Tuesday, March 31, 2020

I agree with Joint Commission!

Is this the part of the movie where the villain switches sides and fights with the heroes? 

The PR folks over at the Joint Commission said "now's our chance!!" 

They stated "We must protect those who are working so heroically to care for people afflicted with COVID-19."

That PR team needs a raise!

Here are some key points: Download the PDF over at eddyjoemd.com

"The Joint Commission supports allowing staff to bring their own standard face masks or respirators to wear at work when their healthcare organizations cannot routinely provide access to protective equipment that is commensurate with the risk to which they are exposed."

"No Joint Commission standards or other requirements prohibit staff from using PPE brought from home."
Regarding N95 respirators vs. Surgical MasksThey state that the CDC changing their recommendations from N95 to surgical masks "may have been precipitated by the emergence of PPE shortages". Ohhhhhh burn!

They state that the understand why healthcare workers have concerns about the adequacy of surgical masks.

Regarding wearing a mask throughout the dayThey state "it is reasonable for staff to want to wear a mask throughout the day".

For our ED friends and colleagues: "Staff in the ED are at particularly high risk because of the high number of patients they see who may be asymptomatic carriers of the virus and the fact that they may have to emergently intubate patients and would be at significant risk without a respirator to protect against aerosolized virus".

The Joint Commission is not siding with hospital administrators on this one, team. We will applaud them, once. I'm still going to drink and eat at the nurses station bc that's where the fun people are.

Link to Statement

Link to FULL PDF

ACE inhibitors and ARBs in COVID-19

We've been hearing a bunch regarding ACE-inhibitors and ARBs in COVID-19 infections. The NEJM finally put out an article on it. Let's review it in plain english and see if it can help us treat our patients. Spoiler alert: like they said in the second paragraph of the article :the data in human are too limited to support or refute these hypothesis and concerns".

Okay I read this paper and didn't get much out of it. Data to be determined.

Vaduganathan M, Vardeny O, Michel T, McMurray JJV, Pfeffer MA, Solomon SD. Renin-Angiotensin-Aldosterone System Inhibitors in Patients with Covid-19 [published online ahead of print, 2020 Mar 30]. N Engl J Med. 2020;10.1056/NEJMsr2005760. doi:10.1056/NEJMsr2005760

Link to Article


Although great care has been taken to ensure that the information in this post is accurate, eddyjoemd, LLC shall not be held responsible or in any way liable for the continued accuracy of the information, or for any errors, omissions or inaccuracies, or for any consequences arising therefrom.






Hydroxychloroquine for COVID-19

This is some actual data regarding the effects of hydroxychloroquine in COVID-19! A hat tip to the authors. This is not the most robust study with the most conventional endpoints but it's something. It is very small but I'd rather it exist than not exist at this juncture. These patients are not ICU level patients. 

Disclaimer: this is a not a peer reviewed article at the time of my writing. This is also my interpretation of the study.

The authors wanted to see the effects of hydroxychloroquine in patients with COVID-19. No azithro was harmed in this study that I can tell.

n=62, RCT
31 received standard treatment PLUS a 5 days course of HCQ 400mg daily
Mean age: 44.7 (not the oldest folks, older tend to be sicker.)
All 62 patients also received antivirals, antibiotics (zero mentions of azithro in the article), immunoglobulins +/- steroids.
Noteworthy excluded patients (cannot discuss all of these): severe and critically ill patients. Renal failure. Others. Bottom line is that these patients are not SICK SICK SICK. 

There's no subgroup analysis to see how the +/- steroids may have influenced the results.

Endpoints and Results (assessed at baseline and after 5 days of treatment)
Time to clinical recovery: body temperature, cough remission time. Fewer patients in the control group had fevers, despite this, fever resolved quicker in the HCQ group. Fewer patients had cough in the control group. Also despite this, fewer patients had cough in the HCQ group. Bottom line, patients with HCQ felt better. This is a strange endpoint.

Radiological results: 

CT scan on day 0 and on day 6. Improved pneumonia in 80.6% of HCQ arm versus 54.8% in the control arm. NNT=3.9. 
61.3% of the patients in the HCQ group had a significant absorption of their pneumonia.

4 patients progressed to severe illness in the control group. That's almost 13% of the group. None in HCQ group.

Adverse reactions: 
in the HCQ group, one patient had a rash, another had a headache. 

The authors concluded that HCQ could shorten the time to clinical recovery and promote the absorption of pneumonia. The mechanisms by which this occurs are postulated in the article. This would support giving HCQ to patients who are not critically ill as we do not know its effects on that population, yet. 


-EJ

Link to FULL FREE Article

Link to Abstract






Although great care has been taken to ensure that the information in this post is accurate, eddyjoemd, LLC shall not be held responsible or in any way liable for the continued accuracy of the information, or for any errors, omissions or inaccuracies, or for any consequences arising therefrom.

The WHO Strikes Back: Droplet and Contact Precautions

The World Health Organization has obtained the paper I referenced yesterday as well as the study in the NEJM that I covered on 3/18/2020. Please read the document for yourself. I have provided links, as always. Please interpret this data yourself. Don't trust me.


Regarding the NEJM study which concluded that the virus could be in the air up to three hours:

Their take: "the finding of COVID-19 virus in aerosol particles up to 3 hours does not reflect a clinical setting in which aerosol-generating procedures are performed—that is, this was an experimentally induced aerosol-generating procedure."

My take: okay then, can you please give us some data as to how long we could expect it during clinical settings of aerosol-generating procedures to be in the room? Can we have some expert guidance?

Regarding the study I posted yesterday, 3/30.
The WHO provided citations for two studies, one published in JAMA (Ong study) and the other in Infection Control and Hospital Epidemiology to disprove the Santarpia study.

Their take: "It is important to note that the detection of RNA in environmental samples based on PCR-based assays is not indicative of viable virus that could be transmissible. Further studies are needed to determine whether it is possible to detect COVID-19 virus in air samples from patient rooms where no procedures or support treatments that generate aerosols are ongoing. As evidence emerges, it is important to know whether viable virus is found and what role it may play in transmission."

My take: since we don't know with reasonable certainty, then we should err on the side of caution and protect our teams.

