January 12, 2021

The 2 View: Episode 1

1 hour 1 minute

View the show notes in Google Docs here: http://bit.ly/3bFS43j

Gonorrhea Updates

Gonorrhea Treatment and Care. Centers for Disease Control and Prevention Website. https://www.cdc.gov/std/gonorrhea/treatment.htm. Published December 14, 2020. Accessed January 11, 2021.

CDC No Longer Recommends Oral Drug for Gonorrhea Treatment. Centers for Disease Control and Prevention. https://www.cdc.gov/nchhstp/newsroom/2012/gctx-guidelines-pressrelease.html. Published August 9, 2012. Accessed January 11, 2021.

Recurrent UTI

Recurrent Uncomplicated Urinary Tract Infections in Women: AUA/CUA/SUFU Guideline (2019). American Urological Association. https://www.auanet.org/guidelines/recurrent-uti?fbclid=IwAR1TwSTQNHv8PDWLfW7WjsDan46D_9b6Qs1ptJxaXr6YFnDpBeptpW3BY. Published 2019. Accessed January 11, 2021.

Combo Ibuprofen and Acetaminophen / Pain

Advil® Dual Action. GSK Expert Portal. https://www.gskhealthpartner.com/en-us/pain-relief/brands/advil/products/dual-action/?utm_source=google&utm_medium=cpc&utm_term=ibuprofen+acetaminophen&utm_campaign=GS+-+Unbranded+Advil+DA+-+Alone+-+PH. Accessed January 11, 2021.

FDA approves GSK's Advil Dual Action with Acetaminophen for over-the-counter use in the United States. GSK. https://www.gsk.com/en-gb/media/press-releases/fda-approves-gsk-s-advil-dual-action-with-acetaminophen-for-over-the-counter-use-in-the-united-states/. Published March 2, 2020. Accessed January 11, 2021.

Tanner T, Aspley S, Munn A, Thomas T. The pharmacokinetic profile of a novel fixed-dose combination tablet of ibuprofen and paracetamol. BMC clinical pharmacology. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2906415/. Published July 5, 2010. Accessed January 11, 2021.

Searle S, Muse D, Paluch E, et al. Efficacy and Safety of Single and Multiple Doses of a Fixed-dose Combination of Ibuprofen and Acetaminophen in the Treatment of Postsurgical Dental Pain: Results From 2 Phase 3, Randomized, Parallel-group, Double-blind, Placebo-controlled Studies. The Clinical journal of pain. https://pubmed.ncbi.nlm.nih.gov/32271183/. Published July 2020. Accessed January 11, 2021.

1000 mg versus 600/650 mg Acetaminophen for Pain or Fever: A Review of the Clinical Efficacy. National Center for Biotechnology Information. https://www.ncbi.nlm.nih.gov/books/NBK373467/. Published June 17, 2016. Accessed January 11, 2021.

Motov S. Is There a Limit to the Analgesic Effect of Pain Medications? Medscape. https://www.medscape.com/viewarticle/574279. Published June 17, 2008. Accessed January 11, 2021.

Motov, Sergey. Faculty Forum: A Practical Approach to Pain Management. YouTube. https://www.youtube.com/watch?v=lJSioPsGw3A. The Center for Medical Education. Published December 2, 2020. Accessed January 1, 2021.

Wuhrman E, Cooney MF. Acute Pain: Assessment and Treatment. Medscape. https://www.medscape.com/viewarticle/735034_4. Published January 3, 2011. Accessed January 11, 2021.

Social Pain

Dewall CN, Macdonald G, Webster GD, et al. Acetaminophen reduces social pain: behavioral and neural evidence. Psychological science. https://pubmed.ncbi.nlm.nih.gov/20548058/. Published June 14, 2010. Accessed January 11, 2021.

Mischkowski D, Crocker J, Way BM. From painkiller to empathy killer: acetaminophen (paracetamol) reduces empathy for pain. Social cognitive and affective neuroscience. https://pubmed.ncbi.nlm.nih.gov/27217114/. Published May 5, 2016. Accessed January 11, 2021.

