Category: Pharmacology & Therapeutics
Keywords: DKA, SGLT2 Inhibitors (PubMed Search)
Posted: 8/3/2019 by Wesley Oliver
(Updated: 12/12/2024)
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The American Diabetes Association requires a plasma glucose concentration greater than 250 mg/dL to diagnose diabetic ketoacidosis (DKA). However, with the new diabetic agents this is not always the case. With the introduction of SGLT2 inhibitors (canagliflozin [Invokana], dapagliflozin [Farxiga], empagliflozin [Jardiance]) there have been reported cases of DKA and patients being euglycemic.
Take Home Point
Patients with a low/normal blood glucose can still have DKA. Especially if they are taking newer medications, such as the SGLT2 inhibitors.
AE Kitabchi, GE Umpierrez, JM Miles, JN Fisher. Hyperglycemic Crises in Adult Patients With Diabetes. Diabetes Care 2009;32:1335-1343.
U.S Food and Drug Administration. FDA warns that SGLT2 inhibitors for diabetes may result in a serious condition of too much acid in the blood. https://www.fda.gov/media/92185/download. Accessed August 3, 2019.
Category: Pharmacology & Therapeutics
Keywords: alteplase, pulmonary embolism (PubMed Search)
Posted: 7/6/2019 by Wesley Oliver
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Alteplase may be considered in some patients with a presumed or confirmed pulmonary embolism. Below is a list of the different patient populations and the associated alteplase dosing.
-Hemodynamically Stable/Submassive: Alteplase usually not indicated.
-Hemodynamically Unstable/Massive: Alteplase IV 100 mg as an infusion over 2 hours.
-Cardiac Arrest: Alteplase IV/IO 50 mg bolus over 2 minutes. Can repeat a second 50 mg bolus 15 minutes later if unable to achieve return of spontaneous circulation.
Alteplase. Lexicomp. UpToDate. Waltham, MA: UpToDate Inc. Available at: https://www.uptodate.com. Accessed on July 6, 2019.
Kearon C, Aki EA, Comerota AJ, et al. Antithrombotic therapy for VTE disease: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest 2012;141:e419-e496S.
Kearon C, Aki EA, Ornelas J, et al. Antithrombotic therapy for VTE disease: CHEST guideline and expert panel report. Chest 2016;149:315-352.
Lavonas EJ, Drennan IR, Gabrielli A, et al. Part 10: Special circumstances of resuscitation: 2015 American Heart Association guidelines update for cardiopulmonary resuscitation and emergency cardiovascular care. Circulation. 2015;132:S501-S518.
Category: Pharmacology & Therapeutics
Keywords: Serotonin Syndrome, SHIVERS (PubMed Search)
Posted: 4/6/2019 by Wesley Oliver
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Identifying serotonin syndrome in the emergency department can be difficult without an accurate patient history. Furthermore, the physical symptoms may look similar to many other disorders such as neuroleptic malignant syndrome and anticholinergic toxicity. If you remember the acronym SHIVERS, you can easily recognize the signs and symptoms of serotonin syndrome.
Shivering: Neuromuscular symptom that is unique to serotonin syndrome
Hyperreflexia and Myoclonus: Seen in mild to moderate cases. Most prominent in the lower extremities. This can help differentiate from neuroleptic malignant syndrome which would present with lead-pipe rigidity.
Increased Temperature: Not always present, but usually observed in more severe cases
Vital Sign Abnormalities: Tachycardia, tachypnea, and labile blood pressure
Encephalopathy: Mental status changes such as agitation, delirium, and confusion
Restlessness: Common due to excess serotonin activity
Sweating: Autonomic response to excess serotonin. This symptom can help differentiate from anticholinergic toxicity in which the patients would present with increased temperature but dry to the touch
Once serotonin syndrome is identified, it is important to discontinue all serotonergic agents, provide supportive care with fluids, and sedate with benzodiazepines. Sedation with benzodiazepines helps to decrease myoclonic jerks which also helps with temperature control. If patients are hyperthermic, they will require intensive cooling. Cyproheptadine, a potent antihistamine and serotonin antagonist, should also be administered. The initial dose of cyproheptadine in serotonin syndrome is 12mg which can be followed by 2 mg every 2 hours as needed for symptom control.
