UMEM Educational Pearls

Cardiovascular Morbidity & Sleep Apnea

Obstructive sleep apnea (OSA) is characterized by sleep-related periodic breathing, upper-airway obstruction, sleep disruption, and hemodynamic perturbations

Epidemiological data shows a strong association between untreated OSA & cardiovascular morbidity/mortality

Two recent studies by Gottlieb et al. (1) & Chirinos et al. (2) elucidated two important explicit and complicit treatment considerations for OSA

(1) In moderate-to-severe obstructive sleep apnea, the use of CPAP alone during sleep may ameliorate systemic hypertension and cardiovascular risk, even in patients who do not have "subjective" sleepiness

(2) Weight loss combined with CPAP use may further decrease cardiovascular morbidity

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The Reverse Segond Fracture

Most people have heard of a segond fracture (avulsion fracture of the lateral tibeal platuea) seen on knee xrays which is a marker for Anterior Cruciate Ligament and medial meniscus injuries. See Pearl https://umem.org/educational_pearls/1015/

However, there is also a Reverse Segond Fracture that is another benign appearing avulsion fracture of the medial tibeal plateau that is marker for significant injury to the Posterior Cruciate Ligament (PCL).

If a Segond or Reverse Segond Fracture is seen consider immobilzing the patients knee until they can follow up with Orthopedics and/or get an MRI to determine if additional injuries are present.

The world of pediatrics is still working on catching up to adult literature in terms of lactate utilization and its implications.  The study referenced looked at over 1000 children admitted to the pediatric intensive care unit. Lactate levels were collected  2 hours after admission and a mortality risk assessment was calculated within 24 hours of admission (PRISM III).  Results showed that the lactate level on admission was significantly associated with mortality after adjustment for age, gender and PRISM III score.

Bottom line:  In your critically ill pediatric patient, lactate may be a useful predictor of mortality.  

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With all the current concern about Ebola, it is important to understand what are quarantine and isolation and who can order these.

Per the Centers for Disease Control:

• Quarantine: separates and restricts the movement of people who were exposed to a contagious disease to see if they become sick.
• Isolation: separates sick people with a contagious disease from people who are not sick

Federal Law allows for quarantine and isolation:

• From the Commerce Clause of the U.S. Constitution
• Delegated to the Centers for Disease Control (CDC) by the U.S. Secretary of Health and Human Services
  • The CDC is "authorized to detain, medically examine, and release persons arriving into the United States and traveling between states who are suspected of carrying these communicable diseases."
• The CDC may issue a federal isolation or quarantine order
  • Last large scale use was during the influenza pandemic of 1918-1919
• Breaking of a federal quarantine order is punishable by fines and imprisonment

State laws allows for the enforcement of isolation and quarantine within their borders.

Bottom Line:

• There have been no large-scale quarantine or isolation orders for 100 years. However, the CDC can issue an order that has the authority of the Constitution and federal law for enforcement.

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Valproic acid (VPA) is often used to treat seizure disorder and mania as a mood stabilizer. The mechanism of action involves enhancing GABA effect by preventing its degradation and slows the recovery from inactivation of neuronal Na⁺ channels (blockade effect).

VPA normally undergoes beta-oxidation (same as fatty acid metabolism) in the liver mitochondria, where VPA is transported into the mitochondria by carnitine shuttle pathway.

In setting of an overdose, carnitine is depleted and VPA undergoes omega-oxidation in the cytosol, resulting in a toxic metabolite.

Elevation NH₃ occurs as the toxic metabolite inhibits the carbomyl phosphate synthase I, preventing the incorporation of NH₃ into the urea cycle.

Signs and symptoms of acute toxicity include:

• GI: nausea/vomiting, hepatitis
• CNS: sedation, respiratory depression, ataxia, seizure and coma/encephalopathy (with serum concentration VPA: > 500 mg/mL)

Laboratory abnormalities

• Serum VPA level: signs of symptoms of toxicity does not correlate well with serum level.
• NH₃: elevated
• Liver function test: elevated AST/ALT
• Basic metabolic panel: hypernatremia, metabolic acidosis
• Complete blood count: pancytopenia

Treatment: L-carnitine

• Indication: hyperammonemia or hepatotoxicity
• Symptomatic patients: 100 mg/kg (max 6 gm) IV (over 30 min) followed by 15 mg/kg IV Q 4 hours until normalization of NH3 or improving LFT
• Asymptomatic patients: 100 mg/kg/day (max 3 mg) divided Q 6 hours.

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Hemoglobin Threshold in Septic Shock

• Numerous trials have demonstrated the benefit of lower hemoglobin thresholds for blood transfusion in critically ill patients.
• The recently published Transfusion Requirements in Septic Shock (TRISS) trial evaluated the effects on mortality of a lower versus higher hemoglobin threshold in ICU patients with septic shock.
• The TRISS trial randomized 1005 patients to a lower hemglobin threshold (7 g/dL) or a higher hemoglobin threshold (9 g/dL). 
• Overall, there was no difference in 90-day mortality between groups.
• Patients randomized to the lower threshold received significantly fewer units without any increase in ischemic or adverse events.
• Take Home Point: A hemoglogin threshold of 7 g/dL for blood transfusion appears effective for most patients with septic shock.

