The Research of Predicting Septic Shock

How computational medicine is changing critical care in 5 questions

Participating in Research

As a new school year approaches, many medical students are opting to take a gap year dedicated to research. This trend is unique for students not in MD/PhD programs in the USA who have a deep interest in understanding and participating in research. A popular emerging field for the future of health care and medicine, known as computational medicine, is become an integral part of patient care. Regardless of location, students, as well as interns and health care professionals around the globe who are interested in emergency and critical care medicine, should consider this unique area of study as a part of their research gap year.

In this blog entry for the International Emergency Medicine Education Project (iEM), I discuss the role of computational medicine in detecting sepsis, one of the most important diagnoses to detect early, with Professor Rai Winslow, Director of the Institute for Computational Medicine at The Johns Hopkins University. As outlined on the Institute’s website, computational medicine “aims to improve health care by developing computational models of disease, personalizing these models using data from patients, and applying these models to improve the diagnosis and treatment of disease.” Patient models are being used to predict and discover novel sensitive and specific risk biomarkers, predict disease progression, design optimal treatments, and discover novel drug targets. Applications include cardiovascular and neurological diseases, cancer, and critical care and emergency medicine (1).

Rai L Winslow, Director Institute for Computational Medicine, The Raj & Neera Singh Professor of Biomedical Engineering, The Johns Hopkins University

How is computational medicine changing critical care?

5 Questions

5 Answers

Why Sepsis

What was the starting point for your work on sepsis and septic shock in adults?

A starting point for my work on sepsis and septic shock was reading a paper that demonstrated how every hour of delayed treatment in patients with septic shock could lead to an eight percent increase in mortality, per hour. That statement really stood out because what it told me was the natural time course of evolution of the disease, and whatever was happening in septic shock, was happening very quickly. Because of this rapid disease progression, this suggested that accurate prediction of those patients with sepsis who would progress to septic shock must be based on data collected from the patient on a time scale of minutes rather than hours. The challenge was that this high-rate data is not routinely collected in hospitals.

Data and algorithms

What live data are the algorithms capturing from patients for studying and understanding sepsis and septic shock?

Today’s electronic health record (EHR) is typically used to store data such as vitals and lab results and clinical observations made at irregular intervals and at low rates. Given the rapid evolution of septic shock, we hypothesized that advanced prediction and early detection of septic shock must be based on data collected at the minute rather than hour time scales. This was the driving interest in developing a novel software platform called PhysioCloud. PhysioCloud captures physiological vital signs data at minute intervals from patient monitors. These data are then stored in a specialized database that is designed to capture large numbers of real-time data streams at high-rate. Data collection also includes waveforms, such as ECG, respiratory rates, and SpO2, sampled at 125 times per second. Nowhere else in the USA that I am aware of, is capturing these physiological data from patients, making them a part of the patient electronic health record. Our algorithm uses these high rate data, as well as low-rate data from the patient EHR, to predict those patients with sepsis who will develop septic shock.

The importance of the transition state to septic shock

Computational medicine and algorithms can be uncomfortable terms for medical students, interns and researchers who do not have experience with it. Simply put, how do research and studies such as this help doctors in emergency medicine and critical care units, in managing their patients?

Everyday critical care and emergency medicine physicians ask two questions of every patient they see: what is the state of my patient?; how will their state change over time? The latter is a prediction problem of the sort that data scientists often confront. In the context of sepsis, the physician would like to know if their patient will at some future time develop septic shock, or will their condition improve. If an algorithm can reliably predict those patients with sepsis who will develop septic shock at some future time point, then physicians will have a window of time in which they can intervene to prevent this transition from happening. Our goal was to develop such an algorithm. To do this, we utilized the obvious fact that if a patient has sepsis and their condition is getting worse and possibly evolving towards septic shock, it means their physiology must be changing over time as they get sicker. We, therefore, decided to develop a “risk score,” a number ranging between 0 and 1 that is the probability that a patient will develop septic shock. This risk score was computed in an optimal way from the minute by minute physiological vital signs data complemented by clinical data from the EHR. If this risk score exceeds a threshold value, then we decide that this patient with sepsis will develop septic shock at some future time point. This approach works very reliably, achieving high sensitivity and specificity. It’s the worlds simplest machine learning method. Predicting the transition from sepsis to septic shock can enable physicians the ability to follow their patients and see how various states are evolving over time, so that they can intervene to deliver earlier care. Right now, this approach is being applied in retrospective studies using patient data. In the future, we plan to compute this risk score in real-time, generating alerts for caregivers when the risk score exceeds threshold signaling that patients are likely to go into septic shock.

