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21-36 of 36 results by Wesley Oliver
The liver performs an essential role in the metabolism and clearance of many drugs. Liver damage due to cirrhosis can decrease first-pass metabolism of oral medications and increase free-drug concentrations of protein-bound medications due to decreased albumin production. In the absence of cirrhosis, patients with chronic hepatitis or hepatic cancer may only have a small decrease in drug clearance. Hepatic dose adjustments are not as prevalent or readily available as renal dose adjustments, which can create difficulty in finding the balance between pain relief and adverse effects.
The most common medications used for pain control in the emergency department are acetaminophen, NSAIDs, and opioids.
Acetaminophen
It is sometimes misconceived that acetaminophen should never be used in patients with cirrhosis due to the common knowledge that acetaminophen overdoses can cause hepatotoxicity. Alcoholics may have an increased risk of hepatotoxicity due to induction of CYP2E1 and decreased glutathione stores. However, acetaminophen is safe in patients with cirrhosis when used at appropriate doses. Limit the total daily dose of acetaminophen to 2 g daily in patients with cirrhosis and avoid acetaminophen in patients that are actively drinking. Also, educate patients that over-the-counter (OTC) and prescription medications may contain acetaminophen.
NSAIDs
In patients with cirrhosis, NSAIDs have increased bioavailability due to decreased CYP metabolism and decreased protein binding. In addition, prostaglandin inhibition can precipitate renal failure and sodium retention, worsening ascites and increasing the risk of hepatorenal syndrome, and increase the risk of gastrointestinal bleeding. Thrombocytopenia from NSAID use can further increase the risk of bleeding. Thus, avoid NSAID use in patients with cirrhosis. Topical NSAIDs can be considered.
Opioids
Opioid metabolism is altered in patients with cirrhosis and can contribute to complications with cirrhosis, such as precipitating encephalopathy. Generally, the bioavailability is increased and half-life is extended; thus, lower doses of immediate-release (IR) formulations at extended dosing intervals should be utilized. Common opioids for acute pain control in the emergency department are fentanyl, hydrocodone/oxycodone, hydromorphone, and morphine.
- Fentanyl: Largely unaffected by cirrhosis. High potency so utilize only in appropriate clinical situations.
- Hydrocodone/Oxycodone: Metabolized by CYP to active metabolites (hydromorphone/oxymorphone). Due to decreased CYP metabolism, analgesia may be less potent and clearance decreased. Also, be aware that some formulations are combined with acetaminophen.
- Hydromorphone: Metabolized by glucuronidation to inactive metabolite. Metabolism and clearance less affected by cirrhosis.
- Morphine: Increased bioavailability and concentration due to decreased first-pass metabolism. Decreased clearance and longer half-life. Avoid use in renal impairment and hepatorenal syndrome due to risk of neurotoxic metabolite accumulation.
- Tramadol, codeine, meperidine, methadone, and buprenorphine not recommended for acute pain control in the emergency department.
Take Home Points
| Drug/Class | Preferred Agent | Considerations |
| Acetaminophen | Max daily dose 2 g/day | Avoid if actively drinking. Be cautious if patient also taking OTC or combination products. |
| NSAIDs | None; Avoid | Topical NSAIDs may be considered. |
| Opioids | Hydromorphone, Fentanyl | Start with IR products at lower doses and extended intervals. |
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While taking metronidazole it is advised that patients avoid ethanol use for at least 3 days after therapy due to the possibility of a disulfiram-like reaction. The disulfiram-like reaction presents as abdominal cramps, nausea, vomiting, headaches, and/or flushing and can cause extreme discomfort for patients. A recent case report describes a case of a disulfiram-like reaction in a patient receiving metronidazole and an oral prednisone solution that contained 30% alcohol. This case highlights an important point. Not only should we counsel patients about avoiding alcoholic beverages for at least 3 days after metronidazole therapy, but they should also avoid all alcohol-containing products, such as oral solutions and mouthwash.
