UMEM Educational Pearls

Xylazine is a central alpha-2 agonist (similar to clonidine) that is used as a veterinary tranquilizer. It also possesses analgesic, and muscle relaxant properties. Heroin/fentanyl is increasingly being adulterated with xylazine and resulting in severe adverse effects (CNS and respiratory depression, bradycardia, and hypotension), including deaths. 

According to CDC, 0.1%-5.5% of IMF death in US between 2019 – 2020 involved xylazine. 

In Philadelphia, PA:

The detection of xylazine in unintentional overdose death increased from

• 2010 – 2015: 2%
• 2016: 11%
• 2017: 10%
• 2018: 18%
• 2019: 31%

Approximately 25% of drug seizures in Philadelphia contained xylazine in 2019

There is no effective pharmacologic agent for xylazine toxicity. Similar to clonidine toxicity, high dose naloxone may be tried. But pediatric data show that approximately 50% of pediatric clonidine toxicity response to high-dose naloxone administration. Thus, naloxone administration may not reverse the CNS/respiratory depression, bradycardia and hypotension.

Conclusion

• There is increasing adulteration of heroin/fentanyl with xylazine
• Naloxone administration may not reverse the toxicity of xylazine

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When we initiate the sepsis bundle in the ED for patients with suspected sepsis, what probability that those patients who received broad spectrum antibiotics in the ED would have bacterial infection.

This study (Shappell et al) provides us with a glimpse of those number.

Settings: Retrospective study of adults presenting to 4 EDs in Massachusetts.

Patients: patients with suspected serious bacterial infection in ED, defined as blood cultures and initiation of at least one broad spectrum antibiotics.  Random selection of 75 patients per hospital.

Patients were categorized in 4 groups:

• Definite bacterial infection: clinical syndrome, pathologic diagnosis of infection (positive cultures from blood, urine; pus; radiographic evidence of abscess, consolidations in lungs)
• Likely bacterial infection: not meeting criteria for definite infection, but having a compatible clinical syndrome responsive to antibiotics and no clear etiology or reason for clinical improvement.
• Unlikely bacterial infection: clinical syndrome consistent with infection, but an alternate diagnosis is more likely.
• Definitely no bacterial infection: there was clear non-infectious diagnosis and no evidence of concurrent bacterial process.

Outcome: Prevalence of each category.

Study Results: 300 patients who received broad spectrum antibiotics.

1. Prevalence of bacterial infection:
   1. 81 (27%) had definite bacterial infection
   2. 104 (34.7%) had likely bacterial infection
   3. 55 (18.3%) had unlikely bacterial infection
   4. 49 (16.3%) with definitely no bacterial infection
2. For 96 patients with suspicion of sepsis vs. the rest of the cohort (P = 0.36)
   1. Definite 42.7%
   2. Likely 29.2%
   3. Unlikely 16.7%
   4. Definitely no 11.5%

       3. For patients who were admitted to the ICU (P = 0.26)

  a.   Definite 16.5%

                b.   Likely 8.6%

  c.   Unlikely 16.4%

                d.   Definitely no 20.4%

4. Source of infection

5.  Definite/Likely bacterial infection
   1. GU = 69 (35%)
   2. Respiratory = 48 (24.4%)
   3. Skin or soft tissue = 45 (22.8%)
   4. Bacteremia or endovascular = 42 (21.3%)
   5. Abdominal = 24 (12.2%) 
6. Unlikely/definitely not bacterial infection

1. Viral = 27%
2. Volume overload/cardiac disease = 10%
3. Hypovolemia = 8%

Discussion:

1. Slightly more than half of the patient we covered with broad spectrum antibiotics would have definitely or likely bacterial infection.
2. This study agreed with previous studies (2), which suggested that for patients treated prophylactically for sepsis, 13% had a “none” likelihood, 30% of only "possible" likelihood for bacterial infection.
3. The study highlighted that it was not easy for Emergency clinicians to recognize bacterial infection when we operate on a limited source of information and a limited timeline (think about the bundle of sepsis).
4. However, overtreatment is also bad, so we just need to be cognizant.

Conclusion:

Approximately 30% of patients who had blood cultures drawn and received broad spectrum antibiotics in ED have low likelihood of bacterial infection.

