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The AACE/ADA Consensus Statement on Inpatient Glycemic Control and Patient Safety – What key points were made and what was still left unsaid?

2009-05-29 14:31:41
By: Dr. Richard Hellman

On May 8th, 2009, the AACE/ADA Consensus Statement on Inpatient Glycemic Control was published on-line, simultaneously in both Diabetes Care and Endocrine Practice. The ten-member panel of experts, co-chaired by Etie Moghissi and Mary Korytkowski, worked together since late 2008 to put together this document. I was honored to be one of the ten members who wrote the paper. My responsibility was to focus on patient safety, systems that promote safety, and also on glucose meters, their deficiencies in the areas of accuracy and precision, and how those deficiencies impact the safety of the patients.

It will be no surprise to all who read the document carefully that patient safety was treated both carefully and in great detail. Perhaps because so many of the outstanding multi-disciplinary panel are deeply involved with the day-to-day problems in safely achieving inpatient glycemic control, great care was made to assure that the document is very balanced, and to not overstate the conclusions of the authors. For example, the statement that the recommended target glycemic level should be 140-180mg% is paired with the statement that "greater benefit may be realized at the lower end of this range". It is then followed by the statement that lower glucose targets may be appropriate in selected patients, but targets under 110mg/dl are not recommended.

The authors' reasoning was that the evidence from numerous recent randomized clinical studies showed increased harm at the lowest targets. Even though there was earlier evidence, both from the Van Den Berghe trials and from other non-randomized trials, of the efficacy and safety of lower targets, those studies were relatively few in number, and in the face of conflicting studies, the writing panel agreed that it was better to be conservative in the recommended targets.

It is noteworthy that both in the article and in the discussions that led to it, many of the panelists, including myself, were concerned that people might look at the target levels noted in the paper and conclude that glucose levels of 180mg% or greater might be acceptable. In fact, there is very strong evidence that such levels are harmful to inpatients with hyperglycemia and lead to adverse outcomes in both mortality and morbidity. Another important conclusion, both stated and implied, that can be fairly drawn from the paper was that the risk/benefit ratio for any individual patient is often not the same and individualization of therapy is important to provide the best outcomes.

In the consensus statement we pointed out the many systemic problems that may present barriers to safer clinical care and how to look for them. There was a brief discussion of the limitation of point-of-care glucose meters, both regarding their inaccuracy in special situations, and the more general issues that currently limit the usefulness of these devices. At present, many hospitals take for granted that the glucose meters they use are giving accurate and reproducible results. Their hospital personnel are basing insulin doses upon the reported glucose levels obtained from these meters. However, the reality is that many of the glucose meters in common use are affected not only by interfering substances that differ between types of glucose meters, but also by other factors such as the hematocrit of the patient. One of the underlying problems for all of the meters is that the standards for the accuracy and precision of the meters, which are set by the FDA, are so low that relatively large and potentially dangerous errors in insulin administration can and do result. Additionally, many hospitals do not either train or supervise how their personnel use these glucose meters, which need to be used in a very consistent way in order to obtain optimal performance. Errors due to faulty operator technique add to the inherent problems of inaccuracy of many of the meters.

An important method that is crucial to maintaining a high quality of glycemic control is to properly use glucose metrics. The consensus statement contains a recommendation that glucose metrics be kept to monitor the performance of glycemic control. These metrics are used for evidence-driven decisions about glycemic control. Keeping glucose metrics regarding the actual day-to-day performance of the hospital staff in glucose control is key to an effective and safe program of glycemic control.

One of the strongest recommendations of the writing panel was regarding sliding scale insulin. Sliding scale insulin as monotherapy is both ineffective in most patients and potentially dangerous in Type 1 diabetes. The paper provided the evidence to support this important conclusion.

As pleased as I was with the high quality of the consensus statement, and as grateful as I was to the expertise of all those who participated, I was keenly aware that for many of us, the consensus statement was the result of a decision to focus on what we could agree upon. Each of the authors could also articulate other areas of importance that were not fully included in the statement.

So, while I agree with what we wrote, I would like to talk about important areas in the field of patient safety that were not included in the very focused document. The first point is regarding the NICE-SUGAR study. Although not included in the published article, the ANCZA website had posted preliminary data from the NICE-SUGAR study that showed how often hypoglycemia was the result of a deviation from their own protocol, most often due to clinician error. In addition, even one of the reviewers of their published article in NEJM was unable to obtain from the authors the data on how often the glucose monitoring was actually done in the NICE-SUGAR study. All we know is how often the glucose monitoring was intended to be performed, and this actual difference could be crucial.