Here are the two studies cited by WHO as to why it is NOT airborne.

Ong study: sampled 3 patients, the one who was the sickest noted the virus in the air outlet fans (airborne infection isolation rooms). Per the article, this suggests "that small virus-laden droplets may be displaced by airflows and deposited on equipment such as vents". The limitation stated by the authors includes that "the volume of air sampled represents only a small fraction of total volume, and air exchanges in the room would have diluted the presence of SARS-CoV-2 in the air. Further studies are required to confirm these preliminary results." In this study they also found the virus on the shoe of a physician.

My take: Hardly concrete not definitive.

Cheng study: "air samples were all undetectable for SARS-CoV-2 RNA when the patients were performing 4 different maneuvers (normal breathing, deep breathing, speaking 1, 2, and 3 continuously, and coughing continuously) while putting on and putting off the surgical mask."

It seems based on the discussion that they did this on only ONE patient. They state "we may not be able to make a definite conclusion based on the analysis of a single patient".

My take: inconclusive.

My understanding is that a viral culture is needed to assess viability rather than PCR. Neither of these studies looked at viral cultures. WHO, can you get this for us?

Citations:
WHO Commentary on Transmission Modalities

Cheng V, Wong S-C, Chen J, Yip C, Chuang V, Tsang O, et al. Escalating infection control response to the rapidly evolving epidemiology of the Coronavirus disease 2019 (COVID-19) due to SARS-CoV-2 in Hong Kong. Infect Control Hosp Epidemiol. 2020 Mar 5 [Epub ahead of print].

Link to Abstract


Link to FULL FREE PDF

Ong SW, Tan YK, Chia PY, Lee TH, Ng OT, Wong MS, et al. Air, surface environmental, and personal protective equipment contamination by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from a symptomatic patient. JAMA. 2020

Link to FULL FREE Article


Although great care has been taken to ensure that the information in this post is accurate, eddyjoemd, LLC shall not be held responsible or in any way liable for the continued accuracy of the information, or for any errors, omissions or inaccuracies, or for any consequences arising therefrom.


Monday, March 30, 2020

COVID: Let's call it airborne already. UPDATED on 4/1/2020

Disclaimers before we get this started. The following is my opinion. This article has not been peer-reviewed. I am going to attempt to be said peer. A hat tip to the folks at the University of Nebraska Medical center who have looked into this. They are working to find the answers to the questions we are all asking to take care of all of us. I encourage you to download the article for yourself and read it. There are many details I am intentionally going to gloss over.

Airborne or droplet? That is the question. This paper is quite concerning. Spoiler alert: they recommend the use of airborne isolation precautions.

n=13 confirmed COVID patients.

Some of these patients were hospitalized (NBU unit) and some of these patients were quarantined (NQU) either asymptomatic or with mild symptoms.

They did the best they could to contain the virus regarding PPE, negative pressure, and the like.

They obtained a total of 163 surface and air samples in these rooms combined. Those samples were analyzed by PCR methods.

77.3% of those samples were positive for SARS-CoV-2.

76.5% of all personal items were positive.

- Cell phones: 83.3% positive

- Toilets: 81% positive

- Remote controls: 64.7% positive

- Bedside tables and rails: 75% positive

- Window ledges (how did it get over there?!!?): 81.8% positive


Here's the kicker, though
- Room air samples: 63.2% positive

- They stated a case where the sampler was greater than 6ft away from a patient who was on 1L NC and the sample was positive for COVID-19.

- The highest airborne concentrations noted on patients receiving nasal cannula. They mentioned that these patients hadn't coughed. Again, they were not looking at any other modality of oxygenation.

- 66.7% of HALLWAY air samples had virus-containing particles. People going in and out of the rooms were carrying the airborne virus.

We are in deep poop, team.

I know the CDC and WHO are saying something different but that can they provide a similar study to this? Crickets.

-EJ

Link to Abstract

Link to FULL FREE Article




Although great care has been taken to ensure that the information in this post is accurate, eddyjoemd, LLC shall not be held responsible or in any way liable for the continued accuracy of the information, or for any errors, omissions or inaccuracies, or for any consequences arising therefrom.



ADDENDUM: The World Health Organization has obtained the paper I referenced above as well as the study in the NEJM that I covered on 3/18/2020. Please read the document for yourself. I have provided links, as always. Please interpret this data yourself. Don't trust me. 

Regarding the NEJM study which concluded that the virus could be in the air up to three hours:

Their take: "the finding of COVID-19 virus in aerosol particles up to 3 hours does not reflect a clinical setting in which aerosol-generating procedures are performed—that is, this was an experimentally induced aerosol-generating procedure."

My take: okay then, can you please give us some data as to how long we could expect it during clinical settings of aerosol-generating procedures to be in the room? Can we have some expert guidance? 

Regarding the study I posted yesterday, 3/30.
The WHO provided citations for two studies, one published in JAMA (Ong study) and the other in Infection Control and Hospital Epidemiology to disprove the Santarpia study. 

Their take: "It is important to note that the detection of RNA in environmental samples based on PCR-based assays is not indicative of viable virus that could be transmissible. Further studies are needed to determine whether it is possible to detect COVID-19 virus in air samples from patient rooms where no procedures or support treatments that generate aerosols are ongoing. As evidence emerges, it is important to know whether viable virus is found and what role it may play in transmission."

My take: since we don't know with reasonable certainty, then we should err on the side of caution and protect our teams. 

Here are the two studies cited by WHO as to why it is NOT airborne. 

Ong study: sampled 3 patients, the one who was the sickest noted the virus in the air outlet fans (airborne infection isolation rooms). Per the article, this suggests "that small virus-laden droplets may be displaced by airflows and deposited on equipment such as vents". The limitation stated by the authors includes that "the volume of air sampled represents only a small fraction of total volume, and air exchanges in the room would have diluted the presence of SARS-CoV-2 in the air. Further studies are required to confirm these preliminary results." In this study they also found the virus on the shoe of a physician. 

My take: Hardly concrete not definitive. 

