M&M - Sickle Cell Disease - Public Health - Heme/onc Emergencies - Burns - Carboxyhemoglobinemia - Methemoglobinemia

Morbidity and Mortality with Dr. Baez

Case 1: STEMI IN LVH

Diagnosis of LVH:

There are several different criteria to diagnose LVH. They are broken down into voltage criteria and non-voltage criteria. All of these criteria are approximately 50% sensitive and >90% specific.

Voltage Criteria:
- Cornell Criteria: R wave in aVL + S wave in V3 > 28mm (males) or 20mm (females)
- Modified Cornell Criteria: R wave in aVL > 11mm
- Sokolow-Lyon Criteria: S wave in V1 + R wave in V5 or V6 > 35mm
Non-voltage criteria:
- Increased R wave peak time > 50ms in V5 or V6
- ST segment depression and T wave inversion in left-sided leads
Other common findings in LVH:
- Left axis deviation
- Left atrial enlargement
- ST elevation in V1-V3 (this makes STEMI diagnosis difficult)

Diagnosis of STEMI in LVH:

There are no guidelines on how to do this. Many sources site various common findings that make ischemia more likely in the setting of LVH. These findings include symmetric T wave inversions and convex ST segments. This paper looked at 79 patients with LVH who were diagnosed with STEMI. The scrutinized the EKGs to try to identify characteristics that were suggestive of true ischemia. Their findings are below:

>3mm ST elevation (vs 1.9mm)
Q waves present
More leads with ST elevation (3.1 vs 1.8)
Reciprocal ST depressions
Greater ratio of ST elevation to RS magnitude (>25%)

The European Society of Cardiology recommend bedside Echo to look for wall motion abnormalities. If there are wall motion abnormalities, STEMI is more likely to be present. However, it has been shown that patients with LVH are less likely to have wall motion abnormalities.

The conclusions from all of this is that it is a difficult diagnosis to make without any firm guidelines. It is important to look for concerning EKG findings, evaluate for wall motion abnormalities, use clinical context, and always discuss with cardiology.

Case 2: Hepatitis A

Transmitted by fecal-oral route. Infected patients typically transmit disease for two weeks prior to developing symptoms.
Risk Factors: homelessness, drug use, MSM, recent incarceration
Presentation: fever, malaise, abdominal pain, nausea/vomiting/diarrhea
Management: mainly supportive. 60% require hospitalization. Less than 1% progress to fulminant liver failure. However, this risk is higher in patients with chronic liver disease.
Vaccination: CDC recommends patients at high risk should get vaccine. Vaccine is a two part series (t=0 and t=6 months). The vaccine is typically very expensive in the ED. However, can often refer to local health department for vaccine. In Cincinnati the health department (513-357-7200) will give this vaccine for free to the uninsured.
Prevention: always wash hands. Alcohol does not kill the virus.

Case 3: IV contrast reactions

There are several different types of IV contrast dye used in the United States. High-osmolar agents typically have less reactions than low-osmolar agents. Non-ionic agents have lower rates of reactions than ionic agents. In general, there is some type of contrast reaction 5% of the time contrast dye is used. The types of reactions that we see can be split into immediate and delayed reactions:

Immediate: occurs within one hour of administration. Most of the time is mild with flushing, itching, and rash. However, serious reactions such as angioedema, hypotension, stridor, and wheezing can occur <1% of the time. The pathophysiology of this reaction is controversial and not well understood.
Delayed: occurs 1 hour to 7 days after administration. Most commonly this is urticaria, but cases of SJS have been reported.

There are only two established risk factors. These are a history of previous reactions to radiocontrast material and a history of atopy. One retrospective study did show increased myasthenic exacerbations in MG patients after contrast administration, but this is controversial and largely unproven. Shellfish allergy is often thought to be a risk factor as well, but there is no data to support this. See this paper for more information.

