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Pain Management in Hospital Medicine

Daniel Burkhardt M.D. Associate Professor Department of Anesthesia and Perioperative Care University of California San Francisco [email protected] burkhardt.us/2015-10-15.pdf

Disclosures

n I have nothing to disclose

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Case: 20 out of 10

n 38 year old male with Sickle Cell Anemia in the ED with severe total body pain. Either moaning and screaming in "20 out of 10" pain or somnolent and unresponsive.

Assessment of Pain

n Scale (0-10) n Various non-verbal pain scales (grimacing, tearing, etc.) n Arousability (RASS in the ICU) n Splinting of the incision n Pupil size n Response to a trial of therapy u "If you give fentanyl, and the blood pressure drops, then you haven't given enough fentanyl"

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Opioid Side Effects Are A Spectrum

n By varying the opioid dose you can move between: u Screaming in pain u Awake and comfortable u Nauseous, itching, somnolent u Dead (from respiratory depression) n You can move up and down the spectrum by: u Changing the opioid dose u Giving a reversal agent u Changing the pain intensity n Match opioid fluctuation to pain fluctuation

Opioid Reversal: Naloxone

n If the patient has stable vital signs, titrate low doses of naloxone to reverse somnolence or respiratory depression u 40 - 80 mcg IV q1-5 min. n Naloxone doesn't cause pain, a naloxone overdose does n Useful as a trial of therapy for altered mental status

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Opioid Toxicity: Respiratory Depression

n Oxygen absorption: u pulse oximetry n Carbon dioxide excretion: u No good non-invasive test u ABG (must be drawn from an arterial line) u RR has a poor correlation with acidosis u Arousability (the “sedation scale”) is the best way to detect acidosis

Post-op Patients Requiring Naloxone Gordon DB et al. Pain Manag Nursing 2005

n All adult inpatient post-op patients at one academic center for one year n 56 out of 10,511 (0.53%) needed naloxone u 63% had RR > 12 u 48% had no sedation scores recorded u 65% of episodes occurred within 24 hours after surgery u Patients were older and received more concomitant sedatives than matched controls u No significant difference in opioid quantity or route

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Postop Opioid Respiratory Depression Lee LA et al. Anes 2015

n Anesthesia Closed Claims Project u 357 acute pain claims between 1990 and 2009 u 92 claims judged possible probable or definite u 77% severe brain damage or death n 88% within 24 hr of surgery n 97% preventable with better monitoring and response n Contributing factors u Multiple prescribers 33% u Concurrent sedatives 34% u Inadequate RN assessment 31% u Time since last check <2hr in 42%, <15min in 16% u Somnolence noted in 62% before event

Pulse Oximetry Can (sort of) Monitor Both Oxygenation and Ventilation

n A normal oxygen saturation on room air rules out severe hypoxia AND hypercarbia.

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PaCO2 > 80 Causes Hypoxia

n Alveolar Gas Equation: PaO2 = FiO2(713) - PaCO2(1.2)

FiO2 PaCO2 PaO2 Normal 0.21 40 102 Opioid Respiratory Depression on 0.21 80 54 Room Air Opioid Respiratory Depression on 0.30 80 118 Supplemental Oxygen

n As your PaCO2 exceeds 80, you become hypoxic unless you are on supplemental oxygen

PaCO2 > 80 Also Means Acidosis

n The Henderson-Hasselbach Equation u pH, pCO2, and HCO3 levels are related by a fixed equation

n If the HCO3 remains normal, as the PaCO2 rises above 80 mmHg, the pH will fall below 7.1

n PaCO2 of 80 mmHg is the "red line” u Acidosis can affect cardiovascular function u Hypercarbia causes somnolence and thus spirals into more hypercarbia

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Opioid Toxicity: Prophylactic Oxygen

n Hypoxia rapidly causes permanent injury

n Acidosis in the absence of hypoxia is relatively well tolerated

n Oxygen may “buy you time” to detect and treat the problem before permanent injury occurs.

Opioid Respiratory Monitoring

n If you can provide highly reliable continuous pulse oximetry (with rapid response to ALL alarms by trained personnel): u Avoid prophylactic oxygen and use oxygenation as a surrogate for ventilation n If you are not willing to bet your patient’s life on continuous pulse oximetry: u Consider prophylactic supplemental oxygen to minimize and delay hypoxia u Regularly assess arousability and respiratory rate as surrogates for ventilation

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Constipation

n Opioid induced constipation is iatrogenic

n Give laxatives BEFORE the problem happens

Opioid Antagonists for Opioid Bowel Dysfunction

n Peripherally acting mu-opioid antagonists u Alvimopan (Entereg) PO u Methylnaltrexone (Relistor) SC n Centrally and peripherally acting mu-opioid antagonist u Naloxone PO

