In our March 2016 What's New in the Patient Safety World column “” we welcomed a new consensus definition for sepsis that did away with the SIRS criteria (Singer 2016). For many years we had been on our soapbox about the games played where the patient with pneumonia happily pushing his IV pole up and down the hallway who meets a couple SIRS criteria gets coded as "sepsis", which of course gets a significantly higher reimbursement than pneumonia. The coding games largely skewed the mortality statistics for both “pneumonia” and “sepsis”. So it was with great enthusiasm that we welcomed the new definition that excluded the SIRS criteria.
But the usefulness of this new definition still needed validation in clinical settings. That validation has now come from 2 studies in several settings. Both studies looked at the ability of the Sequential [Sepsis-related] Organ Failure Assessment (SOFA) score and the quick SOFA (qSOFA) to predict mortality (see our March 2016 What's New in the Patient Safety World column “” for details of the new definitions). One validation study was done retrospectively in the ICU setting, the other prospectively in the emergency department setting.
Freund and colleagues found that among patients presenting to the emergency department with suspected infection, the use of qSOFA resulted in greater prognostic accuracy for in-hospital mortality than did either SIRS or severe sepsis (Freund 2017). These findings provide support for the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3) criteria as a predictive tool, at least in the emergency department setting. The qSOFA in that setting was as good as the full SOFA in predicting mortality. Those patients with a qSOFA score of 2 or more had an in-hospital mortality rate of 24% whereas those with qSOFA scores <2 had a 3% mortality. Moreover, the addition of serum lactate did not further enhance the predictive value.
The SOFA score also does well at predicting mortality in ICU patients with sepsis but the shorter qSOFA may not fare as well in ICU patients. Raith and colleagues found that among adults with suspected infection admitted to an ICU, an increase in SOFA score of 2 or more had greater prognostic accuracy for in-hospital mortality than SIRS criteria or the qSOFA score (Raith 2017). In that study another more complex tool, the Logistic Organ Dysfunction System, also predicted ICU patient mortality better than the qSOFA. These findings suggest that SIRS criteria and qSOFA have limited utility for predicting mortality in an ICU setting. Note, though, that the qSOFA fared as well or better than Logistic Organ Dysfunction System or the full SOFA in sepsis patients not in the ICU.
In the editorial accompanying these two studies, Lamontagne and colleagues (Lamontagne 2017) stress that early identification of sepsis is still key and that, until future rapid diagnostic tests for sepsis are developed, the qSOFA is a simple tool that appears to be useful.
The Surviving Sepsis Campaign promptly responded to the new definition(s) in March 2016, noting that the implementation of the new definitions and related coding changes would take time for hospitals but reiterating that the new definitions do not change the primary focus of early sepsis identification and initiation of timely treatment (response March 2016).
Howell and colleagues also recently provided a summary of the updated guidelines for managing sepsis (Howell 2017). The highlights include:
There were also recommendations regarding mechanical ventilation parameters for patients with sepsis-related ARDS and a general statement that hospitals and health systems should implement formal programs to improve sepsis care that include sepsis screening. The full updated guideline will be in the March 2017 issue of Critical Care Medicine and is now available online (Rhodes 2017).
Time is of the essence in management of sepsis. We still need to focus on early recognition, timely antibiotics and adequate fluid resuscitation to reduce morbidity and mortality from “sepsis”. It does appear that the new definitions are steps in the right direction and will help us better manage sepsis going forward.
Our other columns on sepsis:
Singer M, Deutschman CS, Seymour CW, et al. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA 2016; 315(8): 801-810
Freund Y, Lemachatti N, Krastinova E, et al. for the. Prognostic Accuracy of Sepsis-3 Criteria for In-Hospital Mortality among Patients with Suspected Infection Presenting to the Emergency Department.
Raith EP, Udy AA, Bailey M, et al. Prognostic Accuracy of the SOFA Score, SIRS Criteria, and qSOFA Score for In-Hospital Mortality among Adults with Suspected Infection Admitted to the Intensive Care Unit. JAMA 2017; 317(3): 290-300
Lamontagne F, Harrison DA, Rowan KM. qSOFA for Identifying Sepsis among Patients with Infection. JAMA 2017; 317(3): 267-268
Surviving Sepsis Campaign website.
Surviving Sepsis Campaign. Surviving Sepsis Campaign Responds to Sepsis-3. March 1, 2016
Howell MD, Davis AM. Management of Sepsis and Septic Shock. JAMA 2017; Published online January 19, 2017.
