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2024 Year in Review
3 Plays1 year ago
This episode of Critical Matters will close 2024 with a year in review. Dr. Sergio Zanotti is going solo and will discuss a couple of relevant clinical guidelines and review five clinical trials. To close, he'll share some of his favorite books for 2024.
Additional Resources:
Critical Care Management of Patients Post Cardiac Arrest (AHA/NCS): Hirsch KG, Abella BS, Amorim E, et al. Critical Care Management of Patients After Cardiac Arrest: A Scientific Statement from the American Heart Association and Neurocritical Care Society. Neurocrit Care. 2024;40(1):1-37: https://bit.ly/4087o1w
2024 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations: Summary From the Basic Life Support; Advanced Life Support; Pediatric Life Support: Neonatal Life Support; Education, Implementation, and Teams; and First Aid Task Forces. Circulation 2024: https://bit.ly/4fD4o1R
PREOXI Trial. Gibbs KW, Semler MW, Driver BE, et al. Noninvasive Ventilation for Preoxygenation during Emergency Intubation. N Engl J Med. 2024;390(23):2165-2177. doi:10.1056/NEJMoa2313680: https://bit.ly/4fD4pCX
AMIKINHAL Trial. Ehrmann S, Barbier F, Demiselle J, et al. Inhaled Amikacin to Prevent Ventilator-Associated Pneumonia. N Engl J Med. 2023;389(22):2052-2062. doi:10.1056/NEJMoa2310307: https://bit.ly/4iQQvzU
REVISE Trial. Cook D, Deane A, Lauzier F, et al. Stress Ulcer Prophylaxis during Invasive Mechanical Ventilation. N Engl J Med. 2024;391(1):9-20. doi:10.1056/NEJMoa2404245: https://bit.ly/3Pc4nqH
TIGHT K Trial. O'Brien B, Campbell NG, Allen E, et al. Potassium Supplementation and Prevention of Atrial Fibrillation After Cardiac Surgery: The TIGHT K Randomized Clinical Trial. JAMA. 2024;332(12):979-988. doi:10.1001/jama.2024.17888: https://jamanetwork.com/journals/jama/fullarticle/2823246
BALANCE Trial. Daneman N, Rishu A, et al. Antibiotic Treatment for 7 versus 14 Days in Patients with Bloodstream Infections. N Engl J Med. Published online November 20, 2024. doi:10.1056/NEJMoa2404991: https://www.nejm.org/doi/abs/10.1056/NEJMoa2404991
CMD Study. Bodien YG, Allanson J, Cardone P, et al. Cognitive Motor Dissociation in Disorders of Consciousness. N Engl J Med. 2024;391(7):598-608. doi:10.1056/NEJMoa2400645: https://www.nejm.org/doi/full/10.1056/NEJMoa2400645
Books Mentioned in this Episode:
Slow Productivity: The Lost Art of Accomplishment Without Burnout. By Cal New Port: https://amzn.to/4gTbkJ2
Meditations for Mortals: Four Weeks to Embrace Your Limitations and Make Time for What Counts. By Oliver Burkeman: https://bit.ly/4gURU6N
Knife: Meditations After an Attempted Murder. By Salman Rushdie: https://bit.ly/3ZPsAIt
Recommended
Transcript
Introduction to Critical Matters Podcast
00:00:06
Speaker
Welcome to Critical Matters, a sound podcast covering a broad range of topics related to the practice of intensive care medicine.
00:00:14
Speaker
Sound provides comprehensive critical care programs to hospitals across the country.
00:00:19
Speaker
To learn more about our programs and career opportunities, visit www.soundphysicians.com.
00:00:26
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And now your host, Dr. Sergio Zanotti.
2024 Year-End Review and Listener Gratitude
00:00:33
Speaker
Welcome to the last episode of Critical Matters for 2024.
00:00:36
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For today's episode, we will deviate from our usual pattern of discussing a clinical topic with an expert guest, and instead I'll go solo, and I will do a year-end review for 2024.
00:00:52
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I will comment on a couple of guidelines that I found relevant and would want to make sure every one of our listeners takes a look at,
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And then I'll dive into five clinical trials that I've chosen either because they were highly cited, have an impact on our practice, or just were particular interest to myself.
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And finally, we'll close with the customary non-clinical questions, and I'll share with you some of the favorite books I read this year and why.
00:01:24
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So first, before we start, I would like to thank all of you for listening to Critical Matters throughout 2024.
00:01:33
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I hope that we can continue this journey together in 2025 and can discuss a wide variety of
00:01:41
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clinical and non-clinical topics that are relevant to the practice of critical care medicine at the bedside.
00:01:48
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So without further ado, we'll go ahead and get started.
Guidelines on Post-Cardiac Arrest Care
00:01:51
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I'm always a big believer that clinical guidelines are important documents to read because they summarize the existing literature, try to incorporate newer studies into our practice,
00:02:05
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and I think provide a nice overview and a source to dive deeper into specific topics.
00:02:11
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There was a plethora of excellent clinical guidelines published throughout 2024.
00:02:20
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Obviously, we're not going to go into all of them.
00:02:22
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Some of them were discussed in more detail on the podcast.
00:02:26
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But I do want to point out two important guidelines that I believe everybody should be paying attention to from the last 12 months.
00:02:35
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One was published earlier in the year and one just literally was released a couple weeks ago in December.
00:02:42
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Both of them relate to the care of post-cardic arrest patients in the ICU.
00:02:48
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a topic that for the last decade has really been, I think, fixated on therapeutic hypothermia.
00:02:55
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Yet we do know today with the science that there's perhaps a lot of other things that we should also be paying attention to.
00:03:02
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So I want to make sure that I bring these up to your attention.
00:03:05
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The first one is the critical care management of patients after cardiac arrest, a scientific statement from the American Heart Association and Neurocritical Care Society.
00:03:16
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And really, in this wonderful document, the authors discussed in detail the physiology and clinical care of the post-cardic arrest patient in the ICU.
00:03:27
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and really focus on the interaction between the brain, the cardiovascular system, and the lungs.
