Keywords: lipid emulsion therapy (PubMed Search)
ILE is considered as one of the “last resort” therapy in cases of life-threatening drug-induced cardiogenic shock or cardiac arrest. Although there are numerous case reports and case series that showed “successful” or “positive” outcome with ILE, here is no clear evidence that lipid emulsion therapy is effective.
A group of researcher reviewed the National Poison Data System (NPDS) to investigate the failure of ILE therapy by reviewing the overdose fatalities reported to NPDS between 2010 and 2015.
Response to therapy (study cohort)
Adverse effect (n=49)
Smolinske S et al. Utilization of lipid emulsion therapy in fatal overdose cases: an observational study. Clin Toxicol 2019;57:197-202
Category: Critical Care Literature Update
Keywords: sepsis, septic shock, acute renal failure, acute kidney injury, nephrotoxicity, vancomycin, MRSA, IV antibiotics (PubMed Search)
· Empiric broad spectrum antibiotic therapy is a mainstay of the management of critically ill patients with septic shock.
· Vancomycin is widely used for the coverage of potential MRSA infection
· Continuous infusion of vancomycin has been repeatedly demonstrated to reach target serum concentrations faster, maintain consistent serum vancomycin levels better, with fewer serum concentration sampling required, and less overall vancomycin required to do so, in both adult and pediatric populations.2-5
Flannery AH, Bissell BD, Bastin MT, et al. Continuous Versus Intermittent Infusion of Vancomycin and the Risk of Acute Kidney Injury in Critically Ill Adults: a Systematic Review and Meta-Analysis. Crit Care Med. 2020;48(6):912-8.
· Systematic review and meta-analysis of 11 studies for a total of 2123 patients
· Comparing continuous versus intermittent vancomycin infusion.
· Primary outcome of AKI, secondary outcome of mortality
· Found a reduction in the incidence of AKI in the continuous infusion cohort:
· No association between infusion strategy and mortality
· Initial loading dose used in most of the studies (15 mk/kg) probably underdosed, current recommendation for 25mg/kg initial loading dose7 (which is not even always effective by itself)8 (Reardon)
· Continuous infusion may be difficult with limited IV access
· AKI associated with increased hospital stay, costs, mortality (although didn’t pan out in study) – worth preventing if possible.
· Give a 25-30mk/kg loading dose of vancomycin in critically ill patients with suspicion of MRSA to achieve target serum concentrations sooner.
· Continuous vancomycin is a viable option and could be considered in ED boarders, especially if there is concern for impending renal injury.
1. Luther MK, Timbrook TT, Caffrey AR, Dosa D, Lodise TP, LaPlante KL. Vancomycin Plus Piperacillin-Tazobactam and Acute Kidney Injury in Adults: A Systematic Review and Meta-Analysis. Crit Care Med. 2018;46(1):12?20. doi:10.1097/CCM.0000000000002769
2. Taheri M, Dadashzadeh S, Shokouhi S, Ebrahimzadeh K, Sadeghi M, Sahraei Z. Administration of Vancomycin at High Doses in Patients with Post Neurosurgical Meningitis: A Comprehensive Comparison between Continuous Infusion and Intermittent Infusion. Iran J Pharm Res. 2018;17(Suppl2):195?205.
3. Gwee A, Cranswick N, McMullan B, et al. Continuous Versus Intermittent Vancomycin Infusions in Infants: A Randomized Controlled Trial. Pediatrics. 2019;143(2):e20182179. doi:10.1542/peds.2018-2179
4. Vuagnat A, Stern R, Lotthe A, et al. High dose vancomycin for osteomyelitis: continuous vs. intermittent infusion. J Clin Pharm Ther. 2004;29(4):351?357. doi:10.1111/j.1365-2710.2004.00572.x
5. Hong LT, Goolsby TA, Sherman DS, et al. Continuous infusion vs intermittent vancomycin in neurosurgical intensive care unit patients. J Crit Care. 2015;30(5):1153.e1?1153.e11536. doi:10.1016/j.jcrc.2015.06.012
6. Flannery AH, Bissell BD, Bastin MT, et al. Continuous Versus Intermittent Infusion of Vancomycin and the Risk of Acute Kidney Injury in Critically Ill Adults: a Systematic Review and Meta-Analysis. Crit Care Med. 2020;48(6):912-8.
