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Transcript of Mona K. Patel, PharmD Clinical Pharmacy Manager, Surgical ICU NewYork-Presbyterian Hospital Columbia...
Mona K. Patel, PharmD
Clinical Pharmacy Manager, Surgical ICU
NewYork-Presbyterian Hospital
Columbia University Medical Center
October 2, 2015
WHAT’S NEW IN THE MANAGEMENT OF PAIN IN THE ICU
DISCLOSURES
None
OBJECTIVES
Explain the etiology of pain in critically ill patients
Describe consequences of uncontrolled pain in criticallyill patients
Identify tools for the assessment of pain
Outline methods for the management of pain
INCIDENCE OF PAIN IN CRITICALLY ILL PATIENTS
Leading cause of stress in critically ill patients
Many patients will experience moderate to severe pain at rest and/or during procedures
>50% of medical and surgical ICU patients experience moderate to severe pain at rest
>50% recall moderate to extreme pain after ICU dischargeAnesthesiology 2007;107:858-860.Anesthesiology 2007;106:687-695.Intensive Crit Care Nurs 2007;23:298-303.Crit Care Med 2008;36:2801-2809.
NOCICEPTIVE PAIN
Physiol Rev 2014;94:81-140.
CAUSES OF PAIN
PainSurgical incisions
Tubes, drains,
catheters
Immobility
Tracheal suctioning Turning
Dressing changes
Altered sensorium
Trauma
Anesthesiology 2007;107:858-860.Am J Crit Care 2001;10:238-251.
PROCEDURAL PAIN
Common procedures can be a significant source of pain
Am J Respir Crit Care Med 2014;189:39-47.
Procedure N (%) Pre-procedural pain intensity*
Pain intensity during procedure* P value
Wound drain removal 75 (1.6) 2 (0-4) 4.5 (2-7) <0.0001
Chest tube removal 292 (6.1) 2 (0-4) 5 (3-7) <0.0001
Arterial line insertion 199 (4.1) 1 (0-2.5) 4 (2-6) <0.0001
Endotracheal suctioning 767 (15.9) 1 (0-4) 4 (1-6) <0.0001
Peripheral blood draw 328 (6.8) 0.5 (0-3) 3 (1-5) <0.0001
Positioning 371 (7.7) 1 (0-4) 3 (0-5) <0.0001
* Data are shown as median (IQR)
LITTLE PROGRESS WITH ICU PAIN
Routine aspects of ICU care are the most troublesome for patients
199063% remembered moderate to severe pain
200750% remembered unmet analgesic needs
Heart Lung 1990;19:526-533.Intensive Crit Care Nurs 2007;23:298-303.
LITTLE PROGRESS WITH ICU PAIN
Pain is not being recognized and treated 842 ICU nurses surveyed
•33% used pain assessment tools for patients unable to communicate
•42% targeted treatment to pain score
•61% reported pain scores during nursing handoff
Observational study including 1,381 ICU patients
Am J Crit Care 2012;21:251-259.Anesthesiology 2007;106:687-695.
Day 2(n=1,360)
Day 4(n=1,256)
Day 6(n=1,099)
Analgesia Assessment Treatment
42%90%
39%80%
37%74%
Procedural pain Assessment Treatment
35%22%
35%21%
35%22%
CONSEQUENCES OF PAIN
Inadequate sleep Traumatic memories after ICU
discharge Post traumatic stress disorder Chronic pain Decreased quality of life
Crit Care Med 1998;26:651-659.Intensive Care Med 1979;5:89-92.Crit Care Clin 1999;15:167-184.Arch Surg 1991;126:338-342.
Impairment of tissue perfusion Catabolic hypermetabolism Immune system impairment Difficulty managing severe pain Delirium Agitation
RELATIONSHIP BETWEEN PAIN, AGITATION AND DELIRIUM
N Engl J Med 2014;370:444-454.
NECESSITY OF PAIN CONTROL
Patient comfortMobilization Judicious use of sedative agentsDecrease length of mechanical ventilationReduce ICU length of stay
Crit Care Med 2006;34:1691-1699.Anesthesiology 2009;111:1308-1316.J Trauma Nurs 2011;18:52-60.Anesthesiology 2009;111:1308-1316.
