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.
Nitroglycerin is a potent vasodilator used most commonly for the treatment of angina and ACS. It can also be administered as a continuous infusion for acute management of a hypertensive emergency or sympathetic crashing acute pulmonary edema.
Most are aware of asking men for history of medications for erectile dysfunction (PDE5 inhibitors: sildenafil, tadalafil, vardenafil) but many overlook the fact that men and women may be on these medications chronically for pulmonary hypertension. Men can also be on these medications for the treatment of BPH. Be broad in your history taking and do not limit the discussion to erectile dysfunction or a specific gender.
Drug interaction:
-PDE5 inhibitors prevent the breakdown of cGMP
-Nitrates are nitric oxide donors that increase the production of cGMP
-The combination can lead to excessive vasodilation
If accidentally co-administered:
There is no antidote for this medication error. Support the patient with Trendelenburg positioning, fluid administration, and if needed, vasopressors such as norepinephrine until blood pressure stabilizes.
How long should you wait to administer nitrates after a patient takes a PDE5 Inhibitor?
Sildenafil and vardenafil: 24 h after last dose*
Tadalafil > 48 h after last dose*
*Even if acute ACS event
| | Beta-blockade N=22 | Control N= 44 | OR/CI |
| Temporary ROSC, n (%) | 19 (86.4) | 14 (31.8) | OR 14.46, 95% CI 3.63-57.57 |
| Sustained ROSC, n (%) | 13 (59.1) | 10 (22.7) | OR 5.76, 95% CI 1.79-18.52 |
| Survival with neurological function, n (%) | 6 (27.3) | 4 (9.1) | OR 4.42; 95% CI 1.05-18.56 |
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.
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. |
Pain management can be challenging in patients with acute or chronic renal failure. Opioid medications should always be used with caution, but some are safer than others. Morphine and codeine specifically should be avoided in these patients due to accumulation of active metabolites that can prolong the duration of effect and adverse events.
| Opioid | Renal Failure Impacts | Renal Failure Recommendation | Dialysis Recommendation |
| Morphine | Active metabolites accumulate | | |
| Codeine | Active metabolites accumulate | | |
| Hydromorphone | Minimal active metabolites | | |
| Oxycodone | Minimal active metabolites | | |
| Fentanyl | No active metabolites | | |
| Methadone | Active metabolites are inactive | | |
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.
Short periods of AKI have been linked to prolonged hospitalizations, development of CKD/ESRD and in-hospital mortality. Historically, AKI in the ED has been studied with respect to the receipt of contrast media with little data available on nephrotoxic medications.
A recent 5-year retrospective cohort study sought to determine the impact of prescribing nephrotoxic medications in the ED and the development of AKI within 7 days defined as an increase in SCr of ≥ 0.3 mg/dL or 1.5 x baseline. The categories of potentially nephrotoxic medications included ACE-i/ARB, antibiotics, diuretics, NSAIDs, and other (antifungal, antineoplastic, and antivirals).
Inclusion: Adult patients ≥ 18 years, with an initial and repeat SCr measured 24-168h after the initial test, under admitted or observation status (discharged patients were included if they had a repeat SCr in the time window).
Exclusion: previous hospital or ED visit within 7 days, initial SCr < 0.4 mg/dL, initial SCr > 4.0 mg/dL, missing data, dialysis, or transplant history.
The authors assessed 46,965 hospitalized encounters and found that 13.8% of patients developed AKI. Risk factors included older age, African American patients, history of CHF or CKD, higher initial SCr, and higher complexity and mortality. AKI developed within 48 hours in half of the patients and the reminder did so by 120 hours. Approximately 22% had ≥ 1 potentially nephrotoxic medication administered and 6% had ≥ 2 classes.
Diuretics were associated with the highest risk of AKI (64% increased risk), followed by ACE-i/ARBs (39%), and antibiotics (13%). NSAIDs were not associated with an increased risk. The antibiotics associated with the highest risk of AKI were piperacillin-tazobactam, sulfamethoxazole-trimethoprim, and quinolones.
Bottom Line: Medications prescribed in the ED have an impact on the development of AKI during hospitalization. While these cannot always be avoided, use caution when combining multiple nephrotoxic medications and discontinue therapy early when feasible.