7. Rybak MJ, Le J, Lodise TP, et al. Therapeutic monitoring of vancomycin for serious methicillin-resistant Staphylococcus aureus infections: A revised consensus guideline and review by the American Society of Health-System Pharmacists, the Infectious Diseases Society of America, the Pediatric Infectious Diseases Society, and the Society of Infectious Diseases Pharmacists. Am J Health Syst Pharm 2020 Mar 19. doi: 10.1093/ajhp/zxaa036
8. Álvarez O, Plaza-Plaza JC, Ramirez M, et al. Pharmacokinetic Assessment of Vancomycin Loading Dose in Critically Ill Patients. Antimicrob Agents Chemother. 2017;61(8):e00280-17. doi: 10.1128/AAC.00280-17
Keywords: Concussion, musculoskeletal, injury, lower extremity (PubMed Search)
Post concussion musculoskeletal injuries
Sport related concussion (SRC) impairs numerous functions of the CNS.
Traditional research has focused on risk of repeat concussion following clearance and return to sport
Several studies have shown a consistent elevated risk of lower extremity injuries from 90 days up to one year following SRC.
These include lateral ankle sprains and ACL injuries. Risk ranges, 1.3-3.4x.
This risk may be greater in those with multiple concussions.
This elevated rate has been seen in populations ranging from high school, college to professional athletes and has also been seen in the general population.
Persistent neurological deficits in cognitive and postural control, stability and gait deviations have been postulated as potential mechanisms.
These may be potential modifiable risk factors before return to play/activity. This may be a role best served by sport physical therapists to assist with sport specific rehabilitation post concussion.
Keywords: seat belt, car seats (PubMed Search)
NHTSA recommends that car seats be replaced following a moderate or severe crash. Car seats do not automatically need to be replaced following a minor crash.
A minor crash is one in which ALL of the following apply:
-The vehicle was able to be driven away from the crash site.
-The vehicle door nearest the car seat was not damaged.
-None of the passengers in the vehicle sustained any injuries in the crash.
-If the vehicle has air bags, the air bags did not deploy during the crash
-There is no visible damage to the car seat.
NEVER use a car seat that has been involved in a moderate to severe crash. Always follow manufacturer's instructions.
Car Seat Use After a Crash. https://www.nhtsa.gov/car-
Keywords: Tox image, skin (PubMed Search)
A 19 year old man presents with a scalp lesions/burns after an exposure to incendiary agent. His wounds were smoking and they flouresce under UV light.
What is the causative agent?
Answer: White Phosphorus
White phosphorus is an incendiary agent that is use in certain types of miliary munition (e.g. smoke grenades). It is very lipophilic and penetrates the skin easily.
It self-ignites spontaneously when exposed to ambient air/oxygen and readily burns skin, cloths, and other combustible materials.
Conner JC et al. White phosphorus dermal burns. N Engl J Med. 2007;357:1530
Keywords: traumatic brain injury, clinical decision rule, CT utilization, patient decision, benefit, risk, financial incentive (PubMed Search)
Bottom Line: Discussion of benefit/risk and financial incentive associated with head CT in mild TBI affects patient decision. Interestingly in this population studied, more than half of patients will elect to obtain a head CT even in a low-risk scenario.
Iyengar R, Winkels JL, Smith CM, et al. The effect of financial incentives on patient decisions to undergo low-value head CT scans. Acad Emerg Med. 2019;26(10):1118-24.
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Category: Critical Care
Keywords: PEEP, Driving Pressure, Ventilator Management, ARDS (PubMed Search)
As the debate regarding the pathophysiology and ventilator mechanics of COVID pneumonia rages on, it is important to have a method to evaluate the distensibility of patients' lungs so that we can minimize lung injury. It has been well shown that both under- and over-distention lead to acute lung injury and inducing or worsening ARDS.
One method to find the "best" level of PEEP is through the PEEP titration test (also called a Driving Pressure titration test). High Driving Pressure (DP), which is equal to Plateau Pressure - PEEP, has been shown to be associated with lung injury, and the minimal DP obtainable for a given patient while still meeting ventilatory goals is often an objective in the ICU (common DP goal is < 15 cm H2O). A PEEP titration is optimally done on paralyzed patients, although it can be used on sedated or very calm patients as a "best guess" approximation. It will not work well on agitated patients or those participating heavily in their ventilation. Be sure not to do this if you are not authorized to make vent changes, and always make sure to coordinate appropriately with your RT.
