UMEM Educational Pearls

Diphenhydramine (B) has historically been utilized in combination with haloperidol 5mg (5) and lorazepam 2mg (2) in the treatment of acute agitation.  The most common rationale for adding diphenhydramine is prevention of EPS, however literature to support this is lacking.  A recently published paper examined diphenhydramine/haloperidol/lorazepam combination (B52) vs haloperidol/lorazepam combination therapy (52) to compare the need for additional agitation treatments as a surrogate for clinical efficacy.

This retrospective, multicentered noninferiority study included 400 emergency medicine patients, 200 per treatment arm. On average, the patients were 40 years old, 64% male, and predominantly Caucasian.  More patients in the B52 group had psychiatric illness listed as their primary cause for agitation compared to the 52 group. The two most frequently reported substances on urine drug screens, if collected, were amphetamines (35%) and cannabinoid (35.5%).

Results:

-No difference in the use of additional agitation medications within 2 hours

-More patients in the 52 group were noted to receive anticholinergic medications within 2 days, but indications varied and were not associated with EPS treatment

The B52 combination was associated with:

---Increased length of stay 17 h (10-26) vs 13.8 h (9-12), p = 0.03

---Increased use of restraints 43% vs 26.5%, p = 0.001

---Hypotension 16% vs 3.5%, p <0.001

---Use of nasal canula oxygen 3% vs 0%, p < 0.01

The addition of diphenhydramine may not be necessary to prevent EPS in patients receiving haloperidol for agitation and is associated with increased length of stay and adverse events, likely due to its additive sedative properties. 

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• 2/3’s present in the neonatal period and can mimic conditions such as sepsis, gastroenteritis, and meningitis requiring careful consideration to prompt testing
• Common symptoms are poor feeding, lethargy, irritability, vomiting, and encephalopathy
• May be referred in if detected on newborn screen, but not all are tested on the newborn screen
• Should look on labs for acidosis, elevated anion gap, hyperammonemia, lactic acidosis, ketosis/ketonuria, and hyper/hypoglycemia  
• Emergent treatment includes: identification and treatment of any underlying triggers (such as infection), stopping any protein intake until situation can be clarified, providing fluids with glucose (requirements of 8-10 mg/kg/min of glucose in neonates), and genetics consultation

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The use of catecholamines following OHCA has been a mainstay option for management for decades. Epinephrine is the most commonly used drug for cardiovascular support, but norepinephrine and dobutamine are also used. There is relatively poor data in their use in the out of hospital cardiac arrest (OHCA). This observational multicenter trial in France enrolled 766 patients with persistent requirement for catecholamine infusion post ROSC for 6 hours despite adequate fluid resuscitation. 285 (37%) received epinephrine and 481 (63%) norepinephrine.

Findings

• Deaths from refractory shock (35% vs. 9%, P<0.001) and Recurrent cardiac arrest (9% vs. 3%, P<0.001) were higher in the epinephrine group
• In both univariate/multivariate analyses, use of epinephrine was significantly associated with:
  • All-cause mortality during the hospital stay (83% vs. 61%, P<0.001) / (OR 2.6, 95%CI 1.4–4.7, P=0.002)
  • Cardiovascular-specific mortality (44% vs. 11%, P<0.001) / (aOR 5.5, 95%CI 3.0–10.3, P<0.001)
  • Frequency of unfavorable neurological outcomes (37% vs. 15%, P<0.001) / (aOR 3.0, 95%CI 1.6–5.7, P=0.001)
• While propensity scoring and match analysis largely confirmed these findings, further regression did not associate epinephrine with all-cause mortality.

Limitations:

• Epinephrine arm: significantly longer time to ROSC, lower blood pH at admission, higher rates of unshockable rhythm, higher levels of arterial lactate at admission, lower LV ejection fraction, and higher levels of myocardial dysfunction.
• Propensity matching always has the potential for confounders.

Summary:

Norepinephrine may be a better choice for persistent post-arrest shock. However, this study is not designed to sufficiently address confounders to recommend abandoning epinephrine altogether, but it does give one pause. 

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Acute liver failure is defined as new and rapidly evolving hepatic dysfunction associated with neurologic dysfunction and coagulopathy (INR >1.5). Most common cause of death in these patients are multiorgan failure and sepsis. Drug-induced liver injuy most common cause in US, with viral hepatitis most common cause worldwide.

