Continuous renal replacement therapies: an update

Continuous renal replacement modalities have found widespread use and acceptance over the last decade. The various modalities differ in the kind of access (arteriovenous v venovenous); in the application of convective clearance (continuous hemofiltration), diffusive clearance (continuous hemodialysis), or a combination of both (continuous hemodiafiltration); and in the location where the replacement fluid enters the circuit (predilution v postdilution). Continuous therapies incorporate several advantages, such as improved hemodynamic stability, the possibility for unlimited alimentation, optimal fluid balance, and gradual urea removal without fluctuations. However, it has not yet been shown whether these advantages have a significant impact on outcome and prognosis, the ultimate measure of treatment efficiency. Major disadvantages of continuous therapies are the ongoing necessity for continuous anticoagulation, immobilization of the patient, and possible side effects from lactate-containing replacement fluid or dialysate. Continuous renal replacement procedures have certainly made the management of critically ill patients easier. In particular, oligoanuric patients with diuretic resistant volume overload and hemodynamically unstable patients with acute renal failure and concomitant sepsis or multiorgan failure appear to benefit most from continuous treatment. The role of continuous hemofiltration as a method of removing serum cytokines in septic patients without renal failure is still controversial and needs further clinical assessment. Due to slow efficacy, continuous renal replacement is indicated only in rare circumstances for intoxication; this therapy also is of rather limited use in severe hyperkalemia or acidosis. Noncritically ill patients with uncomplicated renal failure (eg, due to the use of dye or antibiotics) should be treated with intermittent hemodialysis or peritoneal dialysis. Furthermore, intermittent hemodialysis is preferable in patients with hemorrhagic diathesis because it can be easily performed without anticoagulants.     

Pharmacokinetics of anti-infective agents in continuous hemofiltration

NEW ASSIST TECHNIQUES: Continuous hemofiltration and hemodiafiltration are two new renal replacement techniques offering continuous electrolyte regulation and hemodynamic stability in patients with multiple organ failure. These continuous techniques are being used more and more in intensive care, especially as renal replacement in case of septic shock, and probably have the additional benefit of removing toxins. EFFECT ON ANTIMICROBIALS: Little is known about the removal of drugs and in particular antimicrobials during continuous hemofiltration although both the specific pharmacokinetics of each drug and the patient's particular clinical situation plays an important role. DRUG DOSING: In the intensive care unit, knowledge of the effect of continuous hemofiltration on drug removal and pharmacokinetic profile is crucial for practical management due to the importance of avoiding infratherapeutic serum levels, or inversely toxic levels, in these seriously ill patients. Titration equations provided in most of the recent articles are helpful but usually based on a large number of parameters not always easily available in clinical practice. An approximation of the dose can be estimated from dosing guides for continuous dialysis which can be useful in avoiding poorly adapted dosage.     

Choice of renal replacement therapy

Renal replacement therapies (RRT) for acute renal failure patients consist of continuous or intermittent methods. Continuous renal replacement therapies (CRRT) are used in 54% of centers. Determinant for the choice of the continuous versus intermittent method is the clinical status of the patients. Those who are hemodynamically unstable, who receive a large fluid intake, who are anuric, who present with severe and persistent metabolic disorders such as acidosis or hyperkaliemia, and who are in respiratory failure, are preferably treated with CRRT. Once the patient has improved, he can be switched to intermittent RRT (IRRT). Thus CRRT and IRRT are complementary approaches. Dialysis material should be biocompatible; the RRT method used should guarantee stable hemodynamics. Coping with these two requirements reduces the time duration of renal recovery, diminishes the need for catecholamines and may improve the survival rate.     