PAIN ASSESSMENT REDUCES SEDATIVE USE
Day 2 Pain Assessment?P value
No (n=631)
Yes (n=513)
Any sedative 86% 75% < 0.01
Midazolam 65% 57% < 0.01
Propofol 21% 17% 0.06
Other 6% 4% 0.03
Anesthesiology 2009;111:1308-1316.
PAIN ASSESSMENT IMPROVES OUTCOMES
Outcome
Day 2 Pain Assessment? Unadjusted
OR P value Adjusted OR P value
No Yes
ICU Mortality 22% 19% 0.91 0.69 1.06 0.71
ICU LOS 18 d 13 d 1.70 < 0.01 1.43 0.04
MV duration 11 d 8 d 1.87 < 0.01 1.40 0.05
Ventilator Acquired
Pneumonia 24% 16% 0.61 < 0.01 0.75 0.21
Anesthesiology 2009;111:1308-1316.
ASSESSMENT OF PAIN Assess ≥ 4x/shift and before/after any procedure and analgesic
administration
Assessment scales should be used to determine if intervention needed and is adequate Patient self-report (gold standard)
• Numeric Rating Scale (NRS)
• Visual Analog Scale (VAS)
Behavioral Pain Scale (BPS) Critical Care Pain Observation Tool (CPOT)
Vital signs should not be used alone to assess painCrit Care Med 2013;41:263-306.www.iculiberation.org
BEHAVIORAL PAIN SCALE
Crit Care Med 2001;29:2258-2263.
Item Description Score
Facial expressionRelaxed
Partially tightened (e.g. brow lowering)Fully tightened (e.g. eyelid closing)
Grimacing
1234
Upper limbsNo movementPartially bent
Fully bent with finger flexionPermanently retracted
1234
Compliance with ventilationTolerating movement
Coughing but tolerating ventilation for most of timeFighting ventilator
Unable to control ventilation
1234
CRITICAL CARE PAIN OBSERVATIONAL TOOLIndicator Score Description
Facial expressions
Relaxed, neutral 0 No muscle tension observed
Tense 1 Presence of frowning, brow lowering, orbit tightening and levator contraction or any other change (e.g. opening eyes or tearing during nociceptive procedures)
Grimacing 2 All previous facial movements plus eyelid tightly closed (the patient may present with mouth open or biting the endotracheal tube)
Body movements
Absence of movements or normal position 0
Does not move at all (doesn’t necessarily mean absence of pain) or normal position (movements not aimed toward the pain site or not made for the purpose
of protection)
Protection 1 Slow, cautious movements, touching or rubbing the pain site, seeking attention through movements
Restlessness/Agitation 2 Pulling tube, attempting to sit up, moving limbs/thrashing, not following commands, striking at staff, trying to climb out of bed
Compliance with the ventilator (intubated patients)
OR
Vocalization (extubated patients)
Tolerating ventilator or movement 0 Alarms not activated, easy ventilation
Coughing but tolerating 1 Coughing, alarms may be activated but stop spontaneously
Fighting ventilator 2 Asynchrony: blocking ventilation, alarms frequently activated
Talking in normal toneor no sound 0 Talking in normal tone or no sound
Sighing, moaning 1 Sighing, moaning
Crying out, sobbing 2 Crying out, sobbing
Muscle tension
Relaxed 0 No resistance to passive movements
Tense, rigid 1 Resistance to passive movements
Very tense or rigid 2 Strong resistance to passive movements or incapacity to complete them
Am J Crit Care 2006;15:420-427.
Risk assessment
• Severity of illness• Chronic pain conditions• Coexisting symptoms• Frequency and invasiveness of therapies
Early recognition
• Use of validated tools• Frequent assessment
Non-pharmacologic
• Non-pharmacologic (e.g. music therapy, relaxation technique)
• Positioning• Removal of offending agent
Pharmacologic • Non-opioids• Opioids
TREATMENT OF PAIN
Chest 2009;135:1069-1074.
Q1: WHICH OF FOLLOWING ARE BENEFITS OF PAIN ASSESSMENT?
A. Reduce incidence of ileus
B. Decrease use of sedation
C. Increase length of mechanical ventilation
D. Decrease incidence of fractures
E. Improvement in urine output
Q2: ROUTINE PROCEDURES DO NOT CAUSE PAIN IN CRITICALLY ILL PATIENTS
A. True
B. False
First line for the treatment of non-neuropathic painChoice of agent is multi-factorial
Onset of action Duration of action Elimination Adverse effects Cost
OPIOIDS FOR THE TREATMENT OF PAIN
Crit Care Med 2013;41:263-306.