Management of complications associated with acute liver failure

• Hepatic encephlopathy: Administer lactulose orally or via enema if risk of aspiration. Goal is to slow progression to severe encephalopathy and minimize development of cerebral edema.
• Coagulopathy: Reverse if significant bleeding or if patient needs to have invasive procedure. FFP and 4-factor PCC not indicated in absence of bleeding. Additionally these patients may be vitamin-K deficient for which vitamin K can be given.
• Consider empiric antibiotics due to increased susceptibility to infection.
• Renal dysfunction: correct hypovolemia with fluid resuscitation. May require RRT, continuous preferred for hemodynamic stability.
• If persistent hypotension despite adequate volume resuscitation and pressors, IV hydrocortisone indicated as adrenal insufficiency is common in these patients.
• Early consultation with liver transplant center. King's College Criteria and MELD score are most commonly used prognostic tools.

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Treatment of Hamstring Strains in Athletes

28 year old athlete presents to the ED and diagnosed with a hamstring strain

Localized swelling, moderate pain and a small limp. Incomplete tearing of the muscle

He is worried that he will miss the remainder of his season and when he returns will reinjure the same hamstring

Consider referral to sports medicine/orthopedics

A recent study looked at use of ultrasound guided hematoma aspiration followed by platelet-rich plasma (PRP) treatment on recovery in acute hamstring injuries

55 male athletes between ages 18 -32 weighing between 170 and 260lbs

27 with treatment protocol plus rehabilitation and 28 treated conservatively (rehabilitation)

All had Grade 2 hamstring injuries diagnosed on MRI

                Partial muscle tear (<50% cross sectional area)

Note: Grade 2 hamstring injuries are often associated with INTERmuscle hematoma and subsequent scarring. This can lead to persistent pain/discomfort and reinjury

Average return to play time was 32.4 days in the standard of care group

Average return to play time was 23.5 days in the intervention group (P<0.001)

Recurrence rate of hamstring strain was 28.6% in the standard of care group

Recurrence rater of hamstring strain was <4% in the intervention group (P=0.025)

Athletes with grade 2 hamstring injuries treated with hematoma aspiration and PRP injection into the strain had significantly shorter return-to-play and much lower recurrence rate that athletes treated with rehabilitation alone

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Pediatric spines are elastic in nature.

SCIWORA is a syndrome with neurological deficits without osseous abnormality on XR or CT.

Many patients with SCIWORA have myelopathy.

Mechanism of injury: Most commonly caused by hyperextension or flexion. Other possible mechanisms include rotational, lateral bending, or distraction.

Population: More common in younger children. This comprises 1/3 of pediatric trauma cases that have neuro deficits on exam. 

Severity depends on degree of ligamentous injury. It can be mild to severe, and cases have the potential to be unstable. 

Management: Immobilize cervical spine and consult neurosurgery. Patients often need prolonged spinal immobilization.

If the patient is altered and an adequate neurological exam cannot be obtained, a normal CT or XR of the cervical spinal is not sufficient to rule out spinal cord injury. It is important to continue monitoring neurological status. One possible etiology is spinal cord hemorrhage, and serial exams are essential. 

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How to set the correct PEEP remains one of the most controversial topics in critical care.  In fact, just on UMEM Pearls there are 55 hits when one searches for PEEP, including this relatively recent pearl on PEEP Titration.  

A recent Systematic Review and Network Meta-Analysis looked at existing trials on this issue.  They found that:

1) Higher PEEP strategies were associated with a mortality benefit compared to lower PEEP strategies

2) Lung Recruitment Maneuvers were associated with worse mortality in a dose (length of time of the maneuver) dependent fashion.

This fits with recent literature and trends in critical care and bolsters the feeling many intensivists are increasingly having that we may be under-utilizing PEEP in the average patient.  

Bottom Line: As an extremely broad generalization, we would probably benefit the average patient by favoring higher PEEP strategies, and avoiding lung recruitment maneuvers.  Do keep in mind that it is probably best to continue lower PEEP strategies in patient populations at high risk of negative effects of PEEP (e.g. COPD/asthma, right heart failure, volume depleted with hemodynamic instability, bronchopleural fistula) until these groups are specifically studied.

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The knee is one of the most commonly affected joints from osteoarthritis (OA).

Patients will complain of knee pain, swelling and stiffness.

This leads to disability as it interferes with walking, using stairs at home and getting in and out of chairs and the bath without assistance.

Increasing incidence due to aging of the general population and rising rates of obesity.

Patients frequently present to the ED for knee pain and imaging is often obtained.

Diagnosis of knee OA can be made with an appropriate history and imaging that shows osteophytes and joint space narrowing.

