A mortality benefit from combination antimicrobial therapy has not been clearly demonstrated in sepsis. However, when only the most severely-ill patients (i.e., septic shock) are considered in subgroup analysis, there appears to be a mortality benefit to using two antimicrobials against a suspected organism.

Combination antimicrobial therapy may reduce mortality through three mechanisms.

1. Increased probability that the causative organism will respond to at least one drug. 
2. Preventing emergence of antimicrobial resistance.
3. Two antimicrobials may act synergistically.

Always obtain appropriate cultures before initiating therapy. Although identification and susceptibility of the organism may take some time, eventually narrowing antimicrobial therapy to monotherapy in the ICU is still recommended. 

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Question

Patient presents with the following X ray after yawning. Diagnosis?

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Traditional teaching for many years has been that new or presumed new LBBB in patients with anginal type of symptoms should be treated as a STEMI, i.e. with immediate PCI or lytics. However, that teaching is based on poor evidence. Newer, increasing evidence is suggesting that new/presumed new LBBB in patients with anginal symptoms is actually not associated with acute MI any more often than when a patient has an old LBBB with those symptoms.

Probably the best management in patients with anginal type of symptoms and a new/presumed new LBBB is to contact the cardiologist on call and ask them for their preference in terms of treatment. Those patients are not necessarily definite AMIs.

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Gout treatment considerations

Treatment is directed to relieve pain and inflammation

NSAIDs, steroids and narcotics are the mainstays of treatment. All 3 should be used in combination.

Aspirin should be avoided as it may increase uric acid levels

     Note: not in prevention doses (81mg) in treatment doses (325-650mg q4h)

      NSAIDs and steroids take time to be effective.  Provide appropriate analgesia with oral narcotic medication for short term relief

     Don't forget the benefit of splinting a "hot" joint (the ankle or wrist for example)

NSAIDs: Use may be limited in the elderly and in those on coumadin or with peptic ulcer disease. 5-7 days of treatment is usually sufficient. Indomethacin is most commonly used (50 mg TID, which may be tapered to 25 mg TID after 3 days)

Steroids:  Likely more effective than NSAIDs. Oral prednisolone is more effective than naproxen (1). Use prednisone 30-50 mg for 3-5 days without tapering (as we use for asthma). May be useful to supplement with NSAIDs on the tail end to prevent a rebound flare. If tapping the joint consider intraarticular steroids. If there is concern for medical noncompliance with oral steroids consider IM steroids (triamcinolone 60mg or methylprednisolone).

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The ability to determine whether or not a patient is an alcoholic or will go into alcohol withdrawal syndrome (AWS) is not amenable to a clinical decision rule though many attempts have been made. The strongest predictor that a patient can develop AWS is a positive family history of AWS. Some clinical and biochemical predictors are:

ALT >50 U/L

K <3.6

These two in one study have had an odds ratio of 9.0 and 5.7 respectively though specificity was quite low. Ethanol levels has also found to be contradictory. Being able to predict AWS does not currently seem plausible but the treatment of AWS should and can involve a clinical decision rule like CIWA-Ar which is a scoring system that takes into account N/V, tremor, sweats, anxiety, agitation, hallucinations, headache and sensorium. Take a look at the scoring system that is most validated and utilized for symptom triggered therapy - often considered the most effective treatment for alcohol withdrawal.

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Attachments

• 1104212257_CIWA-Ar.pdf (10 Kb)

• Patient positioning is key when measuring opening pressure (OP) of cerebrospinal fluid (CSF) during lumbar puncture. 

• OP is only accurate when measured while the patient is completely horizontal and relaxed, in the lateral decubitus position (i.e. no neck flexion or extension, legs extended, no valsalva).  In order to achieve this, you may need to carefully place patient in a lateral decubitus position if they are initially sitting upright prior to dural puncture and/or be sure to have patient straighten their legs (i.e. abort fetal position) once ready to measure OP.

• Strictly speaking, normal range of CSF pressure is 8 to 21 cm, but obesity can increase it up to 25 cm and still be considered normal.  Thus, while the significance of measurements between 20 and 25 cm in obese patients may be unclear, levels above 25 cm are always abnormal.

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Combination Antimicrobial Therapy for Gram (+) Bacteremia

• Bacteremia is a major cause of morbidity and mortality in the critically ill patient.
• S.aureus remains a common isolate in patients with either hospital-acquired or community-acquired bacteremia.
• In cases of suspected endocarditis due to S.aureus, traditional teaching has been to give an aminoglycoside (i.e. gentamicin) in combination with vancomycin or an antistaphylococcal penicillin.
• Importantly, there is no strong evidence to support this combination in patients with suspected S.aureus bacteremia.
• Furthermore, patients receiving the aminoglycoside combination have higher rates of renal impairment without any added clinical benefit.