1. Christensin RC. Get serotonin syndrome down with cold shivers. [Internet] 2006 [cited 2019 Apr 4]. Available from: https://mdedge-files-live.s3.us-east-2.amazonaws.com/files/s3fs-public/Document/September-2017/0502CP_Pearls2.pdf
2. Ables AZ, Nagubilli R. Prevention, Recognition, and Management of Serotonin Syndrome. AFP. 2010;81(9):1139-1142.
Category: Pharmacology & Therapeutics
Keywords: Flu, Treatment, Oseltamivir (PubMed Search)
Posted: 1/8/2019 by Wesley Oliver
(Updated: 12/12/2024)
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---Early antiviral treatment can shorten the duration of fever and illness symptoms, and may reduce the risk of some complications from influenza.
---Early treatment of hospitalized adult influenza patients with oseltamivir has been reported to reduce death in some observational studies.
---Clinical benefit is greatest when antiviral treatment is administered within 48 hours of influenza illness onset.
Antiviral treatment is recommended for patients with confirmed or suspected influenza who:
---are hospitalized;
---have severe, complicated, or progressive illness; or
---are at higher risk for influenza complications. (See below for in-depth information)
Oral oseltamivir is the recommended antiviral for patients with severe, complicated, or progressive illness who are not hospitalized, and for hospitalized influenza patients.
Treatment:
Doses: Oseltamivir 75 mg twice daily
Renal Impairment Dosing
CrCl >60 mL/minute: No dosage adjustment necessary
CrCl >30 to 60 mL/minute: 30 mg twice daily
CrCl >10 to 30 mL/minute: 30 mg once daily
ESRD undergoing dialysis: 30 mg immediately and then 30 mg after every hemodialysis session
Duration of Treatment:
Recommended duration for antiviral treatment is 5 days for oral oseltamivir. Longer daily dosing can be considered for patients who remain severely ill after 5 days of treatment.
People at higher risk for influenza complications recommended for antiviral treatment include:
---children younger than 2 years;
---adults 65 years and older;
---people with chronic pulmonary (including asthma), cardiovascular (except hypertension alone), renal, hepatic, hematological (including sickle cell disease), and metabolic disorders (including diabetes mellitus), or neurologic and neurodevelopment conditions (including disorders of the brain, spinal cord, peripheral nerve, and muscle, such as cerebral palsy, epilepsy [seizure disorders], stroke, intellectual disability, moderate to severe developmental delay, muscular dystrophy, or spinal cord injury);
---people with immunosuppression, including that caused by medications or by HIV infection;
---women who are pregnant or postpartum (within 2 weeks after delivery);
---people younger than 19 years old who are receiving long-term aspirin- or salicylate-containing medications
---American Indians/Alaska Natives;
---people who are extremely obese (i.e., body mass index is equal to or greater than 40); and
---residents of nursing homes and other chronic care facilities.
Centers for Disease Control and Prevention. Influenza antiviral medications: summary for clinicians. https://www.cdc.gov/flu/professionals/antivirals/summary-clinicians.htm (Accessed on January 8, 2019).
Category: Pharmacology & Therapeutics
Keywords: Intranasal Administration, Alternative Administration (PubMed Search)
Posted: 11/2/2018 by Wesley Oliver
(Updated: 11/8/2018)
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The most common methods of medication administration in the emergency department are oral, intravenous (IV), and intramuscular (IM). If the oral route is not available, if IV/IM are not necessary, or if obtaining IV access is challenging, intranasal (IN) medication delivery is a reasonable alternative. More concentrated products are preferred and a volume of 1 mL or less per nostril should be utilized. Below is a table of the commonly used medications used via the IN route.
Drug | Concentration | Indication | IN Dose | Time to Peak Effect | Adverse Events |
Fentanyl | 50 mcg/mL | Analgesia | 0.5-2 mcg/kg | 5 min | Nasal irritation, rhinitis, headache |
Ketamine | 100 mg/mL | Analgesia, Agitation, Sedation | 3-6 mg/kg | 5-10 min | Poor taste, HTN, hypersalivation, agitation, emergence reaction |
Lorazepam | 2 mg/mL | Agitation, Seizures | 0.1 mg/kg Max: 4 mg | 30 min | Poor taste, lacrimation, nasal/throat irritation |
Midazolam | 5 mg/mL | Agitation, Sedation, Seizures | 0.1-0.4 mg/kg Max: 10 mg | 5-10 min | Same as lorazepam |
Naloxone | 1 mg/mL | Opioid Reversal | 0.1 mg/kg Usual dose: 0.4-2 mg | 1-5 min | N/V, headache, withdrawal symptoms |
Bailey AM, Baum RA, Horn K, et al. Review of intranasally administered medications for use in the emergency department. J Emerg Med. 2017;53:38-48.
