UMEM Educational Pearls

MRI for Concussion Testing in the ED

The increased sensitivity of MRI may have a role in detecting more subtle intracranial injuries.

135 patients with mild TBI were prospectively evaluated for acute head injury in emergency departments of 3 LEVEL I trauma. 

27% of these patients with a normal initial head CT had an abnormal brain MRI including contusions and microhemorrhages. A greater number of these subtle findings was associated with neuropsychological defects on both short-term memory function and with poorer 3 month cognitive outcomes. Inherent difficulties of access, actionable results and reimbursement issues prevent application of MRI for concussion evaluation in the ED.

Note: Mild TBI defined as GCS 13-15 is not the same as sport or activity related concussion which I consider to be GCS 14-15.

Take home: There is currently no role for MRI in the acute evaluation of concussion in the ED.

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If you have an intuition your patients older than 65 are at increased risk of infection, especially pneumonia (4-11 times the risk of the under 65 cohorts), you are correct.

If you are concerned your patients co-morbidities, such as COPD, heart disease, and malnutrition will contribute to prolonged mechanical ventilation (the rate of VAP increases 1-3% every extra day on the vent), you are correct.

After age 70, the ICU length of stay and duration of mechanical ventilation increase by 5 days and 9 days respectively. 

In the age of COVID-19, itself associated with prolonged mechanical ventilation, it's fair to prepare patients and families for this. We are fortunate we do not need to ration ventilators, so our discussions remain centered on the wishes of our patients, informed by a realistic understanding of what treatment and recovery entail.

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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.

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Recently, “disinfectants,” or germicides, has gain public attention during COVID-19 pandemic. So, what types of agents are considered as “disinfectants?”

Germicides as classified into three broad categories

1.    Antiseptics – chemicals applied to living tissue to kill or inhibit microorganisms

a.    Iodine & iodophors (e.g. Povidone-iodine; aka Betadine)

b.    Chlorine, bleach (sodium hypochlorite)

c.     Chlorhexidine

d.    Hydrogen peroxide

e.    Alcohols (ethanol and isopropanol)

2.    Disinfectants – chemicals applied to inanimate objects to kill or inhibit microorganisms

a.    Formaldehyde

b.    Phenol (aka carbolic acid)

c.     Substituted phenols (e.g. hexachlorophene; aka pHisoHex)

d.    Quaternary ammonium compounds (benzalkonium chloride; aka Zephiran)

3.    Sterilants – chemicals applied to inanimate objects to kill all microorganisms including spores

a.    Ethylene oxide

b.    Glutaraldehyde

Although ethanol is frequently found in alcoholic beverage and consumable, no other chemicals should be ingested or injected.

Vitamin C for Septic Shock?

• In 2017, a single center before-and-after study demonstrated benefit for patients with sepsis who received vitamin C, hydrocortisone, and high-dose thiamine.
• At present, there are more than 30 trials evaluating the use of vitamin C in sepsis.
• The VITAMINS Trial was recently published and evaluated shock resolution in patients with septic shock who received vitamin C, hydrocortisone, and high-dose thiamine compared to those that received only hydrocortisone.
• In this randomized controlled trial of 211 ICU patients, the authors found no difference in the primary outcome of time alive and free of vasopressors at 7 days between the two groups.
• There was also no difference in the secondary outcomes of hospital, 28-day, and 90-day all-cause mortality.
• Though we still await the results of ongoing trials, the VITAMINS Trial and the recent CITRIS-ALI Trial have not demonstrated benefit of vitamin C for select patient populations with sepsis.

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Comparison of Oral Ibuprofen at Three Single-dose Regimens for Treating Acute Pain in the Emergency Department: A Randomized Controlled Trial

Ibuprofen is one of the most commonly used medications in the ED for the acute treatment of pain. Analgesic ceiling doses are not well supported. Some adverse effects of NSAIDs are dose dependent (GI and cardiovascular).

A recent study looked to compare the analgesic effect of oral ibuprofen at 3 different doses 

Population:  Adult ED patients (aged 18 and older) with acute pain.

Methods: Randomized double-blind trial.

