Safe hemoglobin or hematocrit levels in surgical patients.

The terminology and fundamental aspects of the delivery, consumption, and deficits of oxygen are recalled. In chronic and acute, nonseptic states, red blood cell (RBC) transfusion is capable of increasing oxygen consumption (VO2). In acute septic states, the response of VO2 to RBC transfusion is variable and unpredictable, but attempts to increase oxygen delivery (DO2) should be made if the clinical picture raises the suspicion of a potentially lethal oxygen deficit. Therapeutic interventions raising the cardiac index to "supranormal" values in critically ill patients improve their chances of survival; and maintenance of hemoglobin or hematocrit values around 11 g/dl or 33%, respectively, is one part of such interventions. Opinions differ on the general tolerance of anemia, as witnessed by postulated "critical levels" of the hemoglobin concentration between approximately 11 and 4 to 5 g/dl or hematocrit values between 33% and 12% to 15%, respectively. The common denominator underlying these vastly different opinions is the variable behavior of several "non-Hb variables," which influence the venous oxygen tensions apart from the hemoglobin or hematocrit. Abnormalities of these non-Hb variables-typically encountered in the critically ill-increase the dependence of patients on hemoglobin or hematocrit levels that suffice to protect them against an oxygen deficit. For this reason, the "critical" hemoglobin or hematocrit is an individual value, and a generally valid "transfusion trigger" does not exist. Finally, the entity now known as silent myocardial ischemia (SMI) is a decisive factor for the tolerance of anemia. Solid clinical evidence is now available to support the concept that patients over age 40 should not, as an elective procedure, be subjected to levels < 10 g/dl or < 30%, respectively, without prior exclusion of SMI by appropriate investigations.

Comparison of the effects of aprotinin and tranexamic acid on blood loss and related variables after cardiopulmonary bypass.

Aprotinin reduces blood loss after cardiopulmonary bypass, but may sensitize recipients and is expensive. Tranexamic acid, a synthetic antifibrinolytic, has less disadvantages, but opinions differ regarding its efficacy. We studied three groups of patients undergoing cardiopulmonary bypass for coronary disease: recipients of aprotinin (total dose 4.2 x 10(6) kallikrein inhibiting units, n = 14), recipients of tranexamic acid (total dose 20 mg/kg body weight, n = 15), and nonmedicated controls (n = 14) during 24 hours after cardiopulmonary bypass. Compared with controls, aprotinin reduced blood loss, the number of patients requiring transfusions, and the mean number of transfused red cell units (all with p < 0.05), whereas the recipients of tranexamic acid did not differ either from aprotinin recipients or from controls. Aprotinin and tranexamic acid both mitigated the early postoperative reduction of adenosine diphosphate-induced platelet aggregation seen in the controls (p < 0.05). Postoperative increases of plasma concentrations of the prothrombin activation fragment F1 + 2 and the thrombin-antithrombin III complex showed an activation of intravascular coagulation, without any intergroup differences. The balance between concentrations of tissue plasminogen activator and the type 1 plasminogen activator inhibitor disclosed an activation of fibrinolysis, without differences between the groups. The concentrations of D-dimer, a breakdown product of cross-linked fibrin, remained at baseline in the recipients of aprotinin and tranexamic acid but tripled in the controls (p < 0.05). By contrast, the plasma antiplasmin activity was equally depressed in the tranexamic acid and the control groups but decreased less in the recipients of aprotinin (p < 0.05). This discrepancy may reflect the different modes of action of the two agents, which may make aprotinin more efficacious than tranexamic acid in the "nonfibrinolytic" act of protecting platelet function against attack by plasmin during cardiopulmonary bypass.

The 'critical hematocrit': a figure differing from patient to patient.

In my opinion, the problem of a 'critical hematocrit' can be summarized in five contentions: First, it is inadmissible to label any single hemoglobin or hematocrit value as being generally acceptable, the reason being, second, that the adequate values differ between patients and sometimes also between various stages of their individual course--for instance during the intra- and the postoperative period. Third, a hemoglobin or hematocrit within the normal range constitutes a natural buffer against encroachments upon the oxygen supply from non-Hb causes. Intentional manipulation of this buffer requires a careful assessment of potential benefits vs. risks. Fourth, a patient in otherwise perfect condition tolerates a hemoglobin or hematocrit below 10 g/dl or 30%, respectively, down to approximately 8 g/dl or 25%- but tolerance is not necessarily equivalent to an optimum. And fifth, the patient most dependent on his 'hemoglobin buffer' is the individual who has to overcome troubles without the monitoring facilities of an intensive care unit, for instance in the peripheral hospital equipped only for primary care.