Pre-Shock

In a recent publication in Scientific Report (2), the new concept of a pre-shock state was outlined. How was this possible to do?

Our work hypothesized that it was possible to identify the presence of a physiological signature in sepsis patients before the clinical onset of septic shock was diagnosed. We were able to identify a signature to calculate a risk score for the pre-shock state. The changes in variables such as lactate and heart rate are so small; they are still statistically significant, but so small. When discussed with physicians, some say that they would not have noticed it. These variables are changing together in a small way, but the algorithm is able to catch the changes together and compute it into a risk score and make useful predictions. Some of our very new work not published yet shows that post-threshold, changes in patient risk score happen very quickly (30-60 minutes) and are very large. We have shown that the larger the post-threshold risk score, the more reliable is our prediction that the patient will go into shock. Positive predictive value can be as high as 80-90%.

Fluids and Vasopressors

Evidence-based studies and protocols such as the SOFA score (3), Surviving Sepsis Campaigns (4) are listed on the American College of Emergency Physician (ACEP) website (5) as well as the SALT-ED (6) and SMART (7) trials. These are referred to by emergency physicians in the emergency department, and EM residents are trained with these resources. How do these studies tie into computational medicine, machine learning and predictive analysis for developing septic shock?

Our algorithm looked at tens of thousands of patients, and computationally phenotyped them through every minute of data using the international consensus definition of septic shock, and based on early warning times, found clinical ground truth. We also discovered that the Sepsis 2 definition had a property that was temporarily unstable. This is to say that the state of a patient with sepsis as defined by Sepsis 2, was changing all the time, and it was not possible to predict ground truth. With found the Sepsis 3 definitions to be temporarily stable with few state transitions. The major factor was that the criteria in Sepsis 2 had included a diagnosis of SIRS before sepsis was considered as a diagnosis, and it was removed from 3. We believe that SIRS was causing frequent state changes, as an ambiguous diagnosis.

We are able to predict those patients with sepsis who will transition to shock many hours before they go into shock. We are also able to identify distinct temporal patterns of the risk score corresponding to patient populations with high (up to 60%) versus low (10-20%) mortality. For each of these groups, we looked at comorbidities, diagnoses such as kidney failure and cancer, but we do not know what the relationship is or what is different about these patient groups and the fact that they are in the 60% mortality pool. We know their physiology is saying they are in the mortality pool, but not why. What this means is how these patients are being treated could be the issue (physicians with different levels of training, and other factors involved in treatment decisions). In our work, patients were classified into high and low risk. We found that patients in the low risk received vasopressors and adequate fluid resuscitation and for patients in the high-risk pool, fewer had received vasopressors or fluids. The question is, why are these patients not getting these things. Our algorithm to predict the transition to septic shock can positively influence treatment decisions made by many physicians, to confirm the value of treatment and prevent the development of septic shock. We’ve also identified and know the time to look for proteomic and genomic biomarkers for the early predictive shock signature that could correlate with this high risk/these measures are not routinely done clinically, and this line of work could be very helpful in understanding the fundamental biology of the very rapid change in patient state when they cross the risk score threshold.

Thank you to Professor Winslow for taking the time to discuss the research involved in computational medicine and investigating the transition from sepsis to septic shock. In closing, regardless of medical specialty interests, medical students around the globe interested in taking a gap year to gain research skills will find the experience invaluable and will be introduced to new ways of thinking, writing, and understanding the scientific influences on patient management and health care. Research such as this in the USA can also be implemented at international hospitals and remote clinics, to further aid patient care and management. There are many areas of interest in which research is taking place in critical care units and emergency departments, and discovering the technology involved such as machine learning and computational medicine, is a step towards understanding the potential advances in the future of medicine and patient care.

