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:
Laboratory abnormalities
Treatment: L-carnitine
During rapid sequence intubation (RSI) we endeavor to avoid positive pressure ventilation, prior to securing a definitive airway. As such, an adequate buffer of oxygen is necessary to ensure a safe apneic period. This process involves replacing the residual nitrogen in the lung with oxygen. It has been demonstrated that a standard nonrebreather (NRB) mask alone does not provide a high enough fractional concentration of oxygen (FiO2) to optimally denitrogenate the lungs (1). Even when a nasal cannula at 15L/min is utilized in addition to the NRB, the resulting FiO2 is not ideal. A bag-valve mask (BVM) with a one-way-valve or PEEP valve has been demonstrated to provide oxygen concentrations close to that of an anesthesia circuit. But its effectiveness is drastically reduced if a proper mask seal is not maintained during the entire pre-oxygenation period (1). This is not always logistically possible in the chaos of an Emergency Department intubation.
A standard NRB with the addition of flush-rate oxygen appears to be a viable alternative. Recently published in Annals of Emergency Medicine, Driver et al demonstrated that a NRB with wall oxygen flow rates increased to maximum levels, rather than the standard 15L/min, provided end-tidal O2 (ET-O2) levels similar to an anesthesia circuit (2).
In a study of alarms from 77 monitored ICU beds over the course of a month at the University of California, San Francisco, false alarms were common. Accellerated Ventircular Rhythms (AVRs) made up roughly one third of the alarms, and of the more than 4,361 AVRs, 94.9% were false while the remaining 5.1% did not result in a clinical action.
While this study had a majority of patients in the Med/Surg ICUs, a minority were from the cardiac and neurologic ICUs giving it some broad applicability. This study adds to the literature indicating there are subsets of alarms which may not be necessary or which may require adjustment to increase specificity.
Suba S, Sandoval CS, Zegre-Hemsey J, et al. Contribution of Electrocardiographic Accelerated Ventricular Rhythm Alarms to Alarm Fatigue. American Journal of Critical Care. 2019; 28(3):222-229
Background:
There have been a few studies that suggested that there may be some neuroprotective effect with a higher MAP goal in post-arrest patients. However, these studies were small and/or observational.
Intervention:
-The BOX trial was a double-blind, dual-center (Denmark), randomized trial
-Study population: >18 yo, OHCA of presumed cardiac cause
-Pts randomized to higher (77 mmHg) vs. lower (63 mmHg) MAP goal
-double-blinded by attaching a module that reported a BP that was 10% higher or lower than the pt’s actual BP
-Notable exclusion criteria:
-unwitnessed asystole or suspected intracranial bleeding/stroke
Results/Primary outcome:
-No sig difference in composite of death + Cerebral Performance Category of 3 or 4 (3= severe disability, 4= coma) within 90 days
-133 patients (34%) in the high-target group vs 127 patients (32%) in the low-target group (hazard ratio, 1.08;95%CI, 0.84 to 1.37; P=0.56)
Caveats/Takeaways:
-Mean difference in BP was 10.7 mmHg (95[CI], 10.0 to 11.4) which is still relatively clinically significant, but was lower than their goal difference of 14 mmHg
-They used IVF resuscitation to a CVP of 10 mmHg prior to initiating norepi and also used dopamine "if necessary"
-Consider generalizability given study population was pts with presumed cardiac cause of arrest
-Keeping a lower MAP goal of >65 mmHg is reasonable in post-arrest patients
The pattern of prescription drug abuse continues to center around semisynthetic opioids like oxycodone and hydrocodone. Federal regulations have now raised hydrocodone to a schedule II drug like oxycodone. Despite efforts, the slope for natural and semisynthetic opioids remains steep. The ED measures of education, limit prescriptions for acute pain, minimize number of days/pills prescribed and utlize the prescription drug monitoring program are some basics that can assist you in better prescribing habits.
The pattern of prescription drug abuse continues to center around semisynthetic opioids like oxycodone and hydrocodone. Federal regulations have now raised hydrocodone to a schedule II drug like oxycodone. Despite efforts, the slope for natural and semisynthetic opioids remains steep. The ED measures of education, limit prescriptions for acute pain, minimize number of days/pills prescribed and utlize the prescription drug monitoring program are some basics that can assist you in better prescribing habits.
A recent article in Pediatrics attempted to estimate the association between fluoroquinolone use and tendon injury in an adolescent population.
Fluoroquinolones are thought to negatively impact tendons and cartilage in the load-bearing joints of the lower limbs through collagen degradation, necrosis, and disruption of the extracellular matrix.
Population: 4.4 million adolescents aged 12–18 years with filled outpatient fluoroquinolone prescription vs. an oral broad-spectrum antibiotic for comparison.
Fluoroquinolones included ciprofloxacin, levofloxacin, moxifloxacin, and gatifloxacin
Comparator antibiotics included amoxicillin-clavulanate, azithromycin, cefalexin, cefixime, cefdinir, nitrofurantoin, and bactrim.
Outcomes: Primary outcome was 90-day tendon rupture (Achilles, patellar, quadricep, patellar, tibial) identified by diagnosis and procedure codes. Secondary outcome was tendinitis.