Reference:

1. Shappell CN, Klompas M, Ochoa A, Rhee C; CDC Prevention Epicenters Program. Likelihood of Bacterial Infection in Patients Treated With Broad-Spectrum IV Antibiotics in the Emergency Department. Crit Care Med. 2021 Nov 1;49(11):e1144-e1150. doi: 10.1097/CCM.0000000000005090. PMID: 33967206; PMCID: PMC8516665.

2. Klein Klouwenberg PM, Cremer OL, van Vught LA, Ong DS, Frencken JF, Schultz MJ, Bonten MJ, van der Poll T. Likelihood of infection in patients with presumed sepsis at the time of intensive care unit admission: a cohort study. Crit Care. 2015 Sep 7;19(1):319. doi: 10.1186/s13054-015-1035-1. PMID: 26346055; PMCID: PMC4562354.

Clinical Pearls for Variceal Hemorrhage

-lower mortality with “restrictive” (Hgb 7-9 g/dL) rather than liberal strategy

• although you should c/w your blood resuscitation according to hemodynamics

-antibiotic “prophylaxis” reduces mortality

• use ceftriaxone rather than quinolone 2/2 increasing resistance

-no need to correct INR with FFP

• FFP transfusions may actually be associated with worse outcomes (e.g. inc’d mortality)

-vasoactives (i.e. octreotide, somatostatin, terlipressin) alone may actually control bleeding

-for your ICU boarders...if persistent or severe rebleeding (despite endoscopic therapy), rescue TIPS is therapy of choice (call IR)

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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.

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Sever Disease

• Calcaneal apophysitis – inflammation of the growth plate of the calcaneus
• One of the most common causes of heel pain in adolescents, caused by repetitive stress (overuse injury)
• Most common in those who are involved in sports, especially those with lots of running and jumping
• Symptoms are heel pain and tenderness at/underneath the heel, with possible mild swelling
• Pain is reproduced by squeezing the posterior calcaneus and standing on tip toes
• Does not require imaging for typical presentation
• Treat with reduction of activity (specifically avoid painful activities), NSAIDs, and stretching exercises

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Presentations of Fracture in Nursemaids Elbow

Study group:   Visits by children younger than 10 years, with a diagnosis of radial head subluxation at 1 of 45 pediatric EDs from 2010 to 2018.

Retrospective cohort study of 88,466 ED visits for radial head subluxation

Outcome:  Missed fracture (return visit for upper extremity fracture within 7 days of the index visit).

Results

Median patient age was 2.1 years,

59% of visits were by female patients,

60% of cases occurred in the left arm.

Radiography was performed at 28.5% of visits (Range 19.8% to 41.7%.)

Extremity fractures were observed in 247 cases, representing 0.3% of the cohort.

The odds of missed fracture were higher in:

1. Children older than 6 years
2. Children who underwent radiography at the index visit
3. Children receiving acetaminophen or ibuprofen in the ED.

Summary:  

Only 0.3% of children with a diagnosis of radial head subluxation subsequently received a diagnosis of an upper extremity fracture within 7 days of the index visit.

Missed fractures were commonly about the elbow such as a supracondylar fracture. However, this study also found a significant proportion of missed fractures in other locations (e.g. shoulder, wrist), highlighting the importance of a careful physical examination, and the limitations of localizing pain in younger children. 

Recurrence was common, and the risk of recurrence decreased with increasing age at first presentation.  Overall, radial head subluxation recurrence was 8.7% after the first visit VERSUS 12%-13% in children younger than 2 years. THese patients are likely to return to the ED with a recurrence within 2 years. These findings should help inform anticipatory guidance to parents regarding the risk of recurrence based on their child’s age.

Myocarditis is a potentially fatal inflammatory disorder of the heart. Viral infection is the most common cause but can also result from toxic, autoimmune, or other infectious etiologies. Complications include life-threatening dysrhythmias, heart failure, and fulminant myocarditis. Typically affects young patients (20-50 years old).

• Diagnosis can be challenging. Presentation can range from nonspecific symptoms and normal hemodynamics to cardiogenic shock.
• Dyspnea was found to be the most common presenting symptom in one study
• Other symptoms include fever, malaise, chest pain, palpitations, fatigue, nausea, vomiting
• Consider the diagnosis in young patient with suspected sepsis but worsens with IV fluids with signs of volume overload
• Initial assessment should include ECG, CBC, CMP, inflammatory markers, cardiac biomarkers, CXR. Obtaining an echo is important. Perform POCUS to assess for global hypokinesis, reduced EF, wall motion abnormalities, pericardial effusion, B-lines.