00:03:34
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There is an enormous amount of data, information, studies reviewed, and really points out to
00:03:43
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how much we still have to learn, but also how much can be done for these patients in terms of optimizing their post-cardiac arrest critical care and focusing on brain oxygenation, perfusion, making sure we understand what the ICPs are, understanding cerebral autoregulation,
00:04:04
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Very, very prolonged conversation, something that we discussed in more detail here on the podcast in terms of the neurological support for these patients with seizure management, understanding abnormal EEGs that are not related to
00:04:22
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to seizures, providing better terminology for myoclonus.
00:04:29
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I think anybody sees abnormal movements and they think this patient has myoclonus, but really understanding that there is a plethora or different types of myoclonus and whether they have EEG correlates or not makes a significant impact on their prognostic importance.
00:04:46
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We also...
00:04:48
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talk about the 2C, which is a spectrum of abnormal periodic or rhythmic EEG patterns that do not meet the criteria for seizure status epilepticus, and try to understand that a little bit more for the non-neurologist or the non-epileptologist, which I think is the majority of our audience.
00:05:10
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They provide the most current available evidence for cardiac management in the ICU, talking about target MAPs, timing to the cardiac cath, and the role of cardiac mechanical support.
00:05:25
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And finally, they also talk about how to organize post-cardiac arrest care and where can we have some protocols, how do we designate a
00:05:39
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special places.
00:05:40
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So I think a lot of very valuable information.
00:05:44
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And I will add the link on the show notes, but highly encourage people to look at this guideline.
00:05:52
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There's a lot of very actionable clinical information.
00:05:56
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And one of the things that I found also a nice refresher was they provide a nice review of the appropriate neuro exam for a comatose patient.
ELCOR Guideline Updates for CPR
00:06:06
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I think that as intensivists, we rely obviously on a lot of monitors and devices, but a good exam, especially for the neuro aspect of our patients is always, I think, important and a good reminder.
00:06:23
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The second guideline that I wanted to bring to your attention in our year-end review is one that came out in the month of December.
00:06:32
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It's the ELCOR summary statement.
00:06:35
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So it's a 2024 international consensus on cardiopulmonary resuscitation and emergency cardiovascular care science with treatment recommendations.
00:06:44
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It's summary from the basic life support, advanced life support, pediatric life support, neonatal life support, education implementation in teams and first aid.
00:06:53
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So really this is an update to the 2020 ILCOR cardiac arrest guidelines.
00:07:00
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They recognize that there are certain areas and certain PICO questions that have had new studies and wanted to reevaluate recommendations in these areas.
00:07:11
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So this is a very lengthy guideline, over 100 pages, and this is just a summary.
00:07:18
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They talk about basic life support, advanced life support, pediatric life support, neonatal life support, education, implementation in teams, and first aid.
00:07:28
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And my focus for this audience, obviously, is advanced life support.
00:07:32
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And I think that there are certain things that are very relevant.
00:07:36
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They review all the recent studies on post-cardiac arrest, oxygenation, and ventilation.
00:07:41
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I think that ultimately...
00:07:43
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What they recommend is that post-cardiac arrest, we continue with 100% oxygen, until oxygenation can be reliably measured, either by arterial sticks or a reliable pulse oximeter.
00:07:57
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And when we have that...
00:08:00
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reliable measurement of oxygen that we should target saturation between 94 and 98 percent and the arterial oxygen between 75 and 100 millimeters of mercury.
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They also review the existing studies on ventilation and ultimately recommend that we target normal capnea, so a PaCO2 of 35 to 45 millimeters of mercury.
00:08:23
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They do talk about post-cardic arrest temperature control.
00:08:26
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As I mentioned earlier, I think this has by far consumed all the air in the room when we talk about post-cardic arrest and people have equated post-cardic arrest care in the ICU with therapeutic hypothermia or with a targeted temperature management.
00:08:43
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However, the last several large randomized studies, some of which we've discussed in detail on critical matters,
00:08:51
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have really not shown the beneficial effects that some people expect or believe in from temperature management, post-cardic arrest.
00:09:02
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And again, they review the existing literature and make comments.
00:09:06
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It's still, I think, an area where some people are having a hard time letting go of what I think is confirmation bias.
00:09:14
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As somebody who endorsed and believed in hypothermia post-cardiac arrest today, I truly believe that today the available evidence does not suggest that this is beneficial for our patients, and we should probably be focusing on all the other things I mentioned in the previous guidelines.
00:09:35
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But in any event, they update the terminology.
00:09:39
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So the term targeted temperature management has been updated to four different terms.
00:09:45
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Number one, hypothermic temperature control, which is active temperature control with target temperature below the normal range.
00:09:52
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Number two, normothermic temperature control, which is active temperature control with the target temperature in the normal range.
00:10:01
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Number three, fever prevention temperature control, which is monitoring temperature and actively preventing or treating temperature above the normal range.
00:10:09
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And finally, no temperature control, which is no protocolized active temperature control strategy.
00:10:15
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And the question really is, is do these active temperature control measures
00:10:21
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therapies or protocols actually help our patients post-cardiac arrest.
00:10:27
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So they review a series of PICO questions and talk about hypothermia, 32 to 34 degrees Celsius compared with normothermia or fever prevention, 33 Celsius compared with 36 Celsius.
00:10:42
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Duration of cooling 12 to 24 hours compared with 36 hours of temperature control or 48 compared with 24 hours.
00:10:51
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They also look at the method of temperature control, look at the rewarming rate and the duration of fever prevention after initial temperature control.
00:10:59
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really review a large amount of available literature.
00:11:05
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Some of these studies obviously are smaller studies, but there are some very important studies in the temperature control area with RCTs that ultimately enroll over 3,000 patients when pulled together, and I think that this is something that we should be paying attention to.
00:11:24
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Ultimately, their recommendations and good practice statements include suggesting actively preventing fever by targeting a temperature of 37.5 or less degrees Celsius for patients who remain comatose after return of spontaneous circulation from cardiac arrest.
00:11:44
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So this was obviously a weak recommendation with low-strainian evidence, but I do believe that
00:11:49
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That is where we should be focusing our protocols on.
00:11:52
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That is where the evidence currently is pointing to.
