Category: Critical Care
The PARAMEDIC2 trial in NEJM 2018 studied the outcomes of the use of epinephrine in outside hospital cardiac arrest (OHCA) on survival and neurological outcome.
Methods: Conducted in Britain, randomized 8007 patients to receive either epinepherine 1mg (n=4012) or placebo (n=3995) as part of standard CPR for out-of-hosptial arrest. Their primary outcome was survival at 30 days and their secondary outcomes included length of stay as well as neurological outcomes at 30 days and 3 months.
Results: The epinepherine group had improved survival to hospital admission (23% vs. 8%), at 30 days (3.2% vs. 2.4%) or at 3 months (3% vs. 2.2%). Favourable neurological outcomes, however, had no statistical difference at both hospital discharge and at 3 months.
Bottom line: Epinephrine improves ROSC, though with poor neurological outcomes.
Recently, a follow up of the PARAMEDIC2 trial was completed in Resuscitation.
They reported long-term survival, quality of life, functional and cognitive outcomes at 3, 6 and 12-months.
Results: At 6 months, 78 (2.0%) of the patients in the adrenaline group and 58 (1.5%) of patients in the placebo group had a favourable neurological outcome (adjusted odds ratio 1.35 [95% confidence interval: 0.93, 1.97]). 117 (2.9%) patients were alive at 6-months in the adrenaline group compared with 86 (2.2%) in the placebo group (1.43 [1.05, 1.96], reducing to 107 (2.7%) and 80 (2.0%) respectively at 12-months (1.38 [1.00, 1.92]). Measures of 3 and 6-month cognitive, functional and quality of life outcomes were reduced, but there was no strong evidence of differences between groups.
Bottom line: Epinephrine improves survival at 12 months, but poor neurological outcomes remain.
Haywood KL, Ji C, Quinn T, Nolan JP, Deakin CD, Scomparin C, Lall R, Gates S, Long J, Regan S, Fothergill RT, Pocock H, Rees N, O'Shea L, Perkins GD. Long term outcomes of participants in the PARAMEDIC2 randomised trial of adrenaline in out-of-hospital cardiac arrest. Resuscitation. 2021 Mar;160:84-93. doi: 10.1016/j.resuscitation.2021.01.019. Epub 2021 Jan 30. PMID: 33524488.
Perkins GD, Ji C, Deakin CD, Quinn T, Nolan JP, Scomparin C, Regan S, Long J, Slowther A, Pocock H, Black JJM, Moore F, Fothergill RT, Rees N, O'Shea L, Docherty M, Gunson I, Han K, Charlton K, Finn J, Petrou S, Stallard N, Gates S, Lall R; PARAMEDIC2 Collaborators. A Randomized Trial of Epinephrine in Out-of-Hospital Cardiac Arrest. N Engl J Med. 2018 Aug 23;379(8):711-721. doi: 10.1056/NEJMoa1806842. Epub 2018 Jul 18. PMID: 30021076.
Keywords: patellofemoral, knee, pain (PubMed Search)
Bottom Line: In a recent meta-analysis the risk factors for patellofemoral syndrome are weak hip abduction strength, quadricep weakness in military recruits, and increased hip strength in adolescence.
PatelloFemoral Syndrome: Patellofemoral pain is not clearly understood and is believed to be multi-factorial. Numerous factors have been proposed including muscle weakness, damage to cartilage, patella maltracking, as well as others. Patient often complain of anterior knee that is aggravated by walking up and down stairs or squatting. Patellofemoral pain is extremely common. In the general population the annual prevalence for patellofemoral pain is approximately 22.7%, and in adolescents it is 28.9%.
Though commonly taught, the following have no evidence to support that they are a risk factor for patellofemoral syndrome: Age, Height, Weight, BMI, Body Fat or Q Angle of patella
Keywords: Idiopathic intracranial hypertension, IIH, pseudotumor cerebri, obesity, healthcare utilization (PubMed Search)
Bottom Line: The incidence and prevalence of IIH is increasing, likely related to rising rate of obesity. This has also been associated with more healthcare utilization compared to the general population.
Category: Critical Care
Keywords: sepsis recognition, antibiotics administration, mortality, (PubMed Search)
The association between time intervals of ED antibiotic administration and outcome has been controversial. While single studies showed there was increased mortality associated with delayed antibiotic administration (1-3). A meta-analysis of 13 studies and 33000 patients showed that there was no mortality difference between septic patients receiving immediate Abx (< 1 hour) vs. those receiving early abx (1-3 hours) (4).
