Coda Change

Antibiotic Use for Sepsis in Critical Care: Steve McGloughlin

Steve McGloughlin presents his thoughts on antibiotics and their use in sepsis and critical care.

Steve discusses the ABC of sepsis… the trouble is after A for Antibiotics there is not a whole lot else! In sepsis and severe infection, the goal is to change the trajectory of the patient, away from death and to a more favourable outcome. The tools that are currently on offer in critical care are pretty simple.

There are things to support the patient such as fluid and ventilators. In addition, we consider goal directed therapy. In terms of definitive therapy, the list is quite small. Perhaps only antibiotics and source control can be turned to.

So much so that the number needed to treat is around four. They are also very commonly used. 70-80% of patients in the ICU will get antibiotics – far higher than nearly all other treatments. Steve has some basic advice for the use of antibiotics to enhance their effectiveness.

Go early as possible when prescribing and administering. In saying that, he cautions to move beyond simple antibiotic prescribing regimes. Whilst we need early antibiotics, we need the right antibiotics.

Why? Alexander Fleming warned against drug resistant bugs when developing penicillin. There has been reports of pandrug resistant organisms (bug against which no known drug is effective) in multiple countries and 214 000 neonatal sepsis deaths per year are attributed to resistant pathogens.

Steve concludes with a discussion on what more we need when considering sepsis. We need more than antibiotics. As it stands one definition covers all categories of sepsis.

The result is a homogenous treatment protocol. In reality, the source, the bug and the pathology all change the disease and all call for an individualised treatment regime. That is the future.

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Per Bredmose discusses the use of inhaled nitric oxide (iNO) in retrieval medicine and critical care. He explains why iNO is useful for retrieval and transport of the critical respiratory failure patient.

iNO is not a magic bullet, but rather a bridge that will help you get to where you need to go when treating a patient.

Furthermore, it can be useful in both pre-hospital and in hospital care.

It is an endothelial derived potent short acting vasodilator mainly found in the pulmonary system. It also exists in other areas of the body. When nitric oxide is delivered via the inhaled route it has local effects only, with no systemic effects.

Most people will be familiar with the use of iNO in persistent pulmonary hypertension of the newborn.

However, there are other uses which are more "off label". For instance, take the case of severe ARDS lungs in pre-hospital settings. These patients present challenges in retrieval for several reasons, including the retrieval ventilation systems being inferior when compared to hospital systems.

Of course, you could turn straight to ECMO. However, setting up ECMO takes time and is complex. It requires a large amount of equipment, skilled operators, and room. Nitric oxide can act as a bridge.

Nitric oxide is simple to use. It is an extra gas that goes into the ventilatory circuit. It is accessible, can be used in any vehicle, is easy to transport, and fast to grab and use. Much faster than a big ECMO set up or retrieval.

A lot of places have stopped using iNO and it has gained something of a bad reputation. The main reason for deleterious effects appears to be kidney injury. Per posits that this may be due to an increased length of time using the drug. Therefore, he advises caution.

Per concludes by explaining other conditions where iNO may be used as an adjunct to standard therapy. These situations include pulmonary hypertension, non-thrombotic pulmonary vasoconstriction, and pulmonary emboli.

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In Critical Care we deal with death on a regular basis and although it seems an 'on or off' issue where you are either dead or you are not, nothing is more true. Not only physicians but scientists, philosophers, writers and theologians have been debating about the subject for as long as we have become aware of the concept of death. To try to create order from chaos I divide the deceased in 5 categories: The soon to be dead, The reversibly dead, The irreversibly dead The walking dead (although this group I will leave to Hollywood to educate us about) and the most curious group The reversibly, irreversibly dead. They are the patients of whom we think they are irreversibly dead, we stop our resuscitation efforts, and then they have return of spontaneous circulation. This is known as the Lazarus phenomenon and although many case reports have been published about this phenomenon over the years, presumably it's only the tip of the iceberg. In providing Critical Care we sometimes need to make immediate decisions on who's dead and who's not. Yet decisions about whether further treatment of patients is futile or not can only be made when one is aware of the limits of extremes in physiology that are survivable. Although not every patient should be treated up to these physiological limits, knowing these extremes can help in making an informed decision of whether to continue treatment.

How do you diagnose death? In Critical Care we deal with death on a regular basis and although it seems black and white, that is often far from the truth.