00:11:57
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And they do obviously raise the question of whether subpopulations of cardiac arrest patients may benefit from targeting hypothermia at 32 to 34 degrees Celsius remains uncertain.
00:12:07
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So I would say that for now we stay away from that unless it's within the context of clinical research.
00:12:15
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Comatose patients with mild hypothermia after ROSC should not be actively warm to achieve normothermia.
00:12:21
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That's a good practice statement.
00:12:24
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They recommend against the routine use of pre-hospital cooling with rapid infusion of large volumes of cold intravenous fluid immediately after ROSC.
00:12:33
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That has been demonstrated to be harmful.
00:12:36
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So that's a strong recommendation.
00:12:38
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They also suggest surface or endovascular temperature control techniques when temperature control is used in comatose patients, so really no difference.
00:12:46
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And when a cooling device is used, we suggest using a temperature control device that includes a feedback system based on continuous temperature monitoring to maintain the target temperature.
00:12:57
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That's a good practice statement.
00:12:59
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So, as you can see, the enthusiasm for therapeutic hypothermia and for targeted temperature management that includes subnormal temperatures for post-cardic arrest patients is slowly, I think, dissipating, despite some people still advocating for it in certain subgroups based on small studies.
00:13:19
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I do believe that in trying to be as impartial as possible, the current evidence would suggest that we should be keeping temperatures below or equal to 37.5, and that should be our focus on these patients.
00:13:35
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In terms of the other suggestion in terms of length that we should focus, the 2024 good practice statement on duration of fever prevention, they suggest active prevention of fever for 36 to 72 hours in post-cardiac arrest patients who remain comatose.
00:13:52
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This is a good practice statement.
00:13:54
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So I think that for the first 36 to 72 hours, that is what we should be focusing on.
Holistic Post-Cardiac Arrest Care
00:14:01
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They also talk about post-cardic arrest seizure management, and I think that one of the most important things here is that it is not suggested that prophylactic anti-seizure medication be utilized in post-cardic arrest adult patients.
00:14:16
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They obviously suggest treatment of clinically apparent and electrocardiographic, e.g., an EEG seizures in post-cardic arrest adults.
00:14:23
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That's a good practice statement.
00:14:25
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And there is still a lot of discussion on what to do with other rhythms, but they do suggest treatment of rhythmic and periodic EEG patterns that are on the ictal, interictal continuum, that's the 2C, in comatose post-cardic arrest adults.
00:14:41
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They also provide standardized critical care EEG terminology.
00:14:45
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I'm not going to go into detail here, but I think it's important to understand that obviously clinical plus EEG correlates is what ultimately determines electroclinical seizures, and that is really what we should be focusing on.
00:15:00
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They review the available literature, which is
00:15:04
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and not very large in the use of ECPR, extracorporeal cardiopulmonary resuscitation.
00:15:10
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All they can really say is that for some patients, it might be indicated more to be studied.
00:15:15
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So these two guidelines, I think,
00:15:20
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illustrate the complex world of caring for post-cardic arrest patients.
00:15:26
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These patients obviously are frequent in our ICUs, as a group have a very poor prognosis, but we do want to make sure that we are focusing on evidence-based strategies that will provide this very sick population
00:15:41
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the best chance for a meaningful neurological recovery.
00:15:44
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There are many other aspects of post-cardic arrest like neuroprognostication that we didn't discuss and were not discussed extensively in these guidelines.
00:15:53
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But I do believe that it is time for us to look at the bigger picture and instead of obsessing over what temperature we should be using and protocols and arguing about this and that, look at the
00:16:09
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whole body of evidence, look at these current guidelines, and just for now, until we have better studies, focus on keeping patients at 37.5 or below, and that we really create protocols and improve care in all the other aspects that are mentioned in these two guidelines.
00:16:29
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So I think that is what I chose to review for the end year review.
Criteria for Selecting Clinical Trials
00:16:35
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Like I mentioned, there are many, many other guidelines of great interest, of great value.
00:16:39
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We can't cover everything, but I do think that these two in particular together, one that came early in the year and one that comes at the end of the year, is something good for people to look at as they prepare for 2025.
00:16:51
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Okay.
00:16:55
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Now we're going to move on to some clinical trials.
00:16:57
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Again, there were multiple clinical trials.
00:17:00
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I'm sure that there's some that I could have mentioned that I don't mention, but I had to pick and choose.
00:17:06
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So I chose based on a couple of criteria.
00:17:09
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One was a number of citations.
00:17:11
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The other one has a direct impact on what we do on a daily basis.
00:17:17
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And number three for some articles, just articles that for whatever reason I found interesting.
00:17:22
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These are...
00:17:24
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all articles that were very well conducted.
00:17:28
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I'm not going to spend time going into depth on what could have been done differently, what are the limitations of the study.
00:17:36
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I think those are well discussed in editorials, well discussed in a
00:17:41
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in the articles themselves.
00:17:43
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But I do encourage you to pick up these articles and look at them yourself.
00:17:48
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I think that running clinical trials is extremely hard, and I'm always more interested in just what can I learn from what's published.
00:17:56
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recognizing that there is a tremendous bias in science and a positive trial is more likely to be published.
00:18:06
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But we should really understand a little bit more about what a p-value means.
00:18:11
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It doesn't mean that it's real, doesn't mean that it's clinically significant, but it just means that it's more likely to be published.
00:18:17
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It could have been totally random, right?
00:18:18
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One out of 20 might give you a positive p-value and still...
00:18:25
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be a false positive.
00:18:26
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So again, I think that just with that, a grain of salt, I'm going to share some studies that quote unquote are considered positive.
00:18:33
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But I also think that they touch on topics that are relevant to our daily practice.
00:18:38
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So the first one, and these go in no particular
Pre-Oxy and Amikacin HAL Trials
00:18:41
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order.
00:18:41
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They might be sort of in a chronological order, but not necessarily.
00:18:46
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The first one was published in the New England Journal of Medicine, Non-Invasive Ventilation for Pre-Oxygenation During Emergency Intubation, the Pre-Oxy Trial.
00:18:56
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This was a multi-center, randomized, pragmatic, obviously unblinded, parallel trial, 24 sites, 7 EDs, and 17 ICUs in the U.S. It enrolled a little bit over 1,300 adults requiring emergent intubation, either in the ED or the ICU.