Other / Recurrent liner notes

Center for Medical Education. https://courses.ccme.org/. Accessed January 11, 2021.

Roberts M, Roberts JR. The Proceduralist. https://www.theproceduralist.org/. Accessed January 11, 2021.

The Procedural Pause by James R. Roberts, MD, & Martha Roberts, ACNP, PNP. Emergency Medicine News. https://journals.lww.com/em-news/blog/theproceduralpause/pages/default.aspx. Accessed January 11, 2021.

The Skeptics' Guide to Emergency Medicine. sgem.ccme.org. https://sgem.ccme.org/. Accessed January 11, 2021.

Trivia Question: Send answers to [email protected]

Please note that you must answer the 2 part question to win a copy of the EMRA Pain Guide.

“What controversial drug was given a black box warning for prolonged QT and torsades in 2012 and now has been declared by WHICH organization to be an effective and safe treatment use for nausea, vomiting, headache and agitation?”

Practical Pain Management in Acute Care Setting Handout

Sergey Motov, MD

@painfreeED

• Pain is one of the most common reasons for patients to visit the emergency department and other acute care settings. Due to the extensive number of visits related to pain, clinicians and midlevel providers should be aware of the various options, both pharmacological and nonpharmacological, available to treat patients with acute pain.

• As the death toll from the opioid epidemic continues to grow, the use of opioids in the acute care setting as a first-line treatment for analgesia is becoming increasingly controversial and challenging.

• There is a growing body of literature that is advocating for more judicious use of opioids and well as their prescribing and for broader use of non-pharmacological and non-opioid pain management strategies.

• The channels/enzymes/receptors targeted analgesia (CERTA) concept is based on our improved understanding of the neurobiological aspect of pain with a shift from a symptom-based approach to pain to a mechanistic approach. This targeted analgesic approach allows for a broader utilization of synergistic combinations of nonopioid analgesia and more refined and judicious (rescue) use of opioids. These synergistic combinations result in greater analgesia, fewer side effects, lesser sedation, and shorter LOS. (Motov et al 2016)

General Principles:

Management of acute pain in the acute care setting should be patient-centered and pain syndrome-specific by using multimodal approach that include non-pharmacological modalities and pharmacological ones that include non-opioid and opioid analgesics.

Assessment of acute pain should be based on a need for analgesics to improve functionality, rather than patients-reported pain scores. Brief pain inventory short form BPI-SF is better than NRS/VAS as it assesses quantitative and qualitative impact of pain (Im et al 2020).

ED clinicians should engage patients in shared decision-making about overall treatment goals and expectations, the natural trajectory of the specific painful condition, and analgesic options including short-term and long-term benefits and risks of adverse effects.

If acute pain lasting beyond the expected duration, complications of acute pain should be ruled out and transition to non-opioid therapy and non-pharmacological therapy should be attempted.

Non-Pharmacologic Therapies

• Acute care providers should consider applications of heat or cold as well as specific recommendations regarding activity and exercise.

• Music therapy is a useful non-pharmacologic therapy for pain reduction in acute care setting (music-assisted relaxation, therapeutic listening/musical requests, musical diversion, song writing, and therapeutic singing (Mandel 2019).

• The use of alternative and complementary therapies, such as acupuncture, guided imagery, cognitive-behavioral therapy, and hypnosis have not been systemically evaluated for use in the Acute care setting including ED. (Dillan 2005, Hoffman 2007)

• In general, their application may be limited for a single visit, but continued investigation in their safety and efficacy is strongly encouraged.

• Practitioners may also consider utilization of osteopathic manipulation techniques, such as high velocity, low amplitude techniques, muscle energy techniques, and soft tissue techniques for patients presenting to the acute care setting with pain syndromes of skeletal, arthroidal, or myofascial origins. (Eisenhart 2003)

Opioids

• Acute Care providers are uniquely positioned to combat the opioid epidemic by thoughtful prescribing of parenteral and oral opioids in inpatient setting and upon discharge, and through their engagement with opioid addicted patients in acute care setting.

