Perfluorocarbons as blood substitutes: the early years. Experience with Fluosol DA-20% in the 1980s.

Clinical testing of perfluorocarbons (PFC) as blood substitutes began in the early 1980's in the form of Fluosol DA-20% (FDA), a mixture of perfluorodecalin and perfluorotripropylamine emulsified with Pluronic F68. We have treated 55 patients (Treatment (T) = 40; Control (C) = 15) with intravenous infusions of 30 cc/kg of FDA as part of either a randomized, clinical trial or a humanitarian protocol. All patients were Jehovah's Witnesses who refused blood transfusion and were severely anemic (mean hemoglobin = 4.6 g/d). FDA successfully increased dissolved or plasma oxygen content (P1O2 in ml/dl), but not overall oxygen content (T group: P1O2 baseline = 1.01 +/- .27, P1O2 12hrs = 1.58 +/- .47 [p = < .0001, t-test]; P1O2 12 hrs: T = 1.58 +/- .47, C = 1.00 +/- .31, p = < .0002, t-test). This effect persisted for only 12 hours post infusion, and had no apparent effect on survival. FDA is an ineffective blood substitute because of low concentration and short half-life. Improved emulsion design may resolve these problems, thereby producing a more effective agent. Our discussion will include a review of our data plus a summary of other reports of FDA efficacy as a blood substitute.

Is hemoglobin level alone a reliable predictor of outcome in the severely anemic surgical patient?

The relationship between outcome and hemoglobin (Hgb), oxygen extraction ratio (ER), history of cardiac, renal, pulmonary, and/or hepatic disease, diabetes, malignancy, sepsis, hypertension, and active bleeding was analyzed in 47 patients with severe anemia (Hgb less than 7.0 gm/dl, mean = 4.6 +/- .2 gm/dl) to evaluate the effect of Hgb on survival and to look for other predictors of outcome. All patients had refused blood transfusion on religious grounds and were participants in a randomized, controlled study of the blood substitute Fluosol DA-20 per cent. Patients were analyzed as a group and after stratifying by Hgb into four levels: (Hgb less than 3.0 gm/dl, N = 7; Hgb less than 3.5 gm/dl, N = 12; Hgb less than 4.0 gm/dl, N = 17; Hgb less than 4.5 gm/dl, N = 23) and by ER into two levels of less than 50 per cent and greater than 50 per cent. Only Hgb, ER, sepsis and active bleeding were predictors of outcome, with sepsis being the only significant, independent predictor of outcome at all levels (P less than .01). Active bleeding was a predictor for levels of Hgb below 4.0 gm/dl. Hgb level alone was a significant predictor only at levels below 3 gm/dl (P less than .05). Extraction ratio interacted with Hgb only below 3 gm/dl (P less than .05). Multiple independent factors influence outcome in the severely anemic patient, the strongest being sepsis and active bleeding. Prevention of sepsis and early intervention to stop bleeding should improve survival in the patient who refuses transfusion.

Fluosol DA-20 in the treatment of severe anemia: randomized, controlled study of 46 patients.

We evaluated the safety and efficacy of Fluosol DA-20% (FDA) as a blood substitute in the treatment of severe anemia. Thirty-six patients received either FDA (n = 21) or crystalloid/hydroxyethyl starch (CHS) (n = 15) as part of a randomized, controlled trial. Ten patients received FDA as part of a humanitarian protocol. All were Jehovah's Witnesses who refused transfusion, had bled recently, and had average Hgb levels of 4.3 g/dl. After pulmonary artery catheter insertion, each patient was infused with CHS to attain a pulmonary artery wedge pressure (WP) of 10 to 18 mm Hg. FDA was given as a one-time dose of 30 ml/kg. Data were collected at baseline, 12, 24, and 48 h. None of the patients with negative reactions to a 0.5-ml test dose of FDA had adverse reactions to the subsequent infusion. The plasma or dissolved component of oxygen content was significantly higher in the FDA group at 12 h (FDA group 1.58 +/- 0.47 ml/dl, control group 1.01 +/- 0.31 ml/dl, p less than .02, t-test). Nineteen patients died: 12 (37.5%) FDA, seven (46.6%) control. The difference was not significant. We conclude the following: a) FDA can be given safely to severely anemic patients in doses of 30 ml/kg; b) FDA significantly increased the dissolved component of oxygen content after 12 h but the effect did not persist; c) severely anemic patients can survive without transfusion although mortality is high. In this study, inability of FDA to sustain increased oxygen content was due in part to the rapid elimination of FDA and also to the limited amount given.(ABSTRACT TRUNCATED AT 250 WORDS)

Preventive effect of Fluosol-DA for paraplegia encountered after surgical treatment of the thoracic aorta. Preliminary results in a dog model.

The effectiveness of Fluosol-DA (Green Cross Corporation, Osaka, Japan) on circulatory dynamics and neurologic outcome in dogs with ischemic spinal cord injury produced by aortic crossclamping was tested. The control group (receiving saline solution) had an elevated mean aortic proximal pressure (112.9 +/- 30.2 mm Hg versus 175.3 +/- 20.5 mm Hg, p greater than 0.05) and a drastic drop in mean distal aortic pressure (112.9 +/- 30.2 mm Hg versus 29.8 +/- 11.2 mm Hg, p less than 0.05). Although the same trend occurred in dogs treated prophylactically with Fluosol-DA, these changes were not statistically significant. However, there was a significant difference in mean distal aortic pressure during the ischemic phase between the two groups (58.9 +/- 16.0 mm Hg versus 29.8 +/- 11.2 mm Hg, p less than 0.05). Postoperatively all animals had mean arterial pressures within the normal range. All dogs in the control group were paraplegic (partial or complete); the treatment group had one dog with partial paraplegia. The difference between the mean neurologic scores of the two groups was of high statistical significance (3.7 +/- 0.5 versus 1.6 +/- 1.0, p less than 0.05). Our preliminary results show that prophylactic use of Fluosol-DA has favorable effects on hemodynamics and neurologic outcome in dogs with spinal cord ischemia produced by aortic crossclamping. The high propensity of the drug to carry oxygen and carbon dioxide and to provide nutritional support to the ischemic area with resultant improvement in local microcirculation and blood rheology are some speculative mechanisms advocated for these changes.

Heparinless extracorporeal bypass for treatment of hypothermia.

In an attempt to assess the changes occurring to the coagulation profile during internal active core rewarming with partial cardiopulmonary bypass (CPB) without heparin anticoagulation, five pigs were anesthetized, and a model for severe to moderate hypothermia was created. Femoral-femoral bypass with Bio-Pump, heat exchanger, and a membrane oxygenator were used during the rewarming for 64.8 +/- 8.5 minutes. There were no statistically significant changes in platelet count, platelet index, activated clotting time (ACT), partial thromboplastin time (PTT), prothrombin time (PT), fibrinogen, fibrinogen index and fibrin split products (p greater than 0.05). There were no thromboembolic sequelae seen at autopsy. The components of the CPB circuit showed no signs of formation of aggregates or thrombi. The results of this study are attributed to the nonthrombogenic, atraumatic design of the Bio-Pump and the enhanced physiological fibrinolysis seen in the first hour of CPB. We concluded that heparinless CPB may serve as a safe alternative for active core rewarming for severe to moderate hypothermia.