00:19:13
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And they were randomized to get pre-oxygenation before their intubation with non-invasive ventilation or with a regular oxygen mask at 100%.
00:19:24
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The primary outcome of the study was hypoxemia during intubation.
00:19:28
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So SAO2 below 85% after induction to two minutes after intubation.
00:19:34
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That was the primary outcome.
00:19:36
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Secondary outcomes were the lowest oxygen saturation.
00:19:40
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They had some exploratory outcomes such as hypotension, need for vasopressors.
00:19:45
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the presence of cardiac arrest, and then they looked at some safety outcomes, in particular aspiration, a new infiltration on the x-ray at 24 hours, and hypoxemia at 24 hours.
00:19:56
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So I think that we intubate on a regular basis.
00:20:00
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optimizing every step of intubation is very important.
00:20:05
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We discussed previously airway management and the use of video laryngoscopy, and there's been trials on that area last year.
00:20:13
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But this one, I think, focuses specifically on the pre-oxygenation, where we use non-invasive ventilation via CPAP or BiPAP machine versus just the usual air mask with oxygen and
00:20:30
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In terms of the intubation procedure, 95.5% of the non-invasive ventilation patients received non-invasive ventilation as pre-oxygenation.
00:20:42
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98.8% of the oxygen mask received oxygen mask.
00:20:45
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It was a little bit of crossover.
00:20:48
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In terms of other important things, the duration of pre-oxygenation greater than three minutes was 96.6% of the non-invasive and 95% of the oxygen.
00:21:02
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And then in terms of the primary and secondary outcomes themselves,
00:21:06
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The primary outcome of hypoxemia during intubation occurred in 9.1% of the non-invasive ventilation versus 18.5% of the oxygen mask.
00:21:16
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So that was considered a positive from a statistical standpoint.
00:21:20
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And the 95% confidence interval was either from, the average was minus 9.4% in terms of the odds ratio, but it went from minus 13.2 to minus 5.6.
00:21:30
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So clearly, the
00:21:35
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very significant in terms that it is less likely to be hypoxemic when you emergently intubate somebody and pre-oxygenate them with non-invasive ventilation.
00:21:48
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In terms of the median lowest oxygen saturation, it was 99 versus 97.
00:21:52
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So that's from 95 to 100 in non-invasive and from 89 to 100 in the
00:21:59
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oxygen mask.
00:22:00
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And then they look at some of the other important ones in the presence of cardiac arrest.
00:22:06
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It was small in both, but 0.2% in non-invasive and 1.1% in the oxygen mask.
00:22:14
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In terms of success for first intubation, 82% versus 81%, no significant difference.
00:22:19
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And the median time from induction to intubation was about the same, 115 versus 113 seconds.
00:22:28
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When you look at some of the safety outcomes, and one of the things that people obviously are concerned about is aspiration.
00:22:35
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There was no difference in new infiltrates.
00:22:38
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Operator reported aspiration actually was lower but not significant in the non-invasive or the presence of new pneumothoraces.
00:22:49
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Some of the exploratory clinical outcomes, there was no significant difference between the median ventilator-free days, the median ICU-free days, or the in-hospital death.
00:22:59
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So from a primary outcome, this was a positive trial.
00:23:03
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I think that there was 9% versus 18.5% incidence of hypoxemia.
00:23:10
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The incidence of aspiration was lower with the non-invasive, 0.9% versus 1.4%.
00:23:16
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And I think it just illustrates that it might be a better way of oxygenating patients.
00:23:21
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I think a lot of people during COVID had that experience when we had patients frequently on non-invasive and then when they had to be intubated, obviously intubating them from non-invasive directly to the intubation.
00:23:37
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But I think that this is an interesting study that suggests that perhaps we need to change a little bit what we do routinely and be a little bit more thoughtful about how we organize every step of an emergent intubation.
00:23:51
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And this is obviously focusing on the pre-intubation or pre-intubation oxygenation.
00:23:56
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They also did a subgroup analysis, and you can see that in general it favors non-invasive ventilation, but of interest and no surprise, I think, for patients who were in the ICU and patients who had a body mass index greater or equal than 30, the effect was even more pronounced.
00:24:17
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So especially when we have patients who might have some hypoventilation at baseline, obviously utilizing non-invasive as our pre-intubation oxygenation is important.
00:24:27
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Now, it might have practical aspects.
00:24:29
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If you have to intubate somebody emergently, are you going to bring in the...
00:24:35
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the non-invasive and try to set that up.
00:24:37
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On the other hand, I think if you have somebody who's having difficulty breathing and the ED or you're trying to figure out what to do, I mean, while you figure out maybe slapping on a non-invasive is a good way to get started and get ready for the intubation procedure itself.
00:24:51
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So clearly, I think this is a valuable study and it should influence what we do at the bedside.
00:24:58
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The second study inhaled amikacin to prevent ventilator-associated pneumonia.
00:25:02
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I'm not going to go into detail here.
00:25:04
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This was the amikane HAL trial published in the New England Journal of Medicine.
00:25:10
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And this was a multicenter perspective randomized double-blind trial in 19 French ICUs.
00:25:16
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A little bit under 1,000 patients, 850 patients with adults on mechanical ventilation for 72 hours or more were randomized to inhaled amikacin at a dose of 20 mg per kg every day times 3 doses versus placebo, similar dosing, similar duration.
00:25:36
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Their primary outcome was first episode of VAP during the 28-day follow-up.
00:25:42
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Secondary outcomes included the incidence density of VAP, so that is VAPs per 1,000 patient days of invasive mechanical ventilation, incidence of VAP with gram-negative susceptible to amicasin, and other ventilator-associated conditions, plus they looked at ICU mortality and hospital mortality.
00:26:07
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So in terms of the outcomes, the incidence of the first VAP episode, the difference was significant.
00:26:15
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It was about 1.5 days in favor of using the inhaled placebo.
00:26:21
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So the incidence of the first VAP and inhaled placebo occurred later.
00:26:30
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They looked also at...
00:26:32
Speaker
Ventilator-associated complications were significantly lower in the inhaled amicacin.