There are many premedication regimens for people with allergies prior to getting a contrast load. These regimens have been shown to decrease breakthrough reactions to 0.13-2.1%. Unfortunately, the literature showing this use regimens that start 12-13hrs prior to a scan. This regimen includes:

Methylprednisolone 40mg or hydrocortisone 200mg IV immediately THEN
Same dose overy 4 hours until contrast administration PLUS
Benadryl 50mg IV one hour prior to scan

Regimens less than 4-5 hours have NOT been shown to be effective. However, the risks of a reaction should be balanced with the benefit of the contrast administration.

Case 4: ANdexxa for Factor xa inhibitor reversal

Andexxa:

genetically modified factor Xa, reversal agent for Xa inhibitors (rivaroxaban, apixaban), half life is 5-7 hours
approved in May 2018 for life-threatening bleeds (only available in 10 US institutions)
expensive (patient cost of $55,000 vs $5,000 for PCCs)
given as bolus and then 2hr infusion
This study showed it reduces Xa activity by 92-94% in 2-5 minutes (This video explains the study)
This study showed it led to hemostasis in 83% of patients with life threatening bleeds, however there were thrombotic events in 18% of patients
No studies comparing Andexxa vs PCCs, stay tuned

Case 5: Pharmacologic Cardioversion of Atrial Fibrillation

This study showed that ED providers management of atrial fibrillation is quite variable. 60% elect to use rhythm control with 44% of them choosing electrical cardioversion. Pharmacologic cardioversion has a lower success rate (50% vs 90%) compared to electricity. However, it does mitigate sedation risk and results in shorter ED stays. Three medications we do not use as often for this are procainamide, ibutilide, and flecainide; so we took a deeper dive into these medications below:

Procainamide:
- Na channel blocker, increases refractory period (prolongs QRS and QTc)
- Dose: 10-15mg/kg up to 1g; maintenance 1-4 mg/min
- Contraindications: CHF, renal failure, myasthenia gravis
- 60-80% conversion rate, faster than amiodarone
- Side Effects: transient hypotension, V tach, GI upset
Ibutilide:
- K rectifier current blocker, prolonged repolarization (prolongs QTc)
- 1mg IV over 10 min, can repeat twice if needed (increased risk of side effects)
- Contraindications: QTc > 440, electrolyte abnormalities
- Side Effects: torsades (1.7%, some providers give 2g Mg with medication), V tach (2.6%)
Flecainide:
- Na channel blocer, slows conduction (prolongs QRS)
- 200-300 mg PO or 2mg/kg IV over 30 min; maintenance 50-150mg q12h
- Contraindications: chronic atrial fibrillation (proarrhythmic), heart failure, ACS
- Side Effects: hypotension, ventricular tachycardia, heart failure

Case 6: Septic Arthritis in Fingers

Antibiotics for open finger fractures:

This study showed no difference in infection rates with antibiotics for open finger fractures
This study was a meta-analysis that also found no difference in rates of cellulitis and osteomyelitis in patients with open distal phalanx fractures
Take away: Empiric antibiotics are not necessarily warranted in open finger fractures, important to irrigate well

Management of traumatic arthrotomy of the finger:

No literature on utility of empiric antibiotics, but in speaking to hand surgery, they would recommend antibiotics in all cases

Septic arthritis in the finger:

<5% of all joint infections
microbiology is more variable (includes oropharyngeal flora)
This study recommended diagnosis made based on high clinical suspicion PLUS purulent synovial fluid, leukocytes present in synovial fluid, or a positive culture
Treatment: Not all patients need OR washout, but should have some sort of joint drainage. This study treated patients with 1 month antibiotics (initially IV, then augmentin), this study used a 2 week course (3 days IV, then augmentin)

Case 7: Scalp Abscess

These abscesses are often more high risk. The scalp has valveless emissary veins that drain into the superior sagittal sinus. The vascularity in general helps decrease infection risk, but the connection to the intracranial vessels make complications more dangerous. There is no good literature on scalp abscesses, however. In general, it is prudent to ensure adequate drainage, treat all of these with antibiotics, and ensure close follow up.