Since delay in recognition of sepsis (defined as ED triage to Abx order) and delay in antibiotics delivery (Abx order to administration) contribute to total delay of Abx administration, a new retrospective study (3) attempted to investigate the contributions of either factor to hospital mortality.
The study used generalized linear mixed models and involved 24000 patients.
For All patients and outcome of hospital mortality:
Recognition delay (ED triage to Abx order): OR 2.7 (95% CI 1.5-4.7)*
Administration delay at 2-2.5 hours (Abx order to administration): OR 1.5 (1.1-2.0)
These results was associated with non-statistical significance in patients with septic shocks.
Delayed recognition of sepsis was associated with higher hospital mortality. Longer delay of abx administration was also associated with increased risk of hospital mortality.
1.Kumar A, Roberts D, Wood KE, et al: Duration of hypotension before initiation of effective antimicrobial therapy is the critical determinant of survival in human septic shock. Crit Care Med. 2006; 34:1589–1596
2. Ferrer R, Martin-Loeches I, Phillips G, et al: Empiric antibiotic treatment reduces mortality in severe sepsis and septic shock from the first hour: Results from a guideline-based performance improvement program. Crit Care Med 2014; 42: 1749–1755
3. Seymour CW, Gesten F, Prescott HC, et al: Time to treatment and mortality during mandated emergency care for sepsis. N Engl J Med 2017; 376:2235–2244.
4. Rothrock SG et al. Outcome of immediate versus early antibiotics in severe sepsis and septic shock: A systematic review and meta-analysis. Ann Emerg Med 2020 Jun 24; [e-pub]. (https://doi.org/10.1016/j.annemergmed.2020.04.042)
Category: Pharmacology & Therapeutics
Tranexamic acid (TXA) is an antifibrinolytic medication that has been trialed in previous small studies to treat epistaxis. The data to this point has not reliably shown a reduction in bleeding at 30 minutes, but has demonstrated an increased rate of discharge at 2 hours and a reduction in re-bleeding events.
The NoPAC study was the largest study to date on TXA for epistaxis. It was a double-blind, placebo-controlled, randomized study of TXA in adult patients with persistent atraumatic epistaxis to determine if TXA use decreased the rate of anterior nasal packing. Patients were excluded if they had trauma, out of hospital nasal packing, allergy to TXA, nasopharyngeal malignancy, hemophilia, pregnancy, or if they were referred to ENT.
Eligible patients completed 10 minutes of first aid measures followed by 10 minutes of topical vasoconstrictor application prior to randomization to either placebo of 200mg TXA soaked dental rolls inserted in the nare.
496 patients were enrolled. The average patient was 70 years old with stable vitals 150/80mmHg, HR 80 bpm with >60% on oral anticoagulants.
TXA did not reduce the need for anterior nasal packing: 100 (41.3% placebo) vs 111 (43.7% TXA) OR 1.11 (0.77-1.59). There were no differences in the rates of adverse events.
Bottom Line: TXA does not improve rates of anterior nasal packing for patients with persistent epistaxis.
Reuben A, Appelboam A, Stevens KN, et al. The use of tranexamic acid to reduce the need for nasal packing in epistaxis (NoPAC): Randomized controlled trial. Ann Emerg Med 2021;1-10. https://doi.org/10.1016/j.annemergmed.2020.12.013
Keywords: massive acetaminophen overdose, standard NAC, hepatotoxicity (PubMed Search)
Recently, there has been questions if standard n-acetylcysteine (NAC) dose is adequate for massive acetaminophen (APAP) overdose (ingestion of > 32 gm or APAP >300 mcg/mL).
A retrospective study from a single poison center (1/1/2010 to 12/31/2019) investigated the clinical outcome of massive APAP overdose (APAP > 300 mcg/mL at 4 hour post ingestion) treated with standard dosing of NAC.
1425 cases of APAP overdose identified; 104 met the criteria of massive APAP overdose.
Among cases that received NAC within 8 hours post ingestion (n=44)
Among cases that received NAC > 8 hours post ingestion (n=60)
Odds of hepatotoxicity
Category: Critical Care
Hughes CG, Mailloux PT, Devlin JW, et al. Dexmedetomidine or propofol for sedation in mechanically ventilated adults with sepsis. N Engl J Med. Published online February 2, 2021:NEJMoa2024922.