Cheng study: "air samples were all undetectable for SARS-CoV-2 RNA when the patients were performing 4 different maneuvers (normal breathing, deep breathing, speaking 1, 2, and 3 continuously, and coughing continuously) while putting on and putting off the surgical mask." 

It seems based on the discussion that they did this on only ONE patient. They state "we may not be able to make a definite conclusion based on the analysis of a single patient".

My take: inconclusive.

My understanding is that a viral culture is needed to assess viability rather than PCR. Neither of these studies looked at viral cultures. WHO, can you get this for us?

Citations:
WHO Commentary on Transmission Modalities

Cheng V, Wong S-C, Chen J, Yip C, Chuang V, Tsang O, et al. Escalating infection control response to the rapidly evolving epidemiology of the Coronavirus disease 2019 (COVID-19) due to SARS-CoV-2 in Hong Kong. Infect Control Hosp Epidemiol. 2020 Mar 5 [Epub ahead of print].

Link to Abstract


Link to FULL FREE PDF

Ong SW, Tan YK, Chia PY, Lee TH, Ng OT, Wong MS, et al. Air, surface environmental, and personal protective equipment contamination by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from a symptomatic patient. JAMA. 2020

Link to FULL FREE Article


Although great care has been taken to ensure that the information in this post is accurate, eddyjoemd, LLC shall not be held responsible or in any way liable for the continued accuracy of the information, or for any errors, omissions or inaccuracies, or for any consequences arising therefrom.

Sunday, March 29, 2020

Hydroxychloroquine and Azithromycin as a treatment of COVID-19: An Appraisal on the Study Published on 3/27/20

We have an update now from the same researchers in France regarding hydroxychloroquine and azithromycin in COVID-19. It's a free PDF and I recommend you read it yourself. Don't trust me. 

This study has me scratching my head. Their first study seemed like they rushed it out the door to light the fire for some more research. This study seems like they're deliberately hiding things from us or trying to remain obscure. 

Methods:

This is an observational study, meaning they didn't have any controls.
80% of patients got a CT chest and (almost) every patient had a daily nasopharyngeal swab.
They all got an EKG before treatment and two days after treatment began. They had criteria to not start therapy based on some findings listed in the article. 

Treatment regimen:

Hydroxychloroquine 200mg three time a day for 10 days
Azithromycin 500mg on day 1, then 250 daily for 4 days


End points (these are not your typical endpoints):

Clinical Outcome (oxygen therapy or ICU transfer)
Contagiousness by PCR and culture
Length of stay in the ID ward

Things to know:

n=80
4 patients were asymptomatic carriers (then why were they in the COVID unit?)
92% of the patients were less ill based on their made up NEWS score
52.8% had lower respiratory infections/pneumonia. 

Results:
We don't have any controls to know if this is the normal course of the infection or if the hydroxychloroquine actually worked or not. I forgive them for not having controls in the prior study but this is now too much. 
93.8% were discharged with a low NEWS score. Don't forget that 92% had a low news score to begin with!
3 patients still ended up in the ICU. 

The nasopharyngeal viral load fell. Sure. Cool. Thanks. But does this normally fall at this rate without treatment? We need controls. Is the decrease in contagiousness the normal evolution or the drugs working? We don't know. No controls. 

I'm tired of reviewing this study. You all get my point. I am in favor of trying it, but I feel like there's some academic dishonesty happening here. 

I really want this to work. I really really do. We need some good news but we also need to solidify our management with better data. 


-EJ

Link to full FREE PDF

Although great care has been taken to ensure that the information in this post is accurate, eddyjoemd, LLC shall not be held responsible or in any way liable for the continued accuracy of the information, or for any errors, omissions or inaccuracies, or for any consequences arising therefrom.

Saturday, March 28, 2020

Plasma to treat COVID-19: First Update

Several days ago I posted about the FDA approval to start clinical trials to see how convalescent plasma of patients who had already beat COVID-19 would hopefully help patients who are currently suffering from COVID-19.

This paper was published in JAMA yesterday states that there was an "improvement in clinical status" in the population it was provided for. Sweet, but let’s start off with a reality check before we get enthusiastic.

This is a report on only five patients. Five. Cinco. We clear? Good. This is also NOT a randomized clinical trial. It’s case series. You know, like if I were to publish the Vitamin C data from my shop, no one will believe it bc it’s full of my bias. Same thing applies here.

Important takeaways:

These patients did not improve overnight which should provide us with some preparation as to when we could see our own FDA approved trials result.

Generally speaking, it took 7 to 12 days to start seeing some benefits on the vent.

These patients were all on the vent for more than 10 days which is what we are seeing here in the US and also quite terrifying. They had all been hospitalized for 10-20 days before this was provided.

The length of stay for all five of these patients was greater than 50 days when all was said and done.

The largest concern is that there was only one patient with a SOFA score greater than 10. That patient actually got worse before he got better and was actually on ECMO.

I really wish they had done some matching with non-plasma receiving patients to learn how these patients behave at baseline.

The viral load was also difficult to predict the efficacy of plasma on. Seems as if there was, at least in my opinion, a large variety of when they cleared the virus.

Multiple interventions: all of these patients were on steroids, 4/5 were on the lopinavir/ritonavir combo which was shown to not have benefit in an NEJM study, and other meds. Obviously they were throwing the kitchen sink at these patients.

Given that it's just five patients, its really hard to know whether the plasma worked, whether it was one of the other meds, or whether they got better on their own. It's too soon to say whether this works or not.

We're in deep poop, team. The largest value of this study is to just see how these five patients behaved overall. The worst is yet to come. Rest up and be prepared.


Link to Abstract

Link to FULL FREE PDF


Shen C, Wang Z, Zhao F, et al. Treatment of 5 Critically Ill Patients With COVID-19 With Convalescent Plasma. JAMA. Published online March 27, 2020. doi:10.1001/jama.2020.4783




Although great care has been taken to ensure that the information in this post is accurate, eddyjoemd, LLC shall not be held responsible or in any way liable for the continued accuracy of the information, or for any errors, omissions or inaccuracies, or for any consequences arising therefrom.