00:26:42
Speaker
So the difference in the VAP episodes was 22% in the inhaled placebo versus 15% in the inhaled amicacin.
00:26:49
Speaker
And that was associated also with a lower infection-related ventilator-associated complications when they didn't meet the criteria.
00:26:56
Speaker
for VAP.
00:26:57
Speaker
In terms of adverse side effects, they were very similar, 2% and 1% in both groups, so no significant difference.
00:27:06
Speaker
So this was considered a positive study.
00:27:09
Speaker
I think that in many ICUs, VAP might still be a problem.
00:27:13
Speaker
So in those cases, I mean, maybe considering the use of inhaled amikacin,
00:27:17
Speaker
might be of value.
00:27:19
Speaker
I think there was also similar studies in TBI patients, but with systemic antibiotics.
00:27:26
Speaker
Obviously, using prophylactic antibiotics always raises the question of generating more resistance.
00:27:34
Speaker
That was not seen with this inhaled dose of amicacin for three days, which obviously relates to
00:27:44
Speaker
to less systemic absorption, but also was effective in preventing VAPs.
00:27:52
Speaker
The third article relates to stress ulcer prophylaxis through an invasive mechanical ventilation, something that we've done for years, and I think almost like dogma for many years.
Pantoprazole and TITE-K Trials
00:28:03
Speaker
However, when people have looked at the evidence, and I think that's why it's important to find reproducible evidence, to look at the evidence over and over again, and when these studies can be done, I think we should be paying attention.
00:28:16
Speaker
This was done by the Canadian Clinical Trials Group.
00:28:20
Speaker
It was an international prospective randomized double-blind trial with 68 hospitals, almost 5,000 adults on mechanical ventilation.
00:28:28
Speaker
The reason for this is that a lot of people have questioned whether pantroposol really has an impact on decreasing GI bleedings.
00:28:35
Speaker
There's concerns of increase with C. diff or VAP and maybe other complications.
00:28:42
Speaker
So they compared pantroposol 40 mg IVQ day while the patient was intubated to placebo at a similar dose while the patient was intubated.
00:28:51
Speaker
And the primary outcome was clinically important upper GI bleeding up to 90 days post-randomization.
00:28:57
Speaker
Clinically important is defined objectively and relates to the need for transfusion or other interventions.
00:29:03
Speaker
Primary safety outcome was death from any cause at day 90, and they looked at secondary outcomes such as C. difficile infection, C. diff, VAP, initiation of RRT, ICU and hospital mortality, and patient-important GI bleeds.
00:29:19
Speaker
The primary safety outcome was significantly lower, 1% versus 3.5%, with an absolute difference of 2.5 or 1.6 to 3.3 in a 95% confidence interval.
00:29:34
Speaker
So that was statistically significant.
00:29:37
Speaker
And the primary safety outcome was very similar at 29.1% for the 90-day mortality versus 30.9%.
00:29:47
Speaker
They looked at other secondary and tertiary outcomes, and again, in terms of the incidence of C. diff infection or the incidence of BAP, no significant difference between pantopressol and placebo.
00:30:03
Speaker
Other tertiary outcomes in terms of number of red cells transfused was...
00:30:10
Speaker
Similar, medium peak serum creatinine, no difference.
00:30:16
Speaker
Medium number of days on mechanical ventilation, no difference.
00:30:19
Speaker
Medium number of days in the ICU was no difference.
00:30:22
Speaker
So again, I think that what this study demonstrated was that pantroposol was better at preventing clinically significant GI bleeds, but did not have an impact on mortality.
00:30:37
Speaker
yet I think it still informs our use of GI prophylaxis for patients on mechanical ventilation.
00:30:44
Speaker
It was a very well-conducted large study, which I think supports the use of pantoprosol to prevent clinically significant GI bleeds.
00:30:53
Speaker
It's not going to improve mortality.
00:30:55
Speaker
It's not going to cause C. diff.
00:30:58
Speaker
It's not going to cause an increased risk of VAP, but it might prevent patients from having significant GI bleeds
00:31:06
Speaker
which I think is a positive outcome and most patients probably would consider to be important.
00:31:12
Speaker
The following study is a study that I just found interesting.
00:31:17
Speaker
I think very well conducted on a topic that I think is dear to all of us since our internship days, which is potassium supplementation and prevention of atrial fibrillation after cardiac surgery.
00:31:30
Speaker
This was the TITE-K randomized clinical trial published in JAMA.
00:31:35
Speaker
And I think that one of the most frequent interventions in the hospital, especially when we were in our training days, was to replace potassium.
00:31:45
Speaker
Today, obviously, many ICUs have protocols for this.
00:31:49
Speaker
And it's interesting that when we revise these protocols, the cardiac ICU and the cardiac surgery ICU teams are always very concerned about
00:31:58
Speaker
At what point should we transfuse potassium?
00:32:00
Speaker
And I think it's been kind of handed down to us as dogma that we should keep the potassiums 4.5 or above for these cardiac patients to prevent arrhythmias.
00:32:11
Speaker
So this was a prospective randomized, multicenter, open-label, non-inferiority trial in 23 cardiac surgical centers in the UK and Germany.
00:32:21
Speaker
Their hypothesis was that we don't have to keep potassium above 4.5.
00:32:26
Speaker
that all we have to do is keep it normal in order to prevent atrial fibrillation.
00:32:31
Speaker
And as I said, this was designed as a non-inferiority trial, so they randomized almost 1,700 post-isolated cabbages to either a tight K group in which potassium was replaced whenever it was below 4.5 and a relaxed K group in which potassium was replaced when it was below 3.6.
00:32:49
Speaker
The primary outcome was confirmed new onset AFib.
00:32:53
Speaker
So AFib after cardiac surgery and first 120 hours post-cabbage or by discharge.
00:32:59
Speaker
And in order for this to be confirmed, it had to be clinical, clinical,
00:33:04
Speaker
documented in the EKG, and also every patient had an ambulatory heart rate monitor, and the three of them had to show AFib.
00:33:12
Speaker
Secondary outcomes included new onset atrial fibrillation after cardiac arrest detected only on the ambulatory heart rate monitor or non-atrial fibrillation episodes detected on the heart rate monitor.