Keywords: Distal radius fracture, wrist, splint (PubMed Search)
Home management versus PCP follow-up of patients with distal radius buckle (torus) fractures
A recent study investigated outcomes of patients with distal radius buckle fractures who were randomized to
Torus/buckle fractures of the distal radius are the most common fractures in childhood occurring on average in 1 in 25 children
This is a stable fracture typically treated with removable wrist splint and very rarely require orthopedic intervention
Outcome: functional recovery at 3 weeks
Randomized controlled trial at a tertiary care children’s hospital
All radiographs reviewed by pediatric radiologist with MSK specialization
149 patients. Mean age 9.5 years. 54.4% male
Telephone follow-up at 3 and 6 weeks following ED discharge by blinded interviewer
Primary outcome was comparison of Activities Scale for Kids-performance scores between groups at 3 weeks
Outcomes: Home management performance score was 95.4% and PCP follow-up group was 95.9%. Mean cost savings were $100.10.
Conclusion: Home management is at least as good as PCP follow-up with respect to functional recovery in ED patients with distal radius buckle fractures.
Colaco et al. Home management versus primary care physician follow-up of patients with distal radius buckle fractures: A randomized controlled trial. Ann Emerg Med. 2021
Keywords: Bell's palsy, facial palsy, Lyme disease, Borrelia burgdorferi (PubMed Search)
Bottom Line: In a Lyme-endemic area, the incidence of positive Lyme tests and Bell’s palsy are highest in the Lyme months. This seasonal variation may help guide the management of patients with Bell’s palsy.
Pacheco A, Rutler O, Valenzuela I, Feldman D, Eskin B, Allegra JR. Positive tests for Lyme disease and emergency department visits for Bell’s Palsy patients. J Emerg Med. 2020;59(6):820-827.
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Category: Critical Care
Keywords: HACOR, NIV, noninvasive ventilation, acute respiratory failure (PubMed Search)
*Note: ABGs were obtained for PaO2 assessment in the above studies -- the use of SpO2 was not evaluated -- but we are often not obtaining ABGs in our ED patients with acute respiratory failure. The following chart provides an estimated SpO2 to PaO2 conversion.
Keywords: Congestive heart failure, trouble breathing, basic natriuretic peptide (PubMed Search)
In children with known congenital heart disease, BNP measurements are higher in those patients with heart failure compared to those without heart failure.
The utility of BNP in differentiating a cardiac from pulmonary pathology in patients with respiratory distress has been studied in pediatrics. In one study involving 49 infants with respiratory distress, the patients with a final diagnosis of heart failure had a higher mean BNP concentration than those patients with other causes. Also, there is a suggestion that the relative change in NT proBNP levels may be useful in patients with underlying pulmonary hypertension. However, currently there is not enough literature to support the routine use of BNP or NT proBNP in acute management.
Bottom line: BNP can be useful in your patient with congenital heart disease who is decompensating and may be used in a patient where there is difficulty in differentiating a primary respiratory from cardiac etiology.
Davis GK, Bamforth F, Sarpal A, et al. B-type natriuretic peptide in pediatrics. Clin Biochem. 2006 Jun;39(6):600-5.
Nir A, Lindinger A, Rauh M, et al. NT-pro-B-type natriuretic peptide in infants and children: reference values based on combined data from four studies. Pediatr Cardiol. 2009 Jan;30(1):3-8.
Ten Kate CA, Tibboel D, Kraemer US. B-type natriuretic peptide as a parameter for pulmonary hypertension in children. A systematic review. Eur J Pediatr. 2015 Oct;174(10):1267-75.
Keywords: Haloperidol, ondansetron, cannabis hyperemesis syndrome (PubMed Search)
Patients with cannabis hyperemesis syndrome experience recurrent/protracted nausea/vomiting. Cases of cannabis hyperemesis syndrome may increase as cannabis use becomes more common in the United States.
A randomized control trial (triple-blind) was conducted to compare haloperidol (0.05 or 0.1 mg/kg) IV or ondansetron 8 mg IV. Primary outcome was reduction of abdominal pain and nausea from baseline (on a 10 cm visual analog scale) 2 hours after treatment.
Ruberto AJ. et al. Intravenous haloperidol versus ondansetron for cannabis hyperemesis syndrome (HaVOC): a randomized controlled trial. Annals of Emergency Medicine. Nov 2020
Keywords: diabetes, exercise, weight loss (PubMed Search)
What time of day is best for exercise to achieve weight loss goals?
Working out in the morning has traditionally held the edge, especially if done on an empty stomach.
Upon walking, elevated levels of cortisol and GH will aid in fat metabolism.
Switching to a morning workout may also decrease appetite throughout the day.
Morning exercise may also induce significant circadian phase?shifting effects. Patients report feeling more alert in the morning and get more tired at night. This may “force” people to get increased rest as poor sleep quality and duration has been associated with weight gain.
Moderate intensity aerobic exercise has been shown to cause immediate mood improvement and mental productivity. These effects can last up to 12 hours and may be a simple aid to combat job stress.
