mona k. patel, pharmd clinical pharmacy manager, surgical icu newyork-presbyterian hospital columbia...

73
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

Upload: nathaniel-osborne

Post on 01-Jan-2016

225 views

Category:

Documents


1 download

TRANSCRIPT

Page 1: Mona K. Patel, PharmD Clinical Pharmacy Manager, Surgical ICU NewYork-Presbyterian Hospital Columbia University Medical Center October 2, 2015 WHAT’S NEW

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

Page 2: Mona K. Patel, PharmD Clinical Pharmacy Manager, Surgical ICU NewYork-Presbyterian Hospital Columbia University Medical Center October 2, 2015 WHAT’S NEW

DISCLOSURES

None

Page 3: Mona K. Patel, PharmD Clinical Pharmacy Manager, Surgical ICU NewYork-Presbyterian Hospital Columbia University Medical Center October 2, 2015 WHAT’S NEW

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

Page 4: Mona K. Patel, PharmD Clinical Pharmacy Manager, Surgical ICU NewYork-Presbyterian Hospital Columbia University Medical Center October 2, 2015 WHAT’S NEW

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.

Page 5: Mona K. Patel, PharmD Clinical Pharmacy Manager, Surgical ICU NewYork-Presbyterian Hospital Columbia University Medical Center October 2, 2015 WHAT’S NEW

NOCICEPTIVE PAIN

Physiol Rev 2014;94:81-140.

Page 6: Mona K. Patel, PharmD Clinical Pharmacy Manager, Surgical ICU NewYork-Presbyterian Hospital Columbia University Medical Center October 2, 2015 WHAT’S NEW

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.

Page 7: Mona K. Patel, PharmD Clinical Pharmacy Manager, Surgical ICU NewYork-Presbyterian Hospital Columbia University Medical Center October 2, 2015 WHAT’S NEW

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)

Page 8: Mona K. Patel, PharmD Clinical Pharmacy Manager, Surgical ICU NewYork-Presbyterian Hospital Columbia University Medical Center October 2, 2015 WHAT’S NEW

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.

Page 9: Mona K. Patel, PharmD Clinical Pharmacy Manager, Surgical ICU NewYork-Presbyterian Hospital Columbia University Medical Center October 2, 2015 WHAT’S NEW

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%

Page 10: Mona K. Patel, PharmD Clinical Pharmacy Manager, Surgical ICU NewYork-Presbyterian Hospital Columbia University Medical Center October 2, 2015 WHAT’S NEW

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

Page 11: Mona K. Patel, PharmD Clinical Pharmacy Manager, Surgical ICU NewYork-Presbyterian Hospital Columbia University Medical Center October 2, 2015 WHAT’S NEW

RELATIONSHIP BETWEEN PAIN, AGITATION AND DELIRIUM

N Engl J Med 2014;370:444-454.

Page 12: Mona K. Patel, PharmD Clinical Pharmacy Manager, Surgical ICU NewYork-Presbyterian Hospital Columbia University Medical Center October 2, 2015 WHAT’S NEW

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.

Page 13: Mona K. Patel, PharmD Clinical Pharmacy Manager, Surgical ICU NewYork-Presbyterian Hospital Columbia University Medical Center October 2, 2015 WHAT’S NEW

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.

Page 14: Mona K. Patel, PharmD Clinical Pharmacy Manager, Surgical ICU NewYork-Presbyterian Hospital Columbia University Medical Center October 2, 2015 WHAT’S NEW

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.

Page 15: Mona K. Patel, PharmD Clinical Pharmacy Manager, Surgical ICU NewYork-Presbyterian Hospital Columbia University Medical Center October 2, 2015 WHAT’S NEW

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

Page 16: Mona K. Patel, PharmD Clinical Pharmacy Manager, Surgical ICU NewYork-Presbyterian Hospital Columbia University Medical Center October 2, 2015 WHAT’S NEW

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

Page 17: Mona K. Patel, PharmD Clinical Pharmacy Manager, Surgical ICU NewYork-Presbyterian Hospital Columbia University Medical Center October 2, 2015 WHAT’S NEW

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.

