In this edition of the series, Dr. Molinar provides an excellent review of the different types of hetastarches available along with associated pharmacokinetic and pharmacodynamic profiles.

CLICK HERE TO VIEW THE RECORDED JOURNAL CLUB WEBINAR

This is followed by Dr. Ahn’s review and discussion of the Schortgen et al. study in Lancet 2001. This was thew first “larger” study to evaluate hetastarch and its possible deleterious effect on the kidneys when compared to Gelatin in a multi-center randomized trial in France.

Finally, not until 2008 did we have a large multi-center German study called the VISEP trial published in NEJM which looked at severe sepsis and septic shock patients and compared Hetastarch to Lactated ringers (along with evaluation of intensive vs conventional glucose control). This too as a secondary endpoint ealuated the effects of therapy on renal failure and need for RRT. Although this trial was stopped prematurely because of severe hypoglycemic episodes in the intensive insulin therapy group, it is still the single largest multicenter trial to date looking at the outcomes of septic patients receiving Hetastarch.

These two trials really are the basis of what I have termed the “anti-hextend” movement in the critical care community however they are marked by a myriad of SIGNIFICANT design and statistical FLAWS which have also led to widespread criticism. This journal club webinar aims to dig deep into the analysis of these two trials and was a very engaging and though provoking session. Please FEEL free to comment below and let the discussion continue!!

In keeping with the spirit of ICU 2.0-3.0, I am proud to announce the introduction of the Critical Care Journal Club Series. The series will feature weekly or bi-weekly online, live, real time broadcasts of journal club conferences in the Surgical Intensive Care. The presenters will be residents and fellows rotating through the Surgical ICU and will be moderated by an attending physician. These discussions, much like the anesthesia ones are lively, educational and usually lead to animated conversations on controversial critical care topics facing us today.

Subscribe to the site via twitter or rss to get regular updates and find out how you can attend the next session LIVE online. In the mean time:

CLICK HERE

to get to the list of recordings of the sessions.  As always, comments, suggestions and lively discussion is heavily encouraged!!

Now featuring live online journal clubs on exciting topics in Anesthesia primarily focused on the ambulatory setting.  Follow the link to the Journal Club Series to explore the site and register for the next event. Theses live journal clubs are moderated, live events that lead to lively discussions and feature some of the experts in the field. After the event, you can find a link to the recording of the event where you can review the conference and continue the conversation online …. click on the link and enjoy …

The Endocrine Society is an multi-national, multidiscipline organization with ~14,000 members from over 100 countries. It was founded in 1916 and publishes 4 peer-reviewed journals. On March 26th, 2009 immediately after the NICE SUGAR study was published they released a statement which supports loosening glycemic control in ICU patients may now be more prudent.  They state that we should be targeting glucose values between 144-180 mg/dl “until we better understand the reasons for these somewhat counterintuitive findings.”
Below is an excerpt from the statement which can be viewed in its entirety here   –>

The Endocrine Society commends the NICE-SUGAR investigators for producing an important and provocative addition to the medical literature and draws the following conclusions and recommendations from their data. First, near-normalization of blood sugar does not clearly improve outcomes in all critically ill hyperglycemic ICU patients, and there is even a suggestion that such an approach may worsen outcomes. Second, looser control of hyperglycemia, i.e., target blood glucose of 144-180 mg/dl, is a reasonable, and perhaps preferable, option in this particular group of very sick patients. Third, it is essential to assess clinically meaningful outcomes, such as mortality, as well as surrogate or intermediate endpoints, such as blood sugar level, in studies of diabetes treatment as the NICE-SUGAR study has done; improvement of blood sugar control may not always translate to better clinical results.

This week’s issue of NEJM features another in a long debated series of trials that investigates the benefits of  “tight” vs “conventional” glycemic control in the ICU.  Is this the one that finally gives us the answer? Let’s find out…

The NICE-SUGAR Study Investigators are a multinational, multicenter and multidisciplinary collaboration. The primary objective of this trial was to find the optimal glycemic level for critically ill patients. Patients expected to stay in the ICU for >3 days were enrolled within 24 hours of admission to the ICU. They were randomized to either recive INTENSIVE (81-108 mg/dl) or CONVENTIONAL (<180 mg/dl) therapy. The primary endpoint was 90 day mortality (any cause / after randomization).

After enrolling 6104 patients, 3054 received intensive rx and 3050 received conventional rx. Groups were relatively well matched at baseline.  The major difference in primary outcome was a RRR of ~ 9% in the conventional group (24.5% vs 27.5%). This corresponded to an odds ratio of 1.14 (95% CI 1.02-1.28),  p=0.02. There was no differernce in the treatment effect when looking at medical vs. surgical patients.  Of note, severe hypoglycemia (<40) occured ~13x more often in the intensive group (0.5% vs 6.8%    p<0.001). No other significant differences upon subgroup analysis or secondary outcomes were found.