A primer on continuous renal replacement therapy for critically ill patients

OBJECTIVES: To characterize the multiple continuous renal replacement therapy (CRRT) techniques available for the management of critically ill adults, and to review the indications for and complications of use, principles of drug removal during CRRT, drug dosage individualization guidelines, and the influence of CRRT on patient outcomes. DATA SOURCES: MEDLINE (January 1981-December 1996) was searched for appropriate publications by using terms such as hemofiltration, ultrafiltration, hemodialysis, hemodiafiltration, medications, and pharmacokinetics; selected articles were cross-referenced. STUDY SELECTION: References selected were those considered to enhance the reader's knowledge of the principles of CRRT, and to provide adequate therapies on drug disposition. DATA SYNTHESIS: CRRTs use filtration/convection and in some cases diffusion to treat hemodynamically unstable patients with fluid overload and/or acute renal failure. Recent data suggest that positive outcomes may also be attained in patients with other medical conditions such as septic shock, multiple organ dysfunction syndrome, and hepatic failure. Age, ventilator support, inotropic support, reduced urine volume, and elevated serum bilirubin concentrations have been associated with poor outcomes. Complications associated with CRRT include bleeding due to excessive anticoagulation and line disconnections, fluid and electrolyte imbalance, and filter and venous clotting. CRRT can complicate the medication regimens of patients for whom it is important to maintain drug plasma concentrations within a narrow therapeutic range. Since the physicochemical characteristics of a drug and procedure-specific factors can alter drug removal, a thorough assessment of all factors needs to be considered before dosage regimens are revised. In addition, an algorithm for drug dosing considerations based on drug and CRRT characteristics, as well as standard pharmacokinetic equations, is proposed. CONCLUSIONS: The use of CRRT has expanded to encompass the treatment of disease states other than just acute renal failure. Since there is great variability among treatment centers, it is premature to conclude that there is enhanced survival in CRRT-treated patients compared with those who received conventional hemodialysis. This primer may help clinicians understand the need to individualize these therapies and to prospectively optimize the pharmacotherapy of their patients receiving CRRT.     

Management of tumor lysis syndrome with standard continuous arteriovenous hemodialysis: case report and a review of the literature

Tumor lysis syndrome (TLS) is a critical illness with few treatment options. This report describes the clinical course of a patient with non-Hodgkin's lymphoma, who developed TLS and required renal replacement therapy. Institution of the standard therapeutic approach, intermittent hemodialysis, was not possible because of persistent hypotension. Instead, the patient was treated with a short course of continuous arteriovenous hemofiltration (CAVH) and conventional continuous arteriovenous hemodialysis (CAVHD) with dialysate flow rate of 1 L/h), which resulted in effective control of serum uric acid, potassium, urea nitrogen, phosphorus, and extracellular fluid volume. This case is in distinction to a previous report of TLS treatment with CAVHD using 4 L/h dialysate flow rate. We conclude that continuous renal replacement therapies with standard dialysate flow rates and replacement volumes should be considered for the treatment of TLS, particulary if the syndrome is accompanied by hypotension.     

Continuous renal replacement therapy: continuous blood purification in the intensive care unit

Severe acute renal failure (SARF) occurs when renal dysfunction is such that haemodialysis or haemofiltration becomes necessary to maintain homeostasis. SARF is increasingly seen in association with multiorgan failure and has become a predominantly Intensive Care Unit disorder. Because of this change in epidemiology, the treatment of SARF has evolved from being exclusively nephrologist and intermittent haemodialysis-based to being mostly intensivist and continuous haemofiltration-based, particularly in European countries with a strong ICU tradition and in Australia. Continuous renal replacement therapy (CRRT) has several advantages in critically ill patients, including greater flexibility, excellent haemodynamic tolerance, outstanding fluid balance control, excellent control of uraemia, prevention of cerebral oedema, ability to provide full and aggressive nutrition, and a possible anti-inflammatory effect. The blood purification effect of CRRT may, in fact, go beyond the simple control of uraemia. Several animal studies have now shown that CRRT attenuates the haemodynamic consequences of bacteraemia or endotoxaemia. Such studies have also shown that increasing the intensity of fluid exchange may offer further beneficial effects in the setting of sepsis. In the light of these findings, CRRT is moving into the area of adjuvant treatment of sepsis, and pilot randomized controlled trials are being conducted to test the hypothesis that CRRT, either in standard or high fluid exchange volumes, attenuates the inflammatory effects of sepsis in humans. In the future, the use of CRRT may extend beyond its initial scope into the area of adjuvant management of sepsis and continuous blood purification may become part of a complex multifaceted approach to multiorgan dysfunction.     