00:33:29
Speaker
They also looked at cost and looked at safety outcomes.
00:33:32
Speaker
So in terms of...
00:33:35
Speaker
The primary outcome.
00:33:39
Speaker
There was no difference.
00:33:40
Speaker
There was a 1.7% difference in the unadjusted, and that was 2.2% in the adjusted.
00:33:48
Speaker
Both of these crossed a line of non-significance in the 95% confidence interval.
00:33:53
Speaker
So bottom line is that the incidence of atrial fibrillation after cardiac surgery seemed to be the same, whether the potassium was kept above 4.5 or was kept just normal above 3.6%.
00:34:06
Speaker
They looked at secondary outcomes.
00:34:08
Speaker
Again, there was no significant difference between these.
00:34:10
Speaker
So this being a non-inferiority trial and the hypothesis that just keeping potassium normal above 3.6 was no different than keeping it above 4.5, I consider this a positive trial.
00:34:25
Speaker
They obviously showed that the frequency of potassium administration was significantly higher in the tight K group and that the potassiums were separated in both groups, but in general in both groups remained normal throughout the first 24-hour period post-surgery.
00:34:46
Speaker
So an interesting study that I think provides some evidence to a practice that is extremely common that I think is hard to study, obviously.
00:34:56
Speaker
I mean, people are not interested in just potassium replacements.
00:34:59
Speaker
But why is this important?
00:35:00
Speaker
Well, I think that...
00:35:02
Speaker
A lot of patients will tell you getting potassium is not always fun.
00:35:05
Speaker
It can cause pain.
00:35:06
Speaker
It's not necessarily comfortable.
00:35:08
Speaker
But also, even though potassium is not an expensive drug, the sheer amount that is utilized is an important cost.
00:35:16
Speaker
And in an era when we're trying to provide value to patients, but also to healthcare in general,
00:35:21
Speaker
I think to continue to do practices that are based on dogma and not current evidence don't make sense if they don't improve outcomes and just increase cost.
00:35:32
Speaker
So some food for thought.
00:35:34
Speaker
I hope you discuss this with your cardiology and CT surgery colleagues.
00:35:38
Speaker
And just I thought I brought up to your bring it to your attention.
BALANCE Trial and Consciousness Study
00:35:45
Speaker
The next study, which I believe is the last clinical trial that I really wanted to focus on, is a recent published antibiotic treatment for seven versus 14 days in patients with bloodstream infections.
00:35:59
Speaker
This is the BALANCE trial published in the New England Journal of Medicine.
00:36:03
Speaker
This was a multi-center, prospective, randomized, non-inferiority trial, 74 hospitals in seven countries.
00:36:11
Speaker
It included 3,600 adults with a bloodstream infection.
00:36:15
Speaker
and they basically got randomized to either seven days of antibiotic versus 14 days.
00:36:21
Speaker
Very important in this particular trial is to recognize exclusion criteria.
00:36:27
Speaker
So they excluded patients who were immunosuppressed, and they have a definition for that.
00:36:31
Speaker
They excluded staph aureus infection, which I think is very important for us in the ICU.
00:36:36
Speaker
They also excluded specific infections that required extended treatment, especially when there are foreign bodies or certain locations, and they didn't include possible contaminants in the study.
00:36:48
Speaker
So the primary outcome was death by any cause at day 90 post-diagnosis of the bloodstream infection.
00:36:55
Speaker
Secondary outcomes included death in the hospital, death in the ICU, relapse of bacteremia with the same pathogen, allergy to antibiotic, adverse events, C. diff colitis, and secondary infections with multi-drug resistant organisms.
00:37:10
Speaker
The patient characteristics were very similar.
00:37:12
Speaker
The median age was 70 years old.
00:37:18
Speaker
The median SOFA score was 4.
00:37:21
Speaker
The percent of patients enrolled in the study that were in an ICU was 55%, so the majority of patients were in the ICU.
00:37:28
Speaker
But in order to get to 3,000-plus patients, they also enrolled patients who were in the hospital.
00:37:34
Speaker
These were all inpatients.
00:37:36
Speaker
21% of these patients received mechanical ventilation, and in terms of the sources of the acquisition of bacteremia, the vast majority, 75.4%, were from the community, and around 13% to 12% were from the hospital, acquired in the hospital, and 11% were acquired in the ICU.
00:37:58
Speaker
When you look at the primary outcome, they looked at intention to treat per protocol, and then they had a modified intention to treat.
00:38:05
Speaker
And then all three of these, there was no difference between seven days or 14 days in the primary outcome.
00:38:13
Speaker
And really just illustrates that for non-staph aureus and for maybe not endocarditis or an infected joint or a foreign body,
00:38:22
Speaker
For many of our documented clinical infections with bacteremia, seven days is as good as 14 days.
00:38:29
Speaker
And I think it just speaks to the fact that for whatever reason, antibiotics seem to be given in multiples of seven.
00:38:37
Speaker
That's a week.
00:38:38
Speaker
I presume it's very arbitrary.
00:38:40
Speaker
I think we really think
00:38:41
Speaker
about infection, we recognize that two patients with the same bug might require different durations of antibiotic therapy.
00:38:51
Speaker
Some people have looked at procalcitonin and other biomarkers to dictate that, but I think that in general terms, this will cut down on the exposure to antibiotics intravenously.
00:39:02
Speaker
I think it has important implications for patients from a disposition perspective, from a cost perspective for healthcare, and
00:39:09
Speaker
And especially in these infections that were studied here, there's no significant difference.
00:39:14
Speaker
I think that amine for seven days as a baseline probably is the way to go.
00:39:21
Speaker
So those were the five main studies that I felt were quite relevant to our practices.
00:39:28
Speaker
Like I mentioned, there are many other studies that were very well conducted that have important implications, but these somehow hit the spot of really being relevant to our daily practices, being well-conducted studies, being large studies, and having some degree of a positive finding that ultimately, I think, can inform our practice.
00:39:50
Speaker
I have one bonus study that I felt to be really interesting and made me think a lot about my patients.
00:39:58
Speaker
And this study was also published in the New England Journal of Medicine, and it relates to cognitive motor dissociation.