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Methylnaltrexone

n FDA approved only for opioid induced constipation in palliative care u Trials in post-operative ileus have not consistently shown a benefit n 8-12 mg SC QOD, use beyond 4 months not well studied n Roughly 40-50% of patients in palliative care do not respond n Possible increased risk of GI perforation: Health Canada Issues Notice August 2010 u Advanced illness and conditions associated with impaired structural integrity of the GI wall (eg, cancer, GI malignancy, GI ulcer, Ogilvie's syndrome, concomitant use of certain medications including bevacizumab NSAIDs and steroids) may be at greater risk of perforation

Oral Naloxone for Ileus

n Extensive elimination by hepatic first pass metabolism, resulting in negligible (<2%) systemic bioavailability n Immediate release oral version difficult to titrate to opioid consumption n Prolonged release version in development might work better u Slow release theorized to avoid saturation hepatic enzymes used for first pass hepatic metabolism

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Oral Naloxone for Ileus

n Liu M Wittbrodt Eur J Pain Symptom Manage 2002 u 9 chronic opioid patients with constipation randomized to 0-2-4 mg PO TID u All patients on active therapy had improvement in bowel function u 3 patients had increased pain n Meissner W et al. Pain 2000 u 22 chronic pain patients with constipation placed on a dose escalation 3 mg po tid then 6 mg then 9 mg then 12 mg u Mean naloxone dose 17.5 mg/d u Mean number of days with laxation increased from 2.1 to 3.5 (p < 0.01) in the 6 day study period u No difference in pain scores

Opioid Induced Constipation: Neostigmine

n Acetylcholinesterase Inhibitor

n Typically used with glycopyrrolate for neuromuscular blockade reversal in the OR

n Up to 2 mg IV

n Can cause significant bradycardia and bronchoconstriction u Cardiac Monitoring u Glycopyrrolate at the bedside

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Opioid Choice

Morphine

n Histamine release n Active metabolites that accumulate in renal failure

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Dilaudid (hydromorphone)

n Unfamiliarity = won't give morphine 10 mg but will give Dilaudid 2 mg

n Also may accumulate in renal failure

Dilaudid vs. Morphine: Meta-analysis Felden L et al. Brit J Anes 2011

n 8 studies 1004 patients n Dilaudid had better acute pain control (-0.4 NRS, p=0.006) but no difference for chronic pain n NON-significant trend towards less N/V/itch

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Dilaudid vs. Morphine: Meta-analysis Felden L et al. Brit J Anes 2011

Hydromorphone not 0.2 Gular P et al. ASRA May 2015 Poster

n UHC Consortium data 10/2010 - 9/2013, 38 hospitals, patients treated with hydromorphone or morphine not both n Medical Patients u Hydromorphone up 17%, morphine down 6% u Rescue drug use higher for hydromorphone (1.11% vs 0.86% p<0.01) u LOS trend shorter for hydromorphone (5.68 vs 6.56 day) u Readmission trend higher for hydromorphone (10.15% vs. 6.54%) n Actual conversion is not 0.2 mg = 1 mg morphine IV u More like 0.15, but that isn’t what everyone uses

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Fentanyl

n May not have metabolites that accumulate in renal failure

n Not a faster offset after prolonged use

n May have better side effect profile (bigger “sweet spot”)

n No oral form u Lollipop / lozenge may be associated with tolerance (and is NOT an oral opioid!!)

n PCA fentanyl patch (40 mcg q10 min !!)

Oral Opioids

n Hydrocodone, hydromorphone, morphine, oxycodone, oxymorphone u All have extended release versions n Hydrocodone (Vicodin, Lortab, Norco) u No pure immediate version commonly available F Can't give acetaminophen separately ATC u Combo agents rescheduled from DEA Schedule III to II in October 2014.

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Methadone

n Dose change takes several days to take effect n PO to IV conversion -> cut in half n Divide up TID for pain n Comes as a liquid u Give down a feeding tube n QT interval prolongation

Long Acting Opioid Choice

n Same drug ER and IR u Almost hopeless now n Can’t crush and give down a feeding tube u Use methadone (only if experienced) u Use a fentanyl patch (and beware CMS) u (Even better for the short term) just give IR formulation q3-4h ATC

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Codeine

n Some patient metabolize to inactive agents so unpredictable n Just a morphine pro-drug

Demerol = not for pain

n Interact with MAO-I inhibitors u And possibly SSRI u MAO-I more common now with Parkinson's Pts.

n Normeperidine causes seizures

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Tramadol

n Weak opioid agonist n Became DEA Schedule IV in August 2014 n ? Some antidepressant effect n May not add much coadministered with conventional opioids (controversial)

Abuse Deterrent Opioids

n OxyContin (oxycodone ER) u Difficult to crush/dissolve/snort n Embeda (morphine ER) u Naltrexone pellets pass thru gut intact if not crushed. n Hysingla ER and Zohydro ER (hydrocodone ER) u Form a viscous gel when dissolved that is difficult to inject n Targiniq ER (oxycodone ER with naloxone) u Not available yet

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Opioid conversion

n Table must have dose intervals

n Cross tolerance imperfect u Reduce answer by 50% u Don't use a conversion table

