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.
While chest X ray (CXR) is routinely obtained in the setting of traumatic injury, ultrasound (US) is a fast and reliable way to evaluate for life-threatening traumatic injuries requiring emergent intervention, and is supported by the Eastern Association for the Surgery of Trauma (EAST) guidelines. A recent Cochrane Review compared the test characteristics of chest US vs CXR for detection of traumatic pneumothorax when using Chest CT or thoracostomy as the gold standard.
There possible weaknesses of this study, including blinding in the original studies, and several studies may or may not have been at risk for bias as their risk of bias was ‘unclear’. However, the results were consistent across the studies analyzed and remained similar after sensitivity analysis.
Several anatomical as well as patient care issues may confound US findings for pneumothorax such as the presence of bleb, prior thoracic surgery or pathology, as well as main stem intubation.
Rapid Assessment of the RV on Bedside Echo
There are several causes of acute RV dysfunction resulting in a patient presenting to the ER with unstable hemodynamics. Some of these include acute cor pulmonale, acute right sided myocardial infarction and acute submassive or massive pulmonary embolism. While bedside assessment of the LV function is often performed by the ED physician, simultaneous evaluation of the RV can provide crucial information that can help guide therapeutic decisions to prevent worsening of the patient’s clinical condition. A rough guideline to determine RV size and function is below using the apical 4 chamber view.
Normal RV size : <2/3 the size of the LV
Mildly enlarged RV : >2/3 the size of the LV, but not equal in size
Moderately enlarged RV: RV size = LV size
Severely enlarged RV: RV size > LV size
Patients who are found to have RV dilation should be given fluids in a judicious fashion as the RV is not tolerant of fluid overload. Early diagnosis of the cause of acute RV failure should be sought to guide definitive therapy, but early institution of inotropic support should be considered. Frequent reassessments of biventricular function during resuscitation should be performed.
1911051940_Presentation2.pptx (178 Kb)
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?
Torsades de pointes and QT prolongation Associated with Antibiotics
Methods
The authors queried the United States FDA Adverse Event Reporting System (FAERS) from 01/01/2015 to 12/31/2017 for reports of Torsade de points/QT prolongation (TdP/QT).
Reporting Odd Ratio (ROR) was calculated as the ratio of the odds of reporting TdP/QTP versus all other ADRs for a given drug, compared with these reporting odds for all other drugs present in FAERS
Results
FAERS contained 2,042,801 reports from January 1, 2015 to December 31, 2017. There were 3,960 TdP/QTP reports from the study period (0.19%).
Macrolides ROR 14 (95% CI 11.8-17.38)
Linezolid ROR 12 (95% CI 8.5-18)
Amikacin ROR 11.8 (5.57-24.97)
Imipenem-cilastatin ROR 6.6 (3.13-13.9)
Fluoroquinolones ROR 5.68 (95% CI 4.78-6.76)
Limitations:
These adverse events are voluntary reports
There might be other confounded by concomitant drugs such as ondansetron, azole anti-fungals, antipsychotics.
Bottom Line:
This study confimed the previously-known antibiotics to be associated with Torsades de pointes and QT prolongation (Macrolides, Linezolid, Imipenem and Fluoroquinolones). However, this study found new association between amikacin and Torsades de pointes/QT prolongation.
Don’t miss the injecting drug users with botulism!
Wound botulism presents as descending paralysis when Clostridium botulinum spores germinate in anaerobic necrotic tissue. There have been hundreds of cases in the last decade, but it is poorly reported outside of California.
Black tar heroin and subcutaneous injection (“skin popping”) carry the highest risk, but other injected drugs and other types of drug use suffice. C botulinum spores are viable unless cooked at or above 85°C for 5 minutes or longer and this is not achieved when cooking drugs.
Early administration of botulism anti-toxin (BAT) not only saves lives but can prevent paralysis and mechanical ventilation. An outbreak of 9 cases between September 2017 and April 2018 cost roughly $2.3 million, in part because patients didn’t present on average until 48 hours after symptom onset and it took an additional 2-4 days before the true cause of their respiratory depression and lethargy were understood. One patient died.
PEARL: talk to your injecting drug users about the symptoms of botulism: muscle weakness, difficulty swallowing, blurred vision, drooping eyelids, slurred speech, loss of facial expression, descending paralysis, and difficulty breathing. Consider botulism early in your patients who inject drugs but who do not respond to naloxone or who exhibit prolonged symptoms. Testing at the health department is performed with mouse antibodies to Botulism Neurotoxin (BoNT) combined with the patient’s serum.
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
33 y/o M with PMH of ETOH induced pancreatitis presents with epigastic/RUQ pain & N/V after drinking last night, per patient his usual “pancreas pain”. The nurse shows you his blood tubes because they look “milky”. Lipase 1200, Ca 6.8.
What lab test would you add?
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/
While lung protective ventilatory strategies have long been accepted as vital to the management of patients undergoing mechanical ventilation, the translation of such practices to the Emergency Department is still limited and inconsistent.
Fuller et al employed a protocol ensuring lung-protective tidal volumes, appropriate setting of positive end-expiratory pressure, rapid weaning of FiO2, and elevating the head-of-bed. The authors found that the number of patients who had lung protective strategies employed in the Emergency Department increased from 46.0% to 76.7%. This increase in protective strategies was associated with a 7.1% decrease in the rate of pulmonary complications (ARDS and VACs), 14.5% vs 7.4%, and a 14.3% decrease in in-hospital mortality, 34.1% vs 19.6%.
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.
It is well documented that when left to our own respiratory devices we will consistently over-ventilate patients presenting in cardiac arrest (1). A simple and effective method of preventing these overzealous tendencies is the utilization of a ventilator in place of a BVM. The ventilator is not typically used during cardiac arrest resuscitation because the high peak-pressures generated when chest compressions are being performed cause the ventilator to terminate the breath prior to the delivery of the intended tidal volume. This can easily be overcome by turning the peak-pressure alarm to its maximum setting. A number of studies have demonstrated the feasibility of this technique, most recently a cohort in published in Resuscitation by Chalkias et al (2). The 2010 European Resuscitation Council guidelines recommend a volume control mode at 6-7 mL/kg and 10 breaths/minute (3).
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).
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.
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
Q: What is wrong with this baby? And what Dx should you entertain?
Previously healthy 7d old presents after difficulty feeding, one episode of vomiting and now with intermittent apneic episodes.
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