OPIOIDS FOR THE TREATMENT OF PAIN
Opiate
IV potency ratio
(relative to morphine)
Onset (IV)
T1/2 (h)
Active metabolite Metabolism Clinical considerations
Fentanyl 100:1 1-2 min 2-4 No Demethylation, CYP3A4 substrate
Accumulation with hepatic impairment
Hydromorphone 5:1 5-15 min 2-3 No Glucuronidation Accumulation with hepatic/renal impairment
Morphine 1:1 5-10 min 1.5-5 Yes Demethylation, glucuronidation
Accumulation with hepatic/renal impairment; histamine release;
active metabolite
Remifentanil 20:1 1-3 min 0.05 No Hydrolysis by plasma esterases
Use ideal body weight for obese patients; cost; glycine neurotoxicity
Crit Care Med 2013;41:263-306.AJHP 2015;72:1531-1543.Chest 2009;135:1075-1086.Chest 2008;133:552-565.Crit Care Clin 2009;25:431-449.
MAXIMIZING OPIOID EFFECTIVENESS
Weigh risks vs benefits when determining dose or duration
Use caution when determination of equipotent doses
Consider all opioids equally effective at equipotent doses
Aggressively treat patients with severe pain
Incorporate non-opioids
Chest 2009;135:1075-1086.
NON-OPIOID MANAGEMENT OF PAIN
Gabapentin (neuropathic pain)Carbamazepine (neuropathic pain)Ketamine Acetaminophen Local and regional anestheticsNonsteroidal anti-inflammatory drugs (NSAIDS)
BENEFITS OF MUTLI-MODAL PAIN REGIMENS
Decrease opioid administration
Decrease incidence of opioid related adverse effects
Reduce severity of opioid related adverse effects
Achieve better neuropathic pain control
Crit Care Med 2013;41:263-306.Anesth Analg 2002;95:1719-1723.Anesth Analg 2005;101:220-225.
CHOOSING THE RIGHT PAIN REGIMEN
Dependent on many factors
Crit Care Med 2013;41:263-306.Chest 2009;135:1075-1086.
Drug pharmacokinetics Active metabolites
Frequency, severity of pain Presence of contraindications
Mental status Unknown drug-nutrient interactions
Gastrointestinal absorption Restricted personnel for administration
Source of pain Intact patient cognition for administration
Chronic pain Possible adverse effects of agents
Pain should be treated first regardless of chosen regimen
ANALGESIA-FIRST SEDATION
“Analgosedation” or “A-1”
Treat pain and discomfort first
Add sedatives, if needed, after treating pain
Crit Care Med 2013;41:263-306.Chest 2009;135:1075-1086.Chest 2008;133:552-565.
WHY DO WE CARE ABOUT ANALGOSEDATION?
Sedation is commonly used to manage patient discomfort
Sedatives are associated with adverse drug effects
Deep sedation is harmful when not indicated
Pain control will help improve comfort and reduce sedation requirements
Ann Pharmacother 2012;46:530-540.
A PROTOCOL OF LIMITED SEDATION FOR CRITICALLY ILL PATIENTS
Lancet 2010;375:475-480.
Mechanically ventilated medical and surgical patients
No sedation(n=55)
prn IV morphine
Continued discomfortNonpharmacologicprn IV haloperidol
Propofol infusion x6h
Sedation(n=58)
prn IV morphine + propofol infusion x 48h, then prn morphine + IV midazolam infusion
Daily interruption of sedationGoal Ramsey 3-4
A PROTOCOL OF LIMITED SEDATION FOR CRITICALLY ILL PATIENTS
Greater days without ventilation in no sedation group Mean difference 4.2 days (95% CI 0.3-8.1), p=0.019
Sedation increased length of stay ICU: HR 1.86 (95% CI 1.1-3.2), p=0.032 Hospital: HR 3.57 (95% CI 1.5-9.1), p=0.004
No difference in mortality between no sedation vs sedation groups ICU: 22% vs 38%, p=0.06 Hospital: 36% vs 47%, p=0.27
Great incidence of delirium in no sedation group
Lancet 2010;375:475-480.