Page 18: Mona K. Patel, PharmD Clinical Pharmacy Manager, Surgical ICU NewYork-Presbyterian Hospital Columbia University Medical Center October 2, 2015 WHAT’S NEW

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.

Page 19: Mona K. Patel, PharmD Clinical Pharmacy Manager, Surgical ICU NewYork-Presbyterian Hospital Columbia University Medical Center October 2, 2015 WHAT’S NEW

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

Page 20: Mona K. Patel, PharmD Clinical Pharmacy Manager, Surgical ICU NewYork-Presbyterian Hospital Columbia University Medical Center October 2, 2015 WHAT’S NEW

Q2: ROUTINE PROCEDURES DO NOT CAUSE PAIN IN CRITICALLY ILL PATIENTS

A. True

B. False

Page 21: Mona K. Patel, PharmD Clinical Pharmacy Manager, Surgical ICU NewYork-Presbyterian Hospital Columbia University Medical Center October 2, 2015 WHAT’S NEW

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.

Page 22: Mona K. Patel, PharmD Clinical Pharmacy Manager, Surgical ICU NewYork-Presbyterian Hospital Columbia University Medical Center October 2, 2015 WHAT’S NEW

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.

Page 23: Mona K. Patel, PharmD Clinical Pharmacy Manager, Surgical ICU NewYork-Presbyterian Hospital Columbia University Medical Center October 2, 2015 WHAT’S NEW

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.

Page 24: Mona K. Patel, PharmD Clinical Pharmacy Manager, Surgical ICU NewYork-Presbyterian Hospital Columbia University Medical Center October 2, 2015 WHAT’S NEW

NON-OPIOID MANAGEMENT OF PAIN

Gabapentin (neuropathic pain)Carbamazepine (neuropathic pain)Ketamine Acetaminophen Local and regional anestheticsNonsteroidal anti-inflammatory drugs (NSAIDS)

Page 25: Mona K. Patel, PharmD Clinical Pharmacy Manager, Surgical ICU NewYork-Presbyterian Hospital Columbia University Medical Center October 2, 2015 WHAT’S NEW

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.

Page 26: Mona K. Patel, PharmD Clinical Pharmacy Manager, Surgical ICU NewYork-Presbyterian Hospital Columbia University Medical Center October 2, 2015 WHAT’S NEW

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

Page 27: Mona K. Patel, PharmD Clinical Pharmacy Manager, Surgical ICU NewYork-Presbyterian Hospital Columbia University Medical Center October 2, 2015 WHAT’S NEW

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.

Page 28: Mona K. Patel, PharmD Clinical Pharmacy Manager, Surgical ICU NewYork-Presbyterian Hospital Columbia University Medical Center October 2, 2015 WHAT’S NEW

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.

Page 29: Mona K. Patel, PharmD Clinical Pharmacy Manager, Surgical ICU NewYork-Presbyterian Hospital Columbia University Medical Center October 2, 2015 WHAT’S NEW

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

Page 30: Mona K. Patel, PharmD Clinical Pharmacy Manager, Surgical ICU NewYork-Presbyterian Hospital Columbia University Medical Center October 2, 2015 WHAT’S NEW

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.

Page 31: Mona K. Patel, PharmD Clinical Pharmacy Manager, Surgical ICU NewYork-Presbyterian Hospital Columbia University Medical Center October 2, 2015 WHAT’S NEW

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.

Page 32: Mona K. Patel, PharmD Clinical Pharmacy Manager, Surgical ICU NewYork-Presbyterian Hospital Columbia University Medical Center October 2, 2015 WHAT’S NEW

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.

Page 33: Mona K. Patel, PharmD Clinical Pharmacy Manager, Surgical ICU NewYork-Presbyterian Hospital Columbia University Medical Center October 2, 2015 WHAT’S NEW

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.

Page 34: Mona K. Patel, PharmD Clinical Pharmacy Manager, Surgical ICU NewYork-Presbyterian Hospital Columbia University Medical Center October 2, 2015 WHAT’S NEW

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

Page 35: Mona K. Patel, PharmD Clinical Pharmacy Manager, Surgical ICU NewYork-Presbyterian Hospital Columbia University Medical Center October 2, 2015 WHAT’S NEW

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

Page 36: Mona K. Patel, PharmD Clinical Pharmacy Manager, Surgical ICU NewYork-Presbyterian Hospital Columbia University Medical Center October 2, 2015 WHAT’S NEW

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.