Sickle Cell Disease WITH DR. Freiermuth

Background:

Results from a mutation of the hemoglobin gene, causing RBCs to sickle leading to many of the manifestations of this disease
Most common inherited blood disorder in the US (100,000 patients)
Average life span is 45 years because of the risks of the disease
Only two medications for Sickle Cell Disease:
- Hydroxyurea: increases fetal hemoglobin
- L-Glutamine: inhibits inflammatory cascade

ED Complications:

Vaso-occulsive Crises: these are unpredictable; 40% of patients have no crises per year, 1% have over 6 per year. There is increased risk of developing complications, no drugs to specifically treat this, only control the pain.
Acute Chest: most common cause of death. Diagnosed by an infiltrate on CXR + cough/fever/increased RR/hypoxia/sputum. There may be benefit to using incentive spirometer in patients with pain crisis to decrease risk of acute chest.
Aplastic Crisis: the bone marrow stops producing RBC, it is rare. This is why we check a reticulocyte count to make sure they are producing RBCs.
Splenic Sequestration: most patients are functionally asplenic by teenage years
Renal Failure: many on dialysis in 4th decade
Stroke: 300x the risk of ischemic stroke, many of silent, resulting in cognitive disability

Treating Pain:

Goal of parental administration of IV opioids within 60 minutes
Subcutaneous dosing: allows for quick pain relief prior to IV access. It is often preferred by patients over the IM route.

R4 Capstone: "Non-Urgent" ED Visits WITH DR. isaac Shaw

Why you should care:
- Insurers, notably Anthem Blue Cross Blue Shield, has been denying ED patients payment for their visits based on discharge diagnosis, not on chief complaint
- This is illegal by the Prudent Layperson Standard
  - In summary, this states that insurers cannot deny payment to patients if they, with average medical knowledge and health literacy, present to the emergency department with symptoms of sufficient severity that they believe not seeking immediate medical care would cause harm
Some legislative history:
- In 1993, Maryland passed the first state-wide law implementing the Prudent Layperson Standard
- In 1997, the Balanced Budget Act was passed, adopting this standard for CMS recipients
- In 1999, all federal employees were covered by this standard
- In 2010, the Affordable Care Act made the Prudent Layperson Standard universal
What is a "non-urgent" visit?
- Only 3.3% of patients present to the ED and receive no diagnostic testing, procedures, or medications
- Using the Emergency Severity Index (ESI) is inaccurate
  - Of those with ESI 4 or 5, 32% receive procedures, 48% receive diagnostic testing, and 6% are admitted
- The NYU Algorithm is inaccurate as well
  - This was developed to categorize all ICD-9 diagnoses into percentage of visits that fall into one of four categories (below). Of patients with an ICD-9 discharge diagnosis classified as "non-emergent" or "primary care treatable", their chief complaint overlapped with those which were classified as "ED care needed" 88.7% of the time.
1. Non Emergent: Not requiring treatment in 12 hours
2. Primary Care Treatable: Requiring treatment in 12 hours, but treatment could be provided at PCP office
3. ED Care Needed - Not Preventable/Avoidable: ED specific care required, but visit not preventable by good primary care
4. ED Care Needed - Preventable/Avoidable: ED specific care needed, but visit could have been avoided by good primary care
Are non-urgent visits truly costing insurance companies significant amounts of money?
- ED care resulting in discharge makes up over 2/3 of ED visits, and 4.2% of national healthcare expenditure (NHE)
- Non-emergent visits make up only 0.75% of NHE
How to get Involved:
- Vote on Nov. 6, 2018
- Join Ohio ACEP
- Join the EMRA Health Policy Committee
- Sign up for the ACEP 911 Legislative Newsletter

Acute Leukemia, GvHD, and CAR-T WITH DR. Essell

Acute Leukemia Emergent Complications

Hyperleukocytosis: blast count > 100k. CLL patients with WBC > 100k are not as risk as the cells are much smaller and pliable. These patients may present with headache, vision changes, neuro changes, respiratory failure, or MI. Treatment is leukophoresis, be reticent to transfuse RBCs as this can increase viscosity and lead to further complications.