ED management pearls

• Initiate vasopressors and inotropic support if hemodynamically unstable: norepinephrine + inotropic agent (e.g. milrinone, dobutamine) is recommended. In a few studies, epinephrine was associated with increased mortality when used in cardiogenic shock.
• Diurese if evidence of volume overload
• NIPPV or intubation if respiratory failure
• Avoid NSAIDs which may worsen mortality
• Consider mechanical circulatory support (e.g. ECMO, IABP, VAD) in refractory hypotension despite appropriate medical therapy

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Fever has long been understood to be associated with worse outcomes in patients post-cardiac arrest. Whether ascribing to the goal of 33-34°C, 36°C, or simply <38°C, close monitoring and management of core temperatures are a tenet of post-cardiac arrest care.

A recently published study compared the effectiveness of several methods in maintaining temperatures <38°C…

• Both ICHA and OHCA, shockable and unshockable, nontraumatic arrests
• Single center retrospective cohort study looking at 1/2012 – 9/2015
• Treatment and temperatures over first 48 hours

Results:

Maintenance of temp <38°C:

• Antipyretics only group: 57.7% 
• Invasive cooling by intravascular catheter +/- antipyretics:  82.1%

Mean change in temp from baseline:

• Antipyretics only: +1.1°C
• Intravascular alone: -3.4°C
• Antipyretics + Intravascular cooling: -5.2°C

Limitations:

• Varied range of antipyretic dosing per body weight
• No mention of noninvasive cooling methods (cooling pads, ice packs, etc.)
• Patients w/ intravascular cooling likely getting more aggressive care in general
• Not powered for clinical outcomes assessment

Bottom Line:

• Antipyretics alone greatly ineffective at preventing fever 
• Even with invasive cooling -- not meeting goal 18% of the time
• With longer ED boarding times nationwide, we must pay active attention to body temperature management and not assume that that we can set it and forget it, even with techniques as invasive as intravascular cooling.

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The classic mechanism for nursemaids elbow is axial traction on a pronated forearm and extended elbow.

The force allows a portion of the annular ligament to slip over the radius.

Consider this diagnosis with other mechanisms of injury especially if the exam is not suggestive of fracture.

Suspect in a patient in minimal distress with arm held semi flexed and pronated.

A recent retrospective study looked at other mechanisms of injury.

69 subjects with a median age of 2.5 years

The most common mechanisms of injury were fall (57%), direct hit to the elbow (16%), and rolling over (7%).

Some studies note the left elbow is more commonly involved but this is likely due to most guardians being right-handed, thereby holding the child’s left hand

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• Antimicrobial medications can be associated with neurological adverse reactions. 
• An individual’s risk is influenced by their age, weight, nutritional status, the medications they are taking concurrently, and pharmacological properties (dosage, half-life, CNS permeability). 
• Encephalopathy 
  • Seen with beta-lactams, fluoroquinolones, clarithromycin, and sulfamethoxazole-trimethoprim. 
  • Most commonly with cefepime. 
  • Higher risk in elderly, renal dysfunction, and preexisting CNS disease. 
• Seizures 
  • Beta-lactams block GABA receptors. 
  • Highest risk with cefepime and imipenem. 
• Peripheral neuropathy 
  • Associated with metronidazole, fluoroquinolones, linezolid, chloramphenicol, and isoniazid. 
  • Most cases are dose dependent. 
  • Some cases are irreversible. 
• Ototoxicity 
  • Aminoglycosides cause cochlear NMDA receptor excitotoxicity. 
• Weakness 
  • Fluoroquinolones, macrolides, and aminoglycosides inhibit acetylcholine release and bind neuromuscular junction receptors. 
  • Should be avoided in myasthenia gravis and Lambert-Eaton syndrome. 
• Movement disorders 
  • Tremors – sulfamethoxazole-trimethoprim 
  • Dyskinesia, dystonic reactions – fluoroquinolones, chloramphenicol 
  • Cerebellar syndrome – metronidazole, aminoglycosides 

Bottom Line: Recognition of antibiotic associated neurotoxicity reduces unnecessary workup and serious adverse effects. 

