ACE-inhibitor (ACEi) induced angioedema is mediated by bradykinin and there are no proven medications for the treatment of this disease. Theoretically, a C1-esterase inhibitor (C1INH) could be beneficial; however, data has not demonstrated any efficacy for these agents.
Strassen et al. recently published a double-blind, randomized, controlled, multicenter trial of 30 patients comparing C1NH (Brand Name: Berinert) to placebo. In addition to standard treatment, a dose of C1INH (Berinert) 20 IU/kg or placebo (0.95% NaCl) was administered intravenously.
The primary endpoint was the time to complete resolution of signs and symptoms of edema (TCER). When compared to placebo, the original primary analysis demonstrated that the placebo arm (15 hours) resolved faster than the C1INH arm (24 hours, p=0.046).
This study is further evidence against the use of C1INH for ACE-inhibitor induced angioedema. The primary focus in the treatment of ACEi induced angioedema should continue to be airway management.
For reference, at our institution we have both C1INH (Berinert) and icatibant on formulary and they are restricted to only being used for acute hereditary angioedema attacks and cannot be used for ACEi induced angioedema.
Magnesium has been associated with function of serotonin and vascular tone regulation, both of which are mechanisms that implicate there may be a role in treatment of migraine. As this is a well-tolerated medication with a good safety profile, there is interest in utilizing this medication in the treatment of migraines. However, studies comparing magnesium to standard migraine treatments are lacking.
A recent single-center, double-blinded, randomized controlled trial compared magnesium, metoclopramide and prochlorperazine for treatment of migraine in the ED. Patients received either magnesium sulfate 2 grams, metoclopramide 10 mg or prochlorperazine 10 mg intravenously over 20 minutes. Adjunctive and rescue medications could be used at the providers discretion.
Pain was assessed with the 11-point Numeric Rating Scale at baseline and at several timepoints after completion of the infusion. Median change in pain score was found to be -3 in all groups at 30 minutes. Post-hoc analysis found magnesium to be non-inferior to prochlorperazine and metoclopramide at this time point. No difference in ED length of stay was found between groups. Adverse events were reported in 5% of patients receiving magnesium, 4.5% in patients receiving metoclopramide and 11.5% in prochlorperazine patients (p = 0.51). The most common adverse events were dizziness, akathisias, and anxiety.
Bottom Line: Magnesium can be used as an adjunctive agent in the treatment of migraines, and may also be considered as an alternative agent when other options such as prochlorperazine and metoclopramide are not appropriate. A reasonable dose would be 2 grams IV infused over 20 minutes. The team should follow-up 30-60 minutes after infusion to assess response to therapy.
Over half of U.S. adults in the United States consume dietary supplements.
Study design: A quality improvement study using data from the FDA’s Center for Drug Evaluation and Research, Tainted Products Marketed as Dietary Supplements
Dates: 2007 through 2016.
Results: Unapproved pharmaceutical ingredients were identified in 776 dietary supplements.
146 different dietary supplement companies were involved.
Most of these products were marketed for sexual enhancement (353 [45.5%]), weight loss (317 [40.9%]), or muscle building (92 [11.9%].
157 adulterated products (20.2%) contained more than 1 unapproved ingredient.
A 2015 NEJM study estimated that 23,000 ED visits per year are attributed to adverse effects associated with dietary supplements.
Estimated 2154 hospitalizations annually.
Frequently involve young adults between 20 and 34 years of age in addition to unsupervised children.
Excluding children, almost 66% of ED visits involve herbal or complementary nutritional products and 31.8% involved micronutrients.
Products for weight loss or increased energy were commonly implicated.
Finally, herbal and dietary supplements now account for 20% of cases of hepatotoxicity in the US.
The major implicated agents include anabolic steroids, green tea extract, and multi-ingredient nutritional supplements.
Anabolic steroids (marketed as bodybuilding supplements) typically induce a prolonged cholestatic, self-limiting liver injury.
Green tea extract and many other products, in contrast, tend to cause an acute hepatitis like injury.