However, a recent small study looked at this question with a group of men at high risk for Type 2 diabetes.
Those that exercised in the morning had better blood sugar control and lost more abdominal fat than those who exercised in the morning.
Study: 32 adult males (58 ± 7 years) at risk for or diagnosed with type 2 diabetes performed 12 weeks of supervised exercise training either:
In the morning (8.00–10.00 a.m., N = 12) OR
In the afternoon (3.00–6.00 p.m., N = 20)
Test: Graded cycling test with ECG monitoring until exhaustion
Results: Compared to those who trained in the morning, participants who trained in the afternoon experienced superior beneficial effects of exercise training on peripheral insulin sensitivity, insulin?mediated suppression of adipose tissue lipolysis, fasting plasma glucose levels, exercise performance and fat mass.
Conclusion: Metabolically compromised patients may benefit from shifting their exercise routine to the afternoon from the morning. Ultimately, any exercise is great in this population, but this study may be worth sharing to your patients.
Mancilla R, Brouwers B, Schrauwen-Hinderling VB, Hesselink MKC, Hoeks J, Schrauwen P. Exercise training elicits superior metabolic effects when performed in the afternoon compared to morning in metabolically compromised humans. Physiol Rep. 2021 Jan;8(24):e14669.
Category: Critical Care
Keywords: Oxygenation, Mechanical Ventilation, Critical Care (PubMed Search)
Optimal oxygenation targets and the possible, theoretical, benefits of hyperoxygenating critically ill patients have long been points of controversy. Multiple studies have suggested harm in pursuing aggressive hyperoxygenation amongst critical patients with various conditions ranging from myocardial infarction to sepsis to neurologic conditions. In addition, oxygen toxicity is a known mechanism causing ARDS.
The HOT-ICU trial adds to the list of arguments against hyperoxygenation, by looking at 2928 ICU patients on high levels of supplemental oxygen and targeting a paO2 of 60 mm Hg (low oxygen group) vs paO2 of 90 mm Hg (high oxygen group). There was no difference in mortality, or other significant difference in outcomes.
Bottom Line: A lower paO2 goal of 60 (correlates to an O2 sat of 90%) is noninferior to a higher paO2 goal of 90 (O2 sat of approximately 96%). When titrating oxygen, targeting a pulse ox of 90-96% is reasonable in critically ill patients. Be sure to include an upper limit on the sat goal, beware an O2 sat of 100%, and titrate down supplemental oxygen when the spO2 is above goal, as the paO2 may be dangerously high.
Schjørring OL, Klitgaard TL, Perner A, Wetterslev J, Lange T, Siegemund M, Bäcklund M, Keus F, Laake JH, Morgan M, Thormar KM, Rosborg SA, Bisgaard J, Erntgaard AES, Lynnerup AH, Pedersen RL, Crescioli E, Gielstrup TC, Behzadi MT, Poulsen LM, Estrup S, Laigaard JP, Andersen C, Mortensen CB, Brand BA, White J, Jarnvig IL, Møller MH, Quist L, Bestle MH, Schønemann-Lund M, Kamper MK, Hindborg M, Hollinger A, Gebhard CE, Zellweger N, Meyhoff CS, Hjort M, Bech LK, Grøfte T, Bundgaard H, Østergaard LHM, Thyø MA, Hildebrandt T, Uslu B, Sølling CG, Møller-Nielsen N, Brøchner AC, Borup M, Okkonen M, Dieperink W, Pedersen UG, Andreasen AS, Buus L, Aslam TN, Winding RR, Schefold JC, Thorup SB, Iversen SA, Engstrøm J, Kjær MN, Rasmussen BS; HOT-ICU Investigators. Lower or Higher Oxygenation Targets for Acute Hypoxemic Respiratory Failure. N Engl J Med. 2021 Jan 20. doi: 10.1056/NEJMoa2032510. Epub ahead of print. PMID: 33471452.
Category: Pharmacology & Therapeutics
Keywords: Buprenorphine, Acute Pain (PubMed Search)
Buprenorphine is a partial opioid receptor agonist that has a higher binding affinity than pure opioid agonists. There can be unease in managing acute pain in patients sustained on buprenorphine for opioid use disorder due to many factors.
The main barriers to effective pain management in these patients are:
Take Home Points
In general, the treatment strategy for acute pain in patients on buprenorphine should be:
Category: Critical Care
Mechanical Ventilation in COPD
Demoule A, et al. How to ventilate obstructive and asthmatic patients. Intensive Care Med. 2020; 46:2436-2449.