To perform a PEEP titration:
*Consider placing the patient on square waveform VC, as this will also allow evaluation of stress index (if patient is not participating). This can be skipped if not evaluating stress index
1) Make a table for yourself on a piece of paper where you can record PEEP, Plateau Pressure, Driving Pressure, Blood Pressure, and SpO2.
2) Write down the initial PEEP, BP, and SpO2. Clearly document for yourself that this is the initial PEEP, so you do not inadvertantly leave the vent on different settings at the end. Perform an inspiratory hold to measure a plateau pressure. Fill in DP by using the equation DP = Pplat - PEEP
3) Change the PEEP. You can either increase or decrease. If you have a suspicion that the patient is over or under distended, go towards optimal distention, but if unsure it is ok to guess. Usually we go by increments of 2 cm H2O. Wait about 20-30 seconds on the new PEEP.
4) Measure a new plateau pressure and calculate a new DP. At each step, write down the BP and SpO2 as well to ensure you are not generating decreased cardiac preload or derecruitment/hypoxia (keep in mind that due to pulse ox lag, you may not see hypoxia for up to a few minutes).
5) Repeat at a few different PEEP levels. Typically in more unstable patients who may not tolerate aggressive vent changes you may only want to check 2-3 levels of PEEP. In more stable patients or if concern for ongoing lung injury is high, you might check up to 5-6 different levels of PEEP. Please note that some COVID ARDS patients are so unstable that they will not tolerate any derecruitment, and this manuever should not be used in those patients as they could desaturate during the titration.
Once you have all of your data, consider changing to whichever PEEP level gives the lowest driving pressure. Keep in mind that while data from a PEEP titration can be very useful, it is only one data point and should be considered in combination with blood pressure, volume status, CXR findings, habitus, FiO2 weaning, and other factors. PEEP titrations should be reperformed periodically (usually daily in most semi-stable ICU patients, more often in unstable patients). it is also recommended to write a note in the chart with your initial vent settings, data from the titration, and settings upon termination of the titration -- and call your RT if you changed the vent settings.
Bottom Line: PEEP titration (aka Driving Pressure titration) aims to identify the PEEP level where (PPlat - PEEP) is minimal and may help reduce risk of ongoing lung injury in ventilated patients.
Keywords: mTBI, concussion, MRI (PubMed Search)
MRI for Concussion Testing in the ED
The increased sensitivity of MRI may have a role in detecting more subtle intracranial injuries.
135 patients with mild TBI were prospectively evaluated for acute head injury in emergency departments of 3 LEVEL I trauma.
27% of these patients with a normal initial head CT had an abnormal brain MRI including contusions and microhemorrhages. A greater number of these subtle findings was associated with neuropsychological defects on both short-term memory function and with poorer 3 month cognitive outcomes. Inherent difficulties of access, actionable results and reimbursement issues prevent application of MRI for concussion evaluation in the ED.
Note: Mild TBI defined as GCS 13-15 is not the same as sport or activity related concussion which I consider to be GCS 14-15.
Take home: There is currently no role for MRI in the acute evaluation of concussion in the ED.
1) Yuh et al., 2013. Magnetic resonance imaging improves 3-month outcome prediction in mild traumatic brain injury. Ann Neurol.
2) Huang et al., 2015. Susceptibility weighted MRI in mild traumatic brain injury. Neurology.
Category: Critical Care
Keywords: Geriatrics, infections, ICU, pneumonia (PubMed Search)
If you have an intuition your patients older than 65 are at increased risk of infection, especially pneumonia (4-11 times the risk of the under 65 cohorts), you are correct.
If you are concerned your patients co-morbidities, such as COPD, heart disease, and malnutrition will contribute to prolonged mechanical ventilation (the rate of VAP increases 1-3% every extra day on the vent), you are correct.
After age 70, the ICU length of stay and duration of mechanical ventilation increase by 5 days and 9 days respectively.
In the age of COVID-19, itself associated with prolonged mechanical ventilation, it's fair to prepare patients and families for this. We are fortunate we do not need to ration ventilators, so our discussions remain centered on the wishes of our patients, informed by a realistic understanding of what treatment and recovery entail.