If the protocol for glycemic control is excellent, but the protocol is not performed as planned, the results should not be expected to be optimal. The systems that we talk about in patient safety discussions most often are the work-flows, equipment, training, teamwork, coordination, and metrics needed to make the protocol work as planned, every time. One of the problems with the negative results reported by some of the authors in both the reported randomized trials and in the meta-analyses, was that the negative results may have been due at least in part to the fact that investigators did not pay as much attention to developing the systems of care as they needed to to get the results they desired.

In fact, it was clear that using sophisticated and effective systems of care, several of the authors of the AACE/ADA consensus statement were able obtain excellent glycemic control with targets in the 110-140mg% range without overly-frequent severe hypoglycemia. The key appears to be setting appropriate glycemic goals that can be achieved safely and consistently. These goals are most often achieved by a multi-disciplinary approach with careful attention to making the system of care sufficiently robust in order to attain the glycemic goals selected. It may be best for an inpatient center to set a goal of 140-180mg% and as they get better in their coordination of their efforts at glycemic control, lower their glycemic target towards 110mg%, while making sure that they keep carefully studied glucose metrics so they can be sure that they are doing what they set out to do without causing harm to the patients in the process.

What we also did not discuss in the consensus statement in great detail is the very large problem of the current accuracy and precision of glucose meters and how important it is to be sure that the method used to obtain timely bedside glucose determinations that work well. There was a statement made in the text of the statement that the FDA standard of accuracy allows a ±20% error for glucose meters, and "questions have been raised about the appropriateness of this criterion". That is, in my opinion, a very large understatement. In fact, many experts agree that improving the accuracy of the glucose meters used in point-of-care testing is crucial, since we make insulin dosage choices based on these numbers. The phrase, "garbage in, garbage out", seems particularly relevant here.

Also, largely because of space considerations, there was not a discussion in the paper about Medicare "Never Events", or preventable diagnostic conditions that have developed in a hospital setting. In the area of glycemic control, the 2007 Medicare data lists hypoglycemia as a far less common diagnosis than either diabetic ketoacidosis or hyperosmolar non-ketotic hyperglycemia. I have been surprised by the relatively large number of hospital acquired DKA and HHNK events reported by Medicare, events that, we would all agree, should never be allowed to occur during a hospital stay. Although this subject was not discussed in the consensus statement, it will be the subject of subsequent editorials on this safety website.

Nearly all of the panelists agreed that more studies are needed comparing different methods, including insulin infusions, in the non-critical areas of hospitals. It is clear that randomized trials in this subject area are far fewer than needed. In recent years, the National Institute of Health has not funded such trials, but if society wants safety in glycemic inpatient care as a feature of the health care system, then society needs to fund appropriate studies. The Agency for Health Care Research and Quality (AHRQ) probably will be the appropriate site of some of the funding. Other not-for-profit agencies interested in patient safety should seriously consider funding more studies in the non-critical areas of hospitals so we can have the appropriate evidence base we need for extending the umbrella of good glycemic control for all hospital inpatients.

In summary, the new AACE/ADA Consensus statement on Inpatient Glycemic Control should be required reading for all clinicians who care for hyperglycemic patients in hospital settings. It is an excellent starting point for further discussions, and we have tried to begin the discussion on this page today. We welcome your comments.

Reference:

American Association of Clinical Endocrinologists and American Diabetes Association consensus statement on inpatient glycemic control.
Moghissi ES, Korytkowski MT, DiNardo M, Einhorn D, Hellman R, Hirsch IB, Inzucchi SE, Ismail-Beigi F, Kirkman MS, Umpierrez GE; American Association of Clinical Endocrinologists; American Diabetes Association. Diabetes Care. 2009 Jun;32(6):1119-31 (co-published in Endocrine Practice, Vol 15, No 4, May/June 2009, pp1-17)

Leave a Comment

There are 7 comments

Prasanna Rao-Balakrishna – UK

July 14, 2009 - 17:23

Subject: Preventing Hypoglycaemia is as important as the tight glycaemic control

Preventing hypoglycaemia is as important as the tight glycaemic control. It is important to note that glycaemic control depends on the insulin regimen, patient's own counter regulatory hormone response & insulin resistance status, the calorie intake, frequency of testing for blood glucose, interpretation and acting on the results. During acute illness it is not possible to control the counter-regulatory hormone response and the insulin resistance status, but with adequate training, frequent testing and appropriate structured response should be possible, thereby preventing a hypoglycaemia. A trial which focuses as much on hypoglycaemia avoidance as well as tight glycaemic control is needed.