Friday, March 27, 2020

Nutrition and Gut Health in the ICU: Citations

References to the Enteral Nutrition Lecture

Lambell KJ, Tatucu-Babet OA, Chapple LA, Gantner D, Ridley EJ. Nutrition therapy in critical illness: a review of the literature for clinicians. Crit Care. 2020;24(1):35. Published 2020 Feb 4. doi:10.1186/s13054-020-2739-4

McClave SA, Martindale RG, Rice TW, Heyland DK. Feeding the critically ill patient. Crit Care Med. 2014;42(12):2600–2610. doi:10.1097/CCM.0000000000000654

McClave SA, Taylor BE, Martindale RG, et al. Guidelines for the Provision and Assessment of Nutrition Support Therapy in the Adult Critically Ill Patient: Society of Critical Care Medicine (SCCM) and American Society for Parenteral and Enteral Nutrition (A.S.P.E.N.) [published correction appears in JPEN J Parenter Enteral Nutr. 2016 Nov;40(8):1200]. JPEN J Parenter Enteral Nutr. 2016;40(2):159–211. doi:10.1177/0148607115621863

Nguyen NQ, Besanko LK, Burgstad C, et al. Delayed enteral feeding impairs intestinal carbohydrate absorption in critically ill patients. Crit Care Med. 2012;40(1):50–54. doi:10.1097/CCM.0b013e31822d71a6

National Heart, Lung, and Blood Institute Acute Respiratory Distress Syndrome (ARDS) Clinical Trials Network, Rice TW, Wheeler AP, et al. Initial trophic vs full enteral feeding in patients with acute lung injury: the EDEN randomized trial. JAMA. 2012;307(8):795–803. doi:10.1001/jama.2012.137

Arabi YM, Aldawood AS, Haddad SH, et al. Permissive Underfeeding or Standard Enteral Feeding in Critically Ill Adults [published correction appears in N Engl J Med. 2015 Sep 24;373(13):1281]. N Engl J Med. 2015;372(25):2398–2408. doi:10.1056/NEJMoa1502826

Arabi YM, Aldawood AS, Al-Dorzi HM, et al. Permissive Underfeeding or Standard Enteral Feeding in High- and Low-Nutritional-Risk Critically Ill Adults. Post Hoc Analysis of the PermiT Trial. Am J Respir Crit Care Med. 2017;195(5):652–662. doi:10.1164/rccm.201605-1012OC

Al-Dorzi HM, Albarrak A, Ferwana M, Murad MH, Arabi YM. Lower versus higher dose of enteral caloric intake in adult critically ill patients: a systematic review and meta-analysis. Crit Care. 2016;20(1):358. Published 2016 Nov 4. doi:10.1186/s13054-016-1539-3

Allingstrup MJ, Kondrup J, Wiis J, et al. Early goal-directed nutrition versus standard of care in adult intensive care patients: the single-centre, randomised, outcome assessor-blinded EAT-ICU trial. Intensive Care Med. 2017;43(11):1637–1647. doi:10.1007/s00134-017-4880-3

Harvey SE, Parrott F, Harrison DA, et al. Trial of the route of early nutritional support in critically ill adults. N Engl J Med. 2014;371(18):1673–1684. doi:10.1056/NEJMoa1409860

Doig GS, Simpson F, Sweetman EA, et al. Early parenteral nutrition in critically ill patients with short-term relative contraindications to early enteral nutrition: a randomized controlled trial. JAMA. 2013;309(20):2130–2138. doi:10.1001/jama.2013.5124

Casaer MP, Mesotten D, Hermans G, et al. Early versus late parenteral nutrition in critically ill adults. N Engl J Med. 2011;365(6):506–517. doi:10.1056/NEJMoa1102662

Halpern SD, Becker D, Curtis JR, et al. An official American Thoracic Society/American Association of Critical-Care Nurses/American College of Chest Physicians/Society of Critical Care Medicine policy statement: the Choosing Wisely® Top 5 list in Critical Care Medicine. Am J Respir Crit Care Med. 2014;190(7):818–826. doi:10.1164/rccm.201407-1317ST

Reignier J, Boisramé-Helms J, Brisard L, et al. Enteral versus parenteral early nutrition in ventilated adults with shock: a randomised, controlled, multicentre, open-label, parallel-group study (NUTRIREA-2). Lancet. 2018;391(10116):133–143. doi:10.1016/S0140-6736(17)32146-3

TARGET Investigators, for the ANZICS Clinical Trials Group, Chapman M, Peake SL, et al. Energy-Dense versus Routine Enteral Nutrition in the Critically Ill. N Engl J Med. 2018;379(19):1823–1834. doi:10.1056/NEJMoa1811687

Wischmeyer PE. Enteral Nutrition Can Be Given to Patients on Vasopressors. Crit Care Med. 2020;48(1):122–125. doi:10.1097/CCM.0000000000003965

Doig GS, Simpson F, Heighes PT, et al. Restricted versus continued standard caloric intake during the management of refeeding syndrome in critically ill adults: a randomised, parallel-group, multicentre, single-blind controlled trial. Lancet Respir Med. 2015;3(12):943–952. doi:10.1016/S2213-2600(15)00418-X

Lambell, K.J., Tatucu-Babet, O.A., Chapple, L. et al. Nutrition therapy in critical illness: a review of the literature for clinicians. Crit Care 24, 35 (2020).

van Niekerk G, Meaker C, Engelbrecht AM. Nutritional support in sepsis: when less may be more. Crit Care. 2020;24(1):53. Published 2020 Feb 14. doi:10.1186/s13054-020-2771-4

Wischmeyer PE, McDonald D, Knight R. Role of the microbiome, probiotics, and 'dysbiosis therapy' in critical illness. Curr Opin Crit Care. 2016;22(4):347–353. doi:10.1097/MCC.0000000000000321

Fay KT, Klingensmith NJ, Chen CW, et al. The gut microbiome alters immunophenotype and survival from sepsis. FASEB J. 2019;33(10):11258–11269. doi:10.1096/fj.201802188R

Robinson CM, Pfeiffer JK. Viruses and the Microbiota. Annu Rev Virol. 2014;1:55–69. doi:10.1146/annurev-virology-031413-085550

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Clark JA, Coopersmith CM. Intestinal crosstalk: a new paradigm for understanding the gut as the "motor" of critical illness. Shock. 2007;28(4):384–393. doi:10.1097/shk.0b013e31805569df