Effects of high-dose aprotinin on blood loss, platelet function, fibrinolysis, complement, and renal function after cardiopulmonary bypass.

The use of aprotinin to reduce blood loss after cardiopulmonary bypass is under debate. Concern has been raised about the renal effects of aprotinin. We administered a mean aprotinin dose of 4.2 x 10(6) kallikrein-inhibiting units to 13 patients with coronary disease undergoing cardiopulmonary bypass for 74 +/- 5 minutes (mean +/- standard error of the mean); 13 comparable patients having cardiopulmonary bypass served as control subjects, and all were studied postoperatively for 24 hours. Aprotinin reduced postoperative blood loss by 50% (p = 0.0082). Two of the 13 patients who received aprotinin needed one red cell unit each versus a total of 18 units in eight of 13 control patients (p = 0.0096). Blood pressure, hemoglobin value and serum protein concentration were higher after operation in the aprotinin group (p less than 0.05 to p less than 0.01). Platelet counts did not differ, but plasma thromboxane was lower in aprotinin recipients (p less than 0.001). In control patients fibrinogen degradation products (D dimer) doubled, and alpha 2-antiplasmin activity was halved during and after cardiopulmonary bypass (p less than 0.01 to p less than 0.001), whereas aprotinin patients showed no changes. The complement breakdown products C4a, C3a, and C3dg as well as C9 neoantigen increased from prebypass baseline in both groups (p less than 0.001); the increment of C3a and C3dg was greater in the aprotinin than in the control patients (p less than 0.001). Serum electrolytes, osmolality, and creatinine remained normal in both groups of patients. Creatinine clearance was normal or above normal and virtually identical in both groups. Osmolar clearance and fractional sodium excretion were higher in the aprotinin group than in the control group shortly after cardiopulmonary bypass (p less than 0.05 to p less than 0.01); renal function was unremarkable the next morning. No adverse clinical effects attributable to aprotinin were seen. In summary, aprotinin offers advantages for cardiopulmonary bypass.

[Hemostatic disorders in anesthesiology and surgical intensive care]. / Hämostasestörungen in der Anästhesiologie und operativen Intensivmedizin.

Apart from straightforward haemorrhage, bleeding problems in anaesthesiology and intensive care are predominantly due to multifactorial haemostatic derangements caused by a depletion of procoagulant factors, inhibitors, and platelets. In certain settings, these events are complicated by an enhanced procoagulant and decreased fibrinolytic activity of the endothelium. This functional turnabout of the vasculature promotes disseminated intravascular coagulation (DIC). A rational therapeutic approach is based on estimates of the patient's losses and his volume of blood, adequate and repeated haemostatic monitoring, and an individually tailored substitution considering the critical levels of the informative parameters, i.e. the platelets, fibrinogen, Quick and aPTT, together with the haemostatic efficacy of the available preparations. Whenever possible, subclinical trends towards abnormal bleeding should be identified and countered by appropriate measures before an actual and potentially life-threatening haemostatic breakdown develops.

[Personal computer-assisted "acceptable hemoglobin concentration". An example of preoperative autologous blood donation]. / PC-gestützte Ermittlung der "akzeptablen Hämoglobinkonzentration". Beispiel der präoperativen Eigenblutspende.

At rest, the actual cardiac output (CO) exceeds the CO required to cover the oxygen consumption VO2, provided the hemoglobin level and the non-Hb parameters impacting on cellular oxygen supply (e.g. paO2, pH and body temperature) are normal. The size of this hemodynamic buffer as a function of Hb levels and the non-Hb parameters can be quantified for any clinically conceivable combination including VO2. As Hb levels decrease, the patient's condition is progressively destabilized in the sense that the gradual vanishing of the buffer makes him increasingly sensitive to abnormalities of the non-Hb parameters, such as hypermetabolism, arterial hypoxemia, and alkalosis. This concept is used to illustrate the course of patients participating in an autologous blood predeposit program.

Is there a generally valid, minimum acceptable hemoglobin level?

