UMEM Educational Pearls

Clinical pearls for hypothermic cardiac arrest

• VA-ECMO is rewarming strategy of choice – consider transport/contacting nearest ECMO center whenever possible
  • HOPE score predicts survival probability after ECLS rewarming and may guide ECLS decision making. Predictors include age, sex, mechanism of hypothermia, CPR duration, potassium, and core temperature at admission
• If access to ECMO center is not available, use external and internal rewarming strategies: removing wet clothes, forced-air heating blankets, warmed IV fluids (38-42C), thoracic and/or peritoneal lavage
• High-quality continuous CPR is key. Use mechanical CPR when available
• Lack of consensus with regards to ACLS guidelines. European Resuscitation Council recommends up to 3 attempts at defibrillation and withholding epinephrine while core temp is < 30C. AHA states reasonable to follow standard ACLS algorithms. It has been suggested that administering up to 3 shocks and 3 doses of epinephrine while core temp is <30 C is a reasonable approach, with additional doses guided by clinical response
• Resuscitate until core temp is at least 32C (warm and dead). Once rewarmed, consider termination of resuscitation with persistent asystole or K >12

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Background: Conventional medical wisdom long held that patients with pneumothorax (PTX) who require positive pressure ventilation (PPV) should undergo tube thoracostomy to prevent enlarging or tension pneumothorax, even if otherwise they would be managed expectantly.¹

• Small retrospective and observational studies have demonstrated safety to an observational approach for both occult (only detectable on CT) and larger PTXs even in patients requiring noninvasive or invasive mechanical ventilation, whether traumatic/iatrogenic or spontaneous.^2-6
• The Western Trauma Association recently released a guideline for the management of traumatic PTX, which includes observation with 6-hour follow up CXR for patients with small (<20% aka <2cm from chest wall on CXR or <35 mm on CT scan) hemodynamically stable pneumothoraces, even if mechanical ventilation is required.⁷
  • They note a 10% subsequent failure rate (i.e. chest tube requirement) with no difference between patients who do or do not undergo PPV. 
• The OPTICC trial, found however, that while the rate of respiratory distress development was not different between those randomized to observation vs initial chest tube management, there was an increase from a 25% chest tube requirement in the obs group to a 40% failure rate in patients requiring >4 days of mechanical ventilation.⁸ 

Bottom Line: The cardiopulmonar-ily stable patient with small PTX doesn’t need empiric tube thoracostomy simply because they’re receiving positive pressure ventilation. If you are unlucky enough to still have them in your ED at day 5 in these COVID times, provide closer monitoring as the observation failure rate may increase dramatically around this time.

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Flumazenil is a reversal agent for benzodiazepine overdose.  Adverse events including seizure, agitation and cardiac arrhythmias have been reported but the frequency of adverse events is unknown.

AE and serious AEs were defined as:

AE: 

• Aggressive behavior, agitation, screaming, restlessness
• Nausea/vomiting, abdominal cramps
• Sweating, shivering, chills, hot flashes
• Headache, dizziness
• Anxiety, distress, depressed mood, abnormal crying
• Tremors 

Serious AE (SAE):

• Seizures
• Supraventricular arrhythmia
• Multiple ventricular beats
• Tachycardia
• Sudden fall in systolic BP

A systematic review/meta-analyses of 13 randomized controlled trials showed

• AEs more common in flumazenil group vs. placebo (risk ratio: 2.85; 95% CI: 2.11-3.84)
• SAEs more common in flumazenil group vs. placebo (risk ratio: 3.81; 95% CI: 1.28-11.39) 

Most common AEs

• Aggressive behavior, agitation, screaming: 26.2% (n=33/126)
• Nausea/vomiting, abdominal cramps: 20.6% (n=26/126)
• Anxiety, distress, depressed mood: 15.7% (n=19/126)

Most common SAEs

• Supraventricular arrhythmia: 30% (n=4/12)
• Seizure: 25% (n=3/12)
• Tachycardia: 25% (n=3/12)

Conclusion

• Administration of flumazenil to patients with known or suspected benzodiazepine overdose is associated with increased risk of AEs

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Hamstring Injury

Prevalence varies by sport ranging from 8 to 25 percent with a high recurrence rate frequently during the ensuing sport season, usually in next 2 months but may extend up to one year!