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Lankelma JM, van Vught LA, Belzer C, et al. Critically ill patients demonstrate large interpersonal variation in intestinal microbiota dysregulation: a pilot study. Intensive Care Med. 2017;43(1):59–68. doi:10.1007/s00134-016-4613-z

McDonald D, Ackermann G, Khailova L, et al. Extreme Dysbiosis of the Microbiome in Critical Illness. mSphere. 2016;1(4):e00199-16. Published 2016 Aug 31. doi:10.1128/mSphere.00199-16

Shimizu K, Ogura H, Goto M, et al. Altered gut flora and environment in patients with severe SIRS. J Trauma. 2006;60(1):126–133. doi:10.1097/01.ta.0000197374.99755.fe

Hempel S, Newberry SJ, Maher AR, et al. Probiotics for the prevention and treatment of antibiotic-associated diarrhea: a systematic review and meta-analysis. JAMA. 2012;307(18):1959–1969. doi:10.1001/jama.2012.3507

Weng H, Li JG, Mao Z, et al. Probiotics for Preventing Ventilator-Associated Pneumonia in Mechanically Ventilated Patients: A Meta-Analysis with Trial Sequential Analysis. Front Pharmacol. 2017;8:717. Published 2017 Oct 9. doi:10.3389/fphar.2017.00717

Manzanares W, Lemieux M, Langlois PL, Wischmeyer PE. Probiotic and synbiotic therapy in critical illness: a systematic review and meta-analysis [published correction appears in Crit Care. 2017 Feb 27;21(1):42]. Crit Care. 2016;19:262. Published 2016 Aug 19. doi:10.1186/s13054-016-1434-y

Goldenberg JZ, Yap C, Lytvyn L, et al. Probiotics for the prevention of Clostridium difficile-associated diarrhea in adults and children. Cochrane Database Syst Rev. 2017;12(12):CD006095. Published 2017 Dec 19. doi:10.1002/14651858.CD006095.pub4

Yelin I, Flett KB, Merakou C, et al. Genomic and epidemiological evidence of bacterial transmission from probiotic capsule to blood in ICU patients. Nat Med. 2019;25(11):1728–1732. doi:10.1038/s41591-019-0626-9

DeFilipp Z, Bloom PP, Torres Soto M, et al. Drug-Resistant E. coli Bacteremia Transmitted by Fecal Microbiota Transplant. N Engl J Med. 2019;381(21):2043–2050. doi:10.1056/NEJMoa1910437

Gaines S, Alverdy JC. Fecal Micobiota Transplantation to Treat Sepsis of Unclear Etiology. Crit Care Med. 2017;45(6):1106–1107. doi:10.1097/CCM.0000000000002382

Alagna L, Haak BW, Gori A. Fecal microbiota transplantation in the ICU: perspectives on future implementations. Intensive Care Med. 2019;45(7):998–1001. doi:10.1007/s00134-019-05645-7

Dai M, Liu Y, Chen W, et al. Rescue fecal microbiota transplantation for antibiotic-associated diarrhea in critically ill patients. Crit Care. 2019;23(1):324. Published 2019 Oct 21. doi:10.1186/s13054-019-2604-5

Wurm P, Spindelboeck W, Krause R, et al. Antibiotic-Associated Apoptotic Enterocolitis in the Absence of a Defined Pathogen: The Role of Intestinal Microbiota Depletion. Crit Care Med. 2017;45(6):e600–e606. doi:10.1097/CCM.0000000000002310

DeFilipp Z, Bloom PP, Torres Soto M, et al. Drug-Resistant E. coli Bacteremia Transmitted by Fecal Microbiota Transplant. N Engl J Med. 2019;381(21):2043–2050. doi:10.1056/NEJMoa1910437


Although great care has been taken to ensure that the information in this post is accurate, eddyjoemd, LLC shall not be held responsible or in any way liable for the continued accuracy of the information, or for any errors, omissions or inaccuracies, or for any consequences arising therefrom.

Multiple Patients on a Ventilator: FAIL

Sometimes medicine behaves like the stock market; a whole bunch of enthusiasm followed by a realistic pullback. This has now occurred with the concept of using one ventilator for multiple patients. I agree that we need to use some ingenuity in this crisis, but this one never sat well with me, hence me not commenting on it at all until now. Too many nuances go into oxygenating and ventilating patients with ARDS. I understand trying this to hold down the fort in a severe crunch, and I tip my hat to those who created the articles and YouTube videos. I'm not trying to be a contrarian or a Debbie Downer.

This statement was put out by the Society of Critical Care Medicine (SCCM), American Association for Respiratory Care (AARC), American Society of Anesthesiologists (ASA), Anesthesia Patient Safety Foundation (ASPF), American Association of Critical-Care Nurses (AACN), and American College of Chest Physicians (CHEST).

Amongst things mentioned here, all patients would need to be paralyzed for this to maybe work. What happens after the 48 hours of paralytics runs it course and they can't play nice on the vent anymore? One always needs an exit strategy. This is something I always teach when taking care of patients in the ICU. I digress, the list provided shows some other safety reasons.

We need to continue thinking outside the box, though, to save all the lives we can. I have never seen our community come together so well. We have done a great job supporting each other. Many have said it already and I agree with them, many of us are going to come out of this psychologically altered. Many of us are, what some would call, jaded in things of life and death. It's part of our daily lives in Critical Care. But this is taking that to another extreme. I appreciate the support that I have received from the community as well. Hope to keep providing you all with great content.

-EJ



Link to ASA Position Statement

Link to SCCM Position Statement

Link to PDF


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Thursday, March 26, 2020

COVID-19 Extubation Protocol (in the works)

Many questions on how to extubate these patients. There's no right answer yet. I've read of a high reintubation rate for these patients and cardiac arrest after extubation we need to be prepared for that. This is a living, breathing document. I would like to make changes as you all point out things that I have missed. 