Keywords: seizure, status epilepticus, nonconvulsive, electrographic, EEG (PubMed Search)
Bottom Line: Persistent or recurrent seizures are not uncommon in the first 24 hours after status epilepticus even in patients with resolved clinical seizure activity. Early use of EEG can help identify patients who need further escalation of treatment.
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Category: Airway Management
Keywords: Myocarditis, Covid-19 (PubMed Search)
Exercise and Covid-19
The majority of COVID-19 cases fall into the mild-to-moderate category, with symptoms lasting less than 6 weeks on average.
The disease presents a challenge for clinicians seeking to offer counsel for patients wishing to return to exercise.
A recent cohort study in Germany looked at 100 patients (avg. age 49, 53% male) who had recovered from Covid-19 infection.
Most had been healthy, with no pre-existing medical conditions, before becoming infected.
The group had cardiac MRI (CMR) performed.
Average time interval between Covid-19 diagnosis and CMR was 71 days.
Cardiac involvement was seen in 78% of patients and ongoing myocardial inflammation in 60%.
Evidence based return to activity guidelines being developed are more conservative than in the past with other viral infections
1) Puntmann VO, Carerj ML, Wieters I, et al. Outcomes of Cardiovascular Magnetic Resonance Imaging in Patients Recently Recovered From Coronavirus Disease 2019 (COVID-19). JAMA Cardiol. 2020;5(11):1265–1273. doi:10.1001/jamacardio.2020.3557
2) Metzl, J.D., McElheny, K., Robinson, J.N. et al. Considerations for Return to Exercise Following Mild-to-Moderate COVID-19 in the Recreational Athlete. HSS Jrnl 16, 102–107 (2020).
Keywords: alcoholic ketoacidosis, toxic alcohol ingestion, anion gap metabolic acidosis (PubMed Search)
Anion gap metabolic acidosis is often found in ED patients. It can be difficult to distinguish between toxic alcohol (TA) ingestion and alcoholic ketoacidosis (AKA). A retrospective study attempted to identify risk factors associated with AKA when TA ingestion was the alternative diagnosis.
New York City poison center data was reviewed from Jan 1, 2000 to April 30, 2019.
Case definition of AKA included
Case definition of TA ingestion
Univariate analysis showed following variables to be associated with AKA diagnosis
Multivariate logistic regression showed elevated ethanol concentration was associated with increased odd of AKA diagnosis
Title: Mammalian meat allergy (alpha-gal syndrome) following tick bites
Author: Dan Gingold, MD, MPH
Development of IgE antibodies to the oligosaccharide galactose-alpha-1-3-galactose (alpha-gal) appears to be responsible for an acquired allergy to non-primate mammalian meat (i.e., beef and pork) and derived products. Antigen in the salivary apparatus of certain ticks (gross!!) can sensitize an IgE-mediated response to alpha-gal which is present in mammalian meat.
Symptoms are similar to other IgE-mediated hypersensitivity reactions, and can cause a delayed-onset reaction with hives, GI upset, or anaphylaxis after ingestion of red meat. Treatment with standard anti-histamines and epinephrine is effective. Individuals with no prior history of meat sensitivity can develop the syndrome at any age, often after exposure to the outdoors in tick-endemic areas. Skin and blood allergy testing can confirm the diagnosis. Symptoms can persist for years, but can recede over time if not exposed to further tick bites.
In the US, the primary tick responsible is Lone Star Tick (Amblyomma americanum), found primarily in the Eastern, Southeastern, and Midwestern US. Other tick species in Europe, Australia, and Asia have been found to induce the syndrome as well. Interestingly, there is a cross-reactivity with the monoclonal antibody Cetuximab (used to treat colorectal and head and neck cancers), an allergic reaction to which can also induce similar alpha-gal meat sensitivity.
Having first been described in 2009, the syndrome often goes unrecognized; increased physician awareness can inform the evaluation, diagnosis, and education of patients presenting to the ED with undifferentiated allergic reaction.
Khoury JK, Khoury NC, Schaefer D, Chitnis A, Hassen GW. A tick-acquired red meat allergy. Am J Emerg Med. 2018 Feb;36(2):341.e1-341.e3. doi: 10.1016/j.ajem.2017.10.044. Epub 2017 Oct 16. PMID: 29074067.
Crispell G, Commins SP, Archer-Hartman SA, Choudhary S, Dharmarajan G, Azadi P, Karim S. Discovery of Alpha-Gal-Containing Antigens in North American Tick Species Believed to Induce Red Meat Allergy. Front Immunol. 2019 May 17;10:1056. doi: 10.3389/fimmu.2019.01056. PMID: 31156631; PMCID: PMC6533943.