Goal: To examine the efficacy of ibuprofen at 400, 600 and 800mg.

Only 225 patients enrolled (75 per group). Outcome was difference in pain scores at 60 minutes.

Results:  Difference in mean pain scores at 60 minutes between 400 and 600mg (0.14), 400 and 800mg (0.14) and 600 and 800mg (0.00).

Conclusion:  Reduction in pain scores was similar between all 3 dosing groups. Consider lower dosing of ibuprofen in ED patients presenting with acute pain. 

This analgesic ceiling dose is lower than recommended by the FDA and most EM textbooks.

Consider using the 400mg ibuprofen dose for ED patients with acute pain

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• A number of small studies in the past suggested that cervical collars can increase intracranial pressure (ICP) in patients with traumatic brain injury (TBI).
• In patients with severe head injury with poor intracranial compliance and impaired cerebral autoregulation, compression on the jugular veins may result in an increase in jugular venous pressure, increase in ICP, and decrease cerebral perfusion.
• A recent meta-analysis included 5 studies comprising 86 adult patients with moderate-severe TBI.
• 3 studies used rigid collars (Stifneck), while 1 used semi-rigid, and 1 used a mix of cervical collars.
• All 5 studies monitored ICP before and after collar application, 2 also monitored ICP after collar removal.
• Cervical collar application was associated with an overall ICP increase of approximately 4.4 mmHg (95%CI 1.70, 7.17; p<0.01), while removal was associated with an overall decrease of approximately 3 mmHg (95%CI -5.45, -0.52; p=0.02).
• The use of rigid cervical collars was strongly associated with raised ICP compared to semi-rigid collars (WMD=4.86; 95%CI 2.13, 7.60; p<0.01).

Bottom Line: Cervical collars can increased ICP in moderate-severe TBI.  In patients with poor cerebral compliance and impaired cerebral autoregulation, even a small increase in ICP can affect cerebral perfusion.

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Buprenorphine (BUP) is increasingly prescribed/used to treat opioid use disorder (OUD) in the United State. BUP is mainly metabolized by CYP3A4 where its enzymatic activity can be either induced or inhibited by many agents. 

For example, a study showed that Rifampin administration for 15 days, a potent 3A4 inducer, resulted in (1): 

• Reduction of plasma BUP concentration (70% reduction in area under the curve [AUC]) 
• 50% of the study subjects (12 out of 24) experienced opioid withdrawal symptoms (OWS)
• 4 out of 12 who experience OWS received transient increase in their BUP dose (25-100%)

On the contrary, exposure to voriconazole – strong 3A4 inhibitor - resulted in (n=12 health volunteers) (2):

• Increased the plasma BUP AUC by 4.3 fold
• Increased peak BUP concentration by 3.9 fold
• Documented adverse effects were dizziness and nausea only

Cannabis use – (CBD is a CYP 3A4 inhibitor) also increased the BUP concentration by 2.7 fold. (3)

Bottom line:

1. Be mindful of drug-drug interaction when initiating a new medication in patients with OUD on BUP
2. Inquire about any recent medication change in patients who may be experiencing OWS while on steady dose of BUP for their OUD. 

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Title: Randomized Trial of Three Anticonvulsant Medications for Status Epilepticus

Settings:

• 57 US hospitals: 26 sites for adults only, 18 sites enrolling only children, 13 sites enroll both.

Patients:

• 384 patients whose ages were 2 years and older. 
• Patients who continued to have generalized seizure for at least 5 minutes after “accepted” cumulative dose of benzodiazepines.

Intervention:

• levetiracetam at a dose of 60 mg per kilogram (maximum, 4500 mg),
• Fosphenytoin at a dose of 20 mg PE per kilogram (maximum, 1500 mg PE),
• valproate at a dose of 40 mg per kilogram (maximum 3000 mg)

Comparison:

• Patients > 32 kg total body weight:  diazepam of 10 mg; Lorazepam 4mg Intravenously; midazolam 10 mg intravenously or intramuscularly.
• Patients < 32 kg total body weight: diazepam at a dose of 0.3 mg per kilogram (administered intravenously or rectally), lorazepam at a dose of 0.1 mg per kilogram (administered intravenously), or midazolam at a dose of 0.3 mg of per kilogram (administered intramuscularly) or 0.2 mg per kilogram (administered intravenously)

Outcome: absence of clinical seizure at 60 minutes after infusion of medication.