Sugammadex works by chelating non-depolarizing neuromuscular blocking agents (NMBA) such as rocuronium and vecuronium to reverse the effects of paralysis. Dosing per package insert varies based on time from administration of the NMBA, and side effects, although rare, include severe bradycardia, hypotension, and asystole. While sugammadex is routinely used by our anesthesia colleagues, it is rarely utilized in the emergency department (ED) or intensive care unit (ICU) setting.
A recent single-center study assessed 11 patients with either a traumatic brain injury (TBI) or intracranial hemorrhage (ICH) who received sugammadex for neurologic assessment in the ED or ICU. The median dose was 240mg and the median time since last NMBA administration was 101 minutes.
In 6/11 patients, the neurosurgical plan changed and it affirmed a poor prognosis in 3/11 patients. In the ICU patients, sugammadex was associated with reduction in unnecessary tests.
All patients had a GCS of 3T prior to administration and 67% responded to sugammadex with a median increase to 8T (P=0.0156). MAP reductions were common with a median of -8 mmHg.
Bottom Line: Sugammadex can assist in determining a neurosurgical or clinical prognosis plan in patients with TBI and ICH. Larger studies are needed in this patient population and caution should be used inpatients who are already hypotensive or bradycardic. A reasonable dose, especially when given >1h from intubation would be 200mg. The team should be available at administration to note changes in GCS.
Piperacillin-tazobactam is one of the most commonly used antipseudomonal antibiotics in the empiric management of patients with septic shock. The package insert recommends dose reductions for renal impairment in other infectious etiologies, but the impact of dose reduction has not been previously studied in patients with septic shock.
A recent retrospective, observational cohort study compared outcomes of patients with septic shock who received ≥ 27 grams (at least 3.375 gm q6 hours x 48 h-“NORM”) versus those who received < 27 grams (“LOW”) over the initial 48 h of septic shock (defined as concomitant norepinephrine infusion).
Patients were excluded if they had death or hospice disposition within the 48h study period. The primary outcome was the number of norepinephrine free days (NFD) at day 28. Propensity matching was utilized to account for confounders.
Results: 351 in the LOW group, 928 in the NORM group with 608 pairs in the propensity matched assessment.
Bottom Line: Dose reductions of piperacillin-tazobactam appears to be harmful early in the management of patients with septic shock.
Intraosseous (IO) administration uses bone marrow to deliver fluids and medications during cardiac resuscitation or other emergent situations where IV access cannot be established.
IV versus IO
Considerations When Using IO Access
Prior studies have found that patients are at an increased risk for hypoglycemia when administered insulin for the acute management of hyperkalemia when they have renal dysfunction. A new single-center, retrospective study investigated the risk of hypoglycemia and the overall effect of potassium lowering in patients with renal dysfunction and stratified outcomes based on the CKD level.
Patients were included if they were ordered insulin for hyperkalemia using a hospital driven order set and had CKD stages 3a, 3b, and 4. They were excluded if they had dialysis within 6h of insulin administration, had DKA, or no repeat labs. The hospital order set encourages 5 units of insulin instead of 10 when “renal failure” is present without clear guidance.
377 patients were included: 186 received 5 units and 191 received 10 units. The average age was 65 years old, predominantly male, weighing 90 kg. In the 5 unit group, significantly more patients had CKD stage 4 (60% v 30%) and in the 10 unit group, significantly more patients were CKD stage 3a (p<0.001). The baseline serum potassium was 6 in each group.
The hypoglycemia incidence was not different between groups, with severe hypoglycemia occurring twice per group. All patients received dextrose according to the protocol.
There was a significant difference in the reduction of serum potassium between the 5 and 10 unit groups: -0.63 mmol/L vs -0.9 mmol/L (p 0.001).
Bottom line: Hypoglycemia occurred even with insulin dose reduction. Potassium lowering was higher in patients who received the 10 unit dose.
A recent prospective cohort study investigated the effect of low-dose droperidol on QTc in an emergency department:
Low-dose droperidol has a small effect on QTc and most patients remained below 500 ms.
Diphenhydramine (B) has historically been utilized in combination with haloperidol 5mg (5) and lorazepam 2mg (2) in the treatment of acute agitation. The most common rationale for adding diphenhydramine is prevention of EPS, however literature to support this is lacking. A recently published paper examined diphenhydramine/haloperidol/lorazepam combination (B52) vs haloperidol/lorazepam combination therapy (52) to compare the need for additional agitation treatments as a surrogate for clinical efficacy.