• Acute Care providers should make every effort to utilize non-pharmacological modalities and non-opioid analgesics to alleviate pain, and to use opioid analgesics only when the benefits of opioids are felt to outweigh the risks. (not routinely)

• When opioids are used for acute pain, clinicians should combine them with non-pharmacologic and non-opioid pharmacologic therapy: Yoga, exercise, cognitive behavioral therapy, complementary/alternative medical therapies (acupuncture); NSAID’s, Acetaminophen, Topical Analgesics, Nerve blocks, etc.

• When considering opioids for acute pain, Acute Care providers should involve patients in shared decision-making about analgesic options and opioid alternatives, risks and benefits of opioid therapies, and rational expectations about the pain trajectory and management approach.

• When considering opioids for acute pain, acute care providers should counsel patients regarding serious adverse effects such as sedation and respiratory depression, pruritus and constipation, and rapid development of tolerance and hyperalgesia.

• When considering administration of opioids for acute pain, acute care providers should make every effort to accesses respective state’s Prescription Drug Monitoring Program (PDMP). The data obtained from PDMP’s to be used to identify excessive dosages and dangerous combinations, identify and counsel patients with opioid use disorder, offer referral for addiction treatment.

• PDMPs can provide clinicians with comprehensive prescribing information to improve clinical decisions around opioids. However, PDMPs vary tremendously in their accessibility and usability in the ED, which limits their effectiveness at the point of care. Problems are complicated by varying state-to-state requirements for data availability and accessibility. Several potential solutions to improving the utility of PDMPs in EDs include integrating PDMPs with electronic health records, implementing unsolicited reporting and prescription context, improving PDMP accessibility, data analytics, and expanding the scope of PDMPs. (Eldert et al, 2018)

• Parenteral opioids when used in titratable fashion are effective, safe, and easily reversible analgesics that quickly relieve pain.

• Acute care clinicians should consider administering these analgesics for patients in acute pain where the likelihood of analgesic benefit is judged to exceed the likelihood of harm.

• Parenteral opioids must be titrated regardless of their initial dosing regimens (weight-based or fixed) until pain is optimized to acceptable level (functionality status) or side effects become intolerable.

• When parenteral opioids are used, patients should be engaged in shared-decision making regarding the route of administration, as repetitive attempts of IV cannulation and intramuscular injections are associated with pain. In addition, intramuscular injections are associated with unpredictable absorption rates, and complications such as muscle necrosis, soft tissue infection and the need for dose escalation. (Von Kemp 1989, Yamanaka 1985, Johnson 1976)

• Morphine sulfate provides better balance of analgesic efficacy and safety among all parenteral opioids.

a. Dosing regimens and routes:

b. IV: 0.05-0.1mg/kg to start, titrate q 10-20 min

c. IV: 4-6 mg fixed, titrate q 10-20 min

d. SQ: 4-6 mg fixed, titrate q 20 min

e. Nebulized: 0.2 mg/kg or 10-20 mg fixed, repeat q 15-20 min

f. PCA: prone to dosing errors

g. IM: should be avoided (pain, muscle fibrosis, necrosis, increase in dosing requirements)

• Hydromorphone should be avoided as a first-line opioid due to significant euphoria and severe respiratory depression requiring naloxone reversal. Due to higher lipophilicity, Hydromorphone use is associated with higher rates of euphoria and subsequent development of addiction. Should hydromorphone be administered in higher than equi-analgesic morphine milligram equivalents, close cardiopulmonary monitoring is strongly recommended.