Coagulopathy: classically this occurs with Acute Promyelocytic Leukemia. This conditions is marked by a low WBC count with auer rods present. Treatment is with all trans retinoic acid. Other care is generally supportive with cryo, FFP, platelets as needed for treatment of DIC. Do not begin chemotherapy as this will worsen the DIC.

Tumor Lysis Syndrome (TLS): patients with acute leukemia can present with TLS even prior to treatment. Similar to hyperleukocytosis, markedly elevated WBC. Other findings include hyperuricemia, hyperphosphatemia, hyperkalemia, hypocalcemia, and acute kidney injury. Treatment is with allopurinol or rasburicase depending on a variety of factors, discuss with heme/onc.

Infection: most common presenting feature. Typically gram negative if there is no obvious source. Cover empirically with antibiotics and search for source.

CNS Events: hemorrhage, cranial nerve anomalies. Treatment is based on specific pathology.

GVHD

Survival after BMT is increasing as our experiences with BMT increase. The cause of death in these patient acutely is often infection, but chronically both GvHD and the primary disease are the likely cause. These patients will be on some sort of immunosuppressant agent (tacrolimus, cyclophosphamide, methotrexate) as prophylaxis for rejection.

Acute GvHD: typically within first 100 days after allogeneic BMT. Can involve multiple organ systems:

Skin: may be severe and present as a 3rd degree burn
GI: nausea/vomit/diarrhea, GI bleed, liver involvement

Treatment: steroids, rituximab, pentostatin. All of these medications then lead to further immune suppression increasing the risk of infections.

Chronic GvHD: > 100d after allogeneic BMT. Often presents with similar organ system involvement:

Sicca syndrome (oral ulcerations, corneal abrasion)
Skin: hypo and hyper pigmentation, scleroderma
Liver: can lead to cirrhosis if untreated.
GI: chronic wasting, diarrhea.

Treatment: steroids, ibrutinib (can lead to bleeding)

Admit these patients for: uncontrolled N/V, bloody diarrhea, infection, or inability to follow up.

CAR-t: Chimeric Antigen Receptor T Cell Therapy

Rationale: patients with refractory DLBCL have poor prognosis. 2/3 are cured initially, but the other 1/3 don't do well. This treatment is target towards those 1/3 of people who don't do well.

The treatment is a mix of cellular therapy, gene therapy, and immunotherapy. It uses the patient's own immune system to treat the disease. T cells are removed from the patient and then genetically modified to target specific cancer cells. They are then put back into the patient as treatment for the cancer.

Complications:

Cytokine Release Syndrome: This is essentially a large immune reaction. Median onset is three days following infusion. Symptoms can range from mild (flu like symptoms) to severe (multi-organ system failure). They often look like a septic patient and so are treated as such while concurrently treating the inflammatory response
Neurologic Toxicity: This can range from mild confusion to aphasia to seizures. It can be early (within 3 days of the infusion) or delayed (up to 8 weeks after the infusion). The presentation can be subtle and so using family is pivotal to pick up some of the personality changes. Patients can also present as a stroke but should not receive the typical stroke treatments. This will be a discussion with neurology and heme/onc.
Sepsis: These patients are still neutropenic and susceptible to infection.

R3 Taming the sru : burns WITH DR. Spigner

Initial burn care can be conceptualized in four basic steps:

Primary Survey
Resuscitation / Volume Replacement
Toxicology
Wound Care

Resuscitation / Volume Replacement:

Burn patients have high sensible losses and require sufficient hydration to offset the risk of kidney injury due to rhabdomyolysis.