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Question

A neck ultrasound is performed during endotracheal intubation. What is labeled "A", what is labeled "B" and what's the diagnosis?

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Kounis Syndrome (Part II)

- KS can develop from multiple etiologies: hymenoptera, proteins, vasoactive amines, histamine, acetylcholine, multiple antibiotics, and various medical conditions (angioedema, serum sickness, asthma, stress-induced cardiomyopathy).

- Hypersensitivity myocarditis and KS are two cardiac entities of allergic etiology affecting the myocardium and coronary arteries, respectively. These two entities can mimic each other and can be clinical indistinguishable.

- Presence of eosinophil’s, atypical lymphocytes, and giant cells on myocardial biopsy suggests hypersensitivity myocarditis.

- There is evidence showing use of corticosteroids with vasospastic angina with evidence of allergy or the presence of symptoms refractory to high-dose vasodilators has been reported to resolve symptoms.

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There is no effective pharmacologic treatment known to hasten recovery from concussion. In future pearls we will examine possible interventions that may help.

The importance of educating our patients was demonstrated in two studies looking at concussion education. Patients were separated into 2 groups. The intervention group received a booklet of information discussing common symptoms of concussion, suggested coping strategies and the likely time course of recovery. At a 3 month follow-up evaluation, the intervention group reported fewer symptoms. This was repeated in pediatric patients with similar results.

Take Home: Consider taking the time to put such an information sheet together for concussed patients seen in the ED.

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• For uncomplicted community acquired pneumonia which is treated as an outpatient, high dose amoxicillin (80-90mg/kg/day) is the first-line antibiotic of choice.
• Macrolides and third-generation cephalosporins are acceptable alternatives, but are not as effective due to pneumococcal resistance and lower systemic absorption, respectivley.
• Hospitalization should be strongly considered for children younger than 2 months or premature due to an increased risk for apnea.
• Patients hospitalized only for pneumonia, should be treated with ampicillin while those who are septic should be treated with a combination of vancomycin along with a second- or third- generation cephalosporin.

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In a precursor to a forthcoming international guideline on the management of calcium channel blocker poisoning, a new systematic review has been published assessing the available evidence.

A few findings from the systematic review:

• The majority of literature on calcium channel blocker overdose management is heterogenous, biased, and low-quality evidence.
• Interventions with the strongest evidence are high-dose insulin and extracorporeal life support.
• Interventions with less evidence, but still possibly beneficial, include calcium, dopamine, norepinephrine, 4-aminopyridine (where available), and lipid emulsion therapy.

Stay tuned for the international guideline coming out soon. One treatment recommendation from the new guideline, reported at the 8th European Congress on Emergency Medicine last month, is not to use glucagon.

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Use of acetazolamide to decrease CSF production is not effective in long-term treatment of hydrocephalus.  About 75% of patients with hydrocephalus require CSF shunt placement.

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Attachments

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• 1410082208_20141008_Figure_2.JPG (45 Kb)

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The ARISE Trial

Early, aggressive resuscitation and attention to detail are essential element of managing critically ill patients.  This past week the ARISE trial was published - a 2nd large, randomized control study to examine the benefit of protocolized vs. usual care in patients with severe sepsis and septic shock. 

What were the main findings?  After enrolling 1,600 patients who presented to the ED in severe sepsis or septic shock:

• They found no difference in mortality between the control (usual care) and treatment arm (early goal-directed therapy)
• Mortality was 18.6% vs. 18.8% at 90 days
• No evidence that continuous ScVO2, Hgb target > 10 mg/dL (check out the TRISS trial), or use of inotropes with a normal cardiac index improved mortality

Bottom Line:  Resuscitation goals for the patient with septic shock should include:

• Early antibiotics (source control)
• Adequate volume resuscitation (preferably balanced, crystalloid solution)
• End-organ perfusion (lactate normalization)

Additional therapeutic goals should be made on a patient by patient basis.  Reassess your patient frequently, pay attention to the details, and you will improve your patient’s mortality.

Suggested Reading

1. The ARISE Investigators and the ANZICS Clinical Trials Group.  Goal-Directed Resuscitation for Patients with Early Septic Shock. N Engl J Med. 2014. [PubMed Link]
2. Wessex ICS: The Bottom Line Review

Follow Me on Twitter: @JohnGreenwoodMD

Question

7d old child presents with difficulty feeding,vomiting one time, and now with intermittent apneic episodes. What's the diagnosis? (Careful....this one is tricky!)

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Kounis Syndrome (Part I)

- Kounis & Zavras (1991) described the syndrome of allergic angina and allergic myocardial infarction, currently known as Kounis syndrome (KS). Braunwald (1998) noted vasospastic angina can be induced by allergic reactions, with mediators such as histamine and leukotrienes acting on coronary vascular smooth muscle.

- Two subtypes have been described: type I, occurring in patients without predisposing factors for CAD often caused by coronary artery spasm and type II, occurring with angiographic evidence of coronary disease when the allergic events induce plaque erosion or rupture.