Reply to Prasanna Rao-Balakrishna

Richard Hellman MD

July 16, 2009 - 11:25

Subject: RE: Preventing Hypoglycaemia is as important as the tight glycaemic control

Dr Rao-Balakrishna makes a very interesting suggestion, that preventing hypoglycemia is as important as the tight glycemic control, and suggests a trial that focuses on two end-points, the avoidance of hypoglycemia as a co-equal goal in importance to tight glycemic control.

In fact, there is a great deal we do not know about hypoglycemia in critically ill states, and it is far from clear what the short and long term consequences are of mild, moderate, or even brief periods of severe ypoglycemia for critically ill patients. We do know that severe hypoglycemia can be a marker for increased mortality, as it was clearly shown in the VADT trial, but interestingly, those deaths did not usually occur during the hypoglycemic episodes, and the relationship between severe hypoglycemia and subsequent mortality was strongest in the conventional therapy group, suggesting that the hypoglycemic events may have been a consequence of an underlying vulnerability rather than the cause of mortality.

One of the limitations of an approach focused just on the outcomes of glycemia is that from the patients' standpoint, the most important issues are their clinical outcomes: mortality, morbidity, and disability. In contrast, those outcomes may not match the relative frequency of hypoglycemia at all. For example, there is a disconnect between the very high frequency of hypoglycemia in the Van Den Berghe RCT's in critical care published in 2001, 2006, and 2009. Both the surgical ICU study of 2001 and the 2009 pediatric studies showed very excellent outcomes with respect to mortaliy and morbidity in the presence of relatively frequent hypoglycemia.

I again would like to thank Dr Rao-Blakrishna for pointing us again to this very unsettled issue of the importance of hypoglycemia prevention, for the debate as to what we can and should do rages on. There are many creative ideas that have been proposed, but we need more data to guide us as to how to obtain the best clinical outcomes with the tools we have without either unacceptably high levels of hypoglycemia or hyperglycemia.

Richard Hellman MD
Editor-In-Chief
Patient Safety Exchange Website

MRR – Texas

March 31, 2009 - 16:29

Subject: NICE_SUGAR

Several interesting points came to mind when I reviewed the NICE-SUGAR study; the degree of severe hypoglycemia, the degree of cardiovascular mortality, the conventional group’s blood glucose levels are significantly lower than the vast majority of other outcome studies, and the number of severe septic patients in the intensive control branch of the study. According to the 2008 sepsis guidelines, the glycemic control target level for the septic patient is already in question and perhaps sepsis should be an exclusion criteria?

I was tasked with the development and oversight of a Tight Glycemic Control Program pilot study from May 2006 through April 2008 for a South Texas community hospital/level 2 trauma center. This included a 14 bed CCU, 12 bed M/S ICU and 12 bed trauma ICU as well as 4 M/S wards. Clinical inertia was our most difficult element to overcome and for the most part this was never accomplished. Clinical inertia was not only evident on physician's part, but also administration, nursing, nutritional services, pharmacy, and the patients themselves. Accountability to noncompliance to protocols was lacking as well. The philosophy that inpatient glycemic control was not necessarily treating diabetes, yet acute hyperglycemia was never fully accepted. When results like ACCORD, ADVANCE, and VADT were released, I would usually take the phone off the hook and leave the hospital because those wbeepdo not support inpatient glycemic control would come out en mass wishing to compare apples to oranges. That is not necessarily the case with NICE-SUGAR. In our Trauma ICU, where support was highest, for the entire year of 2007, we had only 7% BG > 200mg/dL, less than 2% hypoglycemia under 50 mg/dL, and nearly 75% BG between 80 - 150 mg/dL.

Overall, I applaud the NICE-SUGAR research team for a job very well done and thank them for their contribution to this ongoing discussion. I do support further research to differentiate specific glycemic control target ranges for specific diagnosis, but I too fear this could cause a pendulum swing in the opposite direction resulting in less facilities participating in inpatient glycemic control resulting in less data for differentiation.

NISSIM GABAY – VENEZUELA

March 26, 2009 - 15:25

Subject: NICE -SUGAR

I think that the central goal of the ADA/AACE impatient glucose targets is safe with the protocols .
Hospitals should have protocols in place for using insulin to treat and prevent hyperglycemia.
Subcutaneous insulin may be used for both purposes in most noncritically ill patients, whereas intravenous infusion of
insulin is preferred in critically ill patients.
Be careful with this trial [NICE -SUGAR] to overcome clinical inertia.

