ReferencesRhodes A, Evans LE, Alhazzani W, et al. Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock: 2016. Crit Care Med. 2017 Jan 17. doi: 10.1097/CCM.0000000000002255. [Epub ahead of print] PubMed PMID: 28098591.
This video is part of a special 6-episode series of McMaster Perspective focusing on Surviving Sepsis Campaign 2016 guidelines.
Roman Jaeschke: Good morning again. This is another section on Surviving Sepsis Campaign for the McMaster Perspective series. Doctor Waleed Alhazzani is still with us. These are active medications: norepinephrine, epinephrine, dopamine, dobutamine. What kind of messages could we pass to clinicians?
Waleed Alhazzani: It is an important question again. These vasoactive agents are amongst the most common agents used in treating patients with septic shock, and obviously which agent to use first is important to highlight for clinicians because we have different options. The way the guidelines are phrased now, probably norepinephrine will be your first choice. This is mostly based on studies comparing norepinephrine to dopamine, which showed that norepinephrine is associated with less risk of death and less risk of arrhythmias. [...] You will develop more uncertainty when you look at other comparisons, so when comparing norepinephrine with vasopressin, for example, although more studies used vasopressin as an add-on or adjunct to norepinephrine, there was no clear advantage, at least, or effect on mortality with using vasopressin over norepinephrine. Therefore, the panel members decided that probably norepinephrine is your first agent.
However, the guideline also does not tell us which is the best second agent with clarity, and the reason for this is we do not know what is the best second agent. We know that vasopressin is probably more studied than epinephrine as an add-on treatment. There are larger, definitely larger randomized controlled trials (RCTs), definitely larger quality of evidence, higher quality of evidence studies. Epinephrine, unfortunately, was studied in very small RCTs and saying that vasopressin is better than epinephrine or epinephrine is better than vasopressin as a second-line agent is not really… we are not in a position to say which agent is better. There was a network meta-analysis that used indirect comparisons and also failed to show which agent is better than the other.
RJ: Maybe they are equal?
WA: We do not know, therefore we suggested using epinephrine as an add-on treatment or vasopressin to reduce your norepinephrine dosing. The way we practice in Hamilton, we are more comfortable using vasopressin as a second-line agent. There will be some situations, obviously, depending on the clinical status of the patient, when epinephrine will be more useful.
Also, one of the downsides that we discussed with using epinephrine [is that] in this guideline we suggest normalizing lactate levels. Using epinephrine might cause some confusion, because we know epinephrine can lead to higher lactate levels and may confound this management plan. However, we did not feel this is enough for us to say “shy away from epinephrine, use more vasopressin.” Again, it will still be left to the judgment of the clinician.
RJ: So thankfully judgment of physicians still matters. There is a recommendation to have arterial line while using pressors, but I have not seen one for central line. Was it omitted on purpose or...?
WA: Another excellent question. The arterial line question was prioritized by the panel members as an important question to address in the guideline. We did not entertain the central line question separately. About the arterial lines, they are simple to insert, low-risk procedures. When available, it might be a good idea to have continuous monitoring of the blood pressure, and it may also give you an access to get some blood work for patients. Central lines, however, are more invasive, require expertise, although now, in the era of ultrasound, complication rates are lower. Whether a patient needs a central line all the time is hard to say; definitely when using pressors for a prolonged period of time it might be a good idea to use a central line. However, I would not delay giving pressors just based on the fact that there is no central line involved. You can always start peripherally and get the central line access afterwards.
RJ: We are talking about many specific subjects here. Use of steroids in sepsis – was that discussed this time?
WA: The use of steroids in sepsis: in this specific guideline, there were 2 new RCTs; they were on the way, they were not published when we had to publish this version of the guideline, so there was no big changes in recommendation compared to the previous versions. I would, however, wait – I am still waiting to hear about the results of 2 newer studies and see how that will impact practice. So for the time being, we will not change practice or we will not recommend changing what we are doing, we may be giving steroids for patients on vasopressors and you might consider giving steroids, usually...
RJ: High doses?
WA: Yes, high-dose pressors; you might consider giving steroids, usually for a shorter duration and smaller dosing. We know that higher dosing is probably harmful, very prolonged duration [is also] probably harmful. But I think we still need some guidance because the data are not that clear; there is a Cochrane review that looked at this and included a lot of studies, but again, the quality of data was not the highest.
RJ: So when we are still giving up to 200 mg of hydrocortisone per day in people who are on substantial – the question is what is substantial – dose of pressors, it is an acceptable practice.
RJ: Thank you. Another, completely different topic: use of blood products. There is a strong recommendation to transfuse people only once their hemoglobin is less than 70 g/L. If I transfuse it for a person whose hemoglobin is 78 g/L, am I committing an error?
WA: Another excellent question. I do not think there are any studies that looked at these 2 close thresholds. Honestly, […] although this is a strong recommendation, the reason for setting this as a strong recommendation is [that] studies that compared 2 thresholds, liberal thresholds – this is 90 g/L and above, or 70 g/L, sorry, 90 g/L or below or 70 g/L or below – did not show any difference in patient-important outcomes when it came to blood transfusion. And no matter what population you look at, if you look at septic patients, if you look at critically ill patients, if you look at patients with acute upper gastrointestinal (GI) bleeding who are cardiac surgery patients, it has been a consistent message that we have seen. So probably the incremental benefit of using a higher threshold is not worth giving more blood product. However, there are certain patient populations where you may consider giving blood product – or let’s say, the question is not clearly answered – so patients with acute coronary syndrome, for example. In patients who are having active hemorrhage or exsanguinating eye wound, we rarely rely on the thresholds anymore, because there is no appliance in this context. Although this is, again, a strong recommendation, the question you asked me is not addressed by this recommendation. If a physician transfuses a patient with a hemoglobin of 78 g/L, I would think it is still acceptable, I do not think it is an error and I do not think we should be thinking in a dichotomous fashion about this. Also, there will be some patients that might benefit from a higher threshold, it is just we do not know which patient populations [these are]. So again, there should be some rules for clinical sense; all these guidelines to guide help standardize practice. I do not think we should say “okay, you transfused a patient for hemoglobin of 72 g/L, that is a mistake, you should not be doing that.” No, there should be some flexibility. But obviously, if clinicians are routinely transfusing patients to achieve a hemoglobin of 100 g/L, that again, probably, might be wrong.
RJ: Thank you very much for this segment. I think we will still have some topics to discuss. Thank you very much.
WA: Thank you.