Abstract & Commentary
Failure to Adhere to Evidence-Based Guidelines Worsens Outcomes: Support from a Large Study in Trauma Patients
By David J. Pierson, MD, Editor, Professor Emeritus, Pulmonary and Critical Care Medicine, University of Washington, Seattle, is Editor for Critical Care Alert.
Synopsis: In a large international study in patients with severe trauma, patients whose management deviated most from the study's evidence-based guidelines for damage control, transfusion practice, and ventilator management had higher mortality and longer durations of mechanical ventilation.
Source: Rice TW, et al. Deviations from evidence-based clinical management guidelines increase mortality in critically injured trauma patients. Crit Care Med 2012;40:778-786.
Rice and colleagues report a secondary analysis of outcomes among trauma patients in relation to the degree to which the clinicians managing them adhered to a specified set of evidence-based guidelines. The investigators used data from the CONTROL study, a multi-national randomized trial of recombinant activated factor VII (rFVIIa) vs placebo as an adjunct to management conducted between 2005 and 2008. Because that study was negative, data from all the patients were pooled for this analysis.
Adult patients with major blunt or penetrating trauma to the torso or proximal lower extremities who had received 4-8 units of red blood cells and had presented within 4 hours were enrolled within 12 hours of injury, unless they had severe head injuries or were moribund. In addition to being randomized to receive rFVIIa or placebo, all patients were to be managed according to specified protocols with respect to damage control, transfusion, and ventilator management. These protocols were evidence-based reflecting current best practice, and in the case of ventilator management and weaning, they adhered generally to that of the Acute Respiratory Distress Syndrome Network1 with respect to tidal volume, plateau airway pressures, and the titration of FIO2 and positive end-expiratory pressure.
As part of the study design, all data entered on enrolled patients during their initial 5 days were reviewed in near real time by senior critical care and trauma investigators at a coordinating center at Vanderbilt University Medical Center. These investigators classified patients into three levels of protocol adherence for each of the three categories of management, as well as for overall management, as follows:
- No or only minor deviations: trauma care standards for damage control met; transfusion thresholds and other standards met; ventilator management (tidal volume, plateau pressure, FIO2, PEEP, avoidance of paralytics, weaning) adhered to at least 75% of the time; overall, only minor clinically unimportant deviations from guidelines.
- Moderate deviations: some deviations in trauma care but meets overall guidelines; minor departures from transfusion standards; ventilator management guidelines adhered to < 75% of the time; overall, majority of care in keeping with guidelines but with definite departures in one or more categories.
- Major deviations: trauma care standards not met; repeated departure from transfusion guidelines; systematic nonadherence to ventilation guidelines; overall, repeated, or systematic nonadherence to protocols and guidelines.
The study enrolled 573 patients, 556 of whom had complete data for purposes of the present analysis. In terms of overall compliance with the guidelines, 53% of the patients had no or only minor deviations, 37% had moderate deviations, and 10% had major deviations. Compliance was highest for the transfusion protocol (81% compliance) and lowest for ventilation management, with only 46% of patients classified in the highest category. Deviations most often involved tidal volume (36% of patients). Mortality at 30 days was 10% among patients with no or only minor protocol violations, 9% for moderate deviations, and 29% among those with major deviations (P < 0.001). The 90-day mortality findings were similar. Compared to those with no or only minor protocol violations, patients managed with major deviations had more than a three-fold risk of death at 30 and 90 days following injury. Patients with moderate deviations had statistically more organ failure and spent more days on the ventilator than those in the best protocol group, although their mortality did not differ. Those with major deviations were more likely to develop renal failure. Poorer compliance with the weaning protocol was associated with fewer ventilator-free days (i.e., more time on the ventilator).
The CONTROL study was a Phase 3 randomized, clinical trial evaluating efficacy and safety of rFVIIa as an adjunct to direct hemostasis in patients with blunt or penetrating trauma requiring multiple transfusions. It was conducted by Novo Nordisk in 150 hospitals in 26 countries.2 It was negative with respect to the primary endpoint — mortality — and was stopped early for futility, in part because overall mortality was much lower than predicted. Although an expensive failure from the sponsor's perspective, the study has now produced a valuable examination of the impact of evidence-based guidelines on outcomes in major trauma — with findings that should be applicable in critical care well beyond trauma management.
The patients enrolled in this study were critically ill and carefully selected so that the two randomization groups would be well matched with respect to variables of illness and management other than rFVIIa that might affect the outcome of interest. Within this relatively homogeneous population, and because of the careful ongoing prospective assessment of adherence to the study's three sets of guidelines while the study was going on, it is possible to examine the effects of the latter independently of the study's primary intervention. At least with respect to the 10% of patients whose management failed substantially to match what was intended, the results are pretty convincing that rigid adherence to current evidence-based best practice saves lives. As in numerous other studies, the fact that protocolized weaning shortens the duration of mechanical ventilation was once again demonstrated.
- Acute Respiratory Distress Syndrome Network. Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. N Engl J Med 2000;342:1301-1308.
- Hauser CJ, et al; CONTROL Study Group. Results of the CONTROL trial: Efficacy and safety of recombinant activated Factor VII in the management of refractory traumatic hemorrhage. J Trauma 2010;69:489-500.