Rhodes A, Evans LE, Alhazzani W, et al. Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock: 2016. Critical Care Medicine 2017; 45(3): 1-67 Published-Ahead-of-Print Post Author Corrections: January 17, 2017
We’re always looking for good tools we can use when we are doing adult learning sessions on patient safety for patients and families. Recently we came across several useful tools from the Manitoba Institute of Patient Safety. Their S.A.F.E. Toolkit – Self Advocacy for Everyone has available both the toolkit and a guide for leaders of structured sessions on the toolkit.
Topics in the toolkit are:
The Leader’s Guide, in particular, has many useful practical tips on how to prepare for your sessions, including checklists to help in such preparation. It includes discussion of timeframes, ground rules, presentation techniques, and even has sample evaluation forms.
The handouts for patients are excellent and comprehensive. Each helps them prepare for their various meetings with members of the healthcare team and provides them with great lists of the questions they (and their advocate) should ask. For example, the one on preparing for surgery has sections on informed consent and deciding whether to undergo surgery, pre-op testing, who will be doing the surgery and providing anesthesia, anesthesia options, preparing for the surgery, what to expect on the day of surgery, what to expect postoperatively, etc. It even has questions to ask if procedures are to be performed in the office.
The section on patient advocates is excellent, describing not only how to choose an advocate but also discussing questions the advocate might ask, access the advocate might have to your medical records, differences between an advocate and a health care proxy, etc. It even provides a sample “My Patient Advocate Agreement”.
While some of the materials are tailored for the Canadian healthcare system(s), they are easily adaptable to those in other countries.
If your healthcare organization offers such educational sessions on patient safety for your patients and their families (as you should!), you’ll find the resources from the Manitoba Institute of Patient Safety very useful.
Manitoba Institute of Patient Safety. S.A.F.E. Toolkit – Self Advocacy for Everyone.
Given the recent holiday shopping season, most of you are familiar with the acronym “BOGO” (Buy One, Get One). It turns out that with critical adverse events, if you have one on a med-surg unit you are also more likely to get another one!
Researchers at the University of Chicago analyzed data from 13 med-surg wards where rapid response teams were used and looked at cardiac arrests and urgent transfers to ICU’s (Volchenboum 2016). They found that in the 6-hour window following a cardiac arrest or urgent transfer to ICU, the likelihood of a second similar event increased 18%. And if 2 events occurred the likelihood of a third event on that ward increased 53%. These results remained statistically significant when the time window was changed to 3 hours or 12 hours after the first event.
The authors explained the findings by likely diversion of resources to critically ill patients, resulting in less attention to other patients on the ward. Anyone who has observed all the events taking place on a ward when a patient has a cardiac arrest or other critical event would not be surprised that less attention gets paid to other patients on the ward. But this is the first time, to our knowledge, that anyone has formally quantified this phenomenon.
The authors stress that although the absolute increased risk was small, these events were associated with high morbidity and mortality.
We don’t know what the best solution for this issue is. Obviously, key personnel from the ward are needed to work with the Rapid Response Team (or equivalent group of people responding to a critical event) but there probably should always be clear designation of someone to maintain surveillance over the remaining patients on the ward. And that should be an element covered in your training for Rapid Response Teams.
Our other columns on rapid response teams:
Volchenboum SL, Mayampurath A, Göksu-Gürsoy G, et al. Association between In-Hospital Critical Illness Events and Outcomes in Patients on the Same Ward (Research Letter). JAMA 2016; Published online December 27, 2016
The FDA has just approved another long-acting opioid (FDA 2017). So we’ll take this opportunity to repeat our warnings and concerns about the use of such drugs. For quite some time now we have highlighted the dangers of long-acting and/or extended-release opioids (see our Patient Safety Tips of the Week for June 28, 2011 “Long-Acting and Extended-Release Opioid Dangers”, July 24, 2012 “FDA and Extended-Release/Long-Acting Opioids” and February 24, 2015 “More Risks with Long-Acting Opioids”).
The newly approved drug, Arymo ER, is an extended-release tablet formulation of morphine sulfate, designed with properties intended to deter abuse based on its physicochemical properties. The proposed indication is the management of pain severe enough to require daily, around-the-clock, long-term opioid treatment and for which alternative treatment options are inadequate. It is unique in that it is formulated to give it physicochemical properties expected to make abuse by injection difficult. Apparently the manufacturer had hoped to be allowed to claim the drug deters abuse by snorting or chewing it but the FDA approval did not allow that claim.
One of the elements of the FDA Opioids Action Plan is to expand access to abuse-deterrent formulations to discourage abuse. That is essentially developing formulations that abusers cannot manipulate and use the opioid for intravenous, intranasal, or oral abuse.