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The debate around post-arrest management recently has revolved around whether therapeutic hypothermia should go cold, or LESS cold.  But what if we went MORE cold?  While recent TTM trials have compared temps such as 33 to 36 and 33 to 37.5 or less, a recent trial called CAPITAL CHILL looked at 34C vs 31C.  There is a solid physiologic basis for cooling post-arrest patients, so do they do better if we lower their temp even further?  Maybe we're not going cold enough with 33?

Bottom Line: No, 31C is not better than 34C for post-arrest patients.  This study compared death and poor neurologic outcome at 180 days with 31 and 34C targets for post-arrest patients, and found no difference (in fact the 31C group did slightly, but not significantly, worse on the primary outcome, and worse on a few secondary outcomes).  

While debate remains for 33 vs 36 vs afebrile, the literature does not currently support consideration of temps below 33.  

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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:

• Based on recommended monitoring parameters, patients may receive additional doses of Kcentra.
• Idarucizumab (Praxbind) is the preferred agent for dabigatran reversal.

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Incidence of T1DM is 1.93/1000 of youth <20 years old in the United States, with a bimodal distribution of onset. Onset peaks from ages 4-6 and again at puberty. 

Prior to the development of DKA, diabetes often has an insidious onset with symptoms of polydipsia, polyphagia and polyuria with weight loss in children. It can also be asymptomatic. 

When DKA is present, symptoms will include neurological manifestations (confusion, lethargy), GI symptoms (abdominal pain, nausea, vomiting), or respiratory abnormalities (Kussmaul respirations.) Polyuria and polydipsia are frequently present as well.

Diagnosis of DKA includes: serum glucose of >200 mg/dL, serum or urine ketones, and a pH <7.30 or bicarbonate <15 mEq/L. 

DKA is classified as mild, moderate or severe:

Mild: pH 7.21-7.30, HCO3 11-15 mEq/L

Moderate: pH 7.11-7.20, HCO3 6-10 mEq/L 

Severe: pH < 7.10, HCO3 <5 mEq/L

Initial treatment is 10 ml/kg of isotonic fluid bolus to a max of 500 ml, then reassess. Continue to replace fluids gradually to cover maintenance fluids as well as to treat dehydration. Do NOT bolus insulin. Rather, start a drip at 0.05-0.1 units/kg/hr. Continue insulin until acidosis has completely resolved. Once the serum glucose falls below 250 mg/dL, start dextrose to prevent hypoglycemia until the gap closes. 

Cerebral edema can develop 4-12 hours after treatment has been initiated. Observe for change in mental status, posturing, decreased response to pain, cranial nerve palsy, bradycardia, or abnormal respiratory pattern. This is a clinical diagnosis! Although a head CT can be obtained, it is often negative and treatment with mannitol or hypertonic saline should be started as soon as there are clinical changes.

DKA has resolved when pH > 7.3 and HCO3 is >15.

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Substance use disorder contributes significantly to pediatric exposure/poisoning. There has been an increase in the opioid overdose deaths in the US, placing pediatric population to possible exposure. A retrospective study of fatal pediatric poisoning in the US was investigated using the National Violent Death Reporting System (NVDRS) from 2012-2017.

17 US states (AK, CO, GA, KT, MD, MA, NJ, NM, NC, OH, OK, OR, RI, SC, UT, VA, WI) reported to NVDRS from 2012-2017.   

Age was limited to 0-9 years

Results

1850 violent deaths were identified: n=122 (7%) were poisoning related

Characteristics

• Male: 49%
• Approximately 25% were homicide-suicides

Region

• Midwest: 25%
• Northeast: 5%
• South: 53%
• West: 17%

Most common exposure/etiology

1. Opioid (50%)
2. Benzodiazepines (8%)
3. Amphetamines (7%)
4. Antidepressants (5%)

Conclusion

• A large proportion of poisoning related pediatric fatality was due to opioid exposure
• Largest proportion of death was reported from the Southern US.