 
So there you have it. Since the Van den Berghe et al. study was intially published in NEJM in 2001 the issue of glycemic control in the ICU has sparked a viscious debate. Early this century, the hospital administrators, the medicare/private payors and the “quality officers” jumped all over the concept of keeping the glucose tightly controlled. At the surface it certainly seemed to be a reasonable concept – keep the glucose load low and patients will do better! Interestingly, it was also easily marketable. The pharmaceutical and medical device industry was all over it! By the mid 2000s, there was a plethora of instant and fancy glucose measurement tools and database trackers that were developed and sold to the hospitals. In fact, by 2005, glycemic control became a measurement of quality of care in the ICU. BUT, now the paradigm is certainly shifting. More and more evidence has emerged recently that shows the exact opposite. Tight glycemic control may actually be doing harm to patients whilst providing no benefit at all. Incidence of severe hypoglycemia in these patients appears to be a major contributing factor. The process is labor intensive, costly and as the NICE-STUDY investigators show may actually be increasing risk of mortality in critically ill patients.

Until there is a safe way to test tight glucose control (with similar incidence of significant hypoglycemia) we should be no longer be testing this hypothesis. Until then maybe a more reasonable 120-180 mg/dl range might be safer to titrate therapy to. Even that, in my opinion, has not been shown to be beneficial to patients – just “seems to be the right thing to do.” Are we to base the care of the sickest patients in the hospital on a hunch??? There should be good evidence based medicine to support this or we should abandon the practice immediately.

So I ask, Do you believe the hype? Can we finally put this issue to rest …

Wander over to the Evidence Based Medicine section of the website which has recently been opened!

Here you will have an opportunity to review an excellent series from the BMJ by senior lecturer Trisha Greenhalgh entitled “How to read a paper.” This series goes through the basics of a systematic approach on reading, analyzing and critiquing a scientific paper. The BMJ has consistently been a reliable resource for evidence based medical practice sticking to their motto “Helping doctors make better decisions.” Enjoy!

This should at least provide a starting point for our young medical colleagues as well as a good review for the more experienced ones in the art of scientific investigation and evidence based medical decision making. As always please feel free to leave comments and suggestions. Remember, this is an open forum, become part of it!

Dr. Tim Sable’s review of a common and recurrent issue in critical care practice: therapy misalignment. Review the presentation to see how current practitioners use randomized controlled trials to manage ICU patients and whether or not these therapies are in line with the results of the studies. Dr. Sable reviews the TRICC and ARMA trials as examples. This presentation is archived in the section of Journal Club Presentations.

Click on the bottom right “onSlideShare” icon you would like an option to view the show in full screen mode.

Dr. Christofer Utz did an excellent review of the Critical Care Safety Study published in 2005 Critical Care Medicine. The primary objective of this study was to identify the incidence and rates of adverse events in critical care units per 1000 patient days. Dr. Utz reports the study design, methods as well as resuts and finished the presentation with a nice critique on several limitations of this study. The discussion was very engaging and raised several important questions regarding how should we truly define a medical error. The audience also questioned whether we should be reporting some of these errors at all vs. should we be reporting more than we already do today. This presentation is archived in the section of Journal Club Presentations.

Dr. Michael Fernando (CA-2) did an excellent presentation of Acute Renal Failure and Sepsis featured in the July 2004 New England Journal of Medicine. With the significant morbidity and mortality associated with sepsis, septic shock and acute renal failure it is prudent to understand the mechanisms of this disease process as well as evaluate which interventions make therapeutic sense! This review in NEJM gives us some insight and may help intensivists answer some of these questions. This is archived in the collection of Journal Club Presentations.

It was identified that early sepsis maybe a state in which physiologically the body is depleted of vasopressin because the hypothalamic stores empty fast hence theoretically it makes sense to proceed with AVP infusions early in sepsis, however, there are poor outcome studies out there to show any therapeutic benefit. Early goal directed therapy (Rivers et al) may be of some benefit as mortality rates were improved ~16% however these studies are also flawed with biases and a baseline high mortality rate which is of concern. The data on “tight” glycemic control shows that mortality rates were cut in half in post-cardiac surgery patients as well as a 41% reduction in incidence of ARF – but why were they on TPN on day 1 post-op? These are some of the issues raised in this review along with steroid therapy and frequency of RRT.

Dr. Ricardo Riveros (CA-2) presents a thorough review of Mechanisms of Sepsis-Induced Cardiac Dysfuntion featured in the May 2007 Critical Care Medicine. This was a very difficult review of basic science as well as the mechanistic molecular biology of the cardiac dysfunction that occurs in septic patients with myocardial dysfunction. This article focuses on the intracellular pathways that are disrupted by sepsis hence leading to cell death, apoptosis. Dr. Riveros points out the animal models and patient studies used to study these mechanisms as well as their downfalls. A great resource for basic review of what goes wrong within the cell during sepsis. This is archived in the collection of Journal Club Presentations.