Upper extremity vascular access for continuous arteriovenous hemofiltration and dialysis after cardiac operations

BACKGROUND: There is increasing interest in the use of continuous arteriovenous hemofiltration/dialysis for treatment of profound renal failure after cardiovascular operations. Vascular access for this is usually accomplished by percutaneous cannulation of the femoral artery and vein, with the inherent risks of vascular trauma, patient immobilization, hemorrhage, or infectious complications. METHODS: Fifteen (0.36%) of 4,166 patients receiving cardiovascular surgical procedures sustained postoperative renal failure requiring treatment with continuous arteriovenous hemofiltration/dialysis. Each patient had creation of acute arteriovenous forearm access using a modified Allen-Brown shunt. Shunts were monitored continuously for hemorrhage, malfunction, infection, and thrombus, and were explanted when no longer required. RESULTS: Sixteen shunts were implanted in 15 patients over the 41-month period. All shunts functioned satisfactorily, with the duration of implantation ranging from 1 to 64 days. There were no infectious or hemorrhagic complications. CONCLUSIONS: The acute creation of a simple forearm shunt for postoperative continuous arteriovenous hemo-filtration/dialysis is preferred over femoral arterial and venous cannulation because it can be constructed rapidly and easily in the operating room or at the bedside, has a low complication rate, is available for immediate use, may be left in place indefinitely, does not interfere with patient mobilization or ambulation, and is easily removed.     

Effects of mibefradil, a novel calcium channel blocking agent with T-type activity, in acute experimental myocardial ischemia: maintenance of ventricular fibrillation threshold without inotropic compromise

BACKGROUND: We sought to design a simple machine to safely provide continuous veno-venous hemofiltration to acute renal failure patients. RESULTS: The acu-men device uses a pneumatic blood pump with tidal blood flow as the driving force. A volumetric balancing system balances the filtrate with the replacement fluid, and the blood-air interface is eliminated by replacing the conventional venous drip chamber with two air-separating membranes. The extracorporeal circuit is integrated in a disposable cartridge, which is inserted into the machine at the beginning of treatment. The priming and rinsing is done automatically. CONCLUSION: While preliminary data from an ongoing clinic trial on the efficacy of the device are encouraging, further long-term studies are necessary to evaluate its potential to decrease morbidity and mortality in acute renal failure patients.     

Continuous "high flux" dialysis: an effective renal replacement therapy for intensive care patients

Currently available replacement therapies for the treatment of acute renal failure are reviewed. Particular interest is focused on their application in intensive care, especially in septic patients. Underlying principles and mechanisms of action are explained. The continuous "High flux-dialysis" is shown to be a particularly effective form of renal replacement therapy.     

CVVH in postoperative care of liver transplantation

OBJECTIVE: To evaluate CVVH (Continuous Veno-Venous Hemofiltration) as acute renal replacement treatment in postoperative care of liver transplantation. DESIGN: Retrospective study. SETTING: Intensive Care Unit, year 1995. PATIENTS: 86 OLT performed in 1995, 11 of them underwent acute renal replacement treatment. In the same period, in the ICU were admitted 237 patients, and 20 underwent acute renal replacement treatment (control group). Evaluation with SOFA (Sepsis-related Organ Failure Assessment) score. INTERVENTION: CVVH performed heparin free, pump system, polyamide or polysulphone 0.6 mq membrane hemofilter device, blood flow 150-200 ml/min, UF rate 1000-1200 ml/h, clearance 16-20 ml/min. MEASUREMENTS: Coagulation monitoring (PT as INR, PTT, fibrinogen, antithrombin III, d-dimer, platelet count) was performed 3 times a day or on variation of the clinical conditions. RESULTS: SOFA score did not differ between the two groups. Mortality was higher in the patients treated with CVVH. CVVH was performed from 16 to 18 hrs/day for 9.90 +/- 2.33 days. Three patients developed clinical bleeding before CVVH, 3 during CVVH but 1 of them underwent repeated surgical procedures. CONCLUSIONS: We cannot demonstrate that CVVH doesn't affect bleeding, but we can say that, for the complexity of the post OLT patients, CVVH can be the treatment of choice in case of renal replacement treatment.     

