Post Hoc Mortality Analysis of the Efficacy Trial of Diaspirin Cross-Linked Hemoglobin in the Treatment of Severe Traumatic Hemorrhagic Shock

Abstract

Mortality analysis in this shock study involved both clinical case reviews and mortality prediction models. Despite the observation that nearly all of the deaths were clinically justified, the TRISS and PTOS models demonstrated excess unpredicted deaths in the DCLHb subgroup. A combined process, using both mortality prediction models and clinical case reviews, is useful in trauma studies that use a mortality endpoint.

Artificial O2 Carriers: Status in 2005

“…The ultimate reason explaining the excess mortality in α-α-diaspirin cross linked hemoglobin treated patients has not been found so far. There was clearly an excess of desperate cases in the α-α-diaspirin cross linked hemoglobin group in the US Study but this did not explain the difference in mortality [84]. One might hypothesize that a significant vasoconstriction resulting in a rise in blood pressure [85] may have aggravated the blood loss in trauma victims and thereby compromised survival [86].…”

Emerging Role of Hemoglobin Solutions in Trauma Care

“…40 Regarded by some as a major setback for the clinical implementation of HBOCs, it is important to emphasize that this US multicenter trial of diaspirin crosslinked Hb (DCLHb) for the treatment of severe traumatic hemorrhagic shock was based on the explicit proposal that "DCLHb was tested not as a substitute for blood but rather as an adjunct to the currently used therapies for enhancing oxygen delivery: fluids, blood, and operative intervention." Although a post-hoc analysis indicated the study groups were not comparable, 41 the difference in the primary study endpoint was concerning: the 28-day mortality for the DCLHb group was 46% (24 of 52), compared with 17% for the control (normal saline) group (8 of 46). Much expert thought and preparation went into the study design of this human trial, but the scientific justification of using a vasoconstricting agent for the initial resuscitation of acute hemorrhagic shock was questionable.…”

Blood Substitutes

“…After enrolment of 112 patients, an interimanalysis yielded significantly higher 24-and 48 h mortality in patients treated with DCLHb [97]. There were severe deficiencies regarding design and performance of the study (under-resuscitation and over-proportional enrolment of desperate cases in the DCLHb-group),and the study was terminated prematurely and never restarted [96]. Additionally, in a multicenter study of 85 patients with acute ischemic stroke, the infusion of DCLHb was associated with serious adverse events (fatal brain and pulmonary edema, renal and pancreatic insufficiency); severe stroke and treatment with DCLHb were identified as independent predictors of worse outcome [88].…”