Patricia Gerritsen discusses what it means to be dead and how that knowledge can aid you in stopping a resuscitation effort.

1. Soon to be dead
2. Reversibly dead
3. Irreversibly dead
4. Reversibly, irreversibly dead

Changes occur following death that can be proof of death. But not always. Pallor mortis, algor mortis, rigor mortis, livor mortis and decomposition can all indicate someone has died.

There are other clues that can indicate a person is either dead or will soon be dead – with minimal chance of any life saving intervention. The varying ways death presents itself poses a challenge for the clinician. This is especially true when deciding when to stop a resuscitation effort.

Consider the reversibly, irreversibly dead – also known as the Lazarus phenomenon. These patients achieve return of spontaneous circulation AFTER the resuscitation effort has been stopped. There are over 50 cases in the literature, with a wide and unpredictable array of clinical situations.

Therefore, the question becomes - what are the limits that can be survived? Patricia suggests that we must know the extreme limits in order to make an educated decision about resuscitation.

Patricia details some of the most extreme stories of survival in the literature. Submersion has been survived after 66 minutes in a child. An individual survived being in an ice stream after 40 minutes, with a recorded temperature of 13.7 degrees. A man with a potassium of 14 mmol/L made a good recovery.

There is a case of someone with a pH of 6.33 recovery fully and someone surviving a CO2 level of 375mmHg.

Patricia highlights these extreme examples to show what is possible whilst acknowledging the decision to stop resuscitation is a difficult and nuanced one.

When to Stop Resuscitation in Critical Care: Patricia Gerritsen

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Diagnostic medicine is not simple – Casey Parker discusses the finer points of the diagnostic process in critical care.

Diagnosis is not black and white. The world is not black and white. It is all shades of grey and about probability.

One tool that clinicians have to deal with probability is Bayes' theorem. Since it was first described in 1763 Bayes' theorem has been applied, rejected, and rediscovered in many fields. Its use in medical diagnostics is a relatively recent phenomenon.

This talk will review the history of Bayes in medicine. Since 1763 the medical world has made dramatic leaps forward. However, Bayes' theorem still has its place. It has been made more accessible with nomograms and more recently handy clinical decision-making tools in the form of smartphone apps.

Firstly, is the pre-test probability – how likely is a disease in any given population. Not all populations are the same. Therefore, depending on where you work, you need this into account when assessing patients. How do we arrive at pre-test probability? Casey details the three 'G's. Gut feeling, gestalt, or guess work.

Secondly, are likelihood ratios. These exist independently of the population and can be described as a marker of signal to noise. For example, when a radiographer tells you there is a PE on a CT, this is not strictly true. Rather there is a chance of a PE. Next Casey discusses choice of tests. He stresses - do the test with the highest diagnostic yield.

For instance, in a young female with abdominal pain you may consider a diagnosis of appendicitis or pelvic inflammatory disease. Blood tests and ultrasound will not help you in this case. A laparoscope is the diagnostic tool of choice in this case.

Finally, the post-test probability – where the rubber meets the road. Where probability is converted into action. Consider the threshold to treat.

1. How bad is the disease?

2. How good or bad is the treatment?

3. How bad/dangerous is the test?

Join Casey as he challenges you on diagnostics in critical care.

Diagnostics in Critical Care: Casey Parker

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Kate Prior conveys the lessons she has learnt working as a doctor as part of the Medical Emergency Response Team (MERT) in Afghanistan.

"Unexpected survivors" are those patients who, according to their injury severity score, should die of their injuries but they survive against the odds.

The years of conflict in Afghanistan saw increasing numbers of these grievously injured patients surviving to live a fulfilling life. How was this achieved?

In the case of a major trauma with catastrophic bleeding, stopping the bleeding needs to be prioritised above all else. Kate describes the methods she used.

Secondly, she discusses the importance of taking the hospital to the patient. Kate talks about the capability of the Chinook helicopters she worked in.

In her words 'helicopters become flying Emergency Departments'. This enables advanced assessment and interventions to be delivered on scene. This includes IO access, blood transfusion, RSI and high-quality analgesia.

Kate goes on to discuss the important of training and rehearsal. For her role, many months of training are essential, to prepare for the unpredictable nature of a warzone.

This extends to being extremely familiar with all protocols, equipment, and machines, so that it becomes second nature in all situations.

