WHAT’S NEW IN THE MANAGEMENT OF
PAIN IN THE ICU
Mona K. Patel, PharmD
Clinical Pharmacy Manager, Surgical ICU
NewYork-Presbyterian Hospital
Columbia University Medical Center
October 2, 2015
DISCLOSURES
None
OBJECTIVES
 Explain the etiology of pain in critically ill patients
 Describe consequences of uncontrolled pain in critically
ill 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 discharge
Anesthesiology 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
Tracheal
suctioning
Turning
Dressing
changes
Immobility
Tubes,
drains,
catheters
Surgical
incisions
Altered
sensorium
Pain
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
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)
Am J Respir Crit Care Med 2014;189:39-47.
LITTLE PROGRESS WITH ICU PAIN
Routine aspects of ICU care are the most troublesome
for patients
1990
63% remembered moderate to severe pain
2007
50% 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
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%
Am J Crit Care 2012;21:251-259.
Anesthesiology 2007;106:687-695.
CONSEQUENCES OF PAIN
 Inadequate sleep
 Impairment of tissue perfusion
 Traumatic memories after ICU
discharge
 Catabolic hypermetabolism
 Post traumatic stress disorder
 Difficulty managing severe pain
 Chronic pain
 Delirium
 Decreased quality of life
 Agitation
 Immune system impairment
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.
RELATIONSHIP BETWEEN PAIN, AGITATION
AND DELIRIUM
N Engl J Med 2014;370:444-
NECESSITY OF PAIN CONTROL
 Patient comfort
 Mobilization
 Judicious use of sedative agents
 Decrease length of mechanical ventilation
 Reduce 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
8d
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 pain
Crit Care Med 2013;41:263-306.
www.iculiberation.org
BEHAVIORAL PAIN SCALE
Item
Description
Score
Facial expression
Relaxed
Partially tightened (e.g. brow lowering)
Fully tightened (e.g. eyelid closing)
Grimacing
1
2
3
4
Upper limbs
No movement
Partially bent
Fully bent with finger flexion
Permanently retracted
1
2
3
4
Compliance with ventilation
Tolerating movement
Coughing but tolerating ventilation for most of time
Fighting ventilator
Unable to control ventilation
1
2
3
4
Crit Care Med 2001;29:2258-2263.
CRITICAL CARE PAIN OBSERVATIONAL TOOL
Indicator
Score
Description
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)
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
Tolerating ventilator or
movement
0
Alarms not activated, easy ventilation
Compliance with the ventilator
(intubated patients)
Coughing but tolerating
1
Coughing, alarms may be activated but stop spontaneously
Fighting ventilator
2
Asynchrony: blocking ventilation, alarms frequently activated
OR
Talking in normal tone
or no sound
0
Talking in normal tone or no sound
Sighing, moaning
1
Sighing, moaning
Crying out, sobbing
2
Crying out, sobbing
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
Facial expressions
Body movements
Vocalization (extubated patients)
Muscle tension
Am J Crit Care 2006;15:420-427.
TREATMENT OF PAIN
Risk
assessment
•
•
•
•
Severity of illness
Chronic pain conditions
Coexisting symptoms
Frequency and invasiveness of therapies
Early
recognition
• Use of validated tools
• Frequent assessment
Nonpharmacologic
• Non-pharmacologic (e.g. music
therapy, relaxation technique)
• Positioning
• Removal of offending agent
Pharmacologic
• Non-opioids
• Opioids
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
OPIOIDS FOR THE TREATMENT OF PAIN
 First line for the treatment of non-neuropathic pain
 Choice of agent is multi-factorial
 Onset of action
 Duration of action
 Elimination
 Adverse effects
 Cost
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)
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
Accumulation with hepatic/renal
impairment; histamine release;
active metabolite
Use ideal body weight for obese
patients; cost; glycine neurotoxicity
Active
metabolite
Metabolism
Morphine
1:1
5-10 min
1.5-5
Yes
Demethylation,
glucuronidation
Remifentanil
20:1
1-3 min
0.05
No
Hydrolysis by
plasma esterases
Clinical considerations
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 anesthetics
 Nonsteroidal 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
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
Crit Care Med 2013;41:263-306.
Chest 2009;135:1075-1086.