Please feel free to share your own particular research area(s) of interest and pose any questions you may have in the comments section below.

References and Further Reading

  1. The Institute for Computational Medicine (ICM) –  https://icm.jhu.edu/
  2. Liu R, Greenstein JL, Granite SJ, Fackler JC, Bembea MM, Sarma SV, Winslow RL. Data-driven discovery of a novel sepsis pre-shock state predicts impending septic shock in the ICU. Scientific reports. 2019 Apr 16;9(1):6145. – https://www.nature.com/articles/s41598-019-42637-5.pdf
  3. Faust J. No SIRS; quick SOFA instead. Annals of Emergency Medicine. 2016 May 1;67(5). – https://www.annemergmed.com/article/S0196-0644(16)00216-X/pdf
  4. Surviving Sepsis Campaign (SSC) – http://www.survivingsepsis.org/Pages/default.aspx
  5. ACEP Statement on SSC Hour-1 Bundle – https://www.acep.org/by-medical-focus/sepsis/
  6. Self WH, Semler MW, Wanderer JP, Wang L, Byrne DW, Collins SP, Slovis CM, Lindsell CJ, Ehrenfeld JM, Siew ED, Shaw AD. Balanced crystalloids versus saline in noncritically ill adults. New England Journal of Medicine. 2018 Mar 1;378(9):819-28. – https://www.nejm.org/doi/full/10.1056/NEJMoa1711586
  7. Semler MW, Self WH, Wanderer JP, Ehrenfeld JM, Wang L, Byrne DW, Stollings JL, Kumar AB, Hughes CG, Hernandez A, Guillamondegui OD. Balanced crystalloids versus saline in critically ill adults. New England Journal of Medicine. 2018 Mar 1;378(9):829-39. –  https://www.nejm.org/doi/full/10.1056/NEJMoa1711584
Cite this article as: Bryn Dhir, "The Research of Predicting Septic Shock," in International Emergency Medicine Education Project, August 12, 2019, https://iem-student.org/2019/08/12/the-research-of-predicting-septic-shock-how-computational-medicine-is-changing-critical-care-in-5-questions/, date accessed: September 15, 2019

Interview – Vicky Noble – US training in medical schools

We interviewed with world renowned emergency and critical care US expert “Vicky Noble” about US training in medical schools.

Read US Chapters and Posts

Interview: Jesus Daniel Lopez Tapia

We interviewed with Dr. Jesus Daniel Lopez Tapia. He is the Dean of University Monterrey, College of Medicine and immediate past president of Mexican Society of Emergency Medicine. 

Highlights from the interview

How many medical school in Mexico?

180

What percentage medical schools have EM course for medical students?

80%

How many EM residency spot every year?

400

How many EM residency program in Mexico?

75

What do graduates do after the graduation?

80% starts working in the EDs. 20% starts residency.

Video Interview – Rob Rogers – Part 3

Great messages for medical students, interns and new EM residents!

Watch the part 3 here!

You can listen full interview here!

Expert Opinion: Luis Vargas – ED Overcrowding

EMERGENCY DEPARTMENT OVERCROWDING

Dear students, emergency departments are suffering overcrowding since long time. There are various causes of this situation as well as solutions. It is better to know about ED overcrowding before your first shift. Dr. Luis Vargas from Colombia summarizes his lecture presented in 30th Emergency Medicine Congress of Mexican Society in Cancun.

ED Overcrowding - English

Manejo y consecuencias del sobrecupo en urgencias

Cite this article as: iEM Education Project Team, "Expert Opinion: Luis Vargas – ED Overcrowding," in International Emergency Medicine Education Project, March 29, 2019, https://iem-student.org/2019/03/29/expert-opinion-luis-vargas-ed-overcrowding/, date accessed: September 15, 2019

Video Interview – Rob Rogers – Part 2

Great messages for medical students, interns and new EM residents!

Are you ready to meet the genuine people behind the professional?

iEM team proudly presents the ICON360 project. In this pleasantly educational series, world-renowned experts will share their habits, give advice on life, wellness and the profession.

Our guest is Dr. Rob Rogers.