In a rush, any patient with a significant burn burden can be started on 250mL/hr +/- 50mL/hr. Once you have the time to calculate an accurate burn area (ie. Lund and Browder chart), you can apply the Parkland Formula to approximate your fluid requirements.

Parkland Formula = 4mL / kg / %TBSA

Half given over first 8 hours

Other half given over next 16 hours

As the patient starts to produce urine, you can titrate your fluid rate to achieve a urine output of 1mL/kg/hr.

Be wary of complications of such high volume replacement, including compartment syndrome of limbs or abdomen, cerebral edema, pulmonary edema, and electrolyte abnormalities. These patients should receive a more balanced crystalloid with lower chloride content (ie. Normosol).

Toxicology

If concern for carbon monoxide exposure (ie. elevated carboxyhemoglobin level or patient was in a closed-space fire), given higher FiO2 to enhance elimination of CO. For any significant CO exposure in a closed space, or altered mental status, cyanide exposure should be considered. If so, consider giving Cyanokit (hydroxocobalamin), which has few downsides and is most effective when given early. Cyanokit serves as a cyanide-sink, binding cyanide in a urine-excretable form.

Wound Care

Perform escharotomies when there are 3rd/4th degree burns present and there is concern for compartment syndrome or restrictive lung defect. Cut through stiff tissue until the tissue springs apart, revealing healthy subcutaneous tissue. Start and end your incision in healthy tissue. Avoid ulnar nerve in elbow and common peroneal nerve in knee. Do not cut over areas of flexion.

Simplified treatment algorithm:

2nd Degree: Bacitracin & Adaptic
3rd / 4th Degree: Silver Sulfadiazine
Ears: Mafenide
Eyes: Erythromycin ointment and ophthalmology consult

R1 Clinical Knowledge: Carboxyhemoglobinemia and Methemoglobinemia WITH DR. Walsh

Carboxyhemoglobinemia

Background:

Caused by carbon combustion or ingestion of methylene chloride
Effects due to:
- Relative anemia and left shift of O2 dissociation curve
- Myoglobin binding: rhabdomyolysis
- Inhibition of oxidative phosphorylation: lactic acidosis
- Vasodilation & hypotension: ischemia repercussion and MI
- Endothelial damage: neuronal cell death

Presentation:

Mild: flu-like illness
Moderate/Severe: AMS, hypotension, cardiac arrest, metabolic acidosis

Diagnosis:

VBG w/ CO-oximetry
- Non-smokers: < 5%
- Smokers: 8-10%
- Toxicity: >10%
EKG for all patients
Consider:
- CK if concern for rhabdomyolysis
- Troponin if concern for myocardial ischemia
- Cyanide if lactate persistently > 8

Treatment:

Half-life of CO
- Room air: 300 min.
- Non-rebreather: 90 min.
- HBO2: 30 minutes
100% O2 via non-rebreather
Hyperbaric oxygen if:
- Pregnancy + COHb >15%
- COHb >25%
- Cardiac symptoms: syncope, MI
- Neurologic symptoms: confusion/AMS, seizure, coma, focal deficit
If due to Methylene Chloride Toxicity
- Ongoing CO production peaks at 8-13 hours, requires longer duration of treatment
All patients need follow-up at 2-4 weeks for neurologic sequelae

Methemoglobinemia

Background:

Due to oxidation of iron in hemoglobin
Hereditary forms cause baseline cyanosis and hypoxia that does not require treatment

Causative agents

Medications: Phenazopyridine, antimalarials, dapsone, benzocaine, nitrites
Ammonium nitrate - active ingredient in instant ice packs
Well water contaminated with fertilizer

Presentation

Cyanosis out of proportion to pulse-ox
Mild: flu-like illness
Moderate/Severe: myocardial ischemia, Dysrhythmia, AMS, seizure, metabolic acidosis