REMIFENTANIL ANALGOSEDATION
Randomized, multicenter study with mechanically ventilated MICU and SICU patients Remifentanil infusion +/- propofol infusion (n=96) vs morphine or
fentanyl infusion + propofol, midazolam, or lorazepam infusion (n=109) Patients in remifentanil group more likely to be extubated on day 1-3
• OR 1.86 (95% CI 1.11-3.11), p=0.02
No difference in ICU discharge in remifentanil group on day 1-3• OR 1.89 (95% CI 1.00-3.59), p=0.05
Intensive Care Med 2009;35:291-298.
Randomized, multicenter study with mechanically ventilated MICU and SICU patients Remifentanil infusion +/- midazolam bolus (n=57) vs morphine or
fentanyl infusion + midazolam infusion or bolus (n=48) Patients in remifentanil group had shorter time to extubation
• -53.5h (95% CI -111.4 to 4.4), p=0.033
No difference in ICU discharge • -22.5h (95% CI -201.5 to 156.5), p=0.326
REMIFENTANIL ANALGOSEDATION
Crit Care 2005;9:R200-R210.
ADVANTAGES OF ANALGOSEDATION
Reduce sedative use Lower risk of prolonged sedative effects Decrease risk for sedative-related adverse effectsShorten mechanical ventilation timeReduce length of stay
Ann Pharmacother 2012;46:530-540.
DISADVANTAGES OF ANALGOSEDATION
Opioid associated delirium Unpleasant recall Immunosuppression Opioid withdrawal Hyperalgesia
Ann Pharmacother 2012;46:530-540.
Increased opioid requirement Reduced gastrointestinal motility Long term outcomes unknown
ROLE OF ANALGOSEDATION IN CRITICALLY ILL PATIENTS
May be considered prior to initiation of sedation in critically ill patients
Addition of non-opioid therapy may minimize some disadvantages
Avoid in certain patient populations Paralysis Status epilepticus Withdrawal syndromes Elevated intracranial pressures
KETAMINE
Phencyclidine derivative
Commonly used for procedural sedation, intubation, spinal analgesia and postoperative pain management
Antagonism of glutamate at N-methyl-D-aspartate (NMDA) receptor; activation of μ, κ, δ receptors; monoaminergic, muscarinic, nicotinic receptor antagonism
Inhibition of “wind-up phenomenon”
Minerva Anestesiol 2011;77:812-820.J Palliat Care 2012;15:474-483.
KETAMINE Labeled indication: induction and maintenance of general anesthesia
Induction: (IV) 1-4.5 mg/kg (IM) 16.5-13 mg/kg Maintenance of anesthesia: (IV) 15-90 mcg/kg/min
Studied regimens for pain control Oral Epidural IV - PCA, continuous infusion, single dose
Continuous IV infusion of subanesthetic ketamine may have a growing role for the management of pain in ICU patients
J Palliat Med 2012;15:474-483.Anesth Analg 2004;99:482-495.
Patient population Intervention Narcotic reduction Pain scores Adverse effects
Cardiac surgery KET 75 mcg/kg bolus then 1.25 mcg/kg/min (n=44) vs
PL (n=46) x48h
Oxycodone requirements:KET 103±44 mg vs
PL 125±45 mg, p=0.023 No difference
No difference
4 patients with psychomimetic effects with KET vs 0 with PL
Knee arthroplastyKET 0.5 mg/kg then
3 mcg/kg/min during surgery then 1.5 mcg/kg/min (n=20)
vs PL (n=20) x48h
Morphine requirements:KET 45±20 mg vs
PL 69±30 mg, p<0.02No difference No difference
Major abdominal surgery
KET 0.5 mg/kg then 2 mcg/kg/min x 24h then 1
mcg/kg/min x24h (n=41) vs PL (n=52)
Morphine requirements:KET 58±35 mg vs
PL 80±37 mg, p<0.05No difference No difference
REDUCTION OF OPIOID USE WITH KETAMINE
Anesth Analg 2004;99:1295-1301.Anesth Analg 2005;100:475-480.Anesth Analg 2003;97:843-847.KET=ketamine; PL=placebo
Reduction in morphine use after major abdominal surgery
Less morphine use in perioperative group• Perioperative 27 mg vs intraoperative 48 mg vs placebo 50 mg, p=0.008
Better pain scores in perioperative and intraoperative groups vs placebo at H4 (p=0.004), H24 (p=0.0001), H48 (p=0.001)
REDUCTION OF OPIOID USE WITH KETAMINE
Anesth Analg 2008;106:1856-1861.