Category: Pharmacology & Therapeutics
Keywords: Sepsis, Antibiotics, CMS, Core Measures (PubMed Search)
Posted: 9/1/2018 by Wesley Oliver
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The Centers for Medicare and Medicaid Services (CMS) require broad spectrum antibiotics to be administered within 3 hours of presentation of sepsis to be in compliance with the sepsis measure.
Not only do the antibiotics that are chosen determine compliance with this measure, but the order in which antibiotics are given can also significantly affect compliance.
According to CMS, for combination antibiotic therapy, both antibiotics must be started within the three hours following presentation; however, they do not need to be completely infused within this time frame.
Combination therapy typically includes a monotherapy antibiotic (see list in detailed information below) plus vancomycin (daptomycin or linezolid could also be used).
So which antibiotic should be given first?
If a monotherapy antibiotic is given first within the 3 hours of presentation, then compliance for the sepsis measure is met. These antibiotics cover a broader range of bacteria and are typically infused over ~30 minutes, which allows plenty of time for your second antibiotic to be initiated.
If vancomycin is given first, compliance with this measure can become difficult. First, vancomycin has a narrower spectrum of activity and is not a monotherapy antibiotic. Second, vancomycin infusion rates range from 1 to 2 hours. Given that antibiotics are usually given after sepsis is flagged, this infusion rate only gives a short period of time for the second antibiotic to be initiated. Thus, vancomycin should almost always be the second antibiotic infused.
In addition, patients may also have limited intravenous access or antibiotics may not be compatible with resuscitation fluids. All of these factors together must be considered when trying to gain compliance with this measure.
Take-Home Point:
Administer monotherapy antibiotics (e.g. piperacillin/tazobactam and cefepime) prior to administering vancomycin in your septic patients to improve compliance with the sepsis measure.
Specifications Manual for National Hospital Inpatient Quality Measures v5.4. The Joint Commission. https://www.jointcommission.org/specifications_manual_for_national_hospital_inpatient_quality_measures.aspx. Updated December 29, 2017. Accessed August 31, 2018.
Category: Pharmacology & Therapeutics
Keywords: Diabetes, DKA (PubMed Search)
Posted: 7/7/2018 by Wesley Oliver
(Updated: 12/12/2024)
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Woodward RS, Flore MC, Machnicki G, Brennan DC. The long-term outcomes and costs of diabetes mellitus among renal transplant recipients: tacrolimus versus cyclosporine. Value Health. 2011;14(4):443-9.
Category: Pharmacology & Therapeutics
Keywords: Fosfomycin, urinary tract infection, cystitis (PubMed Search)
Posted: 3/3/2018 by Wesley Oliver
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Fosfomycin is an antibiotic infrequently used for the treatment of urinary tract infections (UTIs). It has a broad spectrum of activity that covers both gram-positive (MRSA, VRE) and gram-negative bacteria (Pseudomonas, ESBL, and carbapenem-resistant Enterobacteriaceae), which is useful in the treatment of multidrug-resistant bacteria.
Fosfomycin is FDA approved for the treatment of uncomplicated UTIs in women due to susceptible strains of Escherichia coli and Enterococcus faecalis (3g oral as a single dose). Data has also demonstrated that it can be used for complicated UTIs; however, dosing is different in this population (3 g oral every 2-3 days for 3 doses). Fosfomycin is not recommended for pyelonephritis.
The broad spectrum of activity, in addition to only needing a single dose in most cases, makes fosfomycin an attractive option; however, it should be reserved for use in certain circumstances. Fosfomycin should not be considered as a first-line option. It is also more expensive than other medications (~$100/dose) and in countries with high rates of utilization bacteria are developing resistance to fosfomycin. In addition, most outpatient pharmacies do not keep this medication in stock.
Take-Home Point:
Fosfomycin should be reserved for multidrug-resistant UTIs in which other first-line options have been exhausted.
Gupta K, Hooton TM, Naber KG, et al; Infectious Diseases Society of America; European Society for Microbiology and Infectious Diseases. International clinical practice guidelines for the treatment of acute uncomplicated cystitis and pyelonephritis in women: a 2010 update by the Infectious Diseases Society of America and the European Society for Microbiology and Infectious Diseases. Clin Infect Dis. 2011;52(5): e103-e120. doi: 10.1093/cid/ciq257.
Michalopoulos AS, Livaditis IG, Gougoutas V. The revival of fosfomycin. Int J Infect Dis. 2011;15(11):e732-e739. doi: 10.1016/j.ijid.2011.07.007.