Results: The weighted 90-day tendon rupture risk was 13.6 per 100 000 fluoroquinolone-treated adolescents and 11.6 per 100 000 comparator-treated adolescents.
Fluoroquinolone-associated excess risk: 1.9 per 100 000 adolescents; the corresponding number needed to treat to harm was 52 632.
The weighted 90-day tendinitis risk was 200.8 per 100 000 fluoroquinolone-treated adolescents and 178.1 per 100 000 comparator-treated adolescents
Fluoroquinolone-associated excess risk excess risk: 22.7 per 100 000 adolescents; the corresponding number needed to treat to harm was 4405.
Conclusion:
The excess risk of tendon rupture associated with fluoroquinolone treatment was extremely small, and these events were rare. On average, 50,000 adolescents would need to be treated with a fluoroquinolone for 1 additional tendon rupture to occur
The excess risk of tendinitis associated with fluoroquinolone treatment though larger was also small.
Besides tendon rupture, other more common potential adverse drug effects may be more important to consider for treatment decision-making, in adolescents without other risk factors for tendon injury.
A 3 year old is bitten by a spider on his right ear which is causing him intense pain, tachycardia, and muscle cramping. Identify the spider. What is the treatment?
Sports Hernia/Athletic pubalgia
Hx: Gradually increasing lower abdominal/proximal adductor pain. Usually activity related, resolves with rest. Frequent return despite rest when sports activity resumes.
Most common in athletes who perform cutting/maneuvers in addition to frequent acceleration/deceleration. Think ice hockey and soccer.
Bilateral symptoms not uncommon.
PE: Resisted sit up with palpation of the inferolateral edge of the distal rectus may recreate symptoms. Similarly, resisted hip adduction may elicit symptoms.
If for no other reason than to make the diagnosis harder to make, valsalva induced pain may also occur.
Fluoroscopic guided injections can be helpful to isolate the site of pain generation.
First line therapy is rest, non-narcotic analgesia and physical therapy.
With surgery, >80% return to pre injury level of play.
http://atlantasportsmedicine.com/orthopedic-surgeon/wp-content/uploads/2009/11/groin-injuries.jpg
The Prehospital Acute Neurological Treatment and Optimization of Medical Care in Stroke Study (PHANTOM-S) was a randomized prehospital clinical trial. On certain days, a dedicated Stroke Emergency Mobile (STEMO) responded to possible ischemic stroke incidents. Outcomes measured included time to thrombolysis and adverse events such as intracerebral hemorrhage. As opposed to usual prehospital care, a STEMO ambulance was equipped with a CT scanner, point of care laboratory, and a neurologist. According to the study, STEMO use resulted in reduced time to treatment (tPA) without adverse events.
Though this trial did not specifically measure clinical endpoints, it addresses issues central to the delivery of specialized prehospital care:
1) Are there certain conditions which might warrant a tailored, super-specialized EMS response?
2) Are EMS systems capable of delivering definitive care to the patient as opposed to delivering the patient to definitive care?
Stateside study has already started. The Houston Fire Department, in partnership with UTHeath, has already loosed a "Mobile Stroke Unit" on the streets. Like the STEMO, the specialized ambulance will be University hospital based, carry a neurologist, and have the capability to administer tPA.
STEMO pictures courtesy of the "NeuroEMS Blog"
http://www.neuroems.com/2014/05/14/tpa-in-the-truck-results-of-the-phantom-s-trial/
Identifying patients at risk of hypotension during intubation is not always straight forward. The prevalence of peri-intubation hypotension in the Emergency Department has been demonstrated to be approximately 20%.1 And while certain variables increase the likelihood of peri-intubation hypotension (ex. Shock index> 0.80), no single factor predicts it accurately enough to be used at the bedside.2 In the majority of patients undergoing intubation, clinicians should be prepared for peri-intubation hypotension with either vasopressor infusions or push dose pressors.
Pulmonary Embolism
Oxygenation goals
D-Dimer levels are known to be elevated in pregnancy. But how high is too high and can this test be used in the workup of VTE in pregnant patients?
Recent literature indicates that D-dimer levels in each of the three trimesters are approximately 39% higher: 700, 1000, and 1400 ng/dL for each trimester (normal cutoff 500 ng/dL). So, figure out what trimester your patient is in and use the corresponding D-Dimer level for that trimester.
An alcoholic patient presents with a cough, fever, and very foul smelling breath (worse than usual)
What's the diagnosis? And what are the risk factors?
Trauma patients over age 65 should be cared for by a multidisciplinary trauma team. Here is another study affirming that patients over age 65 do worse when having similar injuries to those under 65. Interestingly, those under 65 had more operative repairs of their orthopedic injuries as well.
The authors conclude: “Although the ISS and NISS were similar, mortality was significantly higher among patients aged ≥ 65 years compared to patients < 65 years of age”.
Also it bears further investigation of why those under 65 received more operative repairs
Methods: A large retrospective case series evaluated 121 children under 6 years old with hypoglycemia from a sulfonylurea ingestion.
Results:
Authors' Conclusion: Octreotide administration decreases the number of hypoglycemic events and increases blood glucose concentrations in children with sulfonylurea ingestion.
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