Low-dose recombinant factor VIIa for massive bleeding: a single centre observational cohort study with 73 patients.

QUESTIONS UNDER STUDY: recombinant activated factor VII (rFVIIa) is used off-label for massive bleeding. There is no convincing evidence of the benefits of this practice and the minimal effective dose is unknown. The aim of the study was to evaluate our in-house guideline recommending a low dose of 60 µg/kg for off-label use of rFVIIa. METHODS: observational cohort study at the Inselspital Bern, a tertiary care University Hospital in Switzerland. All patients with massive bleeding treated off-label with rFVIIa between January 2005 and December 2007 were included. Survival, change of bleeding and transfusion rates, coagulation parameters and complications were analysed. RESULTS: seventy-three patients received rFVIIa. Severe haemorrhage was documented by a bleeding rate of 1000 mL/h (median; interquartile range 350-3000) and total volume replacement of 11.9 L (6.6-15.2) before administration of rFVIIa. The median rFVIIa-dose was 64 µg/kg (56-71). rFVIIa was administered once in 79% patients, twice in 18%. The bleeding rate was reduced in 82% of the patients. Transfused packed red blood cells decreased from 14 units (8-22) over 4.9 h (2.5-8.8) before rFVIIa to 2 (0-6) in 24 h thereafter, platelet concentrates from 2 units (1-3) to 1 (0-2) and FFP from 11 units (6-16) to 2 (0-9). In-hospital mortality was 14% within 24 h and 32% at day 30. There were two arterial thromboembolic complications possibly related to rFVIIa. CONCLUSION: a single injection of 60 µg/kg rFVIIa, a lower dose than usually recommended, appears to be efficacious in controlling massive bleeding with a very low complication rate.

Molecular absorbent recirculating system for the treatment of acute liver failure in surgical patients.

The Molecular Adsorbent Recirculating System (MARS) represents an attractive artificial liver support system for the treatment of liver insufficiency. However, neither indications for MARS treatment (i.e., after extended liver resection) nor criteria for discontinuation of therapy have been evaluated. Therefore, we analyzed the clinical data of all our surgical patients who received MARS treatment for acute liver failure (n = 7). The aim of the study was to identify prognostic indicators for survival. Four of 174 patients resected for hepatic malignancy at our institution received a total of 13 MARS treatments. Two additional patients were successfully bridged to orthotopic liver transplantation with seven MARS treatments and one patient was MARS supported after liver transplantation of a steatotic graft with three MARS treatments. Five of the seven patients survived and were dismissed an average of 31 days, ranging from 17 to 47 days, after the final MARS treatment. No technical complications or adverse effects were observed during the MARS treatments. Important prognostic factors for hepatic recovery and survival were indocyanin green plasma disappearance rates greater than 5%/min and an increase in clotting factor V levels after each MARS treatment. We conclude that MARS therapy can be an effective treatment of postoperative liver insufficiency in the surgical hepatobiliary unit.

Severe transfusion-related acute lung injury.

UNLABELLED: A 46-yr-old man developed severe hypoxemia, pulmonary infiltrates, and an acute decrease in his leukocyte count shortly after transfusion of fresh-frozen plasma (FFP) during recovery from cardiac surgery. Cardiogenic pulmonary edema was excluded. Granulocyte-reactive and agglutinating alloantibodies were detected in the serum of the fresh-frozen plasma donor. The cross-match with the patient's granulocytes revealed antibodies specific for HLA class I. Transfusion-related acute lung injury (TRALI) is a potentially life-threatening, under-recognized and under-reported complication of transfusion. Conservative transfusion strategies and preclusion of the implicated blood donors with granulocyte-reactive antibodies from future blood donation may prevent TRALI and could save lives. IMPLICATIONS: Transfusion-related acute lung injury (TRALI) is a potentially life-threatening, probably under-recognized and under-reported complication of transfusing blood products. Conservative transfusion strategies and preclusion of the implicated blood donors with granulocyte-reactive antibodies from future blood donation may prevent TRALI and potentially save lives.

Comparison of continuous and intermittent renal replacement therapy for acute renal failure.

BACKGROUND: Mortality rates of critically ill patients with acute renal failure (ARF) requiring renal replacement therapy (RRT) are high. Intermittent and continuous RRT are available for these patients on the intensive care units (ICUs). It is unknown which technique is superior with respect to patient outcome. METHODS: We randomized 125 patients to treatment with either continuous venovenous haemodiafiltration (CVVHDF) or intermittent haemodialysis (IHD) from a total of 191 patients with ARF in a tertiary-care university hospital ICU. The primary end-point was ICU and in-hospital mortality, while recovery of renal function and hospital length of stay were secondary end-points. RESULTS: During 30 months, no patient escaped randomization for medical reasons. Sixty-six patients were not randomized for non-medical reasons. Of the 125 randomized patients, 70 were treated with CVVHDF and 55 with IHD. The two groups were comparable at the start of RRT with respect to age (62+/-15 vs 62+/-15 years, CVVHDF vs IHD), gender (66 vs 73% male sex), number of failed organ systems (2.4+/-1.5 vs 2.5+/-1.6), Simplified Acute Physiology Scores (57+/-17 vs 58+/-23), septicaemia (43 vs 51%), shock (59 vs 58%) or previous surgery (53 vs 45%). Mortality rates in the hospital (47 vs 51%, CVVHDF vs IHD, P = 0.72) or in the ICU (34 vs 38%, P = 0.71) were independent of the technique of RRT applied. Hospital length of stay in the survivors was comparable in patients on CVVHDF [median (range) 20 (6-71) days, n = 36] and in those on IHD [30 (2-89) days, n = 27, P = 0.25]. The duration of RRT required was the same in both groups. CONCLUSION: The present investigation provides no evidence for a survival benefit of continuous vs intermittent RRT in ICU patients with ARF.

C1-inhibitor in patients with severe sepsis and septic shock: beneficial effect on renal dysfunction.

OBJECTIVE: To investigate the efficacy and the safety of the parenteral administration of C1-inhibitor to patients with severe sepsis or septic shock. DESIGN: Double blind, randomized, and placebo-controlled trial. SETTING: Surgical and medical intensive care units of a tertiary care university hospital. PATIENTS: Forty consecutive patients (20 C1-inhibitor/20 placebo) who entered the intensive care unit with severe sepsis or septic shock. INTERVENTION: C1-inhibitor intravenously in a 1-hr infusion, starting with 6000 IU, followed by 3000 IU, 2000 IU, and 1000 IU at 12-hr intervals, compared with placebo. MEASUREMENTS AND MAIN RESULTS: C1-inhibitor administration significantly increased plasma C1-inhibitor antigen and activity levels during days 1-4 (p <.007). Patients in the C1-inhibitor group had significantly lower serum creatinine concentrations on day 3 (p =.048) and 4 (p =.01) than placebo patients. Multiple organ dysfunction assessed by logistic organ dysfunction and sepsis-related organ failure assessment scores was less pronounced in patients treated with C1-inhibitor. Mortality rate was similar in both groups. There were no C1-inhibitor-related side effects. CONCLUSIONS: C1-inhibitor administration attenuated renal impairment in patients with severe sepsis or septic shock.