Dosing

h. IV: 0.2-0.5 mg initial, titrate q10-15 min

i. IM: to be avoided (pain, muscle fibrosis, necrosis, increase in dosing requirements)

j. PCA: prone to dosing errors (severe CNS and respiratory depression)

k. Significantly worse AE profile in comparison to Morphine

l. Equianalgesic IV conversion (1 mg HM=8mg of MS)

m. Overprescribed in >50% of patients

n. Inappropriately large dosing in EM literature: 2 mg IVP

o. Abuse potential (severely euphoric due to lipophilicity)

• Fentanyl is the most potent opioid, short-acting, requires frequent titration.

Dosing:

p. IV: 0.25-0.5 μg/kg (WB), titrate q10 min

q. IV: 25-50 μg (fixed), titrate q10 min

r. Nebulization: 2-4 μg/kg, titrate q20-30 min

s. IN: 1-2 μg/kg, titrate q5-10min

t. Transbuccal: 100-200μg disolvable tablets

u. Transmucosal: 15-20 mcg/kg Lollypops

• Opioids in Renal Insufficiency/Renal Failure Patients-requires balance of ORAE with pain control by starting with lower-than-recommended doses and slowly titrate up the dose while extending the dosing interval. (Dean 2004, Wright 2011)

• Opioid-induced pruritus is centrally mediated process via μ-opioid receptors as naloxone, nalbuphine reverse it, and can be caused by opioids w/o histamine release (Fentanyl). Use ultra-low-dose naloxone of 0.25 -1 mcg/kg/hr with NNT of 3.5. (Kjellberg 2001)

• When intravascular access is unobtainable, acute care clinicians should consider utilization of intranasal (fentanyl), nebulized (fentanyl and morphine), or transmucosal (rapidly dissolvable fentanyl tablets) routes of analgesic administration for patients with acute painful conditions.

• Breath actuated nebulizer (BAN): enclosed canister, dual mode: continuous and on-demand, less occupational exposures.

a. Fentanyl: 2-4 mcg//kg for children, 4 mcg/kg for adults: titration q 10 min up to three doses via breath-actuated nebulizer (BAN): systemic bioavailability of 50-60% of IV route. (Miner 2007, Furyk 2009, Farahmand 2014)

b. Morphine: 10-20 mg g10 min up to 3 doses via breath-actuated nebulizer (BAN)-Systemic bioavailability (concentration) of 30-35% of IV Route. (Fulda 2005, Bounes 2009, Grissa 2015)

c. Intranasal Fentanyl: IN via MAD at 1-2 mcg/kg titration q 5 min (use highly concentrated solution of 100mcg/ml for adults and 50 mcg/ml for children)- systemic bioavailability of 90% of IV dosing. (Karisen 2013, Borland 2007, Saunders 2010, Holdgate 2010)

d. IN route: shorter time to analgesia, titratable, comparable pain relief to IV route, minimal amount of side effects, similar rates of rescue analgesia, great patients and staff satisfaction. Disadvantages: requires highly concentrated solutions that not readily available in the ED, contraindicated in facial/nasal trauma.

Oral Opioids

• Oral opioid administration is effective for most patients in the acute care setting, however, there is no appreciable analgesic difference between commonly used opioids (oxycodone, hydrocodone and morphine sulfate immediate release (MSIR).

• When oral opioids are used for acute pain, the lowest effective dose and fewest number of tablets needed should be prescribed. In most cases, less than 3 days’ worth are necessary, and rarely more than 5 days’ worth are needed.

• If painful condition outlasts three-day supply, re-evaluation in health-care facility is beneficial. Consider expediting follow-up care if the patient’s condition is expected to require more than a three-day supply of opioid analgesics.

• Only Immediate release (short-acting) formulary are to be prescribed in the acute care setting and at discharge.

• Clinicians should not administer or prescribe long-acting, extended-release, or sustained-release opioid formulations, which include both oral and transdermal (fentanyl) medications in the acute care setting. These formulations are not indicated for acute pain and carry a high risk of overdose, particularly in opioid-naïve patients.

• Acute care providers should counsel patients about safe medication storage and disposal, as well as the consequences of failure to do this; potential for abuse and misuse by others (teens and young adults), and potential for overdose and death (children and teens).