But our concerns about the safety of long-acting or extended-release opioid formulations extend well beyond the issue of manipulating the product for abuse. Such preparations have other dangers (well described in our Patient Safety Tips of the Week for June 28, 2011 “Long-Acting and Extended-Release Opioid Dangers”, July 24, 2012 “FDA and Extended-Release/Long-Acting Opioids” and February 24, 2015 “More Risks with Long-Acting Opioids”).
First and foremost is that these long-acting and extended-release opioid formulations are not intended for use as first-line agents in opioid-naïve patients. The newer opiate formulations are either more potent or designed to produce a longer peak action, two characteristics that lead to some of the greatest dangers. These have been designed to be used in patients who are opioid-tolerant and have pain of a chronic nature that has not been controlled with more conventional opiates. They were not intended to be used for treatment of acute pain nor to be used as first line agents in patients with pain. But in practice they are often being (mis)used in that way.
A second significant factor related to the association between long-acting opioids and overdoses is dosage equipotency. The amount of morphine equivalents in these preparations is typically higher than that found in most short-acting formulations and many prescribers are not appreciative of this. Of course, the issue of dose is not unique to the long-acting opioids. We’ve highlighted the same problem with HYDROmorphone in our September 21, 2010 Patient Safety Tip of the Week “Dilaudid Dangers” and the other columns on HYDROmorphone safety issues listed below. It is also problematic that when switching from short-acting opioids to long-acting or extended-release opioids it is very common to see misunderstandings of the relative potencies of the various opiate preparations.
We’ve also seen patients develop delayed-onset coma after attempting suicide. If the specific formulation they took is unknown, they may be evaluated in an ER prior to admission to a behavioral health unit, at which time they lack clinical signs of opioid intoxication and may have very low toxicology levels. They are given “medical clearance” and admitted to the behavioral health unit. Overnight they get further release of the opioid into their bloodstream and the following morning they may be comatose.
Another important issue for these long-acting and extended release opioids is the phenomenon of re-narcotization. The effect of the reversal agent naloxone may wear off long before the effect of the opioid wears off, raising the danger of recurrence of respiratory depression.
We’ve also seen rare cases in which patients on these long-acting opioid formulations have developed acute opioid withdrawal symptoms following naloxone injections.
Note that long-acting opioid formulations (particularly those in transdermal patches) are also now frequent causes of accidental overdoses, including those for whom they were not prescribed such as children and pets (see our September 13, 2011 Patient Safety Tip of the Week “Do You Use Fentanyl Transdermal Patches Safely?” and our May 2012 What’s New in the Patient Safety World column “Another Fentanyl Patch Warning from FDA”).
So even though we appreciate the FDA’s vision of abuse-proof formulations, we are concerned about the ever increasing availability of long-acting or extended-release opioid formulations. Ironically, the following quote from the FDA briefing document (FDA 2016) for the advisory committee meeting that evaluated the new opioid formulation says a lot about the siloed nature of our healthcare system: “There has been much discussion at recent advisory committee meetings about whether any new extended-release opioid analgesics are necessary or should be approved. As long as a product meets the regulatory standards for approval, whether or not there is need for a new version of an opioid is not a criterion for not approving the product.”
And as if that were not enough, as we went to post this column we received word the FDA (FDA 2017b) has just approved yet another extended-release opioid formulation: Vantrela ER (hydrocodone bitartrate)! FDA documents (FDA 2017c) note that “the physical and chemical properties of Vantrela ER are expected to make intravenous (injection) abuse difficult and are expected to reduce, but not eliminate, abuse by nasal and oral routes. However, abuse of Vantrela ER by these routes is still possible.”
Our prior articles pertaining to long-acting and/or extended release preparations of opioids:
Our prior columns on patient safety issues related to Dilaudid/HYDROmorphone:
FDA (US Food & Drug Administration). Impact of Exclusivity on Approval of Arymo ER. FDA 2017; January 9, 2017
FDA (US Food & Drug Administration). Fact Sheet – FDA Opioids Action Plan. Accessed January 23, 2017
FDA (US Food & Drug Administration). FDA Briefing Document. Joint Meeting of Anesthetic and Analgesic Drug Products Advisory Committee and Drug Safety and Risk Management Advisory Committee. August 4, 2016
FDA (US Food & Drug Administration). Approval letter for Vantrela ER (hydrocodone bitartrate) extended-release tablets. January 19, 2017
FDA (US Food & Drug Administration). Timeline of Selected FDA Activities and Significant Events Addressing Opioid Misuse and Abuse. January 17, 2017
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