Esme M, Topeli A, Yavuz B, et al. Infections in the Elderly Critically-Ill Patient. Frontiers in Medicine 2019; 6: 118.
Category: Pharmacology & Therapeutics
Keywords: acute kidney injury (PubMed Search)
Short periods of AKI have been linked to prolonged hospitalizations, development of CKD/ESRD and in-hospital mortality. Historically, AKI in the ED has been studied with respect to the receipt of contrast media with little data available on nephrotoxic medications.
A recent 5-year retrospective cohort study sought to determine the impact of prescribing nephrotoxic medications in the ED and the development of AKI within 7 days defined as an increase in SCr of ≥ 0.3 mg/dL or 1.5 x baseline. The categories of potentially nephrotoxic medications included ACE-i/ARB, antibiotics, diuretics, NSAIDs, and other (antifungal, antineoplastic, and antivirals).
Inclusion: Adult patients ≥ 18 years, with an initial and repeat SCr measured 24-168h after the initial test, under admitted or observation status (discharged patients were included if they had a repeat SCr in the time window).
Exclusion: previous hospital or ED visit within 7 days, initial SCr < 0.4 mg/dL, initial SCr > 4.0 mg/dL, missing data, dialysis, or transplant history.
The authors assessed 46,965 hospitalized encounters and found that 13.8% of patients developed AKI. Risk factors included older age, African American patients, history of CHF or CKD, higher initial SCr, and higher complexity and mortality. AKI developed within 48 hours in half of the patients and the reminder did so by 120 hours. Approximately 22% had ≥ 1 potentially nephrotoxic medication administered and 6% had ≥ 2 classes.
Diuretics were associated with the highest risk of AKI (64% increased risk), followed by ACE-i/ARBs (39%), and antibiotics (13%). NSAIDs were not associated with an increased risk. The antibiotics associated with the highest risk of AKI were piperacillin-tazobactam, sulfamethoxazole-trimethoprim, and quinolones.
Bottom Line: Medications prescribed in the ED have an impact on the development of AKI during hospitalization. While these cannot always be avoided, use caution when combining multiple nephrotoxic medications and discontinue therapy early when feasible.
Hinson J, et al. Risk of acute kidney injury associated with medication administration in the emergency department. J Emerg Med. 2020;58(3): 487-496.
Keywords: antiseptics, disinfectants, sterilants (PubMed Search)
Recently, “disinfectants,” or germicides, has gain public attention during COVID-19 pandemic. So, what types of agents are considered as “disinfectants?”
Germicides as classified into three broad categories
1. Antiseptics – chemicals applied to living tissue to kill or inhibit microorganisms
a. Iodine & iodophors (e.g. Povidone-iodine; aka Betadine)
b. Chlorine, bleach (sodium hypochlorite)
d. Hydrogen peroxide
e. Alcohols (ethanol and isopropanol)
2. Disinfectants – chemicals applied to inanimate objects to kill or inhibit microorganisms
b. Phenol (aka carbolic acid)
c. Substituted phenols (e.g. hexachlorophene; aka pHisoHex)
d. Quaternary ammonium compounds (benzalkonium chloride; aka Zephiran)
3. Sterilants – chemicals applied to inanimate objects to kill all microorganisms including spores
a. Ethylene oxide
Although ethanol is frequently found in alcoholic beverage and consumable, no other chemicals should be ingested or injected.
Category: Critical Care
Vitamin C for Septic Shock?
Fujii T, et al. Effect of vitamin C, hydrocortisone, and thiamine vs hydrocortisone alone on time alive and free of vasopressor support among patients with septic shock. JAMA. 2020. epub Jan 17.
Keywords: ibuprofen, analgesia, pain (PubMed Search)
Comparison of Oral Ibuprofen at Three Single-dose Regimens for Treating Acute Pain in the Emergency Department: A Randomized Controlled Trial
Ibuprofen is one of the most commonly used medications in the ED for the acute treatment of pain. Analgesic ceiling doses are not well supported. Some adverse effects of NSAIDs are dose dependent (GI and cardiovascular).
A recent study looked to compare the analgesic effect of oral ibuprofen at 3 different doses
Population: Adult ED patients (aged 18 and older) with acute pain.
Methods: Randomized double-blind trial.
Goal: To examine the efficacy of ibuprofen at 400, 600 and 800mg.