Highest in sports that involve rapid acceleration and deceleration

            3 highest risk sports - football and men’s and women’s soccer

Average time lost 17-21 days

Injury much less common in younger athletes

The hamstring is composed of three muscles: the biceps femoris, semitendinosus, and semimembranosus.

Primarily involved in knee flexion and hip extension

Biceps femoris is most commonly injured

https://www.ncbi.nlm.nih.gov/books/NBK539862/figure/article-28873.image.f1

Simple grading system using 3 grades

Grade 1 – mild strain

Grade 2 – Partial tear

Grade 3 – Complete tear

Proximal injuries are more common than distal injuries, occurring at the musculotendinous junction

Avulsion fractures of the ischium occur rarely occur in adults but may occur in skeletally immature athletes

https://radiopaedia.org/cases/ischial-tuberosity-avulsion

When watching a sporting event you will see the athlete grab the buttock or upper thigh. They usually cannot return to play. Most grade 2 or 3 injuries will require crutches. If seeing them the following day significant bruising may be seen.

Numerous modifiable and non-modifiable risk factors have been identified including:

*Weakness of ipsilateral quadriceps or contralateral hamstring, hamstring, hip & quadriceps tightness/poor flexibility, poor warm-up, sudden increased training volume and muscle fatigue.

*Older age (risk increase may begin as early as age 23)

Prior hamstring injury (up to 6x increased risk)

            **Premature return to sport increases the risk of reinjury

Differential Diagnosis:  Lumbar radiculopathy, sciatic nerve irritation or compression, stress fracture of femur.

Refer to sports medicine/orthopedics for avulsion injuries, complete proximal complete tears and partial or complete distal tears

Many types of foreign bodies may be found in a child's ear. Some examples include: beads, cotton swabs, food, insects, and button batteries. 

Patients can be asymptomatic. However, they often have otalgia, pruritus, fullness, tinnitus, hearing loss, otorrhea, or bleeding. Obtain a history of the type of foreign body, when/how it entered the ear, and if there was a prior attempt at removal. Also ask if there are foreign bodies elsewhere, such as in the nose. Perform Rinne and Weber tests before and after removing the foreign body if the child is old enough to participate. 

Delayed presentation can result in edema and otitis externa. When the foreign body is sharp, there may be damage to the tympanic membrane (TM) and ossicles. 

Consult ENT when there is suspicion of damage to TM, when hearing loss is present, or when removal is especially challenging. Spherical foreign bodies are more difficult to remove. 

Remove foreign body if it can be visualized. Wax curettes, right-angled hooks, alligator forceps, and Frazier tip suctions can facilitate removal. Avoid additional trauma due to concern for edema, bleeding, TM perforation, or distal displacement of the object. Anxiety in the child will lead to increased difficulty with removal. 

A button battery in the ear is an emergency that can result in severe damage, including TM perforation, scarring or stenosis of the ear canal, and deeper injury. Seeds such as beans or peas and other absorptive material in the ear can expand, so do not irrigate when such foreign bodies are present. Living insects should be killed with alcohol, lidocaine, or mineral oil prior to performing foreign body removal. 

After removal, reassess ear canal and TM. Some foreign bodies require removal in the operating room. If the object has been successfully removed, evaluate for otitis externa or iatrogenic injury to the ear canal, and prescribe antibiotic otic drops when needed. When TM has perforated, refer for formal audiogram. ENT follow up is recommended for all patients.  

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   There are several well known medications that we tend to give by default during cardiac arrests.  It seems like for each of them, every few years someone does an RCT to see if they really help anybody, and we're all disappointed by what they find.  Well... prepare to be disappointed again, I'm afraid.

   These Danish authors randomized 391 patients in cardiac arrest to either calcium or saline (given IV or IO).  They gave 2 doses of either calcium chloride or saline, with the first dose being along with the first epi dose.  Primary outcome was ROSC.  They also looked at modified Rankin at 30 and 90 days.