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
Mechanically ventilated medical and surgical patients
No sedation
(n=55)
Sedation
(n=58)
prn IV morphine
prn IV morphine + propofol infusion x 48h, then
prn morphine + IV midazolam infusion
Daily interruption of sedation
Goal Ramsey 3-4
Continued discomfort
Nonpharmacologic
prn IV haloperidol
Propofol infusion x6h
Lancet 2010;375:475-480.
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.
REMIFENTANIL ANALGOSEDATION
 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
Crit Care 2005;9:R200-R210.
ADVANTAGES OF ANALGOSEDATION
 Reduce sedative use
 Lower risk of prolonged sedative effects
 Decrease risk for sedative-related adverse effects
 Shorten mechanical ventilation time
 Reduce length of stay
Ann Pharmacother 2012;46:530-540.
DISADVANTAGES OF ANALGOSEDATION
 Opioid associated delirium
 Increased opioid requirement
 Unpleasant recall
 Reduced gastrointestinal motility
 Immunosuppression
 Long term outcomes unknown
 Opioid withdrawal
 Hyperalgesia
Ann Pharmacother 2012;46:530-540.
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.
REDUCTION OF OPIOID USE WITH KETAMINE
Patient population
Cardiac surgery
Intervention
KET 75 mcg/kg bolus then
1.25 mcg/kg/min (n=44) vs
PL (n=46) x48h
Narcotic reduction
Oxycodone requirements:
KET 103±44 mg vs
PL 125±45 mg, p=0.023
Knee arthroplasty
KET 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<0.02
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<0.05
KET=ketamine; PL=placebo
Pain scores
Adverse effects
No difference
No difference
No difference
No difference
4 patients with
psychomimetic effects
with KET vs 0 with PL
No difference
No difference
Anesth Analg 2004;99:1295-1301.
Anesth Analg 2005;100:475-480.
Anesth Analg 2003;97:843-847.
REDUCTION OF OPIOID USE WITH KETAMINE
 Reduction in morphine use after major abdominal surgery
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)
--
 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)
Anesth Analg 2008;106:1856-1861.
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
 Bronchodilation
 Preservation of cardiac output
 Not 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
Hypersalivation
Hypertension
Nystagmus
Tachycardia
Psychomimetic effects
 Negative inotrope in heart failure or cardiogenic shock states
 Unclear safety in patients with neurological injury, pulmonary
hypertension, cardiac ischemia
 Unknown impact on delirium
 Optimal dosing not known
IV ACETAMINOPHEN – WHAT DO WE KNOW?
 Approved in 2010
 Opioid sparing effects seen in many patient populations
with once or repeat dosing
Total hip or knee replacement
Major abdominal or pelvic surgery
Abdominal laparoscopy
Molar surgery
Abdominal hysterectomy
Tosillectomy
 Well tolerated and safe
Pharmacotherapy 2014;34:34S-39S.
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
Total abdominal
hysterectomies
Retrospective
Bariatric surgery
Retrospective
Surgical knee
procedures
Retrospective,
case-control
Intervention
IVA with opioids (n=50)
vs
OA (n=50)
IVA with opioids (n=38)
vs
OA (n=47)
IVA with opioids (n=25)
vs
OA (n=75)
IVA=IV acetaminophen
OA=opioids only
Morphine equivalents
Pain scores
during
intervention
Length of
stay
Not assessed
Not assessed
Not assessed
Not assessed
Not assessed
No difference
Post-operative day 1-2
IVA 47±24 mg vs OA 68±37 mg, p=0.003
Total perioperative period
IVA 73±24 mg vs OA 99±39 mg, p=0.001
Postoperative day 1
IVA 100 mg vs OA 165 mg, p=0.018
Total postoperative course
IVA 135 mg vs OA 113 mg, p=0.987
Daily
IVA 45 mg vs OA 38 mg, p=0.845
Pharmacotherapy 2014;34:27S-33S.
J Surg Res 2015;195:99-104.
Pharmacotherapy 2014;34:22S-26S.
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 routes
 Unknown 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.
LIPOSOMAL BUPIVACAINE – WHAT DO WE KNOW
THUS FAR?
 Studied in many patient populations
Inguinal hernia repair
Total knee arthroplasty
Hemorrhoidectomy
Breast augmentation
Bunionectomy
Open colectomy
Ileostomy reversal
Abdominal hernia repair
Robotic prostatectomy
 Narcotic reduction and better pain scores noted vs placebo
 Inconsistent benefit when compared to conventional
bupivacaine
J Clin Ther 2015;37:1354-1371.