Only 225 patients enrolled (75 per group). Outcome was difference in pain scores at 60 minutes.
Results: Difference in mean pain scores at 60 minutes between 400 and 600mg (0.14), 400 and 800mg (0.14) and 600 and 800mg (0.00).
Conclusion: Reduction in pain scores was similar between all 3 dosing groups. Consider lower dosing of ibuprofen in ED patients presenting with acute pain.
This analgesic ceiling dose is lower than recommended by the FDA and most EM textbooks.
Consider using the 400mg ibuprofen dose for ED patients with acute pain
Motov et al., 2019. Comparison of Oral Ibuprofen at Three Single-dose Regimens for Treating Acute Pain in the Emergency Department: A Randomized Controlled Trial. Annals of Emergency Medicine. Oct 2019.
Keywords: traumatic brain injury, intracranial pressure, cervical collar, immobilization (PubMed Search)
Bottom Line: Cervical collars can increased ICP in moderate-severe TBI. In patients with poor cerebral compliance and impaired cerebral autoregulation, even a small increase in ICP can affect cerebral perfusion.
Nunez-Latino RA, Rubiano AM, Godoy DA. Impact of cervical collars on intracranial pressure values in traumatic brain injury: a systematic review and meta-analysis of prospective studies. Neurocrit Care. 2020;32(1):469-77.
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Keywords: buprenorphine, CYP3A4, induction, inhibition, metabolism (PubMed Search)
Buprenorphine (BUP) is increasingly prescribed/used to treat opioid use disorder (OUD) in the United State. BUP is mainly metabolized by CYP3A4 where its enzymatic activity can be either induced or inhibited by many agents.
For example, a study showed that Rifampin administration for 15 days, a potent 3A4 inducer, resulted in (1):
On the contrary, exposure to voriconazole – strong 3A4 inhibitor - resulted in (n=12 health volunteers) (2):
Cannabis use – (CBD is a CYP 3A4 inhibitor) also increased the BUP concentration by 2.7 fold. (3)
1. Drug Alcohol Depend. 2011 Nov 1;118(2-3):326-34. doi: 10.1016/j.drugalcdep.2011.04.013. Epub 2011 May 19.
Rifampin, but not rifabutin, may produce opiate withdrawal in buprenorphine-maintained patients.
2. Eur J Clin Pharmacol. 2018 Dec;74(12):1615-1622. doi: 10.1007/s00228-018-2548-8. Epub 2018 Aug 30.
Voriconazole greatly increases the exposure to oral buprenorphine.
3. Eur Arch Psychiatry Clin Neurosci. 2020 Jan 6. doi: 10.1007/s00406-019-01091-0. [Epub ahead of print]
Buprenorphine-cannabis interaction in patients undergoing opioid maintenance therapy.
Category: Critical Care
Keywords: status epilepticus, anticonvulsant medications, fosphenytoin, levetiracetam, valproate (PubMed Search)
Title: Randomized Trial of Three Anticonvulsant Medications for Status Epilepticus
Outcome: absence of clinical seizure at 60 minutes after infusion of medication.
Kapur J, Elm J, Chamberlain JM, Barsan W, Cloyd J, Lowenstein D, Shinnar S, Conwit R, Meinzer C, Cock H, Fountain N, Connor JT, Silbergleit R; NETT and PECARN Investigators.
Randomized Trial of Three Anticonvulsant Medications for Status Epilepticus. N Engl J Med. 2019 Nov 28;381(22):2103-2113. doi: 10.1056/NEJMoa1905795.
Keywords: MVC, anticipatory guidance, seatbelts. (PubMed Search)
The leading cause of death in the US for those aged 16 to 24 years is motor vehicle collisions (MVCs). Teen drivers are more likely than any other age group to be involved in an MVC that result in injury or fatality. Texting while driving, nighttime driving, inexperienced driving, and driving under the influence of alcohol or drugs may play a role in these collisions.
Can anticipatory guidance related to safe driving be done in the ED? YES!
This study implemented a toolkit that contained a copy of the driving law, a sample parent-teen driving contract and statistics on teen driving injuries. Post toolkit questionnaires showed that both teens and their guardians learned new information.
Bottom line: Engage in anticipatory guidance in the ED with teens and their parents about seatbelt use, the dangers of driving under the influence and local driving laws.