Study Results:

• Rates of cessation of status epilepticus were similar in all 3 groups: 47% of levetiracetam vs. 45% Fosphenytoin vs. 46% for valproate.
• Fosphenytoin was associated with non-significantly higher rate of hypotension (3.2%) vs other drugs.
• Levetiracetam was associated with non-significantly higher rate of death (4.7%) vs. other drugs.
• All three medication was associated with similar rate of intubation within 60 minutes of drug infusion.

Discussion:

• The median time interval from start to cessation of status epilepticus appeared to be shorter for valproate but there was no formal analysis yet,
• Valproate (7.0 minutes) vs. levetiracetam (11.7 minutes) vs. Fosphenytoin (11.7 minutes)

Conclusion:

• Three medications, Fosphenytoin, levetiracetam, valproate were equally effective.

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The leading cause of death in the US for those aged 16 to 24 years is motor vehicle collisions (MVCs).  Teen drivers are more likely than any other age group to be involved in an MVC that result in injury or fatality.  Texting while driving, nighttime driving, inexperienced driving, and driving under the influence of alcohol or drugs may play a role in these collisions.

Can anticipatory guidance related to safe driving be done in the ED?  YES!

This study implemented a toolkit that contained a copy of the driving law, a sample parent-teen driving contract and statistics on teen driving injuries. Post toolkit questionnaires showed that both teens and their guardians learned new information.

Bottom line: Engage in anticipatory guidance in the ED with teens and their parents about seatbelt use, the dangers of driving under the influence and local driving laws.

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Clinical Question: Does a lower MAP target (60-65 mmHg) for ICU patients ≥ 65 years-old reduce 90-day mortality?

Methodology:

-Design: multicenter (across 65 UK ICUs), randomized clinical trial (not blinded), ultimately with 2598 patients

-Inclusion criteria: ICU patients ≥ 65 years-old receiving vasopressors for vasodilatory hypotension with adequate fluid resuscitation

-Exclusion criteria: vasopressors being solely used for bleeding or acute RV/LV failure or post-cardiopulmonary bypass vasoplegia, ongoing treatment for brain/spinal cord injury, death perceived as imminent

-Intervention:

• Permissive hypotension group – MAP target of 60-65 mmHg
• Usual care group – received vasopressors at discretion of treating clinician
• Choice of vasopressor (norepi, vaso, terlipressin, phenylephrine, epi, dopamine, and metaraminol) left to discretion of treating clinician

Results:

-Patients in the permissive hypotension group had a lower exposure to vasopressors compared with those in the usual care group

• median duration 33 hours compared with 38 hours (difference, –5.0; 95% CI, –7.8 to –2.2)
• mean duration, 46.0 hours compared with 55.9 hours (mean difference, –9.9 hours; 95% CI, –14.3 to –5.5)

-Mean MAP was on average 6 mmHg lower in permissive hypotension group

-At 90 days, there was no statistically significant difference in all-cause mortality

• 500 deaths (41.0%) among of 1221 patients in the permissive hypotension group compared with 544 (43.8%) among 1242 patients in the usual care group (absolute risk difference, −2.85%, 95% CI, −6.75 to 1.05; P = .15)

-No significant difference in mean duration of ICU and hospital stay, duration and days alive and free from advanced respiratory and renal support to day 28

-No significant different in number of serious adverse events (severe acute renal failure, supraventricular and ventricular cardiac arrhythmia, myocardial injury, mesenteric ischemia, and cardiac arrest)

Bottom line:

A lower MAP goal of 60-65 mm Hg appears to be safe for ICU patients ≥ 65 years-old being treated for vasodilatory hypotension

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Question

A recent study looked at analgesic prescribing patterns for patients with back pain in EDs in the United States.

Back pain is the most common pain complaint worldwide

-Accounted for about 9% of all ED visits.