Automatic continuous venovenous hemodiafiltration in cardiosurgical patients

Intermittent substitutive treatments in severely ill patients with acute renal failure are difficult or not suitable because of technical problems and/or hemodynamic instability. Continuous venovenous hemodiafiltration allows an adequate, slow removal of fluid, electrolytes, and waste products by combining diffusive and convective solute transport. Eight patients with acute renal failure, after cardiovascular surgery and cardiogenic shock, were treated by continuous venovenous hemodiafiltration. An automatic system (Equaline System, Amicon Division, USA) was employed. Venous accesses (femoral or subclavian) were used with double lumen catheters. A polysulfone filter (0.4 m2) was used in the study. Blood flow was 30 ml/min and dialysate flow rate 16.6 ml/min. Sterile pyrogen-free hemofiltration substitution fluid was used as dialysate. Mean duration of treatment was 10.3 +/- 3.2 days. After 72 hours blood urea nitrogen levels dropped from 136 +/- 46.13 to 53.5 +/- 12.3 mg/dl and creatinine levels dropped from 6.9 +/- 1.7 to 2.6 +/- 0.9 mg/dl. A controlled steady-state was then maintained. Mean urea clearance was 21 +/- 5.3 ml/min; mean ultrafiltration rate was 20.3 +/- 4.1 L/day. Continuous venovenous hemodiafiltration, with the Equaline System, is effective for the clearance of waste products and is able to maintain perfect fluid balance in catabolic patients with acute renal failure and multiple organ failure.     

Diffusive vs. convective therapy: effects on mediators of inflammation in patient with severe systemic inflammatory response syndrome

OBJECTIVE: To compare two forms of continuous renal replacement therapy, continuous venovenous hemofiltration (CVVH) vs. continuous venovenous hemodialysis (CVVHD), in terms of the removal of inflammatory mediators from the blood of patients with systemic inflammatory response syndrome and acute renal failure. DESIGN: Randomized crossover, clinical study. SETTING: University teaching hospital. PATIENTS: Thirteen patients with systemic inflammatory response syndrome and acute renal failure receiving continuous renal replacement therapy. INTERVENTION: Patients were randomized to receive either convective clearance using CVVH or diffusive clearance using CVVHD for the first 24 hrs, followed by the other modality for 24 hrs. All treatments utilized AN69 hemofilters. CVVH was performed with an ultrafiltration rate of 2 L/hr and CVVHD with a dialysis outflow rate of 2 L/hr. MEASUREMENTS AND MAIN RESULTS: Plasma and ultrafiltrate concentrations of tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, IL-10, and sL-selectin were measured at 0, 1, 3, 6, 12, and 24 hrs by radioimmunoassay. Plasma endotoxin concentrations were also measured at 0, 12, and 24 hrs by chromogenic assay. CVVH was associated with a 13% decrease in plasma TNF-alpha concentrations compared with a 23% increase while on CVVHD (p < .05). Mean plasma concentrations of IL-6, IL-10, and sL-selectin were unchanged over time and between therapies. Only minimal amounts of mediators were recovered in the effluents with either therapy except for IL-6. The clearances for IL-6 were different between therapies, 1.9+/-0.8 (SD) mL/min for CVVHD and 3.3+/-1.5 mL/min for CVVH, (p< .01). Plasma endotoxin concentrations were not different between therapies. CONCLUSION: CVVH resulted in a decrease in plasma TNF-alpha concentrations as compared with CVVHD, while the type of transport mechanism used did not influence plasma concentrations of IL-6, IL-10, soluble L-selectin, or endotoxin. Differences in clearance for IL-6 between CVVH and CVVHD did not translate into significant changes in circulating IL-6 concentrations.     

A comparison of molecular clearance rates during continuous hemofiltration and hemodialysis with a novel volumetric continuous renal replacement system

We developed a continuous, volumetrically controlled veno-venous renal replacement system that can be operated in filtration or dialysis modes. We compared the clearances of substances with a range of molecular weights (MW) in each mode. Ten patients with acute renal failure underwent serial postdilutional hemofiltration and hemodialysis, for 30 min each, in sequence and in randomized order. All were receiving vancomycin for concurrent sepsis. The system incorporated a Filtral 10 AN69 artificial kidney; blood flow rate was 200 ml/min, and dialysate/filtrate flow rate was 25 ml/min. Sieving (SC) and diffusion (DC) co-efficients, for hemofiltration and hemodialysis, respectively, were identical for urea (MW 60; 1.01 +/- 0.05 vs 1.01 +/- 0.07) and creatinine (MW 113; 1.00 +/- 0.09 vs 1.01 +/- 0.06), and clearance equated with dialysate/filtrate flow. There was a modest difference in uric acid clearance (MW 168; SC 1.01 +/- 0.04 vs DC 0.97 +/- 0.04; p < 0.05). Vancomycin (MW 1,800) removal was 19% greater during filtration compared with dialysis (SC 0.87 +/- 0.10 vs DC 0.74 +/- 0.06; p < 0.01). For small solutes, the two modalities were equivalent. Vancomycin clearance was appreciably greater with hemofiltration, which is consistent with a greater potential for convection-based therapy in the removal of uremic and other middle molecules.     