Page 37: Mona K. Patel, PharmD Clinical Pharmacy Manager, Surgical ICU NewYork-Presbyterian Hospital Columbia University Medical Center October 2, 2015 WHAT’S NEW

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.

Page 38: Mona K. Patel, PharmD Clinical Pharmacy Manager, Surgical ICU NewYork-Presbyterian Hospital Columbia University Medical Center October 2, 2015 WHAT’S NEW

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

Page 39: Mona K. Patel, PharmD Clinical Pharmacy Manager, Surgical ICU NewYork-Presbyterian Hospital Columbia University Medical Center October 2, 2015 WHAT’S NEW

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) --

Page 40: Mona K. Patel, PharmD Clinical Pharmacy Manager, Surgical ICU NewYork-Presbyterian Hospital Columbia University Medical Center October 2, 2015 WHAT’S NEW

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.

Page 41: Mona K. Patel, PharmD Clinical Pharmacy Manager, Surgical ICU NewYork-Presbyterian Hospital Columbia University Medical Center October 2, 2015 WHAT’S NEW

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

Page 42: Mona K. Patel, PharmD Clinical Pharmacy Manager, Surgical ICU NewYork-Presbyterian Hospital Columbia University Medical Center October 2, 2015 WHAT’S NEW

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

Page 43: Mona K. Patel, PharmD Clinical Pharmacy Manager, Surgical ICU NewYork-Presbyterian Hospital Columbia University Medical Center October 2, 2015 WHAT’S NEW

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

Page 44: Mona K. Patel, PharmD Clinical Pharmacy Manager, Surgical ICU NewYork-Presbyterian Hospital Columbia University Medical Center October 2, 2015 WHAT’S NEW

ACETAMINOPHEN PHARMACOKINETICS

Single dose pharmacokinetics of IV vs oral vs rectal

Pain Pract 2012;12:523-532.

Page 45: Mona K. Patel, PharmD Clinical Pharmacy Manager, Surgical ICU NewYork-Presbyterian Hospital Columbia University Medical Center October 2, 2015 WHAT’S NEW

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

Page 46: Mona K. Patel, PharmD Clinical Pharmacy Manager, Surgical ICU NewYork-Presbyterian Hospital Columbia University Medical Center October 2, 2015 WHAT’S NEW

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.

Page 47: Mona K. Patel, PharmD Clinical Pharmacy Manager, Surgical ICU NewYork-Presbyterian Hospital Columbia University Medical Center October 2, 2015 WHAT’S NEW

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

Page 48: Mona K. Patel, PharmD Clinical Pharmacy Manager, Surgical ICU NewYork-Presbyterian Hospital Columbia University Medical Center October 2, 2015 WHAT’S NEW

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

Page 49: Mona K. Patel, PharmD Clinical Pharmacy Manager, Surgical ICU NewYork-Presbyterian Hospital Columbia University Medical Center October 2, 2015 WHAT’S NEW

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.

Page 50: Mona K. Patel, PharmD Clinical Pharmacy Manager, Surgical ICU NewYork-Presbyterian Hospital Columbia University Medical Center October 2, 2015 WHAT’S NEW

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.

Page 51: Mona K. Patel, PharmD Clinical Pharmacy Manager, Surgical ICU NewYork-Presbyterian Hospital Columbia University Medical Center October 2, 2015 WHAT’S NEW

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

Page 52: Mona K. Patel, PharmD Clinical Pharmacy Manager, Surgical ICU NewYork-Presbyterian Hospital Columbia University Medical Center October 2, 2015 WHAT’S NEW

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

Page 53: Mona K. Patel, PharmD Clinical Pharmacy Manager, Surgical ICU NewYork-Presbyterian Hospital Columbia University Medical Center October 2, 2015 WHAT’S NEW

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

Page 54: Mona K. Patel, PharmD Clinical Pharmacy Manager, Surgical ICU NewYork-Presbyterian Hospital Columbia University Medical Center October 2, 2015 WHAT’S NEW

ADVANTAGES OF LIPOSOMAL BUPIVACAINE

May reduce opioid requirements

Decreased need for patient controlled analgesia pumps

Convenience

Good safety profile

Page 55: Mona K. Patel, PharmD Clinical Pharmacy Manager, Surgical ICU NewYork-Presbyterian Hospital Columbia University Medical Center October 2, 2015 WHAT’S NEW

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

Page 56: Mona K. Patel, PharmD Clinical Pharmacy Manager, Surgical ICU NewYork-Presbyterian Hospital Columbia University Medical Center October 2, 2015 WHAT’S NEW

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.