Prior to extubation:
Before getting to the point of extubation, I would favor a prolonged version of 0/5 or 5/5 on PSV due to high rate of reintubation, possibly even T-piece. Allow the lungs to de-recruit. My opinion. Make sure the patient can tolerate this. As mentioned earlier, I have heard of significant reintubation rates with crashing and burning of patients. One must also have to wait a while until the proper crew and gear is ready. 

The extubation itself:
The extubation procedure must be treated like an aerosol generating procedure (bronch, intubation, etc.). Full PPE for staff, N-95, PAPPR, full draping, etc. Should only require 2 people. The unanimous response of everyone I have asked directly have included undoing the restraint, deflating the cuff, and running out the room. This is hilarious but not realistic. We should not encourage the patient to cough. Good luck with that. 

Supplemental O2:
Clinical judgement comes into play here. We all have concerns about aerosolizing the virus and questions regarding which device hypothetically causes more or less of this. Hopefully the patient needs just room air. Then next comes the regular nasal cannula. I'll defer to your clinical judgement and patient scenario on what you choose to use after that. 

Unclear Questions:
How long to remain in airborne precautions?
At least 3 hours (this is based on the NEJM study I reference earlier). After that, I would put a surgical facemask on the patient, if available, for when the cough they don't get it all over the place. My vote would be to be in an N95 anytime around a COVID patient but that's unrealistic. 

Should we check a viral load prior to extubation?
In a perfect world I would love to know whether the patient is still infectious or not. Right now the testing that most institutions is lackluster at best with not enough testing available and too long a turnaround time. Treat everyone as if they're still infectious. 

Addendum: there are photos circling around about putting big plastic bags around patient's head to contain the cough and pre-fill it with heliox. I have zero experience with this. I would like to see how you all do your thang!



Medical Journal of Australia- PDF



IBCC: Josh Farkas



ANZICS Guidelines

-EJ

Although great care has been taken to ensure that the information in this post is accurate, eddyjoemd, LLC shall not be held responsible or in any way liable for the continued accuracy of the information, or for any errors, omissions or inaccuracies, or for any consequences arising therefrom.

Tuesday, March 24, 2020

Plasma to treat COVID-19?

The FDA is opening up clinical trials to see if convalescent plasma (you know, plasma from people who have defeated COVID-19) helps treat individuals with severe COVID-19 infections. I basically took screenshots of the info so we can get some clinical trials going. But first, we need some donors. Lots of limitations to enrolling people simply bc it was so hard to diagnose people in the first place but that’s a story for another day. If you discharge someone from your shop after recovering from COVID, potentially talk to them about donating plasma. Hopefully the data proves it’ll save some more lives.


Link to FDA Document




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Anosmia and dysgeusia

I took a day off from the whole COVID situation yesterday (which I recommend you do if you can) and sat on the sidelines. I didn't see anything monumental to post about and the rest of the social media community posted great work. I didn't have anything important to add. I'm trying to figure out ways to take care of all of us in this order.

That being said, last night when I was scrolling around twitter before going to bed, I ran into many articles regarding the anosmia/hyposmia (loss/decreased of sense of smell) and dysgeusia (loss of sense of taste) in patients with COVID-19. Let's dig into this some more. By no means am I an ENT nor the most knowledgable person in the cranial nerves. This is a relatively new rabbit hole I'm digging into. Join me in this journey.

The reason why I am going into this is because it could be particularly helpful in the healthcare worker population because we are typically quite healthy and may be asymptomatic carriers. This could be the only symptom and may be worth considering self-isolation or testing (or wearing two bandanas instead of one). We can't get ourselves nor our teammates sick. Unfortunately, with how testing is going right now, people presenting with this do not meet criteria for testing or self-isolation.

The links to everything I am mentioning here are on my website: eddyjoemd.com. The AAO (American Academy of Otolaryngology) mentioned in a statement on 3/22 that we are receiving a good amount of anecdotal evidence "from sites around the world that anosmia and dysgeusia are significant symptoms associated with the COVID-19 pandemic." Is this something that's new? Well, no. ENT-UK states that "post-viral anosmia is one of the leading causes of loss of sense of smell in adults, accounting for up to 40% cases of anosmia."

This is particularly a big deal because a basketball player says he has it. Maybe the WHO and CDC will list it as part of the symptoms now.

Anosmia incidence:
South Korea- 30% of patients testing positive have had anosmia as their major presenting symptom in otherwise mild cases. (ENT-UK)
Germany- up to two-thirds “described a loss of smell and taste lasting several days”

While digging into this, since there is nothing in the peer-reviewed journals about the matter, I found it comical how many different news mediums published the same exact article just slightly re-written. You know, similar to what I have done here. Stay safe everyone!

-EJ

ENT-UK Document

American Academy of Otolaryngology— Head and Neck Surgery

Livescience.com

German Data

Rudy Gobert has anosmia


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Saturday, March 21, 2020

Why do we give Corticosteroids during Septic Shock?

Whether you're a med student, intern, resident, or nurse, you've wondered why in the world we give patients who are in septic shock stress dose steroids. This article breaks down in a not-so-easy to understand fashion of the nitty details that are too complex for my post-night shift brain to digest.

The powers that be in Critical Care, SCCM and ESICM, got together for this review with some big guns in the field to write this review discussing Critical Illness-related corticosteroid insufficiency.

Link to Abstract

Link to FULL FREE PDF

Annane D, Pastores SM, Arlt W, Balk RA, Beishuizen A, Briegel J, Carcillo J, Christ-Crain M, Cooper MS, Marik PE, et al.: Critical illness-related corticosteroid insufficiency (CIRCI): a narrative review from a Multispecialty Task Force of the Society of Critical Care Medicine (SCCM) and the European Society of Intensive Care Medicine (ESICM). Intensive Care Med 43(12):1781–1792, 2017.

Although great care has been taken to ensure that the information in this post is accurate, eddyjoemd, LLC shall not be held responsible or in any way liable for the continued accuracy of the information, or for any errors, omissions or inaccuracies, or for any consequences arising therefrom.

Friday, March 20, 2020

Hydroxychloroquine and Azithromycin as a treatment of COVID-19: Updated on 3/29/20

First of all, credit to the authors. Huge hat tip to them.