This retrospective, multicentered noninferiority study included 400 emergency medicine patients, 200 per treatment arm. On average, the patients were 40 years old, 64% male, and predominantly Caucasian. More patients in the B52 group had psychiatric illness listed as their primary cause for agitation compared to the 52 group. The two most frequently reported substances on urine drug screens, if collected, were amphetamines (35%) and cannabinoid (35.5%).
Results:
-No difference in the use of additional agitation medications within 2 hours
-More patients in the 52 group were noted to receive anticholinergic medications within 2 days, but indications varied and were not associated with EPS treatment
The B52 combination was associated with:
---Increased length of stay 17 h (10-26) vs 13.8 h (9-12), p = 0.03
---Increased use of restraints 43% vs 26.5%, p = 0.001
---Hypotension 16% vs 3.5%, p <0.001
---Use of nasal canula oxygen 3% vs 0%, p < 0.01
The addition of diphenhydramine may not be necessary to prevent EPS in patients receiving haloperidol for agitation and is associated with increased length of stay and adverse events, likely due to its additive sedative properties.
Background:
Multisystem inflammatory syndrome in children (MIS-C) as defined by CDC Health Advisory in May 2020 is:
1) An individual aged <21 years presenting with fever*, laboratory evidence of inflammation**, and evidence of clinically severe illness requiring hospitalization, with multisystem (>2) organ involvement (cardiac, renal, respiratory, hematologic, gastrointestinal, dermatologic or neurological); AND
2) No alternative plausible diagnoses; AND
3) Positive for current or recent SARS-CoV-2 infection by RT-PCR, serology, or antigen test; or exposure to a suspected or confirmed COVID-19 case within the 4 weeks prior to the onset of symptoms.
*Fever >38.0°C for ≥24 hours, or report of subjective fever lasting ≥24 hours
**Including, but not limited to, one or more of the following: an elevated C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), fibrinogen, procalcitonin, d-dimer, ferritin, lactic acid dehydrogenase (LDH), or interleukin 6 (IL-6), elevated neutrophils, reduced lymphocytes and low albumin
As of January 31st, 2022 the CDC reports the following statistics related to MIS-C in the United States:
· Total MIS-C patients meeting case definition= 6,851
· Total MIS-C deaths meeting case definition = 59
· The median age of patients with MIS-C was 9 years. Half of children with MIS-C were between the ages of 5 and 13 years.
· 59% of the reported patients with race/ethnicity information available occurred in children who are Hispanic/Latino (1,746 patients) or Black, Non-Hispanic (2,050 patients).
· 98% of patients had a positive test result for SARS CoV-2, the virus that causes COVID-19. The remaining 2% of patients had contact with someone with COVID-19.
· 60% of reported patients were male.
Management:
First-Line Treatment:
· IVIG 2 g/kg dosed based on ideal body weight with a maximum of 100 grams (1000 mL)
o For patients with significant myocardial dysfunction and concern for fluid overload, the infusion can be given in divided doses over 2 days (1g/kg q12 x 2 doses)
PLUS
· Methylprednisolone 1 mg/kg (max of 30 mg/dose) IV twice daily and switch to PO and taper when clinically appropriate
Upon Consultation with Pediatric Hematology/Cardiology will consider adding the following therapies to IVIG and steroids:
· Enoxaparin treatment versus prophylactic dosing depending on D-dimer elevation and whether or not being admitted to PICU
· Aspirin 3-5 mg/kg (max 81 mg/dose) daily unless platelet count < 80 K/mcl
Second-Line Treatment (refractory to IVIG defined by symptoms and fever persisting >36 hours)*:
· Methylprednisolone pulse dosing- 30 mg/kg (max of 1000 mg/dose) x 3-5 days
OR
· High dose anakinra
OR
· Infliximab 5-10 mg/kg IV x1
*All second-line treatment options require peds infectious diseases and PICU attending approval
UMMS COVID/MIS-C Pathway: https://intra.umms.org/-/media/intranets/umms/pdfs/dept/pharmacy-and-therapeutics/guidelines/umms-pediatric-covid-pathway.pdf?upd=20220125144550
Calcium is commonly administered during cardiac arrest, but there is little data to support or refute its use. The Calcium for Out-of-Hospital Cardiac Arrest trial was a randomized, double-blind, placebo-controlled parallel group study conducted in Denmark. Their EMS system responds to all cardiac arrests with an ambulance and a physician-manned mobile emergency care unit.