Page 57: Mona K. Patel, PharmD Clinical Pharmacy Manager, Surgical ICU NewYork-Presbyterian Hospital Columbia University Medical Center October 2, 2015 WHAT’S NEW

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.

Page 58: Mona K. Patel, PharmD Clinical Pharmacy Manager, Surgical ICU NewYork-Presbyterian Hospital Columbia University Medical Center October 2, 2015 WHAT’S NEW

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.

Page 59: Mona K. Patel, PharmD Clinical Pharmacy Manager, Surgical ICU NewYork-Presbyterian Hospital Columbia University Medical Center October 2, 2015 WHAT’S NEW

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.

Page 60: Mona K. Patel, PharmD Clinical Pharmacy Manager, Surgical ICU NewYork-Presbyterian Hospital Columbia University Medical Center October 2, 2015 WHAT’S NEW

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

Page 61: Mona K. Patel, PharmD Clinical Pharmacy Manager, Surgical ICU NewYork-Presbyterian Hospital Columbia University Medical Center October 2, 2015 WHAT’S NEW

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.

Page 62: Mona K. Patel, PharmD Clinical Pharmacy Manager, Surgical ICU NewYork-Presbyterian Hospital Columbia University Medical Center October 2, 2015 WHAT’S NEW

The ultimate question:

How can patient comfort be safely and reliably achieved in the ICU?

Page 63: Mona K. Patel, PharmD Clinical Pharmacy Manager, Surgical ICU NewYork-Presbyterian Hospital Columbia University Medical Center October 2, 2015 WHAT’S NEW

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.

Page 64: Mona K. Patel, PharmD Clinical Pharmacy Manager, Surgical ICU NewYork-Presbyterian Hospital Columbia University Medical Center October 2, 2015 WHAT’S NEW

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?

Page 65: Mona K. Patel, PharmD Clinical Pharmacy Manager, Surgical ICU NewYork-Presbyterian Hospital Columbia University Medical Center October 2, 2015 WHAT’S NEW

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

Page 66: Mona K. Patel, PharmD Clinical Pharmacy Manager, Surgical ICU NewYork-Presbyterian Hospital Columbia University Medical Center October 2, 2015 WHAT’S NEW

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.

Page 67: Mona K. Patel, PharmD Clinical Pharmacy Manager, Surgical ICU NewYork-Presbyterian Hospital Columbia University Medical Center October 2, 2015 WHAT’S NEW

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)

Page 68: Mona K. Patel, PharmD Clinical Pharmacy Manager, Surgical ICU NewYork-Presbyterian Hospital Columbia University Medical Center October 2, 2015 WHAT’S NEW

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

Page 69: Mona K. Patel, PharmD Clinical Pharmacy Manager, Surgical ICU NewYork-Presbyterian Hospital Columbia University Medical Center October 2, 2015 WHAT’S NEW

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

Page 70: Mona K. Patel, PharmD Clinical Pharmacy Manager, Surgical ICU NewYork-Presbyterian Hospital Columbia University Medical Center October 2, 2015 WHAT’S NEW

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

Page 71: Mona K. Patel, PharmD Clinical Pharmacy Manager, Surgical ICU NewYork-Presbyterian Hospital Columbia University Medical Center October 2, 2015 WHAT’S NEW

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

Page 72: Mona K. Patel, PharmD Clinical Pharmacy Manager, Surgical ICU NewYork-Presbyterian Hospital Columbia University Medical Center October 2, 2015 WHAT’S NEW

QUESTIONS?

Page 73: Mona K. Patel, PharmD Clinical Pharmacy Manager, Surgical ICU NewYork-Presbyterian Hospital Columbia University Medical Center October 2, 2015 WHAT’S NEW

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