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Initial Mechanical Ventilation Settings for the Intubated Asthmatic

• Approximately 2% of adult patients who present with an acute asthma exacerbation will require intubation and mechanical ventilation.
• It is critical to provide the intubated asthmatic with sufficient time for exhalation.
• Initial recommended settings for mechanical ventilation include:
  • Tidal volume: 6-8 ml/kg ideal body weight
  • Respiratory rate: 6-10 breaths per minute
  • PEEP: 0-5 cm H2O
  • Inspiratory flow rate: 80-120 L/min
• Permissive hypercapnea is tolerated to a pH of approximately 7.15

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Background: A cornerstone of therapy for cardiogenic shock is inotropic support with medications including dobutamine, epinephrine and milrinone.  Few studies have examined these head-to-head and between dobutamine and milrinone (including only one RCT of 36 patients)

The investigators conducted a RCT of milrinone versus dobutamine for cardiogenic shock in a single quaternary care center cardiac ICU.

Inclusion: Patients over 18 with cardiogenic shock (largely clinical determination)

Exclusion: Out-of-hospital cardiac arrest, pregnancy, prior initiation of dobutamine or milrinone, or physician discretion.

Methods: 1:1 randomization stratified by affected ventricle (LV vs RV). Primary outcome was a composite of in-hospital death, resuscitated cardiac arrest, cardiac transplant, mechanical circulator support, nonfatal MI, TIA, stroke, or renal replacement therapy. Powered to detect a 20% improvement in this measure in the milrinone group (192 pts).

Results:  192 patients enrolled (96 in each arm). Average age was 70, 36% female, 90% LV dysfunction, 67% ischemic disease, 33% non-ischemic, average LVEF 25%, 68% on vasopressors. ICU admission to randomization was 23+/-92.6h for dobutamine and 17.6+/-50.6h for milrinone arms. 80% were SCAI class C shock.

Primary outcome for milrinone 49% versus dobutamine 54%, HR 0.9(0.69-1.19), p=0.47, death was the primary driver of the composite (37% vs 43%).  Arrythmia requiring intervention was not different between groups (50% vs 46%). No difference in a host of other endpoints including AKI (92% vs 90%), RRT (22% vs 17%), HR, lactate, MAP, UOP, and creatinine.

Discussion: No significant differences observed in outcomes for patients with cardiogenic shock randomized to milrinone versus dobutamine.  The trial addressed an important clinical question for management of cardiogenic shock and relied largely on clinical diagnosis for inclusion and likely reflected a somewhat broad range of patients. The trial was too small given observed treatment effects and few patients with RV failure. Notably, similar rates of adverse events observed in each group.  

Many limitations for practice including a single specialized ICU setting, limited information on events leading to ICU admission including invasive or medical interventions during the index visit and no long term follow-up.  Time to randomization, exclusion of cardiac arrest, and lack of reporting pre-ICU setting (ED, floor, cath lab) also significantly limits utility in an emergency setting.

Bottom Line: 192 patient single-center cardiac ICU-based trial shows no difference in composite or secondary endpoints between milrinone and dobutamine for cardiogenic shock, adds to a body of very limited RCTs comparing inotropes in cardiogenic shock but provides no practice changing evidence.

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Ventriculoperitoneal (VP) shunts are common. Unfortunately shunt complications are also common! 

There are 3 major categories of shunt complications:

1. Mechanical Failure - obstruction, fracture, disconnection, migration, perforation
2. Functional Failure - overdrainage, slit ventricle syndrome, pseudocyst, ascites, meastasis
3. Infection - may occur in  up to 10% of patients (bacterial, fungal, parasitic)

Shunt series are helpful, but are NOT 100% sensitive. If you have a clinical concern for a shunt complication, make sure to involve neurosurgery.

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The total number of concussions tripled among female athletes aged 14 to 18 years during a 20-year period from 2000 to 2019.

Query of National Injury Surveillance System

Female athletes with sports-related concussions or closed head injuries who presented to the ED

In 14- to 18-year-old females the number of concussions increased from 9,000 in 2000 to 32,000 in 2019.

65% of all concussions among female athletes occurred in soccer, basketball, cheerleading, softball, and volleyball.

Association between an increase of 308.7 annual concussions per 10,000 annual female participants.

In a study of more than 80,000 teenage players across US high schools, female athletes are 1.9 times more likely to develop a sports-related concussion than are their male counterparts in comparable sports.

In boys, the most common way of becoming concussed was through direct contact with another player (50%)

In girls, the most common way of becoming concussed was after colliding with another object (ball/goalpost).

This mechanism may partly explain another finding:  Boys were also more likely to be removed from play immediately after a suspected head injury than were girls

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