Perioperative (n=23) 0.5 mg/kg bolus then 2 mcg/kg/min x 48h starting intraoperatively
Intraoperative (n=27) 0.5 mg/kg bolus then 2 mcg/kg/min intraoperatively only
Placebo (n=27) --
REDUCTION OF OPIOID USE WITH KETAMINE
Reduction in morphine use after thoracotomy PCA with morphine 1.5 mg + placebo (n=20) vs
PCA morphine 1 mg + ketamine 5 mg (n=21) x 4h Ketamine group required 45% less morphine over 4h (p<0.001)
• Hour 1: 6.8±1.9 mg vs 3.7±1.2 mg, p=0.001
• Hour 2: 5.5±3.6 mg vs 2.8±2.3 mg, p=0.008
Lower maximal pain scores in ketamine group• 5.6±1.0 vs 3.7±0.7, p=0.001
No difference in adverse effects
Chest 2009;136:245-252.
ADVANTAGES OF KETAMINE
BronchodilationPreservation of cardiac outputNot associated with bradycardia or hypotension Low side effect profile at subanesthetic doses No depression of respiratory drive Decrease in opioid tolerance IV administration Low cost
DISADVANTAGES OF KETAMINE
Adverse effects
Negative inotrope in heart failure or cardiogenic shock statesUnclear safety in patients with neurological injury, pulmonary
hypertension, cardiac ischemiaUnknown impact on delirium Optimal dosing not known
Hypersalivation Hypertension Psychomimetic effectsNystagmus Tachycardia
IV ACETAMINOPHEN – WHAT DO WE KNOW?
Approved in 2010
Opioid sparing effects seen in many patient populations with once or repeat dosing
Well tolerated and safe
Pharmacotherapy 2014;34:34S-39S.
Total hip or knee replacement Major abdominal or pelvic surgery
Abdominal laparoscopy Molar surgery
Abdominal hysterectomy Tosillectomy
ACETAMINOPHEN PHARMACOKINETICS
Single dose pharmacokinetics of IV vs oral vs rectal
Pain Pract 2012;12:523-532.
REDUCTION OF OPIOID USE WITH IV ACETAMINOPHEN
Patient population and design Intervention Morphine equivalents
Pain scores during
intervention
Length of stay
Total abdominal hysterectomies
Retrospective
IVA with opioids (n=50) vs
OA (n=50)
Post-operative day 1-2IVA 47±24 mg vs OA 68±37 mg, p=0.003
Total perioperative periodIVA 73±24 mg vs OA 99±39 mg, p=0.001
Not assessed Not assessed
Bariatric surgery
Retrospective
IVA with opioids (n=38) vs
OA (n=47)Postoperative day 1IVA 100 mg vs OA 165 mg, p=0.018 Not assessed Not assessed
Surgical knee procedures
Retrospective, case-control
IVA with opioids (n=25) vs
OA (n=75)
Total postoperative courseIVA 135 mg vs OA 113 mg, p=0.987
DailyIVA 45 mg vs OA 38 mg, p=0.845
Not assessed No difference
Pharmacotherapy 2014;34:27S-33S.J Surg Res 2015;195:99-104.Pharmacotherapy 2014;34:22S-26S.
IVA=IV acetaminophenOA=opioids only
IV VERSUS PO ACETAMINOPHEN
Limited opioid sparing with IV vs PO acetaminophen in cardiac surgery patients
1g po q6h (n=38) vs 1g IV q6h (n=39) until morning after surgery Lower ketobemidone with IV acetaminophen
• 17.4±7.9 mg vs 22.1±8.6 mg (p=0.016) No difference in pain scores No difference in visual analog scores >3 No difference in nausea/vomiting
J Cardiothorac Vasc Anesth 2005;19:306-309.
ADVANTAGES OF IV ACETAMINOPHEN
Faster onset of action compared to other routes
Reduction of opioid requirements
Well tolerated in clinical trials
Administration in patients unable to tolerate alternate routes
DISADVANTAGES OF IV ACETAMINOPHEN
Administration considerations Stable for maximum 6h after vial is opened Fluid restricted patients Single use vials Pregnant patients
Limited evidence comparing to oral and rectal routesUnknown impact on clinical outcomes Cost
LIPOSOMAL BUPIVACAINE – WHAT DO WE KNOW THUS FAR?