MONUROL [prescribing information]. St. Louis, MO: Forest Pharmaceuticals, Inc; 2007. www.accessdata.fda.gov/drugsatfda_docs/label/2008/050717s005lbl.pdf. Accessed 9/7/2017September 7, 2017.
Oteo J, Bautista V, Lara N, et al; Spanish ESBL-EARS-Net Study Group. Parallel increase in community use of fosfomycin and resistance to fosfomycin in extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli. J Antimicrob Chemother. 2010;65(11):2459-2463. doi: 10.1093/jac/dkq346.
Raz R. Fosfomycin: an old—new antibiotic. Clin Microbiol Infect. 2012;18(1): 4-7. doi: 10.1111/j.1469-0691.2011.03636.x
Reffert JL, Smith WJ. Fosfomycin for the treatment of resistant gram-negative bacterial infections. Insights from the Society of Infectious Diseases Pharmacists. Pharmacotherapy. 2014;34(8):845-857. doi: 10.1002/phar.1434.
Vardakas KZ, Legakis NJ, Triarides N, Falagas ME. Susceptibility of contemporary isolates to fosfomycin: a systematic review of the literature. Int J Antimicrob Agents. 2016;47(4):269-285. doi: 10.1016/j.ijantimicag.2016.02.001.
Wankum, Michael, et al. “Fosfomycin Use.” Pharmacy Times, 30 Nov. 2017, www.pharmacytimes.com/publications/health-system-edition/2017/november2017/fosfomycin-use.
Category: Pharmacology & Therapeutics
Keywords: Epinephrine, Asthma (PubMed Search)
Posted: 1/8/2018 by Wesley Oliver
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Patients with severe asthma exacerbations that are unresponsive to inhaled beta-agonists may require the use of epinephrine to control their symptoms. When patients get to this point what route of administration should be used for the administration of epinephrine?
The most recent asthma guidelines (published in 2007) recommend the use of SubQ epinephrine 0.3-0.5 mg every 20 minutes for 3 doses. Drug references typically list SubQ or IM epinephrine 0.01 mg/kg (~0.3-0.5 mg) every 20 minutes as appropriate routes of administration. There is currently no data demonstrating that one route of administration is better than the other in patients with asthma; however, in other disease states, such as anaphylaxis, IM epinephrine is preferred due to the more rapid and reliable absorption over SubQ administration.
Auto-injectors that administer IM epinephrine 0.3 mg are available. These auto-injectors may decrease the risk of medications error; however, they can be expensive. SubQ administration requires the use of a syringe and a vial/ampule of 1 mg/mL epinephrine.
Bottom Line: Either SubQ or IM epinephrine administration is appropriate for patients with severe asthma exacerbations. The preferred method at a given institution will be dictated by historical practice, risk of medication dosing errors, and drug cost.
1. National Asthma Education and Prevention Program, Third Expert Panel on the Diagnosis and Management of Asthma. Expert Panel Report 3: Guidelines for the Diagnosis and Management of Asthma. Bethesda (MD): National Heart, Lung, and Blood Institute (US); 2007 Aug. Available from: https://www.ncbi.nlm.nih.gov/books/NBK7232/
2.Simons FER, Ardusso LRF, Bilo MB, El-Gamal YM, Ledford DK, Ring J, et al. World Allergy Organization Anaphylaxis Guidelines: Summary. J Allergy Clin Immunol. 2011;127(3):587–93. e1-e20.
Category: Pharmacology & Therapeutics
Keywords: Insulin, Hyperkalemia, Dextrose (PubMed Search)
Posted: 11/6/2017 by Wesley Oliver
(Updated: 12/12/2024)
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Strategies for Hyperkalemia Management | |
Stabilize cardiac membrane | Calcium gluconate |
Intracellular movement in skeletal muscles | Albuterol Sodium Bicarbonate Insulin |
Potassium excretion | Loop Diuretics Kayexalate Patiromer (chronic use only) |
Potassium removal | Dialysis |
Insulin mechanism of action for hyperkalemia:
· Binds to skeletal muscle receptors
· Increased activity of the sodium-potassium adenosine triphosphatase and glucose transporter GLUT4
· Glycemic response occurs at lower levels of insulin
· Potassium transport activity increases as insulin levels increase
Patients with insulin resistance due to type-2 diabetes do not become resistant to the kalemic effects of insulin.