Trained in Emergency Medicine and Internal Medicine, Rob Rogers currently practices Emergency Medicine at the University of Kentucky’s Chandler Hospital in the Department of Emergency Medicine. An innovative medical educator on the cutting edge of creativity, he shares his knowledge on the monthly medical education Medutopia Podcast. Rob co-founded The Teaching Institute and in 2014 created The Teaching Course at The University of Maryland. As a passionate medical education enthusiast, podcast evangelist, learning choreographer, and entrepreneur, Rob works tirelessly to change the world of medical education by reinventing it.

The full interview is 24 minutes long and includes many advice on life, wellness, and our profession. We will be sharing short videos from this interview. However, the full interview will be published as an audio file in our Soundcloud account. 

This interview was recorded during the EACEM2018 in Turkey. We thank EMAT.

Arif Alper Cevik

Elif Dilek Cakal

Murat Cetin

Cite this article as: iEM Education Project Team, "Video Interview – Rob Rogers – Part 2," in International Emergency Medicine Education Project, March 25, 2019, https://iem-student.org/2019/03/25/video-interview-rob-rogers-part-2/, date accessed: September 15, 2019

Against Medical Advice and Elopement

In certain circumstances, patients may request to leave prior to completion of their medical evaluation and treatment. In this situation, it is essential for the last health care professional caring for the patient to document clearly why the patient left and attested that the patient had the mental capacity to make such a decision at that time (Henry, 2013). While some electronic documentation systems have templates in place to assist with this documentation, Table 2 provides basic information for against medical advice (AMA) discharge documentation that can be used to create a uniform template (Henry, 2013; Siff, 2011; Levy, 2012; Devitt, 2000).

What to do?

Interventions in the ED Discharge Process

DomainIntervention
ContentStandardize approach
DeliveryVerbal instructions (language and culture appropriate)
Written instructions (literary levels)
Basic Instructions (including return precautions)
Media, visual cues or adjuncts
ComprehensionConfirm comprehension (teach-back method)
ImplementationResource connections (Rx, appointment, durable medical supplies, follow-up)
Medication review

An attempt should be made to provide the patient with appropriate discharge instructions, even if a complete diagnosis may not yet be determined. Include advice for the patient to follow up with his physician, strict return precautions, and concerning symptoms that should prompt the patient to seek further care. It should also be made clear that leaving against medical advice does not prevent the patient from returning to the emergency department for further evaluation if his symptoms worsen, or if he changes his mind. Despite a common notion to the contrary, simply leaving against medical advice does not automatically imply that physicians are immune to potential medical liability (Levy, 2012; Devitt, 2000). If a patient lacks decision-making capacity to be able to adequately understand the rationale and consequences of leaving AMA and his condition places him at risk for imminent harm, involuntary hospitalization is warranted. In unclear circumstances and if available, psychiatry can assist in determining capacity, especially in the case of patients with mental health conditions.

Elopement is a similar process where patients disappear during the care process. While it is difficult to provide discharge paperwork for these patients, documenting the actions taken to find the patient is essential (e.g., searching the ED, having security check the surrounding areas). In addition, attempt to reach the patient by phone to discuss his elopement and any additional care issues or concerns. Documentation of these attempts or any additional conversation is very important (Henry, 2013; Siff, 2011).

To Know More About It?

References

  • Brooten J, Nicks B. Discharge Communications. In: Cevik AA, Quek LS, Noureldin A, Cakal ED (eds) iEmergency Medicine for Medical Students and Interns – 2018. Retrieved February 27, 2019, from https://iem-student.org/discharge-communications/
  • Henry GL, Gupta G. (2013). Medical-Legal Issues in Emergency Medicine. In Adams (Ed.), Emergency Medicine Clinical Essentials, 2nd Ed; 1759-65. Philadelphia, PA: Elsevier.
  • Siff JE. (2011). Legal Issues in Emergency Medicine. In Tintinalli’s (Ed.), Emergency Medicine, 7th Ed; 2021-31. McGraw-Hill.
  • Levy F, Mareiniss DP, Lacovelli C. The Importance of a Proper Against-Medical-Advice (AMA) Discharge. How Signing Out AMA May Create Significant Liability Protection for Providers. J Emerg Med. 2012;43(3):516-520.
  • Devitt PJ, Devitt AC, Dewan M. An examination of whether discharging patients against medical advice protects physicians from malpractice charges. Psychiatr Serv. 2000;51:899-902.