00:40:04
Speaker
So what do we mean by cognitive motor dissociation is when we have basically an exam that...
00:40:11
Speaker
seems to be a comatose patient not responding to anything we do to them, yet we find when we study them deeper, either with a functional MRI or a special EEG, that perhaps there are responses to some of our commands and there are responses to some of our actions.
00:40:31
Speaker
And the idea here is that...
00:40:35
Speaker
our exam might be very superficial and not fine-tuned enough or sensitive enough to really understand the level of consciousness of a patient.
00:40:44
Speaker
Now, obviously, when we're dealing with traumatic brain injury, post-cardic arrest, understanding the level of consciousness and where this patient's brain is is extremely important in terms of making therapeutic decisions.
00:40:56
Speaker
I just found that this was a very interesting study, despite being a little bit smaller, but also one that I'm sure is very difficult to conduct.
00:41:04
Speaker
So what they did here is they evaluated a whole bunch of patients, many of which were in the ICU, who had different disorders of consciousness post-critical illness.
00:41:16
Speaker
And basically, they eventually...
00:41:20
Speaker
found a group of 350 patients who actually had either a common recovery scale completed, which is a large physical exam scale that looks at different points and gives a total score for the for the coma.
00:41:40
Speaker
They had a functional MRI, and they had a complete EEG.
00:41:46
Speaker
So either both a functional MRI and the EEG, or one or the other.
00:41:50
Speaker
So they really looked at 350 patients that had all this testing done.
00:41:56
Speaker
They were able to move them into two different groups.
00:42:00
Speaker
One group, so 32% of these patients, 30% of these patients had observable response to commands.
00:42:06
Speaker
And that obviously was not necessarily the group of interest.
00:42:11
Speaker
That would be like the control group.
00:42:12
Speaker
And then there were 241 or almost 70% of the patients did not have observable response to commands.
00:42:19
Speaker
So these are the patients that we would say no response to commands are not following when I examined them.
00:42:26
Speaker
They're comatose.
00:42:26
Speaker
They're unresponsive.
00:42:29
Speaker
Of these, 25%, so one out of four, had responses to commands on imaging and were considered to have cognitive motor dissociation.
00:42:40
Speaker
So when we looked at them in more
00:42:42
Speaker
death, they were responding appropriately to our commands, either in the functional MRI or in the EEG.
00:42:51
Speaker
So really, when you look at the characteristics of the patients who did not have an observable response to command, the majority of them were either in coma or vegetative state.
00:43:04
Speaker
Some had what they call minimally conscious state.
00:43:07
Speaker
The majority of them were male, 60%, 65%.
00:43:12
Speaker
And the 45% were from brain trauma, 20% were from cardiac arrest or hypoxia, another 20% were from some sort of cerebrovascular event, either a subarachnoid hemorrhage, intraventricular hemorrhage.
00:43:29
Speaker
intracranial hemorrhage or a stroke, and the rest were just miscellaneous.
00:43:34
Speaker
I think that a summary of these findings is that of those, 70% of patients have no observable response post-critical illness affecting the brain in this group, and of that, almost one out of four had actually cognitive motor dissociation.
00:43:55
Speaker
So there was more information
00:43:58
Speaker
response that we were able to ascertain by our physical exam.
00:44:03
Speaker
And this is much more common in younger patients, below 30, which obviously are the majority of patients who have traumatic brain injury, and decreases in the different age groups.
00:44:13
Speaker
So it was lower in 30 to 50, and then lower in over 50 years old.
00:44:17
Speaker
But this is a powerful study because it just reminds you of how little we know about the brain.
00:44:24
Speaker
And how sometimes we just maybe write off somebody as being unresponsive, yet we don't really know what their level of consciousness is.
00:44:32
Speaker
Not to mention that we could miss the lock-in syndrome.
00:44:34
Speaker
That is a little bit more rare.
00:44:36
Speaker
This is just people who our exam is not picking up responses that are picked up by more sensitive testing such as functional MRI and EEG.
00:44:46
Speaker
Now, don't get me wrong, the majority of these patients probably still have a pretty poor prognosis, but I do think that as we evolve, understanding the extent of brain injury, understanding the real level of consciousness, the real ability to respond is something that needs to evolve.
00:45:05
Speaker
And it's something that should provide a lot of pause when we examine somebody, not to just assume that there's nothing there because we might be missing something.
00:45:16
Speaker
So I just found that this six article as a bonus was a good food for thought type of article just to give us a little bit more humility when we're rounding and examining patients.
Year-End Review Summary
00:45:29
Speaker
So with that, I'm
00:45:31
Speaker
We covered two important clinical guidelines, five clinical trials, and this extra bonus study.
00:45:39
Speaker
I will add references in the show notes.
00:45:42
Speaker
I hope you pick up some of these and read them.
00:45:44
Speaker
I highly encourage you to look at the clinical guidelines.
00:45:47
Speaker
A lot of information there that I think informs how we should be organizing protocols for these patients post-cardiac arrest.
00:45:54
Speaker
Also look at these studies.
00:45:55
Speaker
Every single one of these studies, I think, impacts something that is very common in our ICU.
00:45:59
Speaker
I would almost say something that's daily in our ICUs, and that's one of the reasons why I chose them.
00:46:06
Speaker
And to finish, as we always do now, I'll give you some thoughts or some answers on questions that are unrelated to the clinical topics that we discussed.
Recommended Books for 2024
00:46:17
Speaker
And I always start with books.
00:46:19
Speaker
So I will share with you three books that really marked me this year that I found to be extremely valuable.
00:46:28
Speaker
And I'll give you a little bit of what I learned from them and hope that you pick up one of these and read them.
00:46:34
Speaker
I think they'd be great.
00:46:35
Speaker
Any one of these would be, I think, a great read.
00:46:38
Speaker
So the first book is Slow Productivity.
00:46:41
Speaker
The Lost Art of Accomplishment Without Burnout, the New York Times bestseller by Kyle Newport.
00:46:48
Speaker
I think Kyle Newport is a great ideas writer.
00:46:53
Speaker
He's a professor at Georgetown and computer science, but really focuses on the interface of technology with work and how to be productive.