• Oxycodone is no more effective than other opioids (hydrocodone, MSIR). Oxycodone has highest potential for abuse, misuse and diversion as well as increased risks of overdose, addiction and death. Oxycodone should be avoided as a first-line oral opioid for acute pain. ( Strayer 2016)

• If still prescribed, lowest dose (5mg) in combination with acetaminophen (lowest dose of 325 mg) should be considered as it associated with less abuse and diversion (in theory). Potential for acetaminophen overdose exist though with combination.

• Hydrocodone is three times more prescribed than oxycodone, but three times less used for non-medical purpose. Combo with APAP (Vicodin)-Use lowest effective dose for hydrocodone and APAP (5/325). (Quinn 1997, Adams 2006)

• Immediate release morphine sulfate (MSIR) administration is associated with lesser degree of euphoria and consequently, less abuse potential (Wightman 2012). ED providers should consider prescribing Morphine Sulfate Immediate Release Tablets (MSIR) (Wong 2012, Campos 2014) for acute pain due to:

o Similar analgesic efficacy to Oxycodone and Hydrocodone

o Less euphoria (less abuse potential)

o Less street value (less diversion)

o More dysphoria in large doses

o Less abuse liability and likeability

• Tramadol should not be used in acute care setting and at discharge due to severe risks of adverse effects, drug-drug interactions, and overdose. There is very limited data supporting better analgesic efficacy of tramadol in comparison to placebo, or better analgesia than APAP or Ibuprofen. Tramadol dose not match analgesic efficacy of traditional opioids. (Juurlink 2018, Jasinski 1993, Babalonis 2013)

• Side effects are:

o Seizures

o Hypoglycemia

o Hyponatremia

o Serotonin syndrome

o Abuse and addiction

• Codeine and Codeine/APAP is a weak analgesic that provides no better pain relief than placebo. Codeine must not be administered to children due to:

o dangers of the polymorphisms of the cytochrome P450 iso-enzyme:

o ultra-rapid metabolizers: respiratory depression and death

o poor metabolizers: absent or insufficient pain relief

• Transmucosal fentanyl (15 and 20 mcg/kg lollypops) has an onset of analgesia in 5 to 15 minutes with a peak effect seen in 15 to 30 minutes (Arthur 2012).

• Transbuccal route can be used right at the triage to provide rapid analgesia and as a bridge to intravenous analgesia in acute care setting. (Ashburn 2011). A rapidly dissolving trans-buccal fentanyl (100mcg dose) provides fast pain relief onset (median 10 min), great analgesics efficacy, minimal need for rescue medication and lack of side effects in comparison to oxycodone/acetaminophen tablet (Shear 2010)

• Morphine Milligram Equivalent (MME) is a numerical standard against which most opioids can be compared, yielding a comparison of each medication’s potency. MME does not give any information of medications efficacy or how well medication works, but it is used to assess comparative potency of other analgesics.

• By converting the dose of an opioid to a morphine equivalent dose, a clinician can determine whether a cumulative daily dose of opioids approaches an amount associated with increased risk of overdose and to identify patients who may benefit from closer monitoring, reduction or tapering of opioids, prescribing of naloxone, and other measures to reduce risk of overdose.

• Opioid-induced hyperalgesia:

o opioid-induced hyperalgesia (OIH) is a rare syndrome of increasing pain, often accompanied by neuroexcitatory effects, in the setting of increasing opioid therapy.

o Morphine is by far the most common opiate implicated in OIH. Hydromorphone and oxycodone, members of the same class of opiate as morphine (phenanthrenes), can also cause OIH. Fentanyl, a synthetic opioid in the class of phenylpiperidine, is less likely to precipitate OIH.