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Dabigatran is a new oral anticoagulant (direct thrombin inhibitor) which is being marketed as the new drug to replace warfarin in many cardiac patients. You'll hear much more about it in the coming year, but for now you should know the main advantage and disadvantage:
1. advantage: no need to check levels, e.g. INRs
2. disadvantage: no reversal agent; if a patient is actively bleeding, all you can do is to hold further doses and provide supportive therapy, e.g. tranfusions; hemodialysis is another option, but not ideal to place new dialysis catheters emergently in patients that are coagulopathic!

This second point, the disadvantage of having no reversal agent, is potentially a big issue, especially in older patients at risk for falls. Stay tuned for more information...

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Gout Part 2

• Hyperuricemia can result from both uric acid overproduction (metabolic/myeloproliferative diseases) in addition to uric acid underexcretion (more common).
• Consider gout in any patient who complains of joint pain that reaches peak intensity over hours and may wake them from sleep. Septic joints tend to reach peak intensity of days.
• Patients may have multi joint involvement, low-grade fever and leukocytosis (factors that may lead one to consider an alternative diagnosis)
• Remember that gout is also a disease of the synovial tissue (tendonitis and bursitis).
• NSAIDs: Traditional preferred treatment for acute gout
• Colchicine: Less effective if the current attack is >24 hours. Use correct dosage for best effect/side effect ratio.
• Steroids: At least as effective as NSAIDs.

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Kiwi fruit and latex share several antigens in common.  Thus, individuals who are allergic to either kiwi or latex may also suffer hypersensitivity reactions to the other material.

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• Chemoprophylaxis should be given to those individuals who came into "close contact" with someone infected with meningitis due to meningococcal infection (i.e. Neisseria meningitidis).  It should be given as early as possible following the exposure; when there is a high index of suspicion, do not wait for culture results to give prophylaxis.
• Chemoprophylaxis is generally not indicated when the etiology is Streptococcus pneumoniae, and should be reserved for young children who have not received a Haemophilus influenzae type b (Hib) vaccination and immunocompromised close contacts when the etiology is Hib.
• While the definition of a "close contact" remains somewhat ambiguous, it generally refers to individuals who have had prolonged (>8 hours) contact while in close proximity (<3 ft) to the patient, or who have been directly exposed to the patient's oral secretions between one week prior to the onset of the patient's symptoms until 24 hours after initiation of appropriate antibiotic therapy.
• Standard regimens for antimicrobial prophylaxis include ciprofloxicin, ceftriaxone, and rifampin.  Adults typically require a single oral dose of 500 mg of ciprofloxicin or 250 mg of intramuscular (IM) ceftriaxone, while individuals under age 15 may receive a single dose of 150 mg of IM ceftriaxone.

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Vancomycin is often started empirically for gram-positive and MRSA coverage. Although effective and generally well-tolerated, emerging resistance and side-effect profiles limit its use in some patients. Two alternatives are Linezolid and Daptomycin.

Linezolid

• 600 mg IV every 12 hours
• No renal dosing
• Better lung penetration in pneumonia (compared to Vancomycin)
• Side effects: Serotonin Syndrome (w/ concurrent MAOIs), hypersensitivity reaction, and myelosuppresssion

Daptomycin

• 4 mg/kg IV once daily (skin/subcutaneous tissues infection), 6 mg/kg IV once daily (bacteremia or endocarditis), or 6-8mg/kg IV once daily (bacteremia with intravascular line)
• Renally dosed by altering administration frequency; no change in dose.
• NEVER use for pneumonia; pulmonary surfactant binds and inactivates drug.
• Side effects: Reversible rhabdomyolysis (requires weekly CPK levels)

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Question

60 y/o male transferred from local rehab facility c/o abdominal pain.

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We already know that polypharmacy is a big issue in the elderly, but here are a few key points to keep in mind:
1. Adverse drug effects are responsible for 11% of ED visits in the elderly.
2. Almost 50% of all adverse drug effects in the elderly are accounted for by only 3 drug classes:
     a. oral anticoagulant or antiplatelet agents
     b. antidiabetic agents
     c. agents with narrow therapeutic index (e.g. digoxin and phenytoin)
3. 1/3 of all adverse-effect-induced ED visits are accounted for by warfarin, insulin, and digoxin.
4. Up to 20% of new prescriptions given to elderly ED patients represents a potential drug interaction.

