Dr Waleed Alhazzani, associate professor in the Division of Critical Care at McMaster University, chair of Surviving Sepsis Campaign (SSC) guidelines, and lead author of the newest SSC guidelines focusing on coronavirus disease 2019 (COVID-19) in the critically ill, joins Dr Roman Jaeschke to discuss hemodynamic support (vasoactive agents, fluid therapy, neuromuscular blockade).
ReferencesAlhazzani W, Møller MH, Arabi YM, et al. Surviving Sepsis Campaign: guidelines on the management of critically ill adults with Coronavirus Disease 2019 (COVID-19). Intensive Care Med. 2020 Mar 28. doi: 10.1007/s00134-020-06022-5. [Epub ahead of print] PubMed PMID: 32222812; PubMed Central PMCID: PMC7101866.
Roman Jaeschke, MD, MSc: Good morning. Welcome to another edition of McMaster Perspective. We have with us our star guest, Professor Waleed Alhazzani.
We talked about ventilation strategies as part of supportive care. How about other aspects of supportive care? Maybe you could contrast this with the other major guidelines within which you play a leadership role, the Surviving Sepsis Campaign. The floor is yours.
Waleed Alhazzani, MBBS, MSc: We did issue recommendations on hemodynamic support for those patients who develop shock. Fortunately, not many patients with coronavirus disease 2019 (COVID-19) develop shock. However, a proportion of patients develop sepsis and septic shock. There have also been case reports of fulminant myocarditis or cardiac injury that is thought to be related to cytokine release syndrome. But from what I know from personal communication, at least colleagues in Italy did not see cardiac injury or failure very often, as opposed to colleagues in China.
The guideline focused mostly on the management of patients with shock. Almost all recommendations were based on existing evidence on how to treat patients with septic shock.
We addressed vasoactive agents and which vasopressors should be used. We favor using norepinephrine, for obvious reasons: it’s the most studied and it showed some benefit and less harm compared with other agents, like dopamine.
The problem with norepinephrine is that I learned recently it’s not available in some low-income countries. In North America we think norepinephrine is available everywhere, but in some countries it is not. So we said that if norepinephrine is not available, you could use epinephrine or vasopressin as your agent of choice.
We caution people against using dopamine, because it increases the risk of arrhythmias and may increase the risk of death and shock in general compared with norepinephrine, but sometimes it’s the only option that you have.
There’s more uncertainty about other agents, so we did not address them in detail.
We also say to have a lower threshold or suggest to use vasopressin add-on therapy over just titrating up the norepinephrine dose if the pressor requirement is going up and you’re not able to achieve the mean arterial pressure (MAP) target.
Roman Jaeschke: So similarly to the Surviving Sepsis Campaign guidelines.
Waleed Alhazzani: Correct. The main difference [between COVID-19 and] managing septic patients is probably that we reflected on the recent evidence on MAP targets and now we made a suggestion to use an MAP target of 60 to 65 mm Hg, based on the most recent studies that came out.
We also said to use a conservative fluid strategy as opposed to a liberal fluid strategy. One of the reasons is that most of those patients will have a respiratory component, including acute respiratory distress syndrome (ARDS), and keeping them more towards [euvolemia], or avoiding [hypervolemia], is probably helpful for those patients.
Roman Jaeschke: Even at the expense of using some pressors?
Waleed Alhazzani: It goes back to clinical assessment. Based on dynamic measures to predict fluid responsiveness, echocardiographic assessments, or even just a simple clinical examination—whatever is available—if clinicians think the patient is hypovolemic and they need fluid, then you can definitely use fluids, but it might be a good idea not to use too much fluid as it could be harmful. We could not recommend one specific strategy because studies were mixed in terms of strategies they used to define a conservative fluid strategy. The general idea is that in this population probably less is more.
Roman Jaeschke: And which fluids should we use?
Waleed Alhazzani: Good question. We made a conditional, or weak, suggestion to use balanced crystalloids over saline. Again, this is completely indirect evidence, not specific to COVID-19 patients, but we think it might be applicable to patients in the intensive care unit (ICU).
The total body of evidence suggests that maybe there is some benefit, even in terms of the risk of death, if you use balanced crystalloids over saline. There are larger ongoing randomized controlled trials (RCTs). Some have finished recruitment, so hopefully we will have more definitive answers. For the time being, we made a weak recommendation for balanced crystalloids.
We also made a strong recommendation for using crystalloid solutions over albumin solutions for early resuscitation.
Roman Jaeschke: That’s news. Albumin seemed to be quite acceptable in the Surviving Sepsis Campaign guidelines [the 2016 Surviving Sepsis Campaign guidelines for general sepsis management]. Any specific reason?
Waleed Alhazzani: […] Albumin doesn’t seem to be better than crystalloids in this population of patients with sepsis. Also, it’s costly, so if you’re treating a large number of patients, it might be a good idea to start with solutions that are not associated with large costs, as opposed to giving everybody albumin.
Having said that, we also say that supplemental albumin might be an acceptable solution. We made a conditional recommendation, so that people can use some supplemental albumin in certain situations. My usual practice is that if I give 2 to 3 L of crystalloids, sometimes supplementing this with albumin, I find that vasopressor requirements go down. Also, considering some of the studies that looked at diuresis, even in the context of early [stages], the first 24 to 48 hours, some people have used albumin with furosemide (brand name Lasix), especially in patients with ARDS, to try to maintain euvolemia.
I think there may be some rules for albumin use, but in a pandemic, when you have a large number of patients, it’s probably better to use other alternatives.
Roman Jaeschke: The pendulum swings away from albumin, but it’s still not an error to use it.
Waleed Alhazzani: Correct. We don’t say you’re wrong if you use albumin.
Roman Jaeschke: Let’s move to neuromuscular blockade.
Waleed Alhazzani: That’s another important recommendation to talk about. Neuromuscular blockade could be helpful in patients who are invasively mechanically ventilated when there is dyssynchrony with the ventilator that is not controlled with setting adjustment or sedation, and also in situations where plateau pressure targets are not achieved and they’re high or when you’re proning somebody who is invasively mechanically ventilated. These are the common scenarios where paralysis is warranted.
The usual practice before was that we had a lower threshold to start everybody, or a lot of patients, on continuous infusions. We typically use cisatracurium, the most commonly studied drug, at least in the French studies. Having said that, the recently published ROSE (Reevaluation of Systemic Early Neuromuscular Blockade) trial did not reproduce the previous findings of the ACURASYS (ARDS et Curarisation Systematique) trial. However, there were fundamental differences in the design of those 2 studies.
The bottom line, at least from my point of view and the guidelines, is that it’s probably OK to start with intermittent boluses as needed for the indications that I’ve mentioned. So we made a suggestion to use intermittent dosing in moderate to severe ARDS patients who require paralysis. But if this intermittent dosing does not help and you find that the patient requires more dosing or more paralysis, or they require deep sedation just to keep them synchronized with the ventilator, or they’re proned, or they have persistent hypoxemia and high elevated pressures and you think paralysis on an ongoing basis would be helpful, then we issued a suggestion to use a continuous infusion, typically for 48 hours or less.
Roman Jaeschke: So short continuous infusions are still acceptable.
We talked about protection of health-care workers and patients as well as about supportive care, ventilatory and otherwise. What we have left is probably of most interest: treatments, and those are evolving almost on a daily basis. Let’s talk about them next time. Thank you very much for now.
Waleed Alhazzani: Thank you.