Clive Landis (CDRC); Dr. Donald Likosky, Dartmouth College, New Hampshire (Chairman, ICEBP), Dr. Robert Baker, Flinders Medical Centre, Adelaide, Australia (Head, Guideline Writing Committee, ICEBP); Dr. Jeremiah Brown, Dartmouth College, NH
Prof. Landis led the first evidence-based review in Dec 2007 resulting in American College of Cardiology/American Heart Association (ACC/AHA) style clinical recommendations on pharmaceutical strategies to limit the systemic inflammatory response. The work was undertaken on behalf of the Guideline Writing Committee of the International Consortium of Evidence Based Perfusion (ICEBP) as part of a broader investigation into anti-inflammatory strategies employed during adult coronary artery bypass grafting (CABG) surgery.
The review was confined to randomized drug trials published in the peer-reviewed medical literature between 1970-2008. To be included, at least one inflammatory marker had to measured. Pediatric, off-pump, valve, other CT procedures were excluded. For studies satisfying these minimal inclusion criteria, organ function to the following index organs was recorded: heart, lung, kidney, brain, and gut.
Of 645 articles initially identified from a systematic search of the literature using a combination of search terms, 61 met the minimal inclusion criteria of measuring a single inflammatory marker and, of these, only 17 went on to describe drug effect(s) on organs (mostly heart and lung). No meta-analyses satisfied the minimal inclusion criteria. The only drug category to achieve a provisional Class IIa recommendation was the steroids: Methylprednisolone was assigned a Class IIa Level of Evidence A recommendation; Dexamethasone, Class IIa Level B; Hydrocortisone, Class IIa Level B. Antifibrinolytics achieved categories IIb or III recommendations: High dose Aprotinin, Class IIb Level A; Low Dose Aprotinin, Class III Level A; Tranexamic Acid, Class IIb Level B; ε-Aminocaproic Acid, Class III Level B. Finally, Atorvostatin was assigned Class III Level B.
These were the first guidelines aimed at producing ACC/AHA clinical recommendations on pharmaceutical strategies to combat the systemic inflammatory response. The ICEBP review has revealed the tiny proportion of studies that could demonstrate any linkage between drug effects on the systemic inflammatory response and organ function. The majority of studies failed to measure any inflammatory markers at all, while many others studied soft end-points, such as length of hospital stay, and merely assumed this was somehow linked to the systemic inflammatory response. The only drug intervention meriting a provisional Class IIa recommendation based on multiple randomized trials was Methylprednisolone.
This evidence based review into the pharmaceutical suppression of the systemic inflammatory response highlighted the paucity of evidence in the literature and the poor standard of reporting of clinical trials. It has informed the creation of the Outcomes Consensus Statement on the conduct of such clinical and spurred development of more comprehensive clinical practice guidelines carried out under the auspices of the Society of Thoracic Surgeons and the Society of Cardiovascular Anesthetists. A sub-study arising from the review was a first meta-analysis on the anti-inflammatory properties of aprotinin, published recently by Brown and Landis. Other publications in leading cardiothoracic journals are anticipated.
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