Gautret et al. (2020) Hydroxychloroquine and azithromycin as a treatment of COVID‐19: results of an open‐label non‐randomized clinical trial. International Journal of Antimicrobial Agents – In Press 17 March 2020 – DOI : 10.1016/j.ijantimicag.2020.105949


First of all, there are a substantial amount of limitations to the study but in my opinion, not medical advice, it provides a glimmer of hope. 

Let's begin
Where was it performed: French study (thank youuuuuu!)
Population: NOT ICU Patients! But we've learned that non-ICU patients become ICU patients extremely quick! 
n=36 (20 hydroxychloroquine, 16 control)
How did the determine the Viral load? Nasopharyngeal swabs daily
Questions I have: 6 patients (originally n=42) lost to follow up. Patients who were transferred to the ICU were considered to be "lost to follow-up" (n=3). I can't tell if the one patient who died was transferred to the ICU. Hopefully the edits will sort this out. Why didn't they just follow those patients who ended up in the ICU?
Age groups were not matched but this would favor the control group as the experimental group was older. More were male in the experimental group which we assume that males get this worse than females. More asymptomatic patients in the control group, also bodes worse for the experimental arm.

3 classifications: asymptomatic, upper respiratory, lower respiratory

Regimen:
Hydroxychloroquine 600mg daily (200mg TID x 10 days)
+/- azithromycin depending on clinical presentation (500mg on day 1, 250mg x 4 days) 

Results
At day 6, 70% of hydroxychloroquine group were virologically cured vs. 12.5% in control group (p=0.001) NNT = 1.7!! 

100% of hydroxychloroquine + azithromycin were virologically cured vs 57.1% in the hydroxychloroquine only group vs. 12.5% in the control group (p0.001)

Drug effect was higher in URI and LRI than asymptomatic patients (p=0.05)

Starts working in 3-6 days per this data. 

Careful with the QT prolongation on the EKG! Replete the Mg as needed for this. Monitor liver function. My pharmacy friends can contribute some more adverse effect stuff like retinopathy, etc.  

I cannot make any recommendations as I do not give medical advice but I know what I would do with this data to save a life. 

-EJ




An Update on 3/29/2020

We have an update now from the same researchers in France. It's a free PDF and I recommend you read it yourself. Don't trust me.

Interesting that the authors mention potentially using ARBs, metformin, and statins as many have directly messaged me asking what I thought on these particular families of treatments. This study has me scratching my head. Their first study seemed like they rushed it out the door to start some more broad research. This study seems like they're deliberately hiding things from us or trying to remain obscure.

Methods:
This is an observational study, meaning they didn't have any controls.
80% of patients appear to have gotten a CT of the chest and (almost) every patient had a daily nasopharyngeal swab.

They all got an EKG before treatment and two days after treatment began. They had criteria to not start therapy based on some findings listed in the article.

Treatment regimen:Hydroxychloroquine 200mg three time a day for 10 days
Azithromycin 500mg on day 1, then 250 daily for 4 days


End points (these are not your typical endpoints):

Clinical Outcome (oxygen therapy or ICU transfer)
Contagiousness by PCR and culture
Length of stay in the ID ward

Things to know:n=80

4 patients were asymptomatic carriers (then why were they in the COVID unit?)

92% of the patients were less ill based on their made up NEWS score

52.8% had lower respiratory infections/pneumonia.

Results:
We don't have any controls to know if this is the normal course of the infection or if the hydroxychloroquine actually worked or not. I forgive them for not having controls in the prior study but this is now too much.

93.8% were discharged from a low NEWS score. Don't forget that 92% had a low news score to begin with!

3 patients still ended up in the ICU.

The nasopharyngeal viral load fell. Sure. Cool. Thanks. But does this normally fall at this rate without treatment? We need controls. Is the decrease in contagiousness the normal evolution or the drugs working? We don't know. No controls.

I'm tired of reviewing this study. You all get my point. I am in favor of trying it, but I feel like there's some academic dishonesty happening here.

I really want this to work. I really really do. We need some good news but we also need to solidify our management with better data.


Link to full FREE PDF

Although great care has been taken to ensure that the information in this post is accurate, eddyjoemd, LLC shall not be held responsible or in any way liable for the continued accuracy of the information, or for any errors, omissions or inaccuracies, or for any consequences arising therefrom.

SCCM/ESICM Guidelines on COVID-19

The Society of Critical Care Medicine and the European Society of Intensive Care Medicine came together for these guidelines regarding COVID-19. Thank goodness they didn’t include 30cc/kg bolus for an elevated lactate 🤣. I figure this will be revised as more data comes out in the upcoming weeks, especially regarding the therapies as Kaletra was recently mostly disproven to have a benefit. 

Many of the recommendations included are not new to us who are on the cutting edge of Critical Care medicine but it’s always good to share concepts such as conservative fluid management , using balanced crystalloids over 0.9% saline, not using dopamine. They have relaxed their MAP goals. I wonder if that has to do with the new trials on MAP goals in the elderly since this predominantly affects the elderly. Hmmmm need to look into that some more. They also stress the importance of proning patients. If your shop doesn’t prone, I have posts and guidelines for this on this page and my website. 

I’ll try hard to answer your questions but there’s a lot going on and I’m quite busy with a number of other tasks I’m helping out with. Best of luck to you all!

- EJ

Link to FULL FREE PDF

Link to SCCM Page



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Wednesday, March 18, 2020

Kaletra (lopinavir–ritonavir) did not work in COVID-19 :(

Trials are starting to come in. I'm not going to belabor the fact but it appears that Kaletra, also known as lopinavir–ritonavir (400 mg and 100 mg, respectively) does not work for patients with COVID-19. I'm not going to dissect the article for you all as this is more intended to be a news bulletin of sorts. It is important to note that they used the sickest of the sick patients in the study. This does not mean that data in the future will say that it cannot help in those less ill but I really don’t see anyone trying at this point.

No difference in clinical improvement, mortality, nor decrease in viral load. Please read the article for yourself if you're using this at your institution. I do not provide medical advice. A 🎩 tip to the authors.

I have seen it in the protocols for several institutions that have been sent to me. I will never EVER disclose any information that you all send me via email without discussing it with you all first.