Finally, Kate touches on the human impact of the patients she treated. Although you cannot save everyone, there is a need to learn a lesson from every patient.

Learn from them and disseminate the knowledge. In this way, you can continue to get better. This is highlighted by the improved mortality rates in Afghanistan.

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Peer review is at the heart of science. Yet, as Richard Smith explains in this talk, there are many problems with peer reviewed research. As Richard argues, peer review is not an evidence-based process, but rather a faith-based process. Is it time for something different? Peer review has two main functions: 1) Quality assurance and 2) Improving what is published. However, with that in mind, there is no evidence of effectiveness of peer review, and lots of evidence of its ineffectiveness. This is along with peer review being slow, expensive, wasteful, inefficient, prone to bias and being largely irrelevant! Richard discusses a few of the main issues as he sees it. For example, studies in large journals are more likely to be wrong when compared to smaller journals. Some argue that the vast majority of research is a waste of time. Similarly, replication is also a major problem, as Richard explains. A huge number of studies cannot be replicated, raising questions about the initial research. What is published in journals should not be taken to be truth but rather "provisional truth". Richard tells the tale of planting errors in articles and seeing if they are picked up by peer-review. Far more often than not, they are not! On top of this, there is fraud and theft that occurs in the peer review process. Bias exists both positively and negatively. To top it off, much of the time the process does not pick up the errors (or fraud) in papers. A lot of problems and few answers. And it is not necessarily a case of it being the least "bad system" for this process anymore. There has been attempts to improve peer review. Blinding of reviewers to authors has been shown to be ineffective. An open system did not make much difference to the quality of opinion. Checklists and training have likewise been trialled and moved past due to ineffectiveness. Finally, the process has been made as open as possible, and in real time where possible. Richard argues that we may no longer need peer review. In the age of the internet, why would a peer review process be needed when an enormous number of people can access and critique the evidence simultaneously. Journals may be yesterday's way of publishing data.

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The exposure of fabricated numbers in published papers by eagle-eyed readers has been due to sporadic serendipity. I am going to describe a semi-automated method that you can take away with you to do some sleuthing. I am going to describe what I found when I analysed over 4500 papers.

Jeff Drazen delivers a powerful message on the use of medical evidence in critical care. Medicine is powered by knowledge, but how do we know what is true and what is not? How do we deal with uncertainty in a setting where outcomes are not closely related to known variables? For example, although there are a few people who have survived jumping or falling from an airplane at high altitude, it is a rare event. Thus, a test to determine how to prevent death from such a disaster would only take a small number of participants to see if a particular method works. In contrast, when considering a medical condition where a large fraction of people might seemingly "recover" without treatment, such as tuberculosis, how does one determine if a treatment is effective? In this talk Jeff discusses the trials surrounding blood glucose control in the Intensive Care Unit (ICU). The way we have dealt with increased blood sugar levels in critical care has changed over time. Whereas once upon a time there was little thought given to high blood sugar levels, this changed in the 90s. One single centre paper was the catalyst for a move toward tighter glucose control for patients in ICU. Due to the novel question and well-designed study, this paper was published in a prestigious journal – even if there were questions surrounding its validity. Larger, multi-centred papers were not published until many years later due to normal logistical and financial constraints. In the interim, the initial data had informed policy. Therein lies the problem. Join Jeff as he highlights the benefits and potential pitfalls in medical research by telling the story of tight blood glucose control in the ICU.

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Medicine is powered by knowledge, but how do we know what is true and what is not? How do we deal with uncertainty in a setting where outcomes are not closely related to known variables? For example, although there are a few people who have survived jumping or falling from an airplane at high altitude (http://zidbits.com/2010/12/can-you-survive-a-freefall-without-a-parachute/), it is a rare event. Thus, a test to determine how to prevent death from such a disaster would only take a small number of participants to see if a particular method works. In contrast, when considering a medical condition where a large fraction of people might seemingly "recover" without treatment, such as tuberculosis (http://www.who.int/mediacentre/factsheets/who104/en/print.html), how does one determine if a treatment is effective? In this talk, I will examine how we gained knowledge about tuberculosis as an example of a disease where a combination of observational scientific findings and clinical trial data are linked to advance knowledge. I will also discuss other examples of clinical trials challenges and the solutions to these challenges.