Existing data suggests that OIH is caused by multiple opioid-induced changes to the central nervous system including:

-Activation of N-methyl-D-aspartate (NMDA) receptors

-Inhibition of the glutamate transporter system

-Increased levels of the pro-nociceptive peptides within the dorsal root ganglia

-Activation of descending pain facilitation from the rostral ventromedial medulla

-Neuroexcitatory effects provoked by metabolites of morphine and hydromorphone

• OIH can be confused with tolerance as in both cases patients report increased pain on opioids. The two conditions can be differentiated based on the patient’s response to opioids. In tolerance, the patient’s pain will improve with dose escalation. In OIH, pain will worsen with opioid administration. This paradoxical effect is one of the hallmarks of the syndrome.

Non-opioid analgesics

• Acetaminophen is indicated for management of mild to moderate pain and as a single analgesic and has modest efficacy at most. Addition of Acetaminophen to Ibuprofen does not provide better analgesia for patients with acute low back pain. The greatest limitation to the use of intravenous (IV) versus oral acetaminophen is the nearly 100-fold cost differential, which is likely not justified by any marginal improvement in pain relief. Furthermore, IV APAP provide faster onset of analgesia only after an initial dose. (Yeh 2012, Serinken 2012)

• NSAIDs should be administered at their lowest effective analgesic doses both in the ED and upon discharge and should be given for the shortest appropriate treatment course. Caution is strongly advised when NSAIDs are used in patients at risk for renal insufficiency, heart failure, and gastrointestinal hemorrhage, as well as in the elderly. Strong consideration should be given to topical NSAID’s in managing as variety of acute and chronic painful Musculo-skeletal syndromes. The analgesic ceiling refers to the dose of a drug beyond which any further dose increase will not result in additional analgesic efficacy. Thus, the analgesics ceiling for ibuprofen is 400 mg per dose (1200 mg/24 h) and for ketorolac is 10 mg per dose (10 mg/24 h). These doses are less than those often prescribed for control of inflammation and fever. When it comes to equipotent doses of different NSAIDs, there is no difference in analgesic efficacy.

• Ketamine, at sub-dissociative doses (also known as low-dose ketamine or analgesic dose ketamine) of 0.1 to 0.4 mg/kg, provided effective analgesia as a single agent or as an adjunct to opioids (reducing the need for opioids) in the treatment of acute traumatic and nontraumatic pain in the ED. This effective analgesia, however, must be balanced against high rates of minor adverse side effects (14%–80%), though typically short-lived and not requiring intervention. In addition to IV rout, ketamine can be administered via IN,SQ, and Nebulized route.

• Local anesthetics are widely used in the ED for topical, local, regional, intra-articular, and systemic anesthesia and analgesia. Local anesthetics (esters and amides) possess analgesic and anti-hyperalgesic properties by non-competitively blocking neuronal sodium channels.

o Topical analgesics containing lidocaine come in patches, ointments, and creams have been used to treat pain from acute sprains, strains, and contusions as well as variety of acute inflammatory and chronic neuropathic conditions, including postherpetic neuralgia (PHN), complex regional pain syndromes (CRPS) and painful diabetic neuropathy (PDN).

o UGRA used for patients with lower extremity fractures or dislocations (eg, femoral nerve block, fascia iliaca compartment block) demonstrated significant pain control, decreased need for rescue analgesia, and first-attempt procedural success. In addition, UGRA demonstrated few procedural complications, minimal need for rescue analgesia, and great patient satisfaction.

o Analgesic efficacy and safety of IV lidocaine has been evaluated in patients with renal colic and acute lower back pain. Although promising, this therapy will need to be studied in larger populations with underlying cardiac disease before it can be broadly used.

o knvlsd

• Antidopaminergic and Neuroleptics are frequently used in acute care settings for treatment of migraine headache, chronic abdominal pain, cannabis-induced hyperemesis.

• Anti-convulsant (gabapentin and pregabalin) are not recommended for management of acute pain unless pain is of neuropathic origin. Side effects, particularly when combined with opioids (potentiation of euphoria and respiratory depression), titration to effect, and poor patients’ compliance are limiting factors to their use. (Peckham 2018)

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