What every Med Student/Intern should know about EM

james-holliman

Rob Rogers

Joe Lex

C. James Holliman

Learn the secrets of Emergency Medicine from the fabulous four chapters prepared by three worldwide experts. Listen or read, but know these stuff as early as possible in your medicine/emergency medicine career.

Choosing the Emergency Medicine As A Career

by C. James Holliman The specialty of Emergency Medicine (EM) is a great career choice for medical students and interns.  In August 2013, I celebrated

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Thinking Like an Emergency Physician

by Joe Lex Emergency Medicine is the most interesting 15 minutes of every other specialty. – Dan Sandberg, BEEM Conference, 2014 Why are we different?

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The Importance of The Emergency Medicine Clerkship

by Linda Katirji, Farhad Aziz, Rob Rogers Introduction The Emergency Medicine (EM) clerkship typically takes place during the fourth year of medical school. However, some

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Emergency Medicine: A Unique Specialty

by Will Sanderson, Danny Cuevas, Rob Rogers Imagine walking into the hospital to start your day – ambulances are blaring, the waiting room is clamoring, babies

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Being A Woman In Emergency Medicine

being a women in EM

Gül Pamukçu Günaydın

Turkey

Watching the famous TV series “ER” in my 3rd year of medical school I decided to be an “ER doctor.” I started my Emergency Medicine residency in 2003. So this is my 15th year in Emergency Medicine. I have not regretted my choice yet, and I cannot imagine myself being anything else but an Emergency Physician.

Emergency medicine is indeed a fulfilling career choice for a variety of reasons: first of all, we are cool, we never panic over an emergency. Secondly, emergency medicine is never boring, every shift in the Emergency Department is filled with diverse cases waiting to be solved, like a puzzle. We treat patients in every age group with all kinds of chief complaints, and we hear all sorts of exciting stories. We are there for people who need us most, 24/7, on one of the worst days of their lives, regardless of their background and financial status. We bring patients who are near death back to life, and in every shift, we feel that we make a real difference.

Having said all this, I admit that the life of an Emergency Medicine physician is not a perfect fit for everyone. For example, although shift work is flexible by its nature and you have control over your schedule, shift work is not desirable to everyone. If you plan ahead shift work will allow you to take more vacations any time during the year but if something comes up last minute, there is a pretty good chance that you will miss it. Night shifts may easily disrupt your body cycle even if you follow the recommendations for sleep and it gets harder with age. Working weekends and holidays will mean missing some family gatherings or events at your children’s school and may make your social life difficult. On the bright side, you will always have free weekdays to run errands or catch up with friends on their lunch breaks. Although you do not bring work to your home, (when your shift is over you just pass your patients to another doctor, leave emergency department, and you are not on call) sometimes your shift is so physically exhausting and emotionally draining that you have little energy left for home.

If you are living in a culture where child raising, housework or care of the elderly is seen primarily as women’s duty, or you choose a partner that thinks so, you may have a harder time in life regardless of the specialty you choose as a woman. You may solve some of this issue by willing to accept all help you are offered from close ones and purchase help when necessary to share some of these duties. You may find fewer role models in Emergency Medicine compared to your male peers, but if you look carefully, you will recognize female or male leaders close to you, who understand the difficulties you face and offer you their mentorship.

When choosing any specialty, think about not just now but try to imagine what would make you happy in 10-20-30 years. Yes, being an Emergency Medicine specialist has its challenges and is harder in some aspects compared to other specialties, but I think most of the challenges are there regardless of being men or women. I also believe that with a little flexibility and creativity you can overcome the difficulties, so join us who find joy and feel content in the vibrant and exciting environment of emergency medicine.

Suggested Chapters

Choosing the Emergency Medicine As A Career

C. James Holliman

Emergency Medicine: A Unique Specialty

Will Sanderson, Danny Cuevas, Rob Rogers