Approved in 2011
Local anesthetic for use in management of postsurgical pain in adults
Use of DepoFoam technology releases bupivacaine over extended period of time offering lasting pain control without affecting the active ingredient
Exparel (bupivacaine liposomal injectable suspension) [package insert] Pacira Pharmaceuticals, Inc.;2014.
Studied in many patient populations
Narcotic reduction and better pain scores noted vs placebo
Inconsistent benefit when compared to conventional bupivacaine
LIPOSOMAL BUPIVACAINE – WHAT DO WE KNOW THUS FAR?
Inguinal hernia repair Total knee arthroplasty
Hemorrhoidectomy Breast augmentation
Bunionectomy Open colectomy
Ileostomy reversal Abdominal hernia repair
Robotic prostatectomy
J Clin Ther 2015;37:1354-1371.
LIPOSOMAL BUPIVACAINE FOR POSTSURGICAL ANALGESIAEquivalent randomized, controlled trialsStudy Intervention Results
Laparoscopic urologic surgery patients
0.25% bupivacaine (weight based) (n=64) vs LB 266 mg
(60 mL) (n=68)• No difference in median total opioid dose, pain score, length of
hospital stay, time to first opioid use (p>0.05)
Total knee arthroplasty
Periarticular administration
Bupivacaine 150 mg (60 mL)(n=53) vs LB 266 mg (20 mL) +
bupivacaine 75 mg (30 mL) (n=58)
• No difference in pain scores assessed on morning or afternoon on days 1, 2, 3, hospital length of stay, knee range of motion, opioid use, nausea (p>0.05)
Total knee arthroplastyLB 266 mg (60 mL) (n=40) vs 0.5% ropivacaine + 1:200,000 epinephrine + 1% tetracaine
30 mg (40 mL) (n=40)
• No difference in total pain score, passive extension, nausea, vomiting, opioid consumption, ambulation (p>0.05)
• Higher mean pain score with LB on POD 0 (3.84 vs 2.91, p<0.05)
• Lower flexion in with LB (94° vs 101°, p=0.001)• Higher opioid consumption with LB on POD 0
(25.5 mg vs 13.9 mg, p<0.05) and lower with LB on POD 1 (3.9 mg vs 9.1 mg, p<0.05)
J Athroplasty 2015;30:64-67.J Athroplasty 2015;30:325-329.J Endourol 2015;29:1019-1024.LB=liposomal bupivacaine
LIPOSOMAL BUPIVACAINE FOR POSTSURGICAL ANALGESIA Randomized, controlled trial in robotic assisted
hysterectomy patients LB 13 mg (30 mL) (n=28) vs control 0.25% bupivacaine +
1:200,000 epinephrine (30 mL) (n=30) Lower total pain scores and opioid use with LB
Less nausea with LB (25% vs 57%, p=0.01) No difference in hospital length of stay with LB vs control
• 11±9h vs 17±14h, p=0.06
Gynecol Oncol 2015;138:609-613.LB=liposomal bupivacaine
T0-24h(LB vs control)
T24-48h(LB vs control)
T48-72h(LB vs control)
Maximum pain score 5 (0-10) vs 7 (0-10), p=0.01 4 (0-8) vs 5 (1-10), p=0.04 3 (0-8) vs 5 (0-10), p=0.047
Opioid use 13 (0-50) vs 25 (5-88), p=0.02 3 (0-27) vs 8 (0-68), p=0.02 2 (0-12) vs 5 (0-40), p=0.30
Positive, randomized controlled trial in open total hysterectomy patients 0.5% bupivacaine (40 mL) (n=30) vs LB 266 mg (60 mL) (n=30) Marginal benefits in opioid consumption with LB
• Morphine use T0-24h: 47.7 (28.8) mg vs 33.6 (24.3) mg, p=0.05
• Hydrocodone 5mg + acetaminophen 325 mg use T24-48h: 3.6 (2.8) vs 1.9 (1.7), p=0.01
Lower pain scores with LB
Anesth Analg 2015 [Epub ahead of print]
* p<0.01** p<0.001
LIPOSOMAL BUPIVACAINE FOR POSTSURGICAL ANALGESIA
ADVANTAGES OF LIPOSOMAL BUPIVACAINE
May reduce opioid requirements
Decreased need for patient controlled analgesia pumps
Convenience
Good safety profile
DISADVANTAGES OF LIPOSOMAL BUPIVACAINE
Not studied in critically ill patientsNo role in non-surgical patients Unknown impact in chronic pain patientsSafety in pregnant patients unknown Conflicting literatureCost
NSAIDS
Relieve inflammation and associated nociceptive stimuli via inhibition of cylooxygenase
Agents available Ibuprofen (IV, po, topical) Ketorolac (IV, po, nasal, ophthalmic) Diclofenac (IV, po, topical, ophthalmic)
Lancet 2011;377:2215-2225.