  The trial was stopped early for harm.  Now, we all know the dangers of interpreting studies that were stopped early, but this doesn't look great for calcium.  19% of the calcium group had ROSC compared to 27% of the saline group (p = 0.09).  Percentage of patients alive, and with favorable mRS at 30 days also both favored the saline group (although also not statistically significantly).  By the way, of the patients who had calcium levels sent, 74% in the calcium group, vs 2% in the saline group, were hypercalcemic.  Whether that had anything to do with the outcome, we may never know.

Bottom Line:  Is this saying that calcium hurts patients in cardiac arrest?  Maybe... but I don't think this is high quality enough data to draw that conclusion.  At the very least, however, just giving everyone in arrest calcium is probably not terribly helpful.  If you have a reason to give it (known severe hypocalcemia, recent parathyroid surgery, suspected hyperkalemia, etc) then go for it, otherwise you can probably focus your resus on more important things.

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• Pediatric acute gastroenteritis has always been a major cause of ED visits and hospitalizations.
• Pediatric complaints of vomiting and diarrhea have been on the rise, whether it be secondary to the new Omicron-variant of COVID-19, or norovirus and rotavirus which traditionally account for nearly 60% of all cases.
• Zofran (Ondansteron) 4mg for children 4-11yo weighing greater than 40kg, and up to 8mg for those older.
• Zofran prescription at discharge was associated with reduced rate of return at 72-hours and was not associated with masking alternative diagnosis like appendicitis and intussusception.
• Oral rehydration therapy (ORT) consisting of a low osmolarity solution containing sugar and salts along with zinc has also been shown to optimize treatment and diminish return visits. ORT is available in commercial packets, pre-mixed solutions, or can be made at home with table salt and sugar.
• Bottom Line: Consider providing a prescription of Zofran along with recommendations for oral rehydration therapy consisting of a low osmolarity solution containing sugar and salts to prevent outpatient treatment failure and return visits.

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The BOUGIE Trial

• More than 1 million patients undergo endotracheal intubation each year in the US.
• Up to 20% of intubations fail on the first attempt, thereby increasing the risk of adverse outcome.
• Over the past several years, many have become comfortable using the bougie as a rescue device when the first attempt at intubation fails with an endotracheal tube with stylet.
• In contrast to its use as a rescue device, should the bougie be used during the first attempt rather than an endotracheal tube with a malleable stylet?
• The BOUGIE Trial compared the effect of using the bougie to an endotracheal tube with stylet on first attempt success in critically ill patients.
• The trial enrolled 1106 patients in 7 EDs and 8 ICUs at 11 hospitals.
• The primary outcome of first pass success was not statistically different between those randomized to bougie and those randomized to endotracheal tube with stylet for the first attempt at intubation.. 
• Though the trial did not find a statistical difference in first pass success rates, the bougie remains an important device in our management of the critically ill airway.

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Caffeine is probably the most wildly used and studied drug/supplement in the world.

It has been shown to enhance exercise capacity and performance.

Mechanism of action is likely multifactorial and involves adenosine receptor antagonism via direct CNS action improving mental alertness, reaction time and reducing the perceived exertion rate (pain).

To no surprise, amateur and elite athletes use caffeine to improve performance.

The well-accepted dosage of caffeine to improve performance is between 3 and 6 mg/kg, approximately 60 min before exercise. This dosage promotes (between 1 and 8%) performance gains in aerobic exercises and exercises with high glycolytic demand from cyclists to tennis players to weightlifters.

Consider the lower end of this range if interested in trying this on your own.

In an evaluation of 20,686 urine samples of elite athletes, almost 75% of the samples contained caffeine in concentrations higher than 0.1 μg/mL

Caffeine also increases maximal oxygen uptake (VO2 max)

23 elite athletes were tested twice with and twice without caffeine.

Randomized, double-blinded, placebo-controlled study.

Caffeine 4.5 mg/kg taken 45 minutes before exercise

Measures: Time to exhaustion and VO2 max.

Caffeine increased time to exhaustion and VO2 max, thereby increasing overall performance.

If you are going to incorporate using caffeine before your next workout, I suggest espresso shots for extra caffeine without the volume of a large cup of coffee. Beware of known side effects such as jitters, anxiousness and difficulties with sleep if taken later in the day. Also consider stomach upset digestive issues, and increased heart rate.

Happy Holidays!!!!

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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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