Tomorrow is my 38th birthday so I'll be celebrating it with a ton of social distancing and maybe a trip to a more secluded beach.

Thank you for your support. The page is growing fast but I wish it was slower and I didn’t have so much to post about regarding a deadly virus that is changing our lives so rapidly. ☹️


-EJ

Link to Abstract


Link to FULL FREE PDF

Cao B, Wang Y, Wen D, et al. A trial of lopinavir–ritonavir in adults hospitalized with severe Covid-19. N Engl J Med. DOI: 10.1056/NEJMoa2001282.



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COVID-19: Airborne or Droplet Precautions

This is a widely contested topic that I feel we still do not know the full answer on, but I am feeling better about.

As of right now, though, it seems hospital administrators have a leg to stand on when they recommend face masks for the majority of cases and N95's/respirators for NIV, intubations, bronchs, nebs, etc. I don't know if this is an official recommendation by any agency, but patients who have COVID-19 or are being ruled out for this should wear a mask in the hospital and outside the hospital. 

The flip flopping of policies occurs as we learn more data. It seems shady to me that they flipped their policies as shortages occurred, but it seems as if it's defensible at this time.

WHO: The February 27, 2020 guidance paper states:

"Healthcare workers involved in the direct care of patients should use the following PPE: gowns, gloves, medical mask and eye protection (goggles or face shield)."

"Specifically, for aerosol-generating procedures (e.g., tracheal intubation, non-invasive ventilation, tracheostomy, cardiopulmonary resuscitation, manual ventilation before intubation, bronchoscopy) healthcare workers should use respirators, eye protection, gloves and gowns; aprons should also be used if gowns are not fluid resistant."

CDC: updated recommendations on March 10, 2020:

"Based on local and regional situational analysis of PPE supplies, facemasks are an acceptable alternative when the supply chain of respirators cannot meet the demand.
During this time, available respirators should be prioritized for procedures that are likely to generate respiratory aerosols, which would pose the highest exposure risk to HCP."

Essentially, they are acknowledging that we are being put at risk due to the lack of masks.

The most recent stir and adding to the controversy was a recent publication NEJM published on 3/17/20 which states:

"SARS-CoV-2 remained viable in aerosols throughout the duration of our experiment (3 hours)"

"The half-lives of SARS-CoV-2 and SARS-CoV-1 were similar in aerosols, with median estimates of approximately 1.1 to 1.2 hours"

"Our results indicate that aerosol and fomite transmission of SARS-CoV-2 is plausible, since the virus can remain viable and infectious in aerosols for hours and on surfaces up to days (depending on the inoculum shed)"

The key point is that the authors went out of their way to both nebulize the virus AND fed it into a Goldberg drum to further disperse it (I don't know what that is and google wasn't too helpful).

It is admittedly outside my scope of knowledge how to interpret the titers in the air, but it seems as if it's there and transmissible to us, the boots on the ground. I cannot make a concrete declaration based on my level of knowledge. I'd welcome your interpretation. I am curious to see how the ever-intelligent people in the CDC and WHO react to this data and possibly adapt their recommendations. 

We should also reach out to the local news agencies to assist us in asking the N95 hoarders to donate their extras to the local hospitals. We need to protect each other. 

-EJ

Link to the WHO Interim Guidance Paper

Link to the CDC Information

Link to the NEJM Abstract


Link to the NEJM PDF



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Tuesday, March 17, 2020

How to take off your PPE after caring for COVID-19 patients

The first time I walked into a the room of a patient with suspected COVID-19 I was very methodical with every step. I had done my required reading. I had an N95, a face shield over that, a hair net, the stupid yellow contact gown, double gloves. At the same time I felt naked. I had seen the people on TV and in other countries in basically hazmat suits. The uncertainty was driving me bonkers but I needed to take care of the patient ASAP. The nurse and I got everything together and we went in. We took care of the patient. When it was time to come out, the same methodical steps took place. But somewhat in reverse. It’s hot in there with all that gear when you have to put on the sterile gown for procedures and the sterile gloves on top of my double gloves. Since the I have walked into a number of rooms and am getting the feeling that this is going to be the new normal for the next few months. I felt it was important to do a second post today to share the CDC guidelines on how to put on and take off the personal protective equipment. I have attached the images from this as well. Feel free to share with your friends.

I was inspired to create this post after seeing @doctorwarsgame’s similar post. I must give him credit. I also sent meme, as I am not someone who creates them on this medium, to @bedsideroundz for his approval. He actually was the one who suggested that I use it to teach people the correct way to do it.

Thank you all for your support.

CDC Guidelines for Healthcare Personnel PDF



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Monday, March 16, 2020

Airway pressure release ventilation

We are already seeing severe ARDS from these patients infected with COVID-19. There's discussion out there regarding VV-ECMO, proning, and numerous other strategies to help oxygenate and ventilate our patients. There are numerous different modes on the ventilator to help us achieve these goals but I have found none to be more polarizing than airway pressure release ventilation which is also called APRV. On the Servo vents this is called BiVent (just adding to the confusion of terminology).

Since we are in the process of contemplating providing our patients with anti-retrovirals and anti-malarial drugs, I feel that some of us should reach out of our comfort zone and familiarize ourselves with APRV. If I'm being completely honest, I haven't needed this mode of ventilation much since fellowship. I haven't had many patients in whom I have had such a hard time oxygenating them where I have to reach for this mode. I tend to paralyze patients which is definitely NOT recommended in patients with APRV therefore ameliorating the benefit. I am aware of the PETAL study (Early Neuromuscular Blockage in the ARDS, NEJM 5/2019) which did not show a benefit to paralytics, by the way. My experience is therefore limited, thankfully for my patients who haven't needed me to venture down this road.

The data for APRV is not the most robust, but this recently published review this month contains some great tables and recommendations including the indications and contraindications for APRV, how to set up the vent to initiate APRV, how to troubleshoot the vent depending on the different physiological derangements (I find hypercapnia to be the most common of these personally), and lastly how to wean the vent. I feel the authors did a great job and definitely a good resource to have in your article collection. Stay safe everyone!

A hat tip to the authors.

-EJ

Link to Abstract

Link to FULL FREE ARTICLE







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