Summary:  ED use of tramadol for back pain doubled from 2007 to 2016 despite an overall decrease in opioid use (in that period)

Tramadol -- either administered in the ED or prescribed -- was used in 8.4% of back pain visits in 2016, up from 4.1% in 2007 (P=0.001).

In 2007, overall opioid use was 53.5%; in 2016, it was 46.5% (P=0.001). The largest drop was in hydrocodone use.

A recent study in JAMA looked at the risk of death in 90,000 people one year after filling a Rx for tramadol vs. one of several other analgesics such as naproxen, diclofenac or codeine.

All patients were aged 50 years or older and has osteoarthritis.

Initial Rx for tramadol was associated with a higher rate of mortality than with NSAIDs (but not compared to codeine).

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There is currently a high, and appropriate, concern regarding the aerosolization of viral particles during various methods of respiratory support. While studies are limited, here is some of the currently available data (mostly-simulated) on the approximate maximum distances of particle spread:

Nasal Cannula 5LPM:¹ 1 ft 4.5 in

Non-Rebreather Mask, 6-12LPM: 4 in, minimal change with increasing flows¹

High Flow Nasal Cannula

• Simulation:² 30 LPM = 5.6 in / 60 LPM = 8.1 in
• Actual volunteers:³
  • Use of HFNC decreased aerosol dispersion during “violent exhalation” through nares
  • No difference in aerosol dispersion w/normal breathing using HFNC until 60lpm
  • Max spread = 14.4 ft without HFNC (violent exhalation) and 6.2 ft with HFNC (violent exhalation); aerosols airborne for max of 43 seconds

CPAP (20 cmH2O) provided by oronasal mask with good fit (leak from exhaust port):² 11.5 in

Bilevel positive airway pressure w/ oronasal mask (IPAP 10-18/EPAP 4): max dispersal:⁴ 1 ft 7.7 in

Bilevel positive airway pressure with full facemask⁵ (IPAP 18 / EPAP 5): 2 ft 8 in

Bilevel positive airway pressure with helmet:⁴

• IPAP 20 / EPAP 10 = 9 in
• Using helmet w/ air cushion = negligible dispersal

Utility of Surgical Mask:⁶

• No therapy:                 31% of exhaled particles travel, some >3.3 ft
• No therapy + mask:    5% of exhaled particles leak, some >3.3 ft
• 6LPM O2 + mask:       6.9% of exhaled particles leak, some >3.3 ft
• High Velocity Nasal Insufflation (40LPM) + mask: 15.9% of exhaled particles leak, some >3.3 ft

Bottom Line: 

In vivo data from actual patients is lacking, however there is potentially lower risk of aerosol spread with HFNC than regular nasal cannula, perhaps due to higher likelihood of a tighter nare/nasal cannula interface. Nonrebreather mask performs well indirectly with the shortest dispersal distance. Noninvasive positive pressure ventilation with an oronasal mask and good seal has a relatively short dispersal distance, and a surgical mask over respiratory support interventions actively decreases amount, if not distance, of particle spread. Use of appropriate PPE and negative pressure rooms, if available, remains key.

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Question

A 7 year-old Spanish speaking female presents to the emergency room after ingestion of 2 – 3 tablets of her sister’s medication. She complains of nausea/vomiting with diarrhea, periorbital/facial swelling, and flushing of her skin. Her urine is reddish but there is no blood is shown in urinalysis/urine microscopic analysis. The patient's sister is taking the medication for a respiratory condition.

Which medication did she take?

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Cyclopeptides (Amatoxin)-containing mushroom poisoning results in delayed development of gastrointestinal symptoms that may progress to liver failure. There is no established antidotal treatment for cyclopeptide-induced hepatic failure; silibinin is currently under investigation. 

There is a wide range of case fatality reported from cyclopeptides-containing mushroom poisoning: 4.8% to 47%.

National Poison Data System was reviewed from 1/1/2008 to 12/31/2018 for all suspected cyclopeptides containing mushroom poisoning. Out of 8953 suspected cases, 148 cases were included in the study.

