SCCM Resource Library-Improvement in Mortality Linked to Protocol Compliance Guiding Angiotensin II Use

Video Transcription

Good afternoon, everyone. My name is Nicholas Barker, and I'm a clinical pharmacy specialist in the ICU at Emory St. Joseph Hospital.  Today, I'm going to be presenting on the improvement in mortality linked to protocol compliance guiding angiotensin II use.  At this time, neither myself or my co-investigators have anything to disclose. Distributive shock is defined by low systemic vascular resistance with normal or enhanced  cardiac output and accounts for approximately two-thirds of all shock. Traditional first-line therapies include catecholamines and vasopressin, however, at high doses, these  can cause significant adverse effects. Newer and novel agents, such as angiotensin II, methylene blue, and hydroxycobalamin may be used.  The question arises, can ICU mortality decrease with a multimodal therapy? At this point, however, no agent has demonstrated to provide significant mortality benefit.  The 2016 surviving sepsis guidelines do address catecholamine and vasopressin recommendations, however, they do not provide any guidance on angiotensin II.  ATHOS-3 was published after these guidelines were released. ATHOS-3 did demonstrate a rise in MAP and a decrease in catecholamine and vasopressin  rate at hour 3 in angiotensin II use. After this, the FDA approved angiotensin II and Emory developed a protocol.  You can see here that the initiation of norepinephrine was first recommended with titration by the RN.  Once the dose of norepinephrine reached greater than 0.1 micrograms per kilogram minute, vasopressin can be considered at a flat rate of 0.3 or 0.4 units per minute.  The norepinephrine is then subsequently titrated to reach the MAP goal. If norepinephrine reaches greater than 0.2 micrograms per kilogram per minute, angiotensin II can be started.  The norepinephrine is then titrated to the MAP goal and the angiotensin II is adjusted based on the resulting norepinephrine dose.  You can see here in table 1, this is where we calculate the norepinephrine equivalents. This was taken from ATHOS-3.  Table 2 uses the norepinephrine equivalent, vasopressin, and the angiotensin to determine the dose for each of these.  You can see here that at less than 0.1 norepinephrine equivalents, vasopressin should be off and angiotensin II should be off.  At 0.2 to 0.3 norepinephrine equivalents, vasopressin should be on and angiotensin II can be considered at 10 nanograms per kilogram per minute.  Angiotensin II maximum dose at Emory is 40 nanograms per kilogram per minute and can be titrated up or down by 5 nanograms per kilogram per minute when a MAP response necessitates  this. After this protocol was developed, education was given to providers. The use of angiotensin II did significantly increase.  So in June of 2019, providers came together and were required to take a recorded presentation and a post-education exam.  Since that exam, we provide timely feedback to providers when they deviate from the protocol and assess on a weekly basis for compliance.  This was a multi-center retrospective study of 196 patients who received angiotensin II for non-cardiac related shock within Emory HealthCare from 2018 to 2020.  Multimodal therapy with norepinephrine and vasopressin and angiotensin II was intervention  We compared patients' encounters, rating them on protocol compliance, and grouped them as one of three groups, compliant, moderately compliant, or poorly compliant to the multimodal  therapy. The primary outcome was ICU mortality. The scoring was based on four categories, the norepinephrine compliance, vasopressin  compliance, angiotensin II initiation grade, and then the presence of high output shock. The total of compliance scores are listed below, with a compliance score being six or  less, moderately compliant, seven to eight, and poorly compliant, greater than eight. If you look at the norepinephrine equivalent dosing, you can see as the norepinephrine  dose escalates, so does the score. With above 0.5 giving a score of four, we also did notate that a score of five if norepinephrine was less than 0.1.  For vasopressin, it was just a yes or no if they were receiving it, as well as for angi-2, what their starting rate was. Was it 10 or not 10?  For high output shock compliance, we looked if it was documented prior to, after, if it was not documented at all, or if they had a low output documented.  Looking at total demographics of all 196 patients, the mean age was 60 years old, about 60% were  male, the mean SCOFA score was 10.8, our mean compliance grade was 6.8, and our hospital mortality was 64%, with an ICU mortality of 60%, a mean hospital length of stay of 21  days, and a mean ICU length of stay of 12 days. When breaking these patients down to compliant, moderately compliant, and poorly compliant,  you can see about three-fourths of all patients were either compliant or moderately compliant.  You can see that the mean SCOFA score was 11.1 in compliant group, 11.5 in the moderately  compliant group, and 9.4 in the poorly compliant group, excuse me, while the mean compliance grade was 5.2, 7.4, and 9.3, respectively.  You can see that hospital mortality ranged from 56% to 74%, with ICU mortality ranging from 55% to 65%.  Looking at patients' outcomes pre- and post-retraining, you can see that the mean compliance grade  was higher in those total cases before retraining, and significantly lower after retraining at 6.3.  It's also important to note that the norepinephrine at time of order and administration was significantly lower after retraining.  Hospital length of stay was longer in our retraining group, while the ICU length of stay had no difference.  Interestingly, the hospital and ICU mortality was significantly lower in our retrained group, with an odds ratio of hospital mortality at 2.87 and ICU mortality odds ratio at 2.42.  In breaking these down into the three groups, pre-retraining and post-retraining, we saw a significant decrease in the incidence of poorly compliant cases.  We cut those approximately by half, which may explain our benefit in mortality. In conclusion, the study evaluated the use of angiotensin II as an algorithm of multimodal  vasopressor support. The Emory protocol is easy to implement for the treatment of distributive shock in a standardized  approach emphasizing multimodal therapy, which provides guidance on early initiation of non-catecholamines  such as vasopressin and angiotensin II at lower catecholamine doses, coupled with a rigorous protocol for training, may be essential for improving outcomes in shock.  Noted limitations include retrospective chart review. We did not assess the up and down titrations of angiotensin II, and the protocol was based on a group consensus.  I'd like to acknowledge my following investigators, and at this time, I'll take any questions.

