u 10/26/2015 Pain Management in Hospital Medicine Daniel Burkhardt M.D. Associate Professor Department of Anesthesia and Perioperative Care University of California San Francisco daniel.burkhardt@ucsf.edu burkhardt.us/2015-10-15.pdf Disclosures I have nothing to disclose n u 1
u 10/26/2015 Case: 20 out of 10 38 year old male with Sickle Cell Anemia in the ED with n 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 "If you give fentanyl, and the blood pressure drops, then you haven't given u enough fentanyl" u 2
u 10/26/2015 Opioid Side Effects Are A Spectrum By varying the opioid dose you can move between: n u Screaming in pain u Awake and comfortable u Nauseous, itching, somnolent u Dead (from respiratory depression) You can move up and down the spectrum by: n u Changing the opioid dose u Giving a reversal agent u Changing the pain intensity Match opioid fluctuation to pain fluctuation n 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 u 3
u 10/26/2015 Opioid Toxicity: Respiratory Depression Oxygen absorption: n u pulse oximetry Carbon dioxide excretion: n 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 All adult inpatient post-op patients at one academic n center for one year 56 out of 10,511 (0.53%) needed naloxone n 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 u 4
u 10/26/2015 Postop Opioid Respiratory Depression Lee LA et al. Anes 2015 Anesthesia Closed Claims Project n 357 acute pain claims between 1990 and 2009 u 92 claims judged possible probable or definite u 77% severe brain damage or death u 88% within 24 hr of surgery n 97% preventable with better monitoring and response n Contributing factors n 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 u Pulse Oximetry Can (sort of) Monitor Both Oxygenation and Ventilation A normal oxygen saturation on room air rules out severe n hypoxia AND hypercarbia. u 5
u 10/26/2015 PaCO2 > 80 Causes Hypoxia Alveolar Gas Equation: n 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 As your PaCO2 exceeds 80, you become hypoxic unless you are on n supplemental oxygen PaCO2 > 80 Also Means Acidosis The Henderson-Hasselbach Equation n u pH, pCO2, and HCO3 levels are related by a fixed equation If the HCO3 remains normal, as the PaCO2 rises n above 80 mmHg, the pH will fall below 7.1 PaCO2 of 80 mmHg is the "red line” n u Acidosis can affect cardiovascular function u Hypercarbia causes somnolence and thus spirals into more hypercarbia u 6
u 10/26/2015 Opioid Toxicity: Prophylactic Oxygen Hypoxia rapidly causes permanent injury n Acidosis in the absence of hypoxia is relatively well n tolerated Oxygen may “ buy you time ” to detect and treat the n problem before permanent injury occurs. Opioid Respiratory Monitoring If you can provide highly reliable continuous pulse oximetry (with n rapid response to ALL alarms by trained personnel): u Avoid prophylactic oxygen and use oxygenation as a surrogate for ventilation If you are not willing to bet your patient’s life on continuous pulse n oximetry: u Consider prophylactic supplemental oxygen to minimize and delay hypoxia u Regularly assess arousability and respiratory rate as surrogates for ventilation u 7
u 10/26/2015 Constipation Opioid induced constipation is iatrogenic n Give laxatives BEFORE the problem happens n 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 u 8
u 10/26/2015 Methylnaltrexone FDA approved only for opioid induced constipation in palliative care n u Trials in post-operative ileus have not consistently shown a benefit 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 n 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 Extensive elimination by hepatic first pass metabolism, n resulting in negligible (<2%) systemic bioavailability Immediate release oral version difficult to titrate to opioid n consumption Prolonged release version in development might work n better u Slow release theorized to avoid saturation hepatic enzymes used for first pass hepatic metabolism u 9
u 10/26/2015 Oral Naloxone for Ileus Liu M Wittbrodt Eur J Pain Symptom Manage 2002 n 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 Meissner W et al. Pain 2000 n 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 Acetylcholinesterase Inhibitor n Typically used with glycopyrrolate for n neuromuscular blockade reversal in the OR Up to 2 mg IV n Can cause significant bradycardia and n bronchoconstriction u Cardiac Monitoring u Glycopyrrolate at the bedside u 10
u 10/26/2015 Opioid Choice Morphine Histamine release n Active metabolites that accumulate in renal failure n u 11
u 10/26/2015 Dilaudid (hydromorphone) Unfamiliarity = won't give morphine 10 mg but will n give Dilaudid 2 mg Also may accumulate in renal failure n Dilaudid vs. Morphine: Meta-analysis Felden L et al. Brit J Anes 2011 8 studies 1004 patients n Dilaudid had better acute pain control (-0.4 NRS, p=0.006) n but no difference for chronic pain NON-significant trend towards less N/V/itch n u 12
u 10/26/2015 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 UHC Consortium data 10/2010 - 9/2013, 38 hospitals, patients n treated with hydromorphone or morphine not both Medical Patients n 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%) Actual conversion is not 0.2 mg = 1 mg morphine IV n u More like 0.15, but that isn’t what everyone uses u 13
u 10/26/2015 Fentanyl May not have metabolites that accumulate in renal n failure Not a faster offset after prolonged use n May have better side effect profile (bigger “sweet n spot”) No oral form n u Lollipop / lozenge may be associated with tolerance (and is NOT an oral opioid!!) PCA fentanyl patch (40 mcg q10 min !!) n Oral Opioids Hydrocodone, hydromorphone, morphine, oxycodone, n oxymorphone u All have extended release versions Hydrocodone (Vicodin, Lortab, Norco) n 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. u 14
u 10/26/2015 Methadone 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 n u Give down a feeding tube QT interval prolongation n Long Acting Opioid Choice Same drug ER and IR n u Almost hopeless now Can’t crush and give down a feeding tube n 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 u 15
u 10/26/2015 Codeine Some patient metabolize to inactive agents so n unpredictable Just a morphine pro-drug n Demerol = not for pain Interact with MAO-I inhibitors n u And possibly SSRI u MAO-I more common now with Parkinson's Pts. Normeperidine causes seizures n u 16
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