LIPOSOMAL BUPIVACAINE FOR POSTSURGICAL
ANALGESIA
 Equivalent randomized, controlled trials
Study
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
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)
LB 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)
Periarticular
administration
Total knee arthroplasty
LB=liposomal bupivacaine
J Athroplasty 2015;30:64-67.
J Athroplasty 2015;30:325-329.
J Endourol 2015;29:1019-1024.
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
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
 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
LB=liposomal bupivacaine
Gynecol Oncol 2015;138:609-613.
LIPOSOMAL BUPIVACAINE FOR POSTSURGICAL
ANALGESIA
 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
* p<0.01
 Lower pain scores with LB
** p<0.001
Anesth Analg 2015 [Epub ahead of print]
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 patients
 No role in non-surgical patients
 Unknown impact in chronic pain patients
 Safety in pregnant patients unknown
 Conflicting literature
 Cost
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;34:16911699.
Anesth Analg 2010;111:451-463.
ANALGESIA/SEDATION ALGORITHM
1. In Pain?
Analgosedation?
Ketamine?
Acetaminophen?
NSAIDS?
Yes
No
Reassess often
Yes
Analgesia may be
adequate to reach
RASS target
No
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 negative
Reassess q6-12h
RASS=Richmond Agitation Sedation Scale
SAT=Spontaneous awakening trial
SBT=Spontaneous breathing trial
CAM-ICU=Confusion Assessment Method for the ICU
2. At RASS
target?
Yes
Reassess often
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
No
• Fentanyl 50-300 mcg/h infusion
• Fentanyl 25-100 mcg prn pain
No
Over sedated
Hold sedative/analgesic to
achieve RASS target. Restart at
50% if clinically indicated
SAT+SBT daily
physical therapy
3. Delirium?
CAM-ICU positive
• Non-pharmacological
management
• Pharmacological management
www.icudelirium.org
Assess using validated scales
≥4x/shift, before/after any procedure and analgesic administration
Pain
Analgosedation
(assess for contraindications)
Non-pharmacologic
Pharmacologic
(initiate as adjunct when allowable)
•
•
•
•
Music
Relaxation
Positioning
Remove offending
agent
Non-opioid
(initiate as adjunct when allowable)
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
Opioid
(first line for non-neuropathic pain)
NSAIDS
• Route of administration
dependent on access
and absorption
• Avoid in patients with
or at risk for bleeding,
renal dysfunction
Fentanyl
• Caution in patients with
liver 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
Local anesthetics
• Surgical pain only
• Local, regional
administration
Hydromorphone
• Caution in patients with
liver and renal
dysfunction
• Intermittent dosing may
be considered first
before continuous
infusion
Remifentanil
• Continuous infusion
should be used for
sustained pain relief vs
bolus dosing
• Rapid cessation of
analgesia with therapy
discontinuation
Gabapentin,
Carbamazepine
• Neuropathic pain
PAIN METRICS
Assess
Treat
• Percentage of time
patients are monitored
for pain ≥4x/shift
• Percentage of time
patients are in
significant pain
• Compliance with use of
ICU pain scoring
systems
• Percentage of time pain
is treated within 30 min
of detecting significant
pain
Prevent
• Percentage of time
patients receive preprocedural analgesics
and/or nonpharmacological
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
Symptoms
Pain
Monitoring
•
•
•
CPOT
NRS
BPS
•
Richmond Agitation-Sedation
Scale (RASS)
Sedation-Agitation Scale (SAS)
Agitation
•
•
Delirium
•
Confusion assessment method for
intensive care unit (CAM-ICU)
Intensive care delirium screening
checklist (ICDSC)
Care
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
www.iculiberation.org.
Crit Care Med 2013;41:263-306.
Regular
rounding
Collaborate
within
multidisciplinary
team
Avoid drug- drug,
drug-food, drugdisease
interactions
Educate others
Pharmacist’s role in
ABCDEF
Conduct
medication
reconciliation
Identify methods
to minimize
costs
Assist with
dosing therapy
Assist with
development
and compliance
with hospital
protocols or
guidelines
Ensure
appropriate
monitoring
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 recognized
 Multi-modal therapy, non-pharmacologic and
pharmacologic, should be considered
 Treat 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?
WHAT’S NEW IN THE MANAGEMENT OF
PAIN IN THE ICU
Mona K. Patel, PharmD
Clinical Pharmacy Manager, Surgical ICU
NewYork-Presbyterian Hospital
Columbia University Medical Center
October 2, 2015