UMEM Educational Pearls

• 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.

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Methemoglobinemia occurs when iron in the hemoglobin is converted from ferrous (2+) to ferric (3+) state, frequently by substance exposure. There are many medications and chemicals that can induce methemoglobinemia. 

Common agents that induce methemoglobinemia include:

• Nitrites/nitrates
• Local anesthetics (benzocaine, lidocaine)
• Nitroglycerin
• Nitroprusside
• Phenazopyridine
• Quinones
• Sulfonamides
• Analine
• Naphthalene
• Dapsone
• Nitric oxide

Acetaminophen has not been associated with methemoglobinemia. However, two cases of methemoglobinemia in massive acetaminophen overdose were recently reported. Both patients were not on any medication known to cause methemoglobinemia.

Case 1:  54 year-old man with DM, HTN, cognitive impairment and no hx of G6PD deficiency hospitalized for altered mental status

• pH: 7.2
• lactic acid: 14.5 mmol/L
• APAP: 531 mcg/mL
• Discrepancy between pulse oximetry and arterial blood gas led to checking the methemoglobin level – 32%
• Developed coagulopathy (INR 9.8) with AST/ALT 3487/2837

Case 2:  64 year-old man with dementia, polysubstance abuse, depression and hypertension hospitalized from nursing home for altered mental status. 

• pH: 7.25
• AG: 28
• APAP: 730 mcg/mL
• Methemoglobin level: 12%
• AST/ALT: 44/46

Conclusion

• It is unlikely that significant methemoglobinemia will develop in the majority of the APAP overdose.
• However, methemoglobinemia should be considered in a large APAP overdose in select clinical scenarios (e.g. pulse oximetry and arterial blood gas discrepancy).

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Question

This week we anticipate treating more COVID19 cases as they progress to ARDS. The World Health Organization issued guidelines on 3/13/20 for treating Severe Acute Respiratory Infection (SARI) due to COVID19. 

How to identify ARDS?

No different than before COVID. Order a CXR, ABG, and perform bedside ultrasound evaluation of cardiac function and volume status. If there are bilateral opacifications you cannot explain entirely with volume overload, nodules, or lobar collapse, AND if the ratio of PaO2/FiO2 is < 300 (mild), < 200 (moderate), or < 100 (severe), then treat for ARDS.

***While you are waiting for your blood gas, SpO2/FiO2 <315 suggests ARDS.

What is the oxygen goal?

During resuscitation: > 93%

Once stabilized: > 89%

What is the expected clinical course?

Patients experience RAPID deterioration to respiratory failure. You should expect to intubate. This should be performed with N95 protection and should be done by the person with greatest first pass success.

Be CONSERVATIVE with fluids. Do not give a 30mL/kg bolus. Give 250-500mL bolus and re-evaluate. Excess fluid results in prolonged hypoxia and mechanical ventilation.

Should empiric treatments change?

No. Co-infection with influenza, bacterial pneumonia, and all other pathogens is possible, so you should continue to cover all suspected pathogens and de-escalate as microbiology labs result.

Should ventilator settings change?

No. Use lung protective volumes and permissive hypercapnia. The volume is based on the patient's height, not weight. A quick way to do this? Measure the height in cm. Subtract 100 for a man and subtract 110 for a woman and this is the ideal body weight. Provide 6mL/kg of tidal volume with a goal plateau pressure < 30. Use the high PEEP strategy from the ARDSnet trial and even consider clamping the ET tube when transitioning from machine to bag for transport in order to preserve PEEP.

Do patients benefit from proning?

Yes. 12-16 hours/day for severe ARDS. Not true in pregnancy as a whole, though early pregnancy may still benefit.

 Is ECMO beneficial in refractory cases?

Unknown. In the case of MERS-CoV, ECMO reduced mortality.

Are corrticosteroids useful?

No. Do not administer steroids routinely to these patients. You may give steroids where indicated, including cases of refractory shock following pressors.

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Laboratory studies are not often indicated in the early evaluation of low back pain.

Complete blood counts (CBC) have poor sensitivity and specificity for infection. White blood cell  (WBC) counts, have poor sensitivity and specificity for infection. They may be elevated and a left shift or bandemia may be present and increase suspicion for infection, but a lack of these does not rule out infection. Elevated WBC counts are only found in two-thirds of patients with SEA.

Both erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) are highly sensitive (84-100%) for spinal infections and are observed in >80% with vertebral osteomyelitis and epidural abscesses. However, elevated CRP was found in 87% of patients with an epidural abscess as well as half of patients with spine pain not due to an epidural abscess, so is not highly specific.

 CRP levels rise rapidly and decrease rapidly with improvement in disease and may be better used to follow response to treatment. ESR is the most sensitive and specific serum marker of infection. ESR is elevated in 94-100% of patients with an epidural abscess compared to only 33% of those without an epidural abscess. Infection is unlikely in patients with an ESR less than 20 mm/h. Although an elevated ESR (>20 mm/h) is the most specific serum test for infection, it also may indicate occult malignancy (sensitivity, 78%; specificity, 67%).

If infection is suspected, obtain two sets of blood cultures, as a causative pathogen may be identified in ~50% of patients.

(*It is important to note that many of the percentages in these early studies will change as more asymptomatic or minimally symptomatic patients are identified with increased testing)

Epidemiology

Among more than 44,000 confirmed cases of COVID-19 in China as of Feb 11, 2020:

- 30–69 years: ~78%

- severely or critically ill: ~19%

Case-fatality proportion: 

-60-69 years: 3.6%

-70-79 years: 8%

-≥80 years: 14.8%. 

-With no underlying medical conditions: overall case fatality of 0.9%

-With comorbidities: 

-cardiovascular disease (10.5%), diabetes (7%)

-chronic respiratory disease, hypertension, and cancer (6% each)

Presentation

For patients admitted to the hospital, many non-specific signs and symptoms: 

- fever (77–98%) and cough (46%–82%) were most common

- of note, gastrointestinal symptoms (~10%) such as diarrhea and nausea present prior to developing fever and lower respiratory tract signs and symptoms.

Diagnosis

No general lab tests have great sensitivity or specificity            

A normal CT scan does NOT rule out COVID-19 infection

-In an early study, 20/36 (56%) of patients imaged 0-2 days (‘early’) after symptom onset had a normal CT with complete absence of ground-glass opacities and consolidation

Treatment-

Mainstay of treatment will be management of hypoxemia including early intubation if necessary. However, specifically:

-Steroid therapy is controversial and the WHO is currently recommending against it unless it is being administered for another reason

-has not been associated with any benefit

-associated with possible harm in previous smaller studies with SARS and MERS

-associated with prolonged viremia

-intravenous remdesivir (a nucleotide analogue prodrug with promising in-vitro results against SARS-CoV and MERS-CoV) is available for compassionate use

            -lopinavir-ritonavir has been used without any associated benefit

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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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