Trace element and vitamin concentrations and losses in critically ill patients treated with continuous venovenous hemofiltration

OBJECTIVES: To measure the blood concentrations of a number of trace elements and vitamins in critically ill patients and examine their elimination by continuous venovenous hemofiltration (CVVH). SETTING: Intensive care unit of a tertiary institution. DESIGN: Prospective, controlled, clinical study. PATIENTS: Eight critically ill patients requiring renal replacement therapy, nine patients requiring intensive care treatment but not requiring renal replacement therapy, and nine healthy controls. INTERVENTIONS: Measurement of trace element and vitamin concentrations in blood and ultrafiltrate. MEASUREMENTS AND MAIN RESULTS: Compared with normal volunteers, critically ill patients requiring CVVH had significantly lower median blood concentrations of vitamin C, vitamin E, selenium, and zinc. During the first 24 hrs of CVVH, there were no changes in the trace element and vitamin concentrations in blood, nor were there differences between pre- and postfilter samples. Micronutrient losses in the ultrafiltrate were small or undetectable except for Vitamin C, chromium, and copper. Compared with normal volunteers, critically ill patients not requiring CVVH also had significantly lower median blood concentrations of vitamin C, vitamin E, selenium, and zinc. There were no differences between the two critically ill groups. CONCLUSIONS: The clinical significance of the reductions in blood concentrations of selenium, zinc, vitamin C, and vitamin E in critically ill patients and the ultrafiltrate losses of Vitamin C, copper, and chromium remains unclear.     

The safety of treatment with recombinant human erythropoietin in clinical use: a review of controlled studies

Recombinant human erythropoietin (rhEPO) has now been approved for the treatment of renal anemia, anemia of prematurity, cancer-associated anemia, AIDS-associated anemia and as concomitant treatment for patients with or without autologous blood donation awaiting elective surgery. The purpose of this review is to provide an overview, based on the results of controlled studies, of the anticipated safety profile of rhEPO in various indications and to assess whether treatment with rhEPO influences the incidences of certain adverse events in these indications. The anticipated adverse events differ from indication to indication and generally reflect the corresponding underlying illness. With most indications, no relevant differences in the incidences of adverse events are observed between rhEPO and placebo-control/patients. Only in the rhEPO therapy of renal anemia is an increased incidence of hypertensive events observed in the rhEPO groups, a finding that is not reproduced with the other indications. The controlled studies forming the basis of this review provide no evidence of a relevant increase in the risk of thromboembolic events during rhEPO therapy. Overall, it may be stated that rhEPO treatment, where strictly indicated, is a safe form of therapy. As with any other treatment, the risk of side effects in certain predisposed patients must also be weighed against the desired clinical benefits.     

Determination of zinc in serum, blood, and ultrafiltrate fluid from patients on hemofiltration by graphite furnace/atomic absorption spectroscopy or flow injection analysis/atomic absorption spectroscopy

Two methods were optimized for the determination of zinc in samples of blood, serum, and ultrafiltrate fluid from patients with chronic renal impairment undergoing hemofiltration. In the first procedure, after acid digestion of the samples, Zn in blood and serum is determined by a system coupled to flow injection analysis and atomic absorption spectroscopy. The method is rapid, automated, simple, needs small amounts of sample, and has acceptable analytical characteristics. The analytical characteristics obtained were as follows: determination range of method, 0.05-2.0 ppm of Zn; precision as coefficient of variation (CV), 5.3%; recovery, 95-105%; and detection limit (DL), 0.02 ppm. The second method is optimized for ultrafiltrate fluid because the sensitivity of the first procedure is not suitable for the levels of Zn (ppb or ng/mL) in these samples. The technique chosen was atomic absorption spectroscopy with electrothermal atomization in a graphite furnace. The analytical characteristics obtained were as follows: determination range of method, 0.3-2.0 ppb Zn; CV, 5.7%; recovery, 93-107%; and DL, 0.12 ppb. The methods were used to determine zinc in samples of blood, serum, and ultrafiltrate fluid from 5 patients with chronic renal impairment undergoing hemofiltration to discover whether there were significant differences in the zinc contents of blood, serum, and ultrafiltrate fluid after the hemofiltration process. An analysis of variance of the experimental data obtained from a randomly selected group of 5 patients showed that zinc concentrations in the ultrafiltrate fluid, venous blood, and venous serum do not vary during hemofiltration (p < 0.05), whereas in arterial blood and serum, the time factor has a significant effect.     