Video Summary

This video presentation discusses the use of angiotensin II in the treatment of distributive shock. The speaker explains that traditional therapies for distributive shock, such as catecholamines and vasopressin, can have adverse effects at high doses. The speaker then introduces angiotensin II as a potential alternative therapy and explains the protocol for its use at Emory St. Joseph Hospital. They also discuss a retrospective study that evaluated the compliance with the angiotensin II protocol and its impact on ICU mortality. The study found that improved compliance with the protocol led to lower hospital and ICU mortality rates. However, the study has limitations, including its retrospective nature and reliance on a consensus-based protocol.

Asset Subtitle

Pharmacology, Shock Non Sepsis, 2021

Asset Caption

The Society of Critical Care Medicine's Critical Care Congress features internationally renowned faculty and content sessions highlighting the most up-to-date, evidence-based developments in critical care medicine. This is a presentation from the 2021 Critical Care Congress held virtually from January 31-February 12, 2021.

Nicholas Barker

Introduction/Hypothesis: The novel non-catecholamine vasopressor angiotensin II (Ang II) has recently been approved for high output shock, though a standardized approach for use has yet to be firmly established. We developed and trained all appropriate providers over a two-week period on a proprietary protocol at Emory Healthcare (Emory Protocol), which includes guidance on (i) background norepinephrine equivalent dose, (ii) documentation of high output shock, (iii) use of vasopressin, and (iv) starting dose of Ang II. We sought to evaluate whether adherence to the Emory Protocol resulted in an improvement in ICU mortality.

Methods: We recorded ICU mortality and protocol compliance for sequential patient encounters where Ang II was used, which we measured on a point system. Points were awarded for appropriateness of background catecholamine dose (scored 1 to 5), presence of vasopressin (scoreed 1 or 2), documentation of high output shock (scored 1 to 4), and starting dose of Ang II (scored 1 or 2). Compliant was classified as a score of 6 or less and moderately compliant if 7 to 8. A score of 9 or greater was classified as poorly compliant. We further separated all encounters into those that occurred before protocol training and those that occurred after training to compare average compliance score and associated mortality between these two cohorts.

Results: Of the 196 consecutive patients who received Ang II, average SOFA score was 10.8 and overall ICU mortality was 59%, with an average compliance score of 6.8. Of the 112 patient encounters before protocol education, the average compliance score was 7.2, with an associated ICU mortality of 69%. However, in the 74 patient encounters that occurred after protocol education, the average compliance score improved to 6.3, with an associated ICU mortality of 49%. The odds ratio for death in patients who were treated with Ang II prior to protocol training was 2.32 (95% CI: 1.27 to 4.26, P=0.0064).

Conclusions: Compliance with the Emory Protocol was shown to be associated with a statistically significant reduction in ICU mortality in critically ill patients receiving Ang II. A standardized approach emphasizing multi-modal therapy including early Ang II use and correct patient identification, coupled with rigorous protocol training, may be essential for improving outcomes.

Meta Tag

Content Type Presentation

Knowledge Area Pharmacology

Knowledge Area Shock Non Sepsis

Knowledge Level Advanced

Membership Level Select

Tag Vasoactive Agents

Tag Pharmacokinetics Pharmacodynamics

Tag Shock

Year 2021

Keywords

angiotensin II

treatment

distributive shock

alternative therapy

Emory St. Joseph Hospital

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