Red blood cell transfusions—are we narrowing the evidence-practice gap? An observational study in 5 Israeli intensive care units

Purpose

The aim of the study was to document transfusion practices in a cross section of general intensive care units (ICUs) in Israel and to determine whether current guidelines are being applied.

Materials and Methods

This prospective study was performed in 5 general ICUs in Israel over a 3-month period. Red cell transfusion data collected on consecutive patients included the trigger, units transfused per transfusion event, and indications, categorized either to treat a specified condition for which transfusions may be beneficial (acute hemorrhage, acute myocardial ischemia, or severe sepsis) or to treat a low hemoglobin concentration.

Results

Of the 238 patients studied, 50% received at least one red blood cell transfusion. The main indication for transfusion (43.7%, or 162/368 U transfused) was to treat a low hemoglobin concentration, in the absence of one of the specified conditions. Total red cell use was 3.0 ± 2.9 U per admission, and patients received a mean of 1.2 ± 0.4 U per transfusion event. The transfusion trigger for the whole group was 7.9 ± 1.1 g/dL. This did not differ significantly between the indications apart from a significantly higher trigger for patients with acute myocardial ischemia (8.8 ± 0.9 g/dL). In addition, patients with a history of heart disease had a higher trigger irrespective of the primary indication for transfusion and received significantly more units per transfusion event. Patients receiving a transfusion had significantly longer ICU stay and hospital mortality.

Conclusions

Our study showed that evidence-practice gaps continue to exist, and it appears that physician behavior is mainly driven by the absolute level of hemoglobin. Educational interventions focused on these factors are required to limit the widespread and often unnecessary use of this scarce and potentially harmful resource.     

Lipid antioxidants: free radical scavenging versus regulation of enzymatic lipid peroxidation

The essentiality of polyunsaturated lipids makes membranes susceptible to peroxidative modifications. One of the most contemporary examples includes selective peroxidation of cardiolipin in mitochondria of cells undergoing apoptosis. Cardiolipin peroxidation products are required for the mitochondrial membrane permeabilization, release of pro-apoptotic factors and completion of the cell death program. Therefore, search for effective inhibitors of cardiolipin peroxidation is critical to discovery and development of anti-apoptotic antioxidants. Mitochondria contain significant amounts of α-tocopherol, a well known scavenger of reactive free radicals. In the present study, we used an oxidative lipidomics approach to evaluate the effect of α-tocopherol and its homologues with different lengths of the side-chain such as 2,5,7,8,-tetramethyl-2(4-methylpentyl)-6-chromanol and 2,2,5,7,8-pentamethyl-6-chromanol, on oxidation of tetralinoleoyl cardiolipin induced by cytochrome c in the presence of hydrogen peroxide. Our data indicate that vitamin E homologues inhibit not only accumulation of tetralinoleoyl cardiolipin hydroperoxides but also hydroxy-derivatives of tetralinoleoyl cardiolipin formed in the enzymatic peroxidase half-reaction catalyzed by cytochrome c. This suggests that protective effects of vitamin E homologues against tetralinoleoyl cardiolipin peroxidation catalyzed by cytochrome c/hydrogen peroxide are realized largely due to their effects on the peroxidase activity of cytochrome c towards tetralinoleoyl cardiolipin rather than via their scavenging activity.     

Metabolism and pharmacokinetics of indacaterol in humans

The metabolism, pharmacokinetics, and excretion of [(14)C]indacaterol were investigated in healthy male subjects. Although indacaterol is administered to patients via inhalation, the dose in this study was administered orally. This was done to avoid the complications and concerns associated with the administration of a radiolabeled compound via the inhalation route. The submilligram doses administered in this study made metabolite identification and structural elucidation by mass spectrometry especially challenging. In serum, the mean t(max), C(max), and AUC(0-last) values were 1.75 h, 0.47 ng/ml, and 1.81 ng · h/ml for indacaterol and 2.5 h, 1.4 ngEq/ml, and 27.2 ngEq · h/ml for total radioactivity. Unmodified indacaterol was the most abundant drug-related compound in the serum, contributing 30% to the total radioactivity in the AUC(0-24h) pools, whereas monohydroxylated indacaterol (P26.9), the glucuronide conjugate of P26.9 (P19), and the 8-O-glucuronide conjugate of indacaterol (P37) were the most abundant metabolites, with each contributing 4 to 13%. In addition, the N-glucuronide (2-amino) conjugate (P37.7) and two metabolites (P38.2 and P39) that resulted from the cleavage about the aminoethanol group linking the hydroxyquinolinone and diethylindane moieties had a combined contribution of 12.5%. For all four subjects in the study, ≥90% of the radioactivity dose was recovered in the excreta (85% in feces and 10% in urine, mean values). In feces, unmodified indacaterol and metabolite P26.9 were the most abundant drug-related compounds (54 and 17% of the dose, respectively). In urine, unmodified indacaterol accounted for ～0.3% of the dose, with no single metabolite accounting for >1.3%.