Are we mismanaging calcium and phosphate metabolism in renal failure?

Secondary hyperparathyroidism and renal osteodystrophy are the consequences of abnormal calcium, phosphate, and calcitriol metabolism ensuing from renal failure. Evidence suggests that calcium balance tends to become negative as we grow older than 35 years of age; however, the current dialysis modalities provide patients regardless of age with excessive calcium during dialysis. Administration of calcitriol in the management of hyperparathyroidism further increases the calcium and phosphate absorption. Furthermore, the current thrice-weekly renal replacement therapies fail to remove the daily absorbed phosphate, and we have to use calcium carbonate as a primary phosphate-binding agent to reduce intestinal phosphate absorption. The large calcium mass transfer and phosphate retention could lead to soft tissue calcification, especially in older end-stage renal disease (ESRD) patients. Consequently, only by maintaining a negative calcium balance during renal replacement therapy can we safely use calcitriol and calcium carbonate for the management of secondary hyperparathyroidism. Recent studies have indicated that phosphate restriction alone independent of plasma calcitriol or calcium can lower plasma parathyroid hormone (PTH) in renal failure and prevent hyperplasia of parathyroid glands. Therefore, phosphate control perhaps is the most important means to prevent secondary hyperparathyroidism. Previous studies have shown that ferric compounds are potent phosphate-binding agents; hence, these compounds warrant further trial in the management of phosphate metabolism in renal failure.     

Perspectives of end stage renal failure therapy in Singapore

Haemodialysis in Singapore started in 1961 when a patient with kidney failure was dialysed using the twin coil artificial kidney. Over the years, we have seen various new techniques like rapid high efficiency dialysis, haemodiafiltration (HDF) and rapid high flux HDF introduced. Dialysers with newer membranes have improved solute transport, biocompatibility and water removal. Mini heparinisation and heparin-free dialysis have circumvented problems of bleeding in high risk patients. Technological advances in haemodialysis will continue with more new modalities introduced. Newer forms of vascular access through the subclavian and internal jugular veins have phased out the use of chronic arterio-venous (AV) shunts. Continuous ambulatory peritoneal dialysis (CAPD) was introduced in 1980. This has been a boon for cardiac and diabetic patients. The initial problems with peritonitis are now manageable with our current rate of 24.1 patient months compared to 13.2 patient months in 1983. This has been achieved through the use of ultraviolet (UV) germicidal exchange device and transfer tube changes by trained nursing personnel as well as better patient training and education. New techniques have included the "O" disconnect set, the use of 2.5 litre dialysate, low calcium dialysate and the introduction of continuous cycling peritoneal dialysis (CCPD). Future focus will be on the problems of nutrition and protein loss. Renal transplantation remains the ideal renal replacement therapy. Cadaveric renal transplantation was initiated in 1970 and living related donor transplant in 1976. From 1970-1985, immunotherapy was azathioprine-based and from 1985, cyclosporin A (CyA) was introduced. CyA has abrogated many immunological risk factors. Preformed cytotoxic antibodies are still important.(ABSTRACT TRUNCATED AT 400 WORDS)     

Biophysical compensation mechanisms buffering E. coli protein-nucleic acid interactions against changing environments

All diseases related to chronic or intermittent hypoxaemia can be efficaciously treated with the conventional oxygen therapy. The effectiveness of alternative oxygen therapies (oxygen multistep therapy, intravenous oxygen insufflation, haematogen oxidation therapy and ultraviolet blood radiation) has not been proved for any of the alleged numerous indications. Hyperbaric oxygen therapy can be tried, in single cases, outside of its internationally recognized indications, for the treatment of acute hypoxy of the inner ear.     

Hemoglobin solutions: volume replacement or oxygen therapy?

The development of haemoglobin solutions has progressed significantly in the last 15 years because of a perceived short fall in allogeneic blood within the next decades and increased concern about transmitted infectious diseases. Animal studies have shown that modern highly purified and chemically modified haemoglobin preparations are free of toxic side effects, provide adequate volume replacement and have vasoconstrictive effects that enhance systemic vascular resistance and mean arