Category: Pharmacology & Therapeutics
Keywords: steroids, infection, leukocytosis (PubMed Search)
Steroids induce leukocytosis through the release of cells from bone marrow and the inhibition of neutrophil apoptosis. This effect typically occurs within the first two weeks of steroid treatment.
Leukocyte elevation is commonly used in the diagnosis of septic patients; however, this can be hard to discern in patients on concomitant steroid therapy.
A retrospective cohort study of adult patients presenting with fevers and a diagnosis of pneumonia, urinary tract infection, bacteremia, cellulitis, or COPD exacerbation was conducted to determine the maximal level of WBC within the first 24h of admission between patients on acute, chronic, or no steroid treatment.
Results: maximal WBC levels (p< 0.001)
· Acute steroid therapy: 15.4 ± 8.3 x 10 9/L
· Chronic steroid therapy: 14.9 ± 7.4 x 10 9/L
· No steroid therapy: 12.9 ± 6.4 x 10 9/L
An increase in WBC of 5 x 10 9/L can be found in acute and chronic steroid use when presenting with an acute infection and fever.
Frenkel A, Kachko E, Cohen K, Novak V, Maimon N. Estimations of a degree of steroid inducted leukocytosis in patients with acute infections. Am J Emerg Med. 2018;36(5):749-753.
Keywords: Heat, exertion, muscle (PubMed Search)
Exertional rhabdomyolysis (ER)
The warm weather is here and with it comes an increased risk of ER
Risks include the intensity, duration and types of exercises performed
One of the biggest risks is the exercise experience of the participants, both in those with little to no experience and in those experienced athletes less trained than their counterparts.
Multiple case reports find that intense novel exercises early in the preseason before getting acclimatized and “in shape” carry great risk to the participant. These can be summarized as “too much, too soon, too fast.”
Coaches need to be educated about this and be prepared to detect and effectively handle ER through an emergency action plan.
-Conditioning workouts need to be phased in rather than start at maximum intensity on day one.
Eccentric exercises appear worse than concentric exercises.
Has been seen in almost all sports, ranging from swimming to golf.
It’s not just preseason football!
High humidity and high temperature environments increase the likelihood of ER
Males are more vulnerable to ER than females
Increased risk with sickle cell trait and glycogen storage diseases
Multiple drugs may increase individual risk including alcohol, cocaine, amphetamines, MDMA and caffeine.
Implicated medicines include, salicylates, neuroleptics, quinine, corticosteroids, statins, theophylline, cyclic antidepressants and SSRIs
Football Team Rhabdomyolysis: The Pain Beats the Gain and the Coach Is to Blame Eichner, E., Randy, Current Sports Medicine Reports: May 2018
Keywords: myelopathy, myelitis, physical exam (PubMed Search)
Lhermitte’s phenomenon is as a sign of cervical spinal cord demyelination. It is considered positive if flexion of the neck causes a tingling sensation moving down the limbs or trunk, and may be reported as a symptom or elicited as a sign. This is due to stretching of the dorsal column sensory fibers, the commonest cause of which is multiple sclerosis. Other causes include other myelopathies, such as B12 deficiency, radiation and toxic (due to chemotherapy) or idiopathic myelitis. Its sensitivity is low at 16%, but its specificity for myelopathy is high at 97%.
Kempster PA, Rollinson RD. The Lhermitte phenomenon: variant forms and their significance. J Clin Neurosci 2008;15(4):379–81.
Khare S, Seth D. Lhermitte's Sign: The current status. Ann Indian Acad Neurol. 2015 Apr-Jun; 18(2): 154-156.
Category: Critical Care
Keywords: sepsis, septic shock, guidelines (PubMed Search)
Take Home Points:
For additional reading:
EMNerd, Dr. Rory Spiegel https://emcrit.org/emnerd/em-nerd-case-temporal-fallacy/
Surviving Sepsis Campaign http://www.survivingsepsis.org/Guidelines/Pages/default.aspx
Keywords: Button batteries, removal (PubMed Search)
There were 180 battery ingestions over a 5 year period at two tertiary care children’s hospital. The median age was 3.8 years (0.7 to 18 years). The most common symptoms were abdominal pain (17%), and nausea and vomiting (14%). X-rays detected the location in 94% of patients.
Based on these patients, a treatment algorithm was developed (See attached). Prospective validation is needed.
All patients with esophageal batteries had an intervention (foley catheter removal with post procedure esophagram, ridged esophagram or EGD).
The majority of patients with a gastric battery or small bowel battery were managed non operatively.
20 patients had a colonic battery and 7 had symptoms of abdominal pain or nausea or vomiting.
For batteries distal to the gastroesophageal junction, 16 patients had an intervention. 13 had an EGD with a 69% retrieval rate. 1 patient had a colonoscopy with successful retrieval. 2 patients had abdominal surgery with retrieval.
Rosenfled et al. Battery ingestions in children: Variations in care and development of a clinical algorithm. Journal of Pediatric Surgery. 2018. Epub ahead of print.
Keywords: Methylene Blue (PubMed Search)
Methylene Blue Used in the Treatment of Refractory Shock Resulting From Drug Poisoning. Fisher J, et al. Clin Toxicol 2914 Jan;52:63-65.
Calicum channel antagonist and beta blocker overdose: antidotes and adjunct therapies. Graudins A, et al. British Journal of Clin Pharm. 2016;81(3):453-461.
Category: Critical Care
Precedex (dexmedetomidine) is a selective alpha-2 adrenergic receptor agonist used as a sedative.
It is unique among sedatives typically used in the ICU in that it lacks GABA activity and lacks anticholinergic activity.
Previous studies have shown significant positive changes in sleep patterns in critically ill patients sedated with dexmedetomidine:
-improved sleep efficiency – decreased sleep fragmentation, decreased stage 1 sleep, increased stage 2 sleep
-improved distribution of sleep (with more than ¾ sleep occurring at night)
Given importance of sleep and preservation of day-night cycles/ circadian rhythms in prevention of delirium, a recent randomized controlled trial evaluated dexmedetomidine's effect on delirium.
100 delirium-free critically ill adults receiving sedatives were randomized to receive nocturnal (21:30-06:15) IV dexmedetomidine (titrated to RASS -1 or max 0.7 mcg/kg/hr) OR placebo until ICU discharge.
80% of patients in the dexmedetomidine group remained delirium-free vs 54% in the placebo group.
There was no difference in the incidence of hypotension, bradycardia, or both between groups.
Alexopolou, et al. Effects of Dexmedetomidine on Sleep Quality in Critically Ill Patients. Anesthesiology 2014; 121:801-7.
Skrobic, et al. Low Dose Nocturnal Dexmedetomidine Prevents ICU Delirium. Am J Respir Crit Care Med 2018; 197:9, 1147-56.
Keywords: Mild traumatic brain injury, concussion (PubMed Search)
Does mild traumatic brain injury increase risk of dementia?
Background: Most studies of moderate to severe TBI have found an association with increased risk of dementia and earlier onset of Alzheimer’s. There is growing concern that repeated TBIs, even if more mild, can lead to neurodegenerative conditions such as chronic traumatic encephalopathy (CTE). However, the link between mild TBI and dementia risk has not fully been elucidated, especially in the case of mild TBI without loss of consciousness (LOC).
Recent Data: A recent JAMA study evaluated the association between TBI severity, LOC, and dementia diagnosis in 350,000 veterans between 2001-2013. After adjusting for demographics as well as medical and psych comorbidities, veterans with even mild TBI without LOC had more than a 2-fold increase in risk of dementia diagnosis than those with no TBI. The risk increased only slightly if there was LOC (from a hazard ratio of 2.4 to 2.5). Risk was >3-fold for those with moderate-severe TBI.
Take home: TBI of any severity, even without LOC, appears to be associated with long term neurodegenerative consequences. Avoidance of TBI is of the utmost importance, and if TBI occurs, close neurocognitive follow up should occur.
Barnes DE, et al. Association of Mild Traumatic Brain Injury With and Without Loss of Consciousness With Dementia in US Military Veterans. JAMA Neurol. Online May 7, 2018.
Keywords: Factor Xa inhibitor, reversal agent, adexanet alfa, andexxa (PubMed Search)
On May 3, the FDA approved adexanet alfa, the reversal agent for factor Xa inhibitors - apixaban and rivaroxaban. It received both U.S. Orphan Drug and FDA Breakthrough Therapy designations.
Unlike indarucizumab (a monoclonal antibody fragment) to reverse dabigatran (direct thrombin inhibitor) associated bleeding, adexanet alfa is a recombinant modified human factor Xa decoy protein.
A phase 3 study showed that adexanet alfa decreased the anti-factor Xa activity of rivaroxaban by 92% from baseline and by 94% in apixaban treated participants.
ANNEXA-4 study involving participants with acute major bleeding (GI and intracranial) showed a significant decrease in the anti-factor Xa activity after the bolus dose of adexanet alfa and "effective" hemostasis was noted in 79% of the participants at 12 hours post infusion.
Andexanet alfa is expected to become available in June 2018.
Keywords: Intracerebral hemorrhage, ICH, hematoma expansion, prediction score, BAT score (PubMed Search)
Morotti A, Dowlatshahi D, Boulouis G, et al. Predicting intracerebral hemorrhage expansion with noncontrast computed tomography: The BAT score. Stroke 2018;49(5):1163-9.
Follow me on Twitter @EM_NCC
Keywords: pneumonia, infection, delirium, atypical (PubMed Search)
- Half of elderly patients presenting with pneumonia will manifest signs of delirium
- Tachypnea is the most reliable and earliest vital sign abnormality
- Classic symptoms are not often helpful at predicting severity of illness
- Symptoms are unreliable
- Cough (63-84%)
- Dyspnea (58-74%)
- Fever by history (53-60%)
- Fever at arrival (12-32%)
- Pleuritic chest pain (8-32%)
- Sputum (30-65%)
Caterino JM. Evaluation and management of geriatric infections in the emergency department. Emerg Med Clin N Am 2008;26:319-343.
Keywords: supination with flexion, hyperpronation (PubMed Search)
Nursemaid’s elbow is a common pediatric injury with peak incidence occurring between two and three years of age. It is a condition that typically arises from a sudden upward pull of the arm as an axial traction is placed on the forearm, and the radius is pulled through the annular ligament, resulting in subluxation of the radial head. Over the years, various maneuvers have been attempted, but the two most common are supination with flexion and hyperpronation. A 2017 Cochrane meta-analysis analyzed 8 trials specifically comparing supination with flexion versus hyperpronation. Data from those trials suggested that hyperpronation resulted in less failures at ?rst attempt than the supination-?exion, and although there was limited data, there was no obvious difference in adverse events or pain between the two techniques.
Bottom Line: There is likely a lower risk of failure with first attempt reduction with hyperpronation than with supination-flexion for nursemaid’s elbow.
1. Schutzman SA, Teach S. Upper-extremity impairment in young children. Ann Emerg Med. 1995;26:474-479.
2. Hart GM. Subluxation of the head of the radius in young children. J Am Med Assoc. 1959;169:1734-1736.
3. Vitello S, Dvorkin R, Sattler S, Levy D, Ung L. Epidemiology of Nursemaid’s Elbow. Western Journal of Emergency Medicine, Vol 15, Iss 4, Pp 554-557 (2014). 2014:554.
4. Macias CG, Bothner J, Wiebe R. A comparison of supination/flexion to hyperpronation in the reduction of radial head subluxations. Pediatrics. 1998;102:e10-e10.
5. Bexkens R, Washburn FJ, Eygendaal D, van den Bekerom M,P.J., Oh LS. Effectiveness of reduction maneuvers in the treatment of nursemaid's elbow: A systematic review and meta-analysis. Am J Emerg Med. 2016;34.
6. Krul M, van der Wouden J,C., van Suijlekom-Smit LW, Koes BW. Manipulative interventions for reducing pulled elbow in young children. Cochrane Database Syst Rev. 2009:CD007759.
7. Krul M, van der Wouden JC, van Suijlekom-Smit LW, Koes BW. Manipulative interventions for reducing pulled elbow in young children. Cochrane Database Syst Rev. 2012.
8. Krul M. Manipulative interventions for reducing pulled elbow in young children. Cochrane Database of Systematic Reviews. 2017.
Keywords: Intralipid Emulsion (PubMed Search)
Despite initial excitement for the use of intravenous lipid emulsion (ILE) therapy as an antidote for serious poisonings due to lipohphilic drugs there remains an absence of evidence combined with an incomplete understanding of its efficacy, mechanisms of action, safety, and analytical interferences to recommend its use except in a few clinical scenarios.
The lipid emulsion workgroup performed a comprehensive analysis of four systematic reviews and based recommendations from consensus of expert panelists from the American Academy of Clinical Toxicology, the European Association of Poison Centres and Clinical Toxicologists, the American College of Medical Toxicology, the Asia Pacific Association of Medical Toxicology, the American Association of Poison Control Centers, and the Canadian Association of Poison Control Centers. Toxins evaluated had to have a minimum of three human cases reported in the literature.They concluded that ILE could be indicated for the following clinical situations:
The Bottom Line:
The use of Intravenous Lipid Emulsion in severe poisoning is recommended only for a few poisoning scenarios and was based on very low quality of evidence, and consideration of risks and benefits, adverse effects, laboratory interferences as well as related costs and resources.
Evidence-based recommendations on the use of intravenous lipid emulsion therapy in poisoning. Goseslin S. Hoegeberg L, Hoffman R, et al. Clinical Toxicology, 54:10, 899-923.
Intravenous Lipid Emulsion Therapy and VA-ECMO rescue therapy for Massive Venlafaxine and Clonazepam Overdose. Thomas A, Ovakim D, et al. J Clin Toxicol 2017 7: 368.
Category: Critical Care
DOACs and the Critically Ill
Stensballe J, Moller MH. Ten things ICU specialists need to know about direct oral anticoagulants (DOACs). Intensive Care Med. 2018: epub ahead of print.
Keywords: Pregnancy, sports medicine (PubMed Search)
Exercise talking points for the pregnant patient
(from ACSM 2017 Consesnsus statement)
Exercise throughout pregnancy is generally safe but should be monitored
No evidence of higher rates of preterm or prolonged labor, or deliveries that require induction or episiotomy
No evidence of negative effect on APGAR scores
Avoidance of excessive weight gain, improved balance, and decreased back pain
Improved well-being, energy levels, and sleep patterns
Improved labor symptoms and facilitation of post-partum recovery
Lower risk of C-section
Reduced risk of having a large for gestational age (LGA) or small for gestational age (SGA) infant
Risks include environmental exposure, dehydration, hypoxia, and uterine trauma:
High impact or high-strain physical activity during the fetal implantation phase may lead to slightly higher risk of miscarriage
Sports with high risk of trauma last in pregnancy could result in placental abruption
Scuba diving is contraindicated because the fetus is not protected from decompression problems
Limit use of sauna or hot tub to fewer than ten minutes or omit altogether
Female athlete issues for the Team Physician: A consensus statement- 2017 Update
American College of Sports Medicine, 2018
Keywords: fentanyl overdose, observation period (PubMed Search)
Non-pharmaceutical fentanyl (NPF) is a major contributor to opioid overdoses and overdose fatality. In certain urban areas such as Vancouver, over 80% of heroin samples contain NPF. For isolated heroin overdose ED patients, they can be safely discharged after brief observation period (~2 hours). However, “safe” observation time for fentanyl is unknown.
Recently, a retrospective study evaluating the safe observation period in 1009 suspected (uncomplicated) fentanyl overdose ED visits (827 unique patients).
In the field:
In the ED:
Scheuermeyer FX et al. Safety of a brief emergency department observation protocol for patients with presumed fentanyl overdose. Ann Emerg Med 2018 (PMID: 29530654)
Category: Critical Care
Keywords: acute hypoxic respiratory failure, intubation, noninvasive positive pressure ventilation, high flow nasal cannula, BiPAP, vapotherm (PubMed Search)
ED physicians frequently utilize modailities such as noninvasive positive pressure ventilation (NIV) and high flow nasal cannula (HFNC) to support and potentially avoid intubation in patients presenting with acute hypoxic respiratory failure. Unfortunately, failure of these measures, resulting in "delayed" intubation, has been associated with increased mortality.1,2
A recent post-hoc analysis of data from a multicenter randomized controlled trial evaluated 310 patients with acute hypoxic respiratory failure managed with supplemental O2 by regular nasal cannula, HFNC, or NIV.3
The following factors were predictive of eventual intubation in the different groups:
Of note, 45% of the 310 patients eventually required intubation, and these patients in general had a higher initial respiratory rate and lower PaO2 at presentation, and were more likely to have bilateral infiltrates on CXR.
Bottom Line: Reevaluate your patients frequently. If RR remains high, P:F ratio remains low, or patient respiratory effort/work of breathing is not alleviated by noninvasive measures, consider pulling the trigger on intubation earlier.
Keywords: Infant fever, lumbar puncture, risks, ultrasound (PubMed Search)
Unsuccessful lumbar punctures (LP) may lead to epidural hematoma (EH) formation at the site of needle insertion which may affect subsequent attempts and lead to no success or a grossly bloody sample. There is no standard definition of a traumatic LP based on CSF red blood cell counts. Gross blood may also be obtained by interrupting the vascular structures outside the spinal canal which would not result in EH formation.
This was a prospective study of children younger than 6 months who had an LP at a single children’s hospital. Post LP ultrasounds were completed by the investigating team and interpreted by a pediatric radiologist. 74 patients were included in the study. 31% of the patients had evidence of a post LP EH. 17% fully effaced the thecal sac which would likely preclude future success at that anatomic site. 25% of patients where the clinician did not feel there was a traumatic attempt had evidence of an EH.The study was not powered to determine the risk factors for EH formation. The study also did not look at any other consequences to EH.
Key points: Point of care ultrasound to evaluate EH and bleeding at the failed LP site my provide useful information for a location of subsequent attempts. Also US to evaluate for bleeding in the spinal canal may help with interpretation of the CSF when a large number of red blood cells are present.
Kusulas MP, Eutsler EP, DePiero AD. Bedside Ultrasound for the Evaluation of Epidural Hematoma After Infant Lumbar Puncture. Pediatric Emergency Care. Epub ahead of print. Feb 2018.
Bradycardias caused by poisoning are due to the toxin's effects on cardiovascular receptors and cellular channels and transport mechanisms and are often refractory to standard ACLS drugs. The most common drug classes responsible for bradycardias are calcium channel and beta blockers and digoxin (cardiac glycosides). Sodium channel blockers, clonidine, and opiates also can cause bradycardias. Antidotes are as follows:
** ILE is recommended only in life threatening poisonings where other accepted therapies have been use first or in cardiac arrest clinical scenarios.
Toxic Bradycardias in the Critically Ill Poisoned Patient. Givens M. Emergency Medicine International. Vol 2012.
The safety of high-dose insulin euglycaemia therapy in toxin-induced cardiac toxicity.Page CB, Ryan NM, et al. Clin Toxicol. 2017 Oct 26:1-6
Category: Critical Care
Linezolid, an antimicrobial agent in the oxazolidinone class, often used to cover MRSA and/or VRE, is a reversible MAOI that increases the risk of serotonin syndrome, particularly when administered with other serotonergic agents.
In 2011, the US FDA issued a warning against concomitant use of Linezolid and other serotonergic agents, particularly SSRIs and SNRIs. When use of linezolid is absolutely indicated, an appropriate washout period prior to initiation was recommended.
Based on published reports and retrospective reviews, the incidence of linezolid-associated serotonin toxicity is between 0.54% and 18.2%.
A study published in the Journal of Clinical Psychopharmacology in Oct 2017 examined the incidence of serotonin syndrome with combined use of linezolid and SSRIs/SNRIs compared with linezolid alone and though there was a trend toward increased incidence in patients on SSRI/SNRIs, the authors were unable to find a statistically significant difference.
-Study was retrospective
-Incidence of serotonin syndrome in both groups was very low: 1/87 (1.1%) in Linezolid + SSRI/SNRI group compared to 1/261 (0.4%) in Linezolid alone group.
-Patients in “Linezolid alone” group were not on SSRIs or SNRIs, but were allowed to be on other serotonergic medications.
Despite this study, there are many (>30) case reports of Linezolid-associated serotonin syndrome in patients taking other serotonergic agents.
Cyproheptadine (the “antidote”) is an H1 antagonist and nonspecific serotonin antagonist. A single case study published in 2016, reported successful use of cyproheptadine for prophylaxis against serotonin toxicity in a patient with schizophrenia, depression, and severe osteomyelitis requiring treatment with linezolid while on fluoxetine.
Risk of linezolid-associated serotonin syndrome may be lower than previously thought, however, it is still not recommended for use in patients taking concomitant serotonergic agents without an appropriate washout period.
In case of resistant infection with no other antibiotic treatment options, the risks and benefits of concomitant administration must be weighed seriously and providers must familiarize themselves with and be vigilant in watching for signs/symptoms of serotonin toxicity.
In situations where use of linezolid is unavoidable in patients on concomitant serotonergic agents, prophylactic cyproheptadine may be considered.
Karkow DC, Kauer JF, Ernst EJ. Incidence of Serotonin Syndrome With Combined Use of Linezolid and Serotonin Reuptake Inhibitors Compared With Linezolid Monotherapy. J Clin Psychopharmacol. 2017;37(5):518-523. doi:10.1097/JCP.0000000000000751.
Deardorff OG, Khan T, Kulkarni G, Doisy R, Loehr C. Serotonin Syndrome: Prophylactic Treatment With Cyproheptadine. Prim Care Companion CNS Disord. 2016;18(4). doi:10.4088/PCC.16br01966.
Woytowish MR, Maynor LM. Clinical Relevance of Linezolid-Associated Serotonin Toxicity. Ann Pharmacother. 2013;47(3):388-397. doi:10.1345/aph.1R386.
Ramsey TD, Lau TT, Ensom MH. Serotonergic and Adrenergic Drug Interactions Associated with Linezolid: A Critical Review and Practical Management Approach. Ann Pharmacother. 2013;47(4):543-560. doi:10.1345/aph.1R604.