The best views for knee OA include 1) PA weight-bearing & 2) 45 degree of knee flexion

https://d3i71xaburhd42.cloudfront.net/6f8ce215fb4bcd153a478187c9a6a2ae652a5fc4/250px/1-FigureI-1.png

Note: Weight-bearing radiographs will demonstrate greater joint space narrowing than non-weight-bearing radiographs

Of the 3 compartments of the knee, the medial tibiofemoral compartment is most commonly affected > patellofemoral compartment > lateral tibiofemoral compartment.

Examples of knee OA

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https://orthoinfo.aaos.org/link/e7e6933819db4020bc2f3822c45c538f.aspx

Hyperglycemic Hyperosmolar State (HHS)

• Though less common, HHS has a mortality rate that is 10x greater than DKA.
• The hallmark features of HHS include severe hyperglycemia (> 600 mg/dL), hyperosmolality (> 320 mOsm/kg), minimal to no ketosis, and severe dehydration.
• Though the management of HHS is similar to DKA and includes fluid resuscitation, correction of hyperglycemia, and correction of electrolyte abnormalities, it is important to also monitor serum osmolality.
• Too rapid correction of serum osmolality can cause cerebral edema and worsen patient outcomes.
• Current recommendations are to monitor serum osmolality every 1-2 hours with a correction of no more than 3 mOsm/kg/hr.

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Question

23 y/o otherwise healthy Male presents for approx. 3 month history of Right  leg mass. It is painful with activity (deep and sharp) but not enlarging. Patient remembers a fall from a bicycle 6 months ago, with negative imaging for fracture.

What is the diagnosis?

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The debate is still going on: Whether we should give balanced fluids or normal saline.  

Settings: PLUS study involving 53 ICUs in Australia and New Zealand. This was a double-blinded Randomized Control trial.

• Patients: A total of 5037 adults who were admitted to any ICU.
• Intervention: Balanced multielectrolyte solutions (BMES). Once patient is outside the ICU, the type of fluid was decided by the treating physicians.
• Comparison: Normal saline
• Outcome: 90-day all cause mortality.

Study Results:

• Patient characteristics:
  • 2515 patients in BMES group vs. 2522 in Saline group.  Characteristics were similar in both groups.
  • Median fluid amount = 3.9L (BMES group) vs. 3.7L (Saline group).
• Primary outcome:
  • Mortality = 21.8% (BMES group) vs. 22.0 (Saline), (OR 0.99, 95% CI 0.86-1.14)
• Secondary outcomes:
  • Requiring Dialysis: OR 0.98 (95% CI 0.83-1.16)
  • Requiring vasopressor: OR 0.92 (95% CI 0.78-1.09)
  • Maximum creatinine level: similar between groups (155.5 umol/L for BMES vs. 154.5 umol/L for Saline group)

Discussion:

• Treatment with saline increased serum chloride, and lower pH than BMES, but kidney function was not affected.

• An updated meta-analysis including this trial was also published in January 2022. This updated meta-analysis showed that the risk ratio for 90-day mortality for BMES was 0.96 (95% CI 0.91-1.01).  This data suggested that using BMES could reduce risk of death (up to 9%) or increase risk of death (up to 1%).
• Appropriate volume resuscitation is still more important than the type of fluid.

Conclusion:

• BME treatment was not associated with improved mortality.

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Background:

Multisystem inflammatory syndrome in children (MIS-C) as defined by CDC Health Advisory in May 2020 is:

1) An individual aged <21 years presenting with fever*, laboratory evidence of inflammation**, and evidence of clinically severe illness requiring hospitalization, with multisystem (>2) organ involvement (cardiac, renal, respiratory, hematologic, gastrointestinal, dermatologic or neurological); AND

2) No alternative plausible diagnoses; AND

3) Positive for current or recent SARS-CoV-2 infection by RT-PCR, serology, or antigen test; or exposure to a suspected or confirmed COVID-19 case within the 4 weeks prior to the onset of symptoms.

*Fever >38.0°C for ≥24 hours, or report of subjective fever lasting ≥24 hours

**Including, but not limited to, one or more of the following: an elevated C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), fibrinogen, procalcitonin, d-dimer, ferritin, lactic acid dehydrogenase (LDH), or interleukin 6 (IL-6), elevated neutrophils, reduced lymphocytes and low albumin

As of January 31^st, 2022 the CDC reports the following statistics related to MIS-C in the United States:

·         Total MIS-C patients meeting case definition= 6,851

·         Total MIS-C deaths meeting case definition = 59

·         The median age of patients with MIS-C was 9 years. Half of children with MIS-C were between the ages of 5 and 13 years.