IV DICLOFENAC
FDA approval in December 2014
Significant improvement in pain intensity and opioid reduction compared to placebo
Limited data comparing to other NSAIDS
Anesth Analg 2012;115:1212-1220.
IV DICLOFENAC
Randomized controlled trial in abdominal or pelvic surgery patients IV diclofenac (n=173) vs ketorolac (n=82) vs placebo (n=76) Significant analgesia with IV diclofenac vs placebo IV diclofenac vs IV ketorolac
• No difference in sum of pain intensity difference, median time to >30% pain intensity reduction, opioid requirements, total pain relief
• No difference in adverse effects
Anesth Analg 2012;115:1212-1220.
IV DICLOFENAC
Randomized controlled trial in orthopedic surgery patients IV diclofenac (n=145) vs ketorolac (n=60) vs placebo (n=72) Significant analgesia with IV diclofenac vs placebo IV diclofenac vs IV ketorolac
Less morphine used in patients receiving diclofenac than ketorolac • 11.8 mg vs 18.1 mg, p=0.008
Less severe pain (VAS≥70 mm) with diclofenac than ketorolac• 42.1% vs 51.7%, p≤0.05
Incidence of adverse effects were similar
Clin J Pain 2013;29:655-663.
ADVANTAGES OF NSAIDS
Several products available
Administration to patients unable to tolerate oral agents
Reduction in opiate use and better pain control
Targeting pain secondary to inflammation
DISADVANTAGES OF NSAIDS
Role of NSAIDS is limited for pain control in ICU patients
Increased risk for bleeding and renal dysfunction
FDA warning for increased risk of heart attack, heart failure and stroke in patients with or without heart disease or risk factors for heart disease Increased risk with higher doses, longer duration
Animal and in vitro data showing impaired bone healing
http://www.fda.gov/Drugs/DrugSafety/ucm451800.htmCurr Opin. Rheumatol 2013;25:524-531.
The ultimate question:
How can patient comfort be safely and reliably achieved in the ICU?
PAIN PROTOCOL
Systematic assessment, treatment and prevention is necessary
Pain protocols are associated with positive outcomes Decrease use of psychoactive medications Reduce medication induced coma Decrease pain and agitation Reduce ICU length of stay Shorten duration of mechanical ventilation
Incorporate multi-modal therapy
Crit Care Med 2006;34:1691-1699.Anesth Analg 2010;111:451-463.Crit Care Med 2013;41:263-306.
ANALGESIA/SEDATION ALGORITHM
1. In Pain?
2. At RASS target?
3. Delirium?
Yes
Reassess often
Analgesia may be adequate to reach RASS target
YesReassess often
SAT+SBT dailyphysical therapy
No
Bolus dosing prn with either• Fentanyl 50-100 mcg• Hydromorphone 0.1-0.3 mg• Morphine 2-5 mg
Controlled or anticipated control with <3 bolus/doses/h
Yes
No• Fentanyl 50-300 mcg/h infusion• Fentanyl 25-100 mcg prn pain
Over sedated Hold sedative/analgesic to achieve RASS target. Restart at 50% if clinically indicated
NoNo
Under sedated• Propofol 5-30 mcg/kg/min• Dexmedetomidine 0.2-1.5 mcg/kg/hr
(if delirious/weaning)• Midazolam 1-3 mg prn (alcohol
withdrawal or propofol intolerance)
CAM-ICU positive• Non-pharmacological management• Pharmacological management
CAM-ICU negativeReassess q6-12h
www.icudelirium.org
RASS=Richmond Agitation Sedation ScaleSAT=Spontaneous awakening trialSBT=Spontaneous breathing trialCAM-ICU=Confusion Assessment Method for the ICU
Analgosedation?Ketamine?