Dr. Orlin Sergev – Charleston, SC

March 16, 2009 - 16:28

Subject:

Dear Dr Hellman:
I enjoyed all the editorials on patients' safety that you have recently published. I think that they raise questions which we as physicians are not always open about. Safety itself is frequently a topic that we love to discuss but it's never our fault. In this connection, the article about overconfidence and medical errors is timely - especially, at this time of expected health care changes. Briefly, I do not think we as physicians are different from any other specialists in different areas. Lack of adequate knowledge in a special area is always a good reason to be noisy and seemingly overconfident. Most of us agree that the more you know the more you realize how much more you do not know. Overconfident behavior in front of outsiders seem to be the cover of ignorance. I think we have to improve medical education in order to make medical decisions safer. Just remember the pilot of the plane that landed in Hudson river - quiet professional on top of his performance. We in medical profession must lead in patients' safety. In order to do that we have to lead the health care reform. We have to regain our authority, responsibility and accountability. (accountability without authority and responsibility is meaningless - see Dr Hellman's article on Medicare). We have to lead the health education of the society - most of the tragic mistakes in life happen from ignorance. First and foremost, of course, we have to maintain the superiority in medical knowledge. We must improve the quality of medical education. Instead of multiple choice questions we have to put back in place the stern professor wbeepmade clinical judgements based on knowledge, experience, and gut feeling and set up a good personal example for the next generation of physicians. Pilot "Sully" did not read the manual and the guidelines how to handle the critical situation - all his life before, however, prepared him for the right on the spot decision. Decisions based on profound knowledge and experience are the safest! Let's start the health care reform with ourselves.
Do not stop learning and teaching your team about sound and safe medical practices. When we have achieved that, we can confidently go out and regain our authority over various bureaucracies (government agencies-Medicare, insurances, medical malpractice law, etc).

james t poulos – west lafayette in

March 03, 2009 - 15:09

Subject: NICE-SUGAR

There was an article in acta scandinavia in january that showed very little hypoglycemia when intensive therapy is done right! I came across the article on medlinx in mid January, but it was actually published in October 2008. authors: Kaukonen KM et al in acta anaethesiol scandinavia and titled severe hypoglycemia in intensive insulin therapy.

Reply to james t poulos

Dr Hellman

March 04, 2009 - 16:12

Subject: Further thoughts related to the NICE-SUGAR study

Dear Dr. Poulos,

Thank you for calling attention to the study by Kaukonen KM et al. Your excellent point adds to the discussion generated by the NICE-SUGAR study. Their preliminary data analysis showed that error by provider was the most common cause of hypoglycemia. Their data implied, as I stated in my recent editorial, that improving the training and performance of those managing the insulin infusions greatly decreases the threat of hypoglycemia.

In this study by Kaukonen, done at the Helsinki University Central Hospital in Helsinki, Finland, the authors evaluated the incidence of hypoglycemia in all patients treated in two intensive care units between February 2005 and June 2006. They showed that severe hypoglycemia during intensive insulin therapy was rare in clinical practice. Analyzing data for 1124 patients and 61,203 glucose measurements, they found 36 measurements of severe (≤ 2.2mmol/L) hypoglycemia in 25 patients, with an incidence of 0.06% of severe hypoglycemia.

They commented that the frequency of blood glucose monitoring correlated inversely with the frequency and magnitude of severe hypoglycemia. In surgical patients, it is of note that five of the six instances of hypoglycemia occurred when a nurse failed to comply with the protocol.

The Helsinki group’s observations are entirely in keeping with the preliminary data from the NICE-SUGAR study and make a good deal of common sense. When the rate of decrease of glucose is rapid, for example greater than 1mg/dl/minute, simple arithmetic can tell us when the next glucose determination needs to occur to be able to safely avoid severe hypoglycemia. But if the frequency of checking of glycemic levels is arbitrary, and set too low, then hypoglycemia is to be expected much more often. The Kaukonen group avoided this by making sure the blood glucose sampling was relatively frequent.

In our clinical practice setting as well, the principles of safe handling of insulin infusions have been:

1.frequent monitoring, always at least hourly in ICU settings, more often when dealing with lower glycemic levels;
2.intensive training of nurses to make them expert in understanding how best to use algorithms;
3.specific points at which prolonged hyperglycemia or hypoglycemia necessitates immediate consultation with the responsible physician;
4.review of data to indicate variations in performance and appropriate correction and retraining when appropriate.

We too have extensive experience over many years with the safe use of insulin infusions in inpatient settings with relatively rare severe hypoglycemic episodes and little morbidity.

The NICE-SUGAR study should provide important information. We should not get too far ahead of their forthcoming data, but there is already abundant data, such as the important study from Helsinki, which show us that with a safer system of care, more ambitious glycemic control is both achievable and safe.

Kaukonen KM et al. Severe hypoglycemia during intensive insulin therapy, Acta Anaesthesiol Scand. 2009 Jan;53(1):61-65. Epub 2008 Oct 20.