00:47:03
Speaker
And three things that I really learned from slow productivity is that if you do fewer things, you're going to be much more productive, which I think in a world where there's so many distractions is an important reminder.
00:47:16
Speaker
Number two, that we should work at a natural pace, not always be rushed and really be present in whatever task we are doing at this moment.
00:47:26
Speaker
And I think that's the way to achieve more, but also to achieve better things.
00:47:30
Speaker
And finally, I think he talks a lot about obsessing over quality.
00:47:35
Speaker
And this in particular, I think, is important.
00:47:38
Speaker
Whenever we do something, no matter what it is, we should really be present and try to do it the best we can.
00:47:45
Speaker
That is really, I think, where flow comes from, where joy comes from.
00:47:49
Speaker
And I think it's perhaps the biggest antidote to burnout in the workplace.
00:47:56
Speaker
The second book is called Meditations for Mortals.
00:48:00
Speaker
Four weeks to embrace your limitations and make time for what counts.
00:48:04
Speaker
This is from Oliver Berkman, who also wrote 4,000 Weeks, a phenomenal book.
00:48:10
Speaker
For Meditations for Mortals, I think it's the perfect book to read as the year starts.
00:48:15
Speaker
The intention is for you to read one chapter every day for four weeks.
00:48:19
Speaker
And really, I think he focuses on the idea of embracing imperfection.
00:48:25
Speaker
We can't do everything we have to do.
00:48:28
Speaker
So we should just embrace that and pick the things that are important.
00:48:31
Speaker
Focus on what matters.
00:48:33
Speaker
And what matters is uniquely individual for each one of us.
00:48:38
Speaker
So taking the time to really identify what is important for us in the ICU at the bedside, what's important for us at home, what's important for us in our work.
00:48:49
Speaker
And making sure that we create time and effort for that, I think, is very, very important.
00:48:55
Speaker
And finally, it's really about letting go of control.
00:48:59
Speaker
We think we have control over things we don't.
00:49:02
Speaker
And I think that if we instead focus on the things we do control, which is how present are we, what are we choosing to spend our time on,
00:49:10
Speaker
Who are we choosing to spend our time with?
00:49:14
Speaker
I think that we will have a much more meaningful life.
00:49:16
Speaker
So these two actually, I think, have some overlap, although they focus on different things.
00:49:23
Speaker
One is very specific to work and the other one is more specific to life.
00:49:27
Speaker
I highly recommend it.
00:49:28
Speaker
And then finally, the last book, which I recently finished, is called Knife, Meditations After an Attempted Murder.
00:49:37
Speaker
And it's from Salman Rushdie, which many of you might know as a very prolific author, fiction author, who many years ago wrote a book called The Satanic Verses and had a fatwa or a order to kill him placed.
00:49:52
Speaker
That was 30 years ago.
00:49:54
Speaker
And a couple of years ago, actually, somebody went through with that.
00:49:57
Speaker
and stabbed him at an event, I think 15 times.
00:50:01
Speaker
And he writes about his ordeal of surviving that.
00:50:05
Speaker
And he writes about his recovery from that trauma.
00:50:10
Speaker
And really, what was very interesting from this book is it forces you to really understand the importance of confronting our personal demons.
00:50:21
Speaker
We all have demons and grappling with them, accepting them and understanding them, I think is quite important.
00:50:28
Speaker
I also appreciated the complexity of identity from this book.
00:50:31
Speaker
I don't know much about Salman Rushdie.
00:50:33
Speaker
I haven't read many of his books.
00:50:35
Speaker
Obviously, I think a lot of people made opinions about him based on his history.
00:50:39
Speaker
But the truth is, when you read this very personal and vulnerable account, you see that like any person, he has many, many facets, very complex, like every one of us.
00:50:49
Speaker
And I think that's an important point for empathy, right?
00:50:52
Speaker
Empathy and compassion towards others.
00:50:55
Speaker
We never know what people are going through, and I think we should always think about that.
00:50:59
Speaker
And finally, I think it's a great, great testament to the power of storytelling and just, I mean, how we learn from stories and how, whether it's fiction or nonfiction, our ability to tell a story is ultimately what allows us to communicate ideas.
00:51:15
Speaker
So those are three books that I highly recommend from 2024.
00:51:20
Speaker
Pick up one of those.
00:51:21
Speaker
I'm sure that you will enjoy them.
Shifting Perspectives and Encouraging Curiosity
00:51:24
Speaker
The second question that I usually ask my guest is, what is something that you have changed your mind about?
00:51:30
Speaker
And I think especially in an election year, one of the things that I've changed my mind about is my tendency to be judgmental about others who think differently about me.
00:51:44
Speaker
And recognize that people feel differently politically, religiously, spiritually, even scientifically for a platitude of reasons.
00:51:53
Speaker
And then instead of me trying to explain my position and trying to convince others, which I think is really a lost battle, I should ask more questions.
00:52:02
Speaker
I should try to learn.
00:52:04
Speaker
I think that is much more valuable.
00:52:07
Speaker
And it's something that I really changed my mind about over the last couple of years.
00:52:11
Speaker
And I've tried to implement on a regular basis where it's discussing science, discussing science,
00:52:19
Speaker
sports, discussing politics, discussing the spiritual, is to be more curious and not try to tell people what I think, but try to learn from them or try to see why are they thinking what they're thinking, even if I don't agree.
00:52:32
Speaker
And that leaves me with my closing statement, which I think is tied to this.
00:52:38
Speaker
And it's also very important when conflict arises, where it be at home,
00:52:45
Speaker
or at work.
00:52:47
Speaker
And it's something I read that is very powerful.
00:52:51
Speaker
And basically it states that you can't be furious and curious at the same time.
00:52:58
Speaker
Choose to be curious.
00:53:00
Speaker
So I hope you have a curious 2025, that you ask a lot of questions, that you always seek to learn, and look forward to talking with you again soon on the podcast and meeting you in person and talking about, obviously, critical care topics, but also topics just related to life.
00:53:20
Speaker
So Happy New Year and see you in 2025.
00:53:25
Speaker
Thank you for listening to Critical Matters, a sound podcast.
00:53:28
Speaker
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00:53:34
Speaker
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00:53:39
Speaker
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