·         59% of the reported patients with race/ethnicity information available occurred in children who are Hispanic/Latino (1,746 patients) or Black, Non-Hispanic (2,050 patients).

·         98% of patients had a positive test result for SARS CoV-2, the virus that causes COVID-19. The remaining 2% of patients had contact with someone with COVID-19.

·         60% of reported patients were male.

Management:

First-Line Treatment:

·         IVIG 2 g/kg dosed based on ideal body weight with a maximum of 100 grams (1000 mL)  

o   For patients with significant myocardial dysfunction and concern for fluid overload, the infusion can be given in divided doses over 2 days (1g/kg q12 x 2 doses)

PLUS

·         Methylprednisolone 1 mg/kg (max of 30 mg/dose) IV twice daily and switch to PO and taper when clinically appropriate

Upon Consultation with Pediatric Hematology/Cardiology will consider adding the following therapies to IVIG and steroids:

·         Enoxaparin treatment versus prophylactic dosing depending on D-dimer elevation and whether or not being admitted to PICU

·         Aspirin 3-5 mg/kg (max 81 mg/dose) daily unless platelet count < 80 K/mcl

Second-Line Treatment (refractory to IVIG defined by symptoms and fever persisting >36 hours)*:

·         Methylprednisolone pulse dosing- 30 mg/kg (max of 1000 mg/dose) x 3-5 days

OR

·         High dose anakinra

OR

·         Infliximab 5-10 mg/kg IV x1  

*All second-line treatment options require peds infectious diseases and PICU attending approval

UMMS COVID/MIS-C Pathway: https://intra.umms.org/-/media/intranets/umms/pdfs/dept/pharmacy-and-therapeutics/guidelines/umms-pediatric-covid-pathway.pdf?upd=20220125144550

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Acute facial palsy is common in children and while bell’s palsy is significant proportion, there are other more concerning etiologies that make up a number of cases. A retrospective cohort study of pediatric patients with an ED diagnosis of Bell’s palsy was done using the Pediatric Health Information System and showed an incidence of 0.3% (0.03% in control) for new diagnosis of malignancy within the 60 days following the visit at which bell’s palsy was diagnosed. Younger age increased the risk. There was also a subset of patient’s excluded for diagnosis of bell’s palsy as well as malignancy at the index visit.

These numbers are small but may be clinically significant. They likely do not warrant laboratory or imaging workup as a rule but do make a case for detailed history taking and thorough exam. Consider avoiding steroids which are used commonly but lack high quality data and may undermine later efforts at tissue diagnosis of malignancy or even worsen prognosis.

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A prospective, randomized, open-label, parallel assignment, single-center clinical trial performed by an anesthesiology-based Airway Team under emergent circumstances at UT Southwestern.

801 critically ill patients requiring emergency intubation were randomly assigned 1:1 at the time of intubation using standard RSI  doses of etomidate and ketamine.

Primary endpoint: 7-day survival, was statistically and clinically significantly lower in the etomidate group compared with ketamine 77.3% (90/396) vs 85.1% (59/395); NNH = 13.

Secondary endpoints: 28-day survival rate was not statistically or clinically different for etomidate vs ketamine groups was no longer statistically different: 64.1% (142/396) vs 66.8% (131/395). Duration of mechanical ventilation, ICU LOS, use and duration of vasopressor, daily SOFA for 96 hours, adrenal insufficiency not significant.

Other considerations:

1. Similar to a 2009 study, ketamine group had lower blood pressure after RSI, but was not statistically significant. 2

2. Etomidate inhibits 11-beta hydroxylase in the adrenals. Associated with positive ACTH test and high SOFA scores, but not increased mortality.2

3. Ketamine raises ICP… just kidding.

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Quadriceps contusion

Mechanism:  Blunt trauma from ball, helmet, stick

Usually to the central region

Damage to highly vascular area of the muscle and to local blood vessels can cause hematoma formation

Typical trauma history and pain worse with muscle activation (knee flexion)

Physical exam:  Bruising, tenderness, palpable mass/hematoma

Goals of care: Minimize intramuscular bleeding

Treatment:  NSAIDS, crutches, unique type of immobilization 

Attempt to increase resting length of the quadriceps muscle to facilitate early healing and return to function

• Immediately immobilize the affected leg in 120°of flexion with an elastic wrap x 24 hr
• https://img.medscapestatic.com/pi/meds/ckb/18/43218.jpg
• Frequent icing
• Followed by early stretching/ROM (Consider referral for formal PT)
• Continue restricted weight bearing on crutches as needed

Note:  Left untreated, large contusions may result in myositis ossificans

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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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