Adult patients were included if they had out of-of-hospital (OOH) cardiac arrest and received at least 1 dose of epinephrine. Exclusion criteria were traumatic arrest, known or suspected pregnancy, prior enrollment in the trial, receipt of epinephrine from an EMS unit not in the trial, or a clinical indication for calcium during the arrest (i.e. hyperkalemia or hypocalcemia).
Patients received 735mg calcium chloride dihydrate (5 mmol CaCl –US standard product is 1000mg) or saline control immediately after the first dose of epinephrine. A second dose was administered after the second dose of epinephrine if cardiac arrest ongoing. Teams were blinded to the treatments. The primary outcome was ROSC for at least 20 minutes.
397 patients were randomized (197 calcium, 200 saline). The average age was 68 years old, 70% were male, and over 80% of the cardiac arrests occurred at home, 60% witnessed arrests, and 82% received bystander CPR. Only 25% were in a shockable rhythm. The time to first epinephrine and study drug was approximately 17 minutes and over 70% received two doses.
ROSC rates were low and not statistically different between groups, 19% in the calcium group vs 27% in the saline group. There was no difference in survival to 30d or neurologic function. In the patients who did achieve ROSC in the calcium arm, 74% had hypercalcemia.
Bottom Line: The routine use of calcium in out-of-hospital cardiac arrest is not recommended.
Kcentra (four-factor prothrombin complex concentrate, 4f-PCC) is approved for the reversal of warfarin using a weight-based dosing strategy based on INR. However, since the approval of Kcentra, data has shown a fixed-dose strategy and use for direct-acting oral anticoagulants (DOAC) is appropriate. There are even recommendations to use a fixed-dose for DOACs in some situations. Utilizing a fixed-dose strategy can help with decreasing drug preparation/delivery times and costs.
Our institution now only uses a weight-based Kcentra dose of 50 units/kg for patients on DOACs with ICH or trauma-induced coagulopathy. All other patients receive a fixed-dose of Kcentra 1,500 units or 2,000 units based on anticoagulant and other criteria.
Below is a diagram summarizing our current dosing strategy for Kcentra at our institution.
ICH=intracerebral hemorrhage
DOAC=direct-acting oral anticoagulant (rivaroxaban, apixaban, and edoxaban)
Other points of interest at our institution:
| Uncomplicated Gonococcal Infections | 2015 Recommendations [1] | 2020 Recommendations [2] |
| Cervical, urethral, rectal, and pharyngeal infection | Ceftriaxone 250 mg IM x 1 dose, plus azithromycin 1 g PO x 1 dose | Ceftriaxone 500 mg IM x 1 dose |
| >=150 kg | No recommendation | Ceftriaxone 1 g IM x 1 dose |
| If coinfection with chlamydia cannot be excluded | Coverage provided by gonococcal treatment regimen | Add doxycycline 100 mg PO BID x 7 days |
Vancomycin infusion reactions can manifest as pruritus and an erythematous rash of the neck, face, and torso during or after a vancomycin infusion. This is a histamine reaction caused by degranulation of mast cells and basophils, and can be caused short infusion times <60 min. It is commonly treated with antihistamines and/or a slowing of the infusion rate.
While fluoroquinolones have fallen out of favor for many indications due to the ever growing list of adverse effects, they still play an important role in the outpatient treatment of pyelonephritis. Fluoroquinolones and TMP-SMX are the preferred agents due to higher failure rates with beta-lactams.
Preferred Therapies:
Ciprofloxacin 500 mg PO BID*
Levofloxacin 750 mg PO daily*
TMP-SMX 1 DS tab PO BID**
*Consider a single dose of long-acting parenteral agent, such as ceftriaxone, if community prevalence of fluoroquinolone resistance >10%.