Spears et al. Teen driving education in the pediatric emergency department: effectiveness of a tool kit. Southern Medical Journal 2019; 112(11): 562-565.
Category: Critical Care
Clinical Question: Does a lower MAP target (60-65 mmHg) for ICU patients ≥ 65 years-old reduce 90-day mortality?
-Design: multicenter (across 65 UK ICUs), randomized clinical trial (not blinded), ultimately with 2598 patients
-Inclusion criteria: ICU patients ≥ 65 years-old receiving vasopressors for vasodilatory hypotension with adequate fluid resuscitation
-Exclusion criteria: vasopressors being solely used for bleeding or acute RV/LV failure or post-cardiopulmonary bypass vasoplegia, ongoing treatment for brain/spinal cord injury, death perceived as imminent
-Patients in the permissive hypotension group had a lower exposure to vasopressors compared with those in the usual care group
-Mean MAP was on average 6 mmHg lower in permissive hypotension group
-At 90 days, there was no statistically significant difference in all-cause mortality
-No significant difference in mean duration of ICU and hospital stay, duration and days alive and free from advanced respiratory and renal support to day 28
-No significant different in number of serious adverse events (severe acute renal failure, supraventricular and ventricular cardiac arrhythmia, myocardial injury, mesenteric ischemia, and cardiac arrest)
A lower MAP goal of 60-65 mm Hg appears to be safe for ICU patients ≥ 65 years-old being treated for vasodilatory hypotension
Lamontagne F, Richards-belle A, Thomas K, et al. Effect of Reduced Exposure to Vasopressors on 90-Day Mortality in Older Critically Ill Patients With Vasodilatory Hypotension: A Randomized Clinical Trial. JAMA. 2020;
Keywords: Analgesia, muscle injury, pain control (PubMed Search)
A recent study looked at analgesic prescribing patterns for patients with back pain in EDs in the United States.
Back pain is the most common pain complaint worldwide
-Accounted for about 9% of all ED visits.
In 2007, overall opioid use was 53.5%; in 2016, it was 46.5% (P=0.001). The largest drop was in hydrocodone use.
A recent study in JAMA looked at the risk of death in 90,000 people one year after filling a Rx for tramadol vs. one of several other analgesics such as naproxen, diclofenac or codeine.
All patients were aged 50 years or older and has osteoarthritis.
Initial Rx for tramadol was associated with a higher rate of mortality than with NSAIDs (but not compared to codeine).
Zeng et al., 2019. Association of Tramadol With All-Cause Mortality Among Patients With Osteoarthritis. JAMA 2019 March 12;321(10):969-982.
Mullins et al., 2020. Trends in Evaluation and Management of Back Pain in United States Emergency Departments (2007-2016). AAAPM 2020.
Category: Critical Care
Keywords: Acute respiratory failure, respiratory distress, Coronavirus, COVID-19, SARS-CoV-2 (PubMed Search)
There is currently a high, and appropriate, concern regarding the aerosolization of viral particles during various methods of respiratory support. While studies are limited, here is some of the currently available data (mostly-simulated) on the approximate maximum distances of particle spread:
Nasal Cannula 5LPM:1 1 ft 4.5 in
Non-Rebreather Mask, 6-12LPM: 4 in, minimal change with increasing flows1
High Flow Nasal Cannula
CPAP (20 cmH2O) provided by oronasal mask with good fit (leak from exhaust port):2 11.5 in
Bilevel positive airway pressure w/ oronasal mask (IPAP 10-18/EPAP 4): max dispersal:4 1 ft 7.7 in
Bilevel positive airway pressure with full facemask5 (IPAP 18 / EPAP 5): 2 ft 8 in
Bilevel positive airway pressure with helmet:4
Utility of Surgical Mask:6
In vivo data from actual patients is lacking, however there is potentially lower risk of aerosol spread with HFNC than regular nasal cannula, perhaps due to higher likelihood of a tighter nare/nasal cannula interface. Nonrebreather mask performs well indirectly with the shortest dispersal distance. Noninvasive positive pressure ventilation with an oronasal mask and good seal has a relatively short dispersal distance, and a surgical mask over respiratory support interventions actively decreases amount, if not distance, of particle spread. Use of appropriate PPE and negative pressure rooms, if available, remains key.