Results:

• Northeast 50 (33.8%)
• West cost: 46 (31.1%)
• Southeast: 22 (14.9%)
• Midwest: 24 (16.2%)
• Southcentral: 6 (4.1%)

Therapy:

• NAC: 101 (68.2%)
• Penicillin: 42 (28.4%)
• Multi-dose activated charcoal: 35 (23.6%)
• Silibinin IV: 30 (20.3%)
• Silibinin PO: 12 (8.1%)

Case fatality

• Overall: 8.8%
• Treated with silibinin/silymarin: 9.5%
• Not treated with silibinin/silymarin: 8.5%

Conclusion:

• Overall fatality of cyclopeptide mushroom poisoning was 8.8%
• In this retrospective study, silibinin treatment did not appear to decrease the fatality rate.

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Please see Part I from 12/24/19 for information about causes and symptoms.

Diagnosis:

The diagnosis of HLH is challenging, as it often mimics sepsis or other critical illness.  A high index of suspicion is vital and early treatment, imperative.

Diagnostic criteria in adults include 5 of 8 of the following:

(based on the Hscore:  https://www.mdcalc.com/hscore-reactive-hemophagocytic-syndrome#use-cases)

·      Presence of known immunosuppression

·      Fever >38.5

·      Splenomegaly or hepatomegaly

·      Cytopenias

·      Ferritin elevation (usually markedly elevated)

·      Elevated triglycerides

·      Low fibrinogen level

·      ALT elevation

Immunologic testing:

·      CD25 levels are elevated

·      NK cell activity is low or absent

In adults, highly elevated ferritin levels (>10,000) are highly suggestive of HLH.

Elevated LDH, Ddimer, and multisystem organ dysfunction (especially CNS) is common.

Immunologic testing should not delay treatment if other lab values suggestive of HLH.

Treatment:

Given the high mortality rate, treatment should be initiated if the symptoms are suggestive of HLH.  In the setting of a critically ill individual, hematology consultation is warranted for treatment guidance as treatment is based on lab values and clinical picture. Treatment usually starts with high dose , IV steroids (dexamethasone) and may include chemotherapeutic agents, such as Etoposide. For those patients with CNS involvement, intrathecal chemotherapy is usually a mainstay of treatment

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Studying the demographics of all both sports and recreation related injuries is important for the development of effective preventive strategies.

Methods: National electronic injury surveillance system all injury program from 2005 to 2013 (367,300 sports and recreation related ED visits).  

18 common sports and recreational activities in the United States

Results:  A fracture occurred in 20.6% and a joint dislocation in 3.6% in ED visits for a sport related visit

Most of the fractures occurred in football (22.5%) and occurred in autumn and summer. Most fractures occurred in arm/hand (finger most common). Most fractures occurred in school or sporting venues.

The OR for fracture was greatest for inline skating (6.03), males (1.21) and those between 10 and 14 years of age and those older than 84 years (4.77).

Dislocations were highest in basketball (25.7%) and occurred in the autumn and on weekends. Most dislocations occurred in school or sporting venues.

The OR for dislocation was greatest in gymnastics (4.08), males (1.50) and those aged 20 to 24 years (9.04)

The most common fracture involved the finger and the most common dislocation involved the shoulder, followed by finger and knee.

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COVID-19 pandemic has brought two old medications – chloroquine and Hydroxychloroquine – back from the past. 

A couple in Arizona self-medicated with chloroquine this week and experienced chloroquine toxicity; the man died and his wife was admitted to the ICU.

https://www.cnn.com/2020/03/23/health/arizona-coronavirus-chloroquine-death/index.html

Chloroquine and hydroxychloroquine overdose result in cardiotoxicity by Na and K channel blockade (similar to other membrane stabilizing agents such as TCAs, loperamide, etc.). Onset of toxicity is usually within 1 – 3 hours after ingestion.

Other symptoms of toxicity include: nausea/vomiting, respiratory depression/apnea, altered mental status and seizure. Hypokalemia is often encountered.

Use of sodium bicarbonate is controversial due to worsening of hypokalemia. Instead, administration of high dose diazepam and epinephrine (EPI) infusion has shown to decrease mortality (see below).