The different versions of autologous blood transfusion have rekindled interest in a generally valid 'minimum acceptable hemoglobin concentration' of patients around or below 10 g Hb/dl. The adequate Hb concentration capable of covering the oxygen demands of the body depends on several variables measurable at the bedside: oxygen consumption VO2, arterial oxygen tension paO2, body temperature, arterial and mixed venous pH, and cardiac output CO as the most important compensatory variable in anemia. Because of the strain imposed on the myocardium and the coronary circulation, anemia should not raise CO to more than twice the resting value, i.e. less than 10 l/min. Similarly, the mixed venous pO2, as an indicator of tissue oxygenation, should not fall below 35 mm Hg. With these two restrictions, we studied the relationships of the above-mentioned parameters in a computer-supported model. Under otherwise similar conditions, pvO2 falls with an increase in VO2, a decrease in paO2, a decrease in the temperature, an increase in pH, and a decrease in CO. A resting and slightly acidotic patient without other impediments of his cellular oxygen supply--e.g. the patient on chronic hemodialysis--tolerates a Hb level of 6-7 g/dl with a pvO2 barely exceeding 35 mm Hg and a CO approximately 50% above baseline. By contrast, the hypermetabolic and hypoxemic intensive care patient needs Hb levels in the low normal range, i.e. 12-13 g/dl, especially if he is also alkalotic. A generally valid 'minimum acceptable hemoglobin level' does not exist; the adequate Hb concentration is an individual characteristic needing careful attention.(ABSTRACT TRUNCATED AT 250 WORDS)

Role of the reticuloendothelial system in the pathogenesis of organ damage.

Macrophages ingest foreign materials, effete and damaged tissues, and bacterial products. They also secrete biologically active products which promote and regulate host inflammatory responses. The balance between these macrophage activities may lead to the development of an effective and self-limiting inflammatory response or one that results in tissue damage and potentially in organ failure.

[Relation of hypoxia and edema of the intestinal wall and skin to colloid osmotic pressure]. / Die Beziehung von Hypoxie und Odem in Darmwand und Haut zum kolloidosmotischen Druck.

Whereas the impact of colloids and crystalloids on hypoxia and edema has been extensively debated with respect to pulmonary function, their corresponding effects on the systemic circulation have been largely ignored. Manifest edema of the intestine and skin develops, however, when the serum colloid osmotic pressure (COP) is lowered to 15 mm Hg or less by crystalloid infusions. Hypoxia of wounds, which may be aggravated by crystalloids, impairs healing and antibacterial defense, and its has been speculated that edema and/or hypoxia of the intestine may be associated with postoperative gastrointestinal dysfunction. We therefore studies the relationship between lowering and restoration of the COP, the pO2 of the intestinal surface and skin, and tissue edema. We generated an acute hypoproteinemic fluid overload reducing the COP from around 20 to 10 mm Hg in 56 rabbits by means of a 50% plasma loss and excess replacement with Ringer's lactate. We measured the COP with a membrane having a cut-off level of 20,000 d, the cardiac output (with derivation of further hemodynamic data) with an electromagnetic flow probe around the ascending aorta, and the tissue pO2 (pO2t) in mm Hg with the Dortmund 8-channel surface electrode. After 30 min without infusion (Fig. 1), we assigned 14 animals each at random to 4 treatment groups: (1) no treatment (O); (2) 20% albumin 7.5 ml/kg (A); (3) furosemide 2 mg/kg i.v. given three times at 30-min intervals (F); and (4) the combination of both agents (AF). During the infusion-free interval, the cardiac output and pO2t fell by 20%-30% of baseline (Table 1).(ABSTRACT TRUNCATED AT 250 WORDS)

[Review. The intensive medical care relevance of plasma fibronectin]. / Ubersicht. Die akutmedizinische Relevanz von Plasma-Fibronectin.

Plasma Fibronectin (Fn) has been viewed as an essential opsonic mediator of the clearance function of the reticuloendothelial system (RES). An acute depletion of Fn would thus weaken the RES defense potential, which could be restored by Fn repletion. This concept, which was developed by Saba, has attracted considerable attention. Upon closer inspection, however, it turns out to be more complex and less clear cut than is commonly appreciated. The recent interest of acute care physicians is focussed on the behaviour of Fn during intravascular coagulation, organ failure, and sepsis. However, the informative content of plasma Fn levels in this setting is limited, too. The behaviour of Fn is only one part of a broader plasma protein "depletion and recovery syndrome" and therapeutic effects of Fn repletion have as yet not been adequately documented by controlled clinical trials. The use of plasma fibronectin as a part of intensive care is therefore premature, and the concept underlying its use requires further investigation.

Plasma fibronectin: relevance for anesthesiology and intensive care.