Hypoglycemia following insulin administration for hyperkalemia:
· Occurs 1-3 hours post dose, even with initial bolus of dextrose
· The amount of glucose is insufficient to replace the glucose utilized in response to the administered dose of insulin
· Insulin’s half-life is increased in ESRD leading to longer duration of action
A systematic review of 11 studies regarding insulin dosing for hyperkalemia:
· 22 patients (18%) experienced hypoglycemia
· Studies that only gave 25 grams (1 amp) of dextrose had the highest incidence of hypoglycemia (30%)
Tips:
· Consider insulin dose reduction in patients with renal failure
· Use an order set to ensure patients receive appropriate POC glucose monitoring to detect delayed onset of hypoglycemia
· Dextrose 50% (25 grams) should be given to all patients with pre-insulin BG <350 mg/dL
Subsequent PRN dextrose 50% (25 grams) should be used to maintain BG >100 mg/dL after insulin administration
References:
1. Sterns RH, Grieff M, Bernstein PL. Treatment of hyperkalemia: something old, something new. Kidney International 2016;89(3):5460554.
2. Harel Z, Kamel KS (2016) Optimal Dose and Method of Administration of Intravenous Insulin in the Management of Emergency Hyperkalemia: A Systematic Review. PLoS ONE 11(5): e0154963. doi:10.1371/journal.pone.0154963
Category: Pharmacology & Therapeutics
Keywords: Ureteral stones, Alpha-blockers (PubMed Search)
Posted: 9/2/2017 by Wesley Oliver
(Updated: 12/12/2024)
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Alpha-blockers (tamsulosin, alfuzosin, doxazosin, and terazosin) are antagonists of alpha1A-adrenoreceptors, which results in the relaxation of ureteral smooth muscle. Current evidence suggests alpha-blockers may be useful when ureteral stones are 5-10 mm; however, there is no evidence to support the use of alpha-blockers with stones <5 mm. Patients with ureteral stones >10 mm were excluded from studies utilizing these medications.
The size of most ureteral stones will be unknown due to the lack of need for imaging able to measure stone size. Given that the median ureteral stone size is <5 mm, most patients will not benefit from the use of an alpha-blocker.
Also, keep in mind that the data for adverse events with alpha-blockers used for ureteral stones is limited and that these medications have a risk of hypotension.
Ferre RM et al. Tamsulosin for ureteral stones in the emergency department: a randomized, controlled trial. Ann Emerg Med 2009.
77 patients
Ibuprofen + oxycodone + tamsulosin vs. ibuprofen + oxycodone
Stone expulsion at 14 days: Tamsulosin group=77.1% vs. Standard therapy=64.9%
-Difference=12% (95% CI: -8.4-32.8%)
No clinically/statistically significant differences
Pickard R et al. Medical expulsive therapy in adults with ureteric colic: a multicentre, randomised, placebo-controlled trial. Lancet 2015.
1,136 patients
Tamsulosin vs. nifedipine vs. placebo
No further intervention at 4 weeks: Tamsulosin=81% vs. Nifedipine=80% vs. Placebo=80%
No clinically/statistically significant differences
Furyk JS et al. Distal ureteric stones and tamsulosin: a double-blind, placebo-controlled, randomized, multicenter trial. Ann Emerg Med 2016.
403 patients
Tamsulosin vs. placebo
Stone passage at 28 days: Tamsulosin=87% vs. Placebo=81.9%
-Difference=5% (95% CI: -3-13%)
Found difference in subgroup analysis of large stones (5-10 mm)
-Tamsulosin=83.3% vs. Placebo=61%
-Difference=22.4% (95% CI: 3.1-41.6%)
No other clinically/statistically significant differences
Hollingsworth JM et al. Alpha blockers for treatment of ureteric stones: systematic review and meta-analysis. BMJ 2016.
Meta-analysis of 55 trials
No benefit in patients with smaller stones (<5 mm): RR=1.19 (95% CI: 1.00-1.98)
Benefit in patients with larger stones (5-10 mm): RR=1.57 (95% CI: 1.39-1.61)
1.) Ferre RM, Wasielewski JN, Strout TD, Perron AD. Tamsulosin for ureteral stones in the emergency department: a randomized, controlled trial. Ann Emerg Med 2009;54:432-9.
2.) Furyk JS, Chu K, Banks C, et al. Distal ureteric stones and tamsulosin: a double-blind, placebo-controlled, randomized, multicenter trial. Ann Emerg Med 2016;67:86-95.
3.) Hollingsworth JM, Canales BK, Rogers MAM, et al. Alpha blockers for treatment of ureteric stones: systematic review and meta-analysis. BMJ 2016;355:i6112.
4.) Pickard R, Starr K, MacLennan G, et al. Medical expulsive therapy in adults with ureteric colic: a multicentre, randomised, placebo-controlled trial. Lancet 2015;386:341-9.