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Empirical Anti-MRSA vs Standard Antibiotic Therapy and Risk of 30-Day Mortality
A recent article published in JAMA Internal Medicine questioned the utility of empiric anti-MRSA pneumonia therapy. It was a retrospective multicenter cohort study conducted in the Veteran’s Health Administration healthcare system that looked at 88,605 patients with community-onset pneumonia. They compared 30-day mortality of patients hospitalized for pneumonia receiving empirical anti-MRSA therapy plus standard therapy against standard therapy alone. Secondary outcomes analyzed development of kidney injury and secondary infections with C. difficile, VRE, or gram-negative rods. They also analyzed subgroups: ICU admission, MRSA risk factors, positive MRSA surveillance test, and positive MRSA culture on admission.
Anti-MRSA Therapy: Vancomycin (98%), Linezolid (2%)
Standard Therapy: Beta-lactam + macrolide/tetracycline, or respiratory fluoroquinolone
Outcomes
Mortality: aRR=1.4 [95% CI, 1.3-1.5]
Kidney Injury: aRR=1.4 [95% CI, 1.3-1.5]
Secondary C. difficile: aRR=1.6 [95% CI, 1.3-1.9]
Secondary VRE: aRR=1.6 [95% CI, 1.0-2.3]
Secondary gram-negative rods: aRR=1.5 [95% CI, 1.2-1.8]
Mortality in Subgroups
ICU: aRR=1.3 [95% CI, 1.2-1.5]
MRSA Risk Factors*: aRR=1.2 [95% CI, 1.1-1.4]
Positive MRSA Surveillance: aRR=1.6 [95% CI, 1.3-1.9]
MRSA Detected on Culture: aRR=1.1 [95% CI, 0.8-1.4]
*MRSA Risk Factors
-History of MRSA infection/colonization within the past year
-Or 2 of the following: previous hospitalization, nursing home residence, and previous intravenous antibiotic therapy
Take-Home Point
Empirical anti-MRSA therapy did not decrease mortality for any groups of patients hospitalized for pneumonia. Given that healthcare-associated pneumonia is no longer a definition supported by the IDSA/ATS, be judicious in your use of anti-MRSA therapy in community-onset pneumonia and reserve for those patients at higher risk for MRSA, such as those with post-influenza pneumonia.
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Influenza is a common cause of community-acquired pneumonia and invasive bacterial coinfection may occur. In addition, secondary bacterial pneumonia due to MRSA is becoming more prevalent. Due to the higher incidence of MRSA, it is recommended that antibiotics with activity against MRSA (vancomycin or linezolid) be included in the empiric treatment regimen, especially if the patient is critically ill.
Take Home Point: Don’t forget to add MRSA coverage to your empiric treatment regimen in those influenza patients with severe disease or secondary bacterial pneumonia.
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Phenytoin can be a complex medication. There are different levels than can be ordered, adjustments based on albumin, various pharmacokinetic equations, and multiple formulations. Below are the simplified answers to some of the most common questions (see in-depth section for explanations):
Which phenytoin level (free or total) do I order?
Total Phenytoin Level.
What do I do after the level results?
Undetectable Level: Load patient with 20 mg/kg of total body weight (max dose 1,500 mg).
Subtherapeutic Level (<10 mcg/mL): Calculate an approximate loading dose using this equation….Phenytoin Dose (mg)=(15-measured total level)*(0.7*patient weight).
Therapeutic Level (10-20 mcg/mL): Add an additional agent.
Supratherapetutic/Toxic Level (>20 mcg/mL): Contact Poison Center (1-800-222-1222).
What formulation do I order for loading?
IV: Use fosphenytoin.
PO: Any formulation will work. Give as a single loading dose or, if concerned for GI upset, give in 2-3 divided doses separated by 2 hours.
***Disclaimer: These answers are simplified for the initial management of most patients in the ED. More complex answers may be required in some situations.***
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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.
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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.
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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.
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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.
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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 |
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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.
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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.
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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.
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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
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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.