Plasma fibronectin has been postulated to be an essential mediator of normal reticuloendothelial system (RES) function. The acute depletion of fibronectin is thought to impair RES function, whereas its repletion in states of deficiency has been reported to improve RES function. In vitro studies have documented fibronectin's ability to bind to some nonbacterial microaggregates and to promote the phagocytosis of bound targets by the RES. These properties may, however, be influenced by the in vivo milieu. There is substantial evidence for a parallelism between RES function and plasma fibronectin levels following blunt trauma in animal models; however, this association is not seen in experimentally induced intravascular coagulation, acute inflammation, and sepsis. Clinically, subnormal fibronectin levels are clearly associated with the triad of intravascular coagulation, organ failure and sepsis. Fibronectin is, however, not the only plasma protein reduced in these patients, nor is it an outstanding predictor of such complications. The therapeutic efficacy of fibronectin administration remains controversial. Whereas initial reports suggested therapeutic benefits of fibronectin-enriched cryoprecipitates, subsequent studies have produced negative results. Prospective, randomized, controlled clinical trials with purified fibronectin are needed before fibronectin should be recommended as an adjunct to the established principles of intensive care.

Purified fibronectin administration to patients with severe abdominal infections. A controlled clinical trial.

Subnormal plasma fibronectin (Fn) levels are found in patients with severe abdominal infections (SAI). The repletion of Fn has been postulated to have therapeutic benefit by virtue of its opsonic, reticuloendothelial system (RES) stimulating effects. A controlled, prospective trial of Fn administration was performed in patients with SAI to assess its use as an adjunct to standard procedures of intensive care. Thirty-three SAI patients were given daily doses of 0.8 g of purified Fn on days 1-5 following admission to the ICU, whereas 34 control patients received no Fn. All patients received the clinical care, antibiotics, and pharmacologic agents appropriate to their individual needs. The admission status and laboratory profiles of the two patient groups (+ and -Fn) were comparable on admission to the study. No side effects of the Fn preparation were observed. As judged by subgroup averages, the Fn replacement regimen was effective in elevating Fn levels to within normal range from day 2 onwards, as measured by immunological and functional assays. The estimated intravascular recovery of Fn averaged 82% in those patients who survived, yet only 52% in the nonsurvivors. Ultimate hospital mortality was 9/33 (27.3%) in the +Fn group versus 13/34 (38.2%) in the -Fn group (p = 0.244, Fisher's exact test). Although ultimate mortality was not significantly changed by the administration of Fn, the Fn treated patients appeared to survive longer than did the control patients. This trend was confirmed through the analysis of expected survival curves (D = 3.12, 0.1 greater than p greater than 0.05). When compared to the survivors, the ultimate nonsurvivors entered the study with statistically higher group averages of bilirubin and creatinine concomitant with lower averages of Fn, antithrombin III, C4, C3, C3b-INH, and transferrin. These differences persisted throughout the 11-day monitoring period; differences between survivors and nonsurvivors with respect to platelets, plasminogen, B-1-H, alpha-2-macroglobulin, and prealbumin appeared during the same period. Dramatic differences between the +Fn and -Fn treatment groups were not seen. Other than Fn, the Fn recipients only developed higher levels of the acute phase reactants C4, C3b-INH, B-1-H and alpha-1-antitrypsin (p less than 0.05) than did their non-Fn treated counterparts. In the present study, we again found a highly significant pattern of correlations between the absolute levels as well as the changes of Fn and other plasma proteins.(ABSTRACT TRUNCATED AT 400 WORDS)

Antithrombin III and related parameters in surgical patients receiving blood components.

We examined the intra- and postoperative behavior of antithrombin III (AT), factor V, VIII, and fibrinogen in 27 elective surgical patients without evidence of disseminated intravascular coagulation (DIC) and treated according to the concept of blood component therapy inaugurated at our hospital in 1975. The intraoperative depletions of AT and fibrinogen were proportional to the transfusion volumes and correlated significantly. AT, fibrinogen, and especially factor V and VIII were significantly mobilized during surgery. A greater intraoperative depletion of AT was significantly associated with a faster recovery during the first 24 postoperative h. The AT activity was virtually stable over a period of 4 weeks in CPD-adenine red cell concentrates; fresh frozen plasma and whole blood are thus not essential as a source of AT. The application of our concept did not increase the frequency of thromboembolic complications, despite the fact that the intraoperative AT values fell below the presumed 'critical' level of 60-70% in some patients. The probable reasons are the brief duration of such levels, the simultaneous depletion of coagulation-promoting plasma constituents (e.g. fibrinogen), and the use of antithrombotic prophylaxis. Our results suggest no reasons for a routine use of fresh frozen plasma in patients with a loss and replacement of less than about 75% of their blood volume.