Opioid titration (PCA as example)

n Hit rate a marker of strength u 1/hr is strong, 3/hr is weak u Can’t sustain more than 3 demand injections/hr u Demand dose must be big enough to work, or they won't hit it n Basal rates are not for pain u Basal rates bad (mortality) u Ignore opioid dose need to "break" the crisis

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The Safety and Utilization of Patient-Controlled Analgesia (J. Pain Sym. Man. 14:202-209, 1997)

n Results of 6000 patients utilizing PCA n Retrospective chart review n Overall incidence of “life threatening” complication = 0.28% n When used with basal rate life threatening complications increased to 1% n Hypoxemia = 6% (<90%) n Respiratory depression = 2% (<8 b/m)

Opioid prescription style

n One short acting agent, always PRN n One long acting agent, always ATC n Use the same drug for short and long if possible (insurance making this impossible) n Dose range orders, not numeric based pain scales n Divide up the doses in small frequent doses n Non-opioid adjuncts ATC u Split opioid out from tylenol F Pure hydromorphone usually not available

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Oral opioid are superior in (almost) EVERY way

Oral opioid are superior in (almost) EVERY way

n Cheap n Not dependent on IV access n No conversion needed for hospital discharge n Guaranteed to get an arousability assessment before each dose n No (real world) difference in speed of onset u IV prn for procedures n EXCEPT can't store at the bedside for oral PCA

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Getting off IV / PCA

n Don't need permission n Don't get a hamburger and a PCA n Don't hit your button unless you've taken your pill u Make pill prn frequent (so they can stack) u Take button away if they aren't taking their pill

The drug seeking patient

n Another advantage or oral opioids: can't get Rush Limbaugh'ed u If they stay, they may actually need to stay

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Inpatient pain "contracts"

n You get "x" when you come to the hospital n You agree to go back to orals at "y" rate u Otherwise it is not a contract, it is just a recipe u Ok to delay conversion if they can't take PO's yet

Outpatient pain "contracts"

n Only get meds from me u Call me immediately if you get run over by a bus n Agree to random drug tests u Looking for other drugs u Looking for the drugs they are SUPPOSED to be taking n If you are non-compliant you will be fired from my clinic u "It isn't safe to prescribe these medications if you don't cooperate with the safety measures"

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Pill count

n What "extra" do they have on hospital discharge because they weren't using it at home? n Book quick outpatient visit so you don't have to prescribe much

Stick to their outpatient meds while an inpatient

n "Leftovers" at home

n Primary care doc familiar with the drug and it's titration

n Local pharmacy stocks it

n Insurance covers it

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Non-Opioid Adjuncts

Tylenol

n 4 mg too much u Cutting all PO combo agents to lower doses n IV available u $35++ per vial u Split the vial 500/500 u Insurance carve-out

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NSAIDS

n Renal

n Bone

n GI bleed

n MI / CVA u Naprosyn better

n SAIDS

Cardiovascular Safety of NSAIDs Trelle S et al. BMJ 2011

n 31 RCT with 116K patients n MI (Rate Ratio) u Naprosyn 0.82 (0.37 to 1.67) u Ibuprofen 1.61 (0.5 to 5.77) u Rofecoxib 2.12 (1.26 to 3.56) n Cardiovascular Death (Rate Ratio) u Naprosyn 0.98 (0.41 to 2.37) u Ibuprofen 2.39 (0.69 to 8.64) u Rofecoxib 1.58 (0.88 to 2.84)

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Cardiovascular Safety of NSAIDs Trelle S et al. BMJ 2011

Cardiovascular Safety of NSAIDs Trelle S et al. BMJ 2011

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Other non-opioid adjuncts

n Gabapentin / pregabalin u Don’t have to load pregabalin as much u Gabapentin can start at 300 - 600 mg po TID as an inpatient

n Tricyclic Antidepressents's u Sleep

n Lidocaine Patch

n Ketamine

n Local Anesthetics

Pregabalin: Postop Pain Metaanalysis Mishriky BM et al. Brit J Anaes 2014

n 55 RCTs with 4155 patients n Significant reduction in u Pain score at rest (-0.38) u Pain with movement (-0.47) u Morphine equivalents (-8.27 mg) u PONV (RR 0.62, 0.48-0.80) u Pruritus (RR 0.49, 0.34-0.70) n Significant increase in u Sedation (RR 1.46, 1.08-1.98) u Dizziness (RR 1.33, 1.07-1.64) u Visual disturbance (RR 3.52, 2.05-6.04)

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Non-pharmacologic adjuncts

n Exercise / PT u Improve sleep n The gold standard: cure the underlying disease u Remove the painful stimulus F Trach the intubated ICU patient F Remove foley, NG tube, etc.

Danger of a Pain Service

n Separates the symptom management from the disease treatment u Serve as a consult service: do not write orders if possible

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Multi-disciplinary pain clinic

n Interventional therapy n Exotic non-opioid adjuncts n Physical therapy n Psych n Support / Advice

Daniel Burkhardt, M.D. [email protected] burkhardt.us/2015-10-15.pdf

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