2009; 38:418-425. 2015 MFMER slide-74

Opioid Rotation Fentanyl 150 200 mcg/hr Bolus hydromorphone 2mg Initiate hydromorphone infusion with ~25% reduction 2015 MFMER slide-75