Acetaminophen?NSAIDS?
Assess using validated scales≥4x/shift, before/after any procedure and analgesic administration
Pain
Analgosedation (assess for contraindications)
Non-pharmacologic(initiate as adjunct when allowable) Pharmacologic
• Music • Relaxation• Positioning• Remove offending
agent
Non-opioid(initiate as adjunct when allowable)
Opioid(first line for non-neuropathic pain)
Ketamine• Caution in patients with
heart failure, cardiogenic shock, neurological injury, pulmonary hypertension, cardiac ischemia
Acetaminophen• Route of administration
dependent on access and absorption• Avoid in patients with
liver dysfunction
NSAIDS• Route of administration
dependent on access and absorption• Avoid in patients with
or at risk for bleeding, renal dysfunction
Local anesthetics• Surgical pain only• Local, regional
administration
Gabapentin, Carbamazepine• Neuropathic pain
Fentanyl• Caution in patients with
liver dysfunction• Intermittent dosing may
be considered first before continuous infusion
Hydromorphone• Caution in patients with
liver and renal dysfunction• Intermittent dosing may
be considered first before continuous infusion
Morphine• Caution in patients with
liver and renal dysfunction• Consider histamine
release especially in hypotensive patients
Remifentanil• Continuous infusion
should be used for sustained pain relief vs bolus dosing• Rapid cessation of
analgesia with therapy discontinuation
PAIN METRICS
Assess
• Percentage of time patients are monitored for pain ≥4x/shift
• Compliance with use of ICU pain scoring systems
Treat
• Percentage of time patients are in significant pain
• Percentage of time pain is treated within 30 min of detecting significant pain
Prevent
• Percentage of time patients receive pre-procedural analgesics and/or non-pharmacological interventions
• Percentage compliance with institutional/ICU pain protocol
www.iculiberation.org.Crit Care Med 2013;41:263-306.
ABCDEF BUNDLE Goal is to improve pain management and reduce delirium and
long-term consequences
www.iculiberation.org.Crit Care Med 2013;41:263-306.
Symptoms Monitoring Care
Pain• CPOT• NRS• BPS
A: Assess, prevent and manage pain
B: Both spontaneous awakening trials (SAT) and spontaneous breathing trials (SBT)
C: Choice of analgesia and sedation
D: Delirium: assess, prevent and manage
E: Early mobility and exercise
F: Family engagement and empowerment
Agitation• Richmond Agitation-Sedation
Scale (RASS)• Sedation-Agitation Scale (SAS)
Delirium• Confusion assessment method for
intensive care unit (CAM-ICU)• Intensive care delirium screening
checklist (ICDSC)
Pharmacist’s role in ABCDEF
Avoid drug- drug, drug-food, drug-
disease interactions
Educate others
Identify methods to minimize costs
Assist with dosing therapy
Ensure appropriate monitoring
Assist with development and compliance with
hospital protocols or guidelines
Conduct medication
reconciliation
Collaborate within multidisciplinary
team
Regular rounding
PAIN MANAGEMENT IN CRITICALLY ILL PATIENTS
Uncontrolled pain is common in critically ill patients and is associated with numerous consequences
Pain is under assessed and under recognizedMulti-modal therapy, non-pharmacologic and
pharmacologic, should be consideredTreat pain first before use of sedatives Bundles addressing pain control should be implemented
Q3: WHICH OF THE FOLLOWING ARE CONSEQUENCES OF UNCONTROLLED PAIN?
A. Post traumatic stress disorder
B. Sleep disorders
C. Delirium
D. Agitation
E. All of the above
Q4: WHICH OF THE FOLLOWING ARE BENEFITS OF ANALGOSEDATION?
A. Reduced pressure ulcers
B. Increased urine output
C. Decreased length of mechanical ventilation
D. Greater muscle mass
E. None of the above
QUESTIONS?
Mona K. Patel, PharmD
Clinical Pharmacy Manager, Surgical ICU
NewYork-Presbyterian Hospital
Columbia University Medical Center
October 2, 2015
WHAT’S NEW IN THE MANAGEMENT OF PAIN IN THE ICU