Riou B et al. NEJM 1988 DOI: 10.1056/NEJM198801073180101

• A retrospective control (n=11) vs. prospective diazepam (2 gm/kg daily) and EPI (0.25 microgm/kg/min with titrate to SBP >= 100 mmHg) group (n=11) involving large chloroquine ingestion (> 5 mg)

Survival:

• Combination treatment group: 91%
• Control: 9%

Clemessy JL et al. Crit Care Med 1996. DOI:10.1097/00003246-199607000-00021

• 5 year retrospective study (n=167)
• Mean chloroquine ingestion: 4.5 gm +/- 2.8 gm
• >5 gm ingestion: 43 (26%)

Treatment: 87% received at least one of the interventions below.

• 79/167 (48%) received EPI infusion
• 142/167 (85%) received diazepam
• Mechanical ventilation: 123/167 (74%)

Mortality

• Overall: 8.4%
• >5 gm ingestion: 9.3%

Bottom line

• Chloroquine and hydroxychloroquine toxicity may increase due to COVID19 pandemic
• Limited studies show that combined therapy of high dose diazepam and epinephrine infusion may decrease mortality associated with chloroquine and hydroxychloroquine toxicity.

• Human coronaviruses generally cause GI and respiratory diseases.
• However, myocarditis, meningitis, and multi-organ failure have also been reported.
• Like other viruses, human coronaviruses may enter the central nervous system (CNS) hematogenously or through neuronal retrograde.
• The novel coronavirus (SARS-CoV-2) that emerged in Wuhan, China in December 2019 shares similar pathogenesis with SARS-CoV and MERS-CoV, and has been identified to use the same ACE2 receptor as SARS-CoV.
• Experimentally, SARS-CoV has been shown to cause neuronal death by invading the brain close to the olfactory epithelium.
• Patients with SARS have also been found to have the virus in their cerebrospinal fluid (CSF).
• An altered sense of smell, or hyposmia, has been observed in COVID-19 and may warrant an evaluation for potential CNS involvement.

Bottom Line: SARS-CoV has been associated with CNS involvement. Given their similar pathogenesis and finding of hyposmia in COVID-19, SARS-CoV-2 may be associated with risk of CNS involvement.

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Within the past few days we completed a review of complications of COVID-19, to describe what sequelae and clinical patterns, besides the obvious (URI, respiratory failure, ARDS, sepsis, etc), are noted in the literature.  This review, along with a plethora of other information focusing on critical care of the COVID-19 patient, will be posted in the next few days to http://covid19.ccproject.com/.  Below are the key points from that review:

• Acute cardiovascular complications appear to be the most common and concerning sequelae:  

                 -Acute myocardial injury (7-17% of hospitalized patients in one study),   

                 -Myocarditis (primary cause of death in 7% of COVID deaths in one study),  

                 -Arrhythmias (16.7% of hospitalized and 44.4% of ICU patients in one study), 

                  -Venous thromboembolism (incidence unknown).   

• Concerns for sudden cardiac death, even after recovery, have been raised but are not well documented in the literature.  Proposed mechanisms include respiratory compromise, myocarditis, malignant tachydysrhythmias, heart failure, and coronary plaque instability (i.e. Type 1 MI) secondary to inflammation 

• Co-infection and secondary infection rates are unknown but estimates range from 4.8% to 21%, with higher rates in sicker patients. Viral co-infection is more common than bacterial co-infection, but both may be seen. The ability to rule out COVID-19 by a positive multiplex respiratory viral panel is questionable. 

• Cytokine release syndrome and secondary HLH are both described complications, but their incidence is unknown.  The relation of this finding to purported benefits of tocilizumab (which is also a therapy for HLH) is unknown. 

• Other extrapulmonary complications are relatively typical of sepsis, such as kidney injury, abnormal LFTs, and delirium 

If anyone would like a copy of the full document, which details known complications by organ system, please feel free to email me at msutherland@som.umaryland.edu.  Thanks to David Gordon for organizing the project.

Everyone stay safe, and be sure to take care of each other, as well as our patients.