The bottom line here is very simple--scrutinize that medication list and any new prescriptions in the elderly patient!

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Knee dislocations are uncommon, and prosthetic knee dislocations even rarer.  Some general facts about prosthetic knee dislocations are:

• Posterior dislocations typically occur in the post-operative period and are usually the result of trauma that disrupts the PCL ligament.
• Factors that predispose a person to posterior dislocations are valgus deformity of the knee, malposition or improper selection of prosthetic components, patellar instability, and extensor mechanism dysfunction.
• The mechanism for this dislocation is typically flexion and external rotation of the knee when the lateral side of the knee is too loose.
• Anterior dislocations more commonly occur months to years after surgery and usually are not associated with trauma.
• Many of these dislocations result from loss of integrity of the posterior cruciate ligament, which provides anteroposterior stability of the knee and assists in femoral rollback. This motion is essential for the extensor mechanism of the knee to function.
   

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So the magnesium didn't work, and the baby is on the way!  You're prepared with everything you need for the delivery from bulb suction to a tripod for Dad's camera...  But what is going to special about this baby?  

Babies born to mothers who received magnesium therapy for any reason are at risk for hypotonia and severe respiratory depression.

• DO provide respiratory support as needed, as respiratory depression is the only dangerous side effect of hypermagnesemia in the neonate (be prepared to provide supplemental oxygen, positive pressure ventilation (PPV), and possibly intubation)
• DO recognize that generalized hypotonia may be a clue as to how significantly affected the neonate may be, however, don't let the hypotonia itself scare you - it will go away, and is not dangerous in and of itself
• DO follow neonatal resus guidelines (PPV for HR<100, CPR for HR<60), but remember that supportive measures will resolve all problems related to hypermagnesemia in the neonate...if there are other issues, don't blame the mag
• DO NOT give calcium as, in contrast to their mothers, these patients are not hypocalcemic (and the hypermagnesemia will spontaneously resolve in 48 hours)
• DO remember that these infants frequently require a brief NICU stay until they no longer require respiratory support

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·      In the event a nuclear power plant accident, people may be exposed to a mixture of radioactive products. The main radionuclides representing health risk are radioactive caesium and radioactive iodine.

·      Iodine-131 is concentrated in the thyroid gland and may eventually lead to development of thyroid nodules and thyroid cancer.

·      Radioiodine uptake by the thyroid can be blocked by taking potassium iodide (KI) pills or solution, preventing these effects.

·      KI should not be taken in the absence of a clear risk of exposure to a potentially dangerous level of radioactive iodine because KI can cause allergic reactions, skin rashes, salivary gland inflammation, hyperthyroidism or hypothyroidism.

·      Since radioactive iodine decays rapidly, current estimates indicate there will not be a hazardous level of reaching the United States from this accident.

·      There are three FDA approved KI products: Iosat, Thyrosafe and ThyroShield.

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• Trigeminal Neuralgia (TN) presents with unilateral, lancinating head and facial pain, affecting one or more of Cranial Nerve V's divisions.

• The pain occurs in 1 to 5 second multiple attacks throughout the day.  Symptoms may remit and recur.

• TN is associated with trigger points, but lacks any associated focal neurologic deficit or abnormality.

• These characteristics will help distinguish TN from other sources of unilateral headache, such as migraines, cluster headaches, sinusitis, and glaucoma.

• There are a host of treatments for TN, including options such as medical management with anti-convulsants and/or muscle relaxants, surgical ablation, alcohol injection (induces numbness), glycerol injection (destroys affected part of nerve), balloon compression, and administration of electrical current.

• Medical management with analgesics and muscle relaxants is typically the most appropriate, first-line treatment in the emergency department.

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Hemorrhagic bullae in an ill-appearing patient with underlying cirrhosis should prompt consideration for an invasive infection due to Vibrio vulnificus.

V. Vulnificus is a gram negative rod and causes a highly lethal infection in patients with cirrhosis.

Antibiotics for these patients should include coverage for this organism. This should include doxycycline and a third genaration cephalosporin.

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Severe hemolysis/hemolytic anemia in a patient with a prosthetic cardiac valve suggests a paravalvular leak. In this condition, a portion of the valve becomes dislodged from the valve annulus. It can occur immediately after surgery or delayed if from endocarditis. Paravalvular leaks are more common with mechanic valves. Patients may also present with sudden pulmonary edema.

The treatment will focus on management of the pulmonary edema and prompt surgical repair.

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