- This syndrome has been reported in association with a variety of medical conditions, environmental exposures, and medication exposures. Entities such as Takotsubo cardiomyopathy, drug-eluted stent thrombosis, and coronary allograft vasculopathy also appear to be associated with this syndrome.

-  Clinical presentation includes: symptoms and signs of an allergic reaction and acute coronary syndrome: chest pain, dyspnea, faintness, nausea, vomiting, syncope, pruritus, urticaria, diaphoresis, pallor, palpitations, hypotension, and bradycardia. 

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Beta-lactam antimicrobials (penicillins, cephalosporins, and carbapenems) are frequently used for empiric and targeted therapy in critically ill patients. They display time-dependent killing, meaning the time the antibiotic concentration is above the minimin inhibitory concentration (MIC) is associated with improved efficacy.

Two new pharmacodynamic/pharmacokinetic studies suggest that current beta-lactam antimicrobial dosing regimens may be inadequate.

• In patients from 68 ICUs across 10 countries, use of intermittent infusions (compared to extended and continuous infusions) and increasing creatinine clearance were risk factors for MIC target non-attainment. [1]
• A second group specifically investigated the pulmonary penetration of piperacillin/tazobactam in critically ill patients and found that intrapulmonary exposure is highly variable and unrelated to plasma exposure and pulmonary permeability. [2]

Antimicrobial dosing in critically ill patients is complex. Current dosing of beta-lactams may be inadequate and needs to be studied further with relation to clinical outcomes.

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INFLUENZA

What is it?

• Common disease that causes significant morbidity and mortality worldwide
  • Both seasonal and pandemic influenza occurs
  • Vaccination can decrease disease incidence and spread
  • Treatment can decrease disease severity
• Orthomyxoviruses (RNA virus)
  • 6 genera

Why do we care about influenza?

• Pandemic Influenza
  • Can infect and kill young, healthy people
  • 1918 H1N1 Influenza pandemic infected an estimated 500 million globally
    • Approximately 20% of the world’s population
  • Killed an estimated 50 million (may be as high as 100 million)
    • 2%-3% of the world’s population died

• Seasonal Influenza
  • Most often causes severe disease in the very young, very old, and those with chronic illnesses
  • Estimated between 3-5 million cases of severe illness around the world annually
  • Between 250,000 and 500,000 deaths

Bottom line

• Influenza is a potentially life threatening disease.
• Both seasonal and pandemic influenza are global concerns.
• Morbidity and mortality can be decreased through appropriate vaccination and treatment

Cardioactive steroids are among the many treatments used for CHF, and for the control of ventricular response rate in atrial tachydysrhythmias. There are many sources of cardioactive steroids:

Pharmaceutial: Digoxin, Digitoxin

Plants: Oleander, Yellow Oleander, Foxglove, Lily of the Valley, Dogbane, Red Squill

Animal: Bufo marinus toad

It is a potent Na⁺-K+-ATPase inhibitor and can lead to hyperkalemia in acute ingestion with associated signs and symptoms of N/V, abdominal pain, bradycardia and possibly, hypotension.

Toxicity should be suspected with bidirectional ventricular tachycardia or atrial tachycardia with high-degree AV block

Therapeutic range of digoxin of 0.5 - 2.0 ng/mL is helpful but not a sole indicator of toxicity

Indication for antidote (Digoxin-specific Antibody Fragments) include:

1) Digoxin-related life-threatening dysrhythma

2) Serum K+ > 5.0 mEq/L in acute ingestion

3) Serum digoxin concentration >15ng/mL at any time, or >10 ng/mL 6 hours postingestion

4) Ingestion of 10 mg in adult; 4 mg in pediatric

5) Poisoning by non-digoxin cardioactive steroid

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The last Back to the Basics post discussed the use of vasopressors to improve hemodynamics by increasing arterial (and venous) tone. This time we’ll discuss the use of agents to increase inotropy for patients with severe systolic dysfunction / failure.

Dobutamine: a direct b1 and b2-receptors agonist. It has no peripheral vasoconstrictor properties, so if blood pressure increases it occurs secondary to increased cardiac output. Unfortunately, blood pressure may be decreased in some patients due to its peripheral vasodilatory effects; in these cases it may need to be used with a vasopressor.

Milrinone: augments contractility by increasing intracellular Ca levels via cellular phosphodiesterase inhibition. Because it does not work on beta-receptors, it might be preferred for patients taking beta-blockers requiring inotropic support. It may cause peripheral vasodilation and hypotension, but this may be a benefit if pulmonary artery pressure is elevated as reductions in pulmonary artery pressure lead to improvements in right ventricular function. It has a long-half life and should be avoided in patients with renal impairment.

Dopamine: chemical precursor to norepinephrine and technically a vasopressor. At moderate doses (3-10 mcg/kg/min) it works on beta-receptors to increase myocyte contractility. At higher doses works primarily as a vasopressor, which may reduce cardiac output due to higher afterload.

Norepinephrine/epinephrine: has alpha and beta properties that lead to increased peripheral vasoconstriction, but also increases inotropy and chronotropy (faster heart rate)

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