**Consider a single dose of long-acting parenteral agent, such as ceftriaxone, if using TMP-SMX.
Alternative Therapies#:
Cefpodoxime 200 mg PO BID
Cefdinir 300 mg PO BID
#Beta-lactams are not preferred agents due to higher failure rates when compared to fluoroquinolones. Consider a single dose of long-acting parenteral agent, such as ceftriaxone, if using beta-lactams.
Duration of Therapy: 10-14 days
Take Home Point:
Utilize ciprofloxacin, levofloxacin, or TMP-SMX over beta-lactams when discharging patients with oral antibiotics for pyelonephritis.
Tranexamic acid (TXA) is an antifibrinolytic medication that has been trialed in previous small studies to treat epistaxis. The data to this point has not reliably shown a reduction in bleeding at 30 minutes, but has demonstrated an increased rate of discharge at 2 hours and a reduction in re-bleeding events.
The NoPAC study was the largest study to date on TXA for epistaxis. It was a double-blind, placebo-controlled, randomized study of TXA in adult patients with persistent atraumatic epistaxis to determine if TXA use decreased the rate of anterior nasal packing. Patients were excluded if they had trauma, out of hospital nasal packing, allergy to TXA, nasopharyngeal malignancy, hemophilia, pregnancy, or if they were referred to ENT.
Eligible patients completed 10 minutes of first aid measures followed by 10 minutes of topical vasoconstrictor application prior to randomization to either placebo of 200mg TXA soaked dental rolls inserted in the nare.
496 patients were enrolled. The average patient was 70 years old with stable vitals 150/80mmHg, HR 80 bpm with >60% on oral anticoagulants.
TXA did not reduce the need for anterior nasal packing: 100 (41.3% placebo) vs 111 (43.7% TXA) OR 1.11 (0.77-1.59). There were no differences in the rates of adverse events.
Bottom Line: TXA does not improve rates of anterior nasal packing for patients with persistent epistaxis.
Buprenorphine is a partial opioid receptor agonist that has a higher binding affinity than pure opioid agonists. There can be unease in managing acute pain in patients sustained on buprenorphine for opioid use disorder due to many factors.
The main barriers to effective pain management in these patients are:
Take Home Points
In general, the treatment strategy for acute pain in patients on buprenorphine should be:
With a national shortage of octreotide an alternative treatment plan had to be implemented at our institution for patients presenting with variceal bleeding.
Drug references recommend a continuous infusion of vasopressin at 0.2 to 0.4 units/minute. Dose may be titrated as needed to a maximum dose of 0.8 units/minute with maximum duration of 24 hours to reduce incidence of adverse effects. Administer IV nitroglycerin concurrently to prevent ischemic complications and monitor closely for signs/symptoms of myocardial, peripheral, and bowel ischemia.
Protocol at our institution:
Vasopressin
Initiate vasopressin at 0.2 units/min.
Increase by 0.2 units/min if bleeding is not controlled after one hour (max dose: 0.8 units/min).
If bleeding controlled for 2 hours, can decrease by 0.2 units/min and reassess.
Limit use to 24 hours.
Nitroglycerin
Use nitroglycerin infusion to prevent adverse effects from vasopressin.
Initiate nitroglycerin at 40 mcg/min, titrate by 40 mcg/min to a max dose of 400 mcg/min.
Goal systolic blood press pressure of 90-100 mmHg. Do not start nitroglycerin if SBP <90 mmHg.
***Please note the vasopressin dose for this indication is significantly higher than the typical dose of 0.03 units/min we use for shock.***
Opioid Conversion Updates
Updated in 2018, some clinicians are unaware of the changes to the opioid conversion tables.
|
| 2010 Recommendations |
| 2018 Updates | ||
| Opioid | IV (mg) | PO (mg) |
| IV (mg) | PO (mg) |
| Morphine | 10 | 30 |
| 10 | 25 |
| Fentanyl | 0.1 | NA |
| 0.15 | NA |
| Hydromorphone | 1.5 | 7.5 |
| 2 | 5 |
| Oxycodone | NA | 20 |
| NA | 20 |
When converting between opioids, it is important to remember the following steps:
While online calculators can be helpful, opioid conversions should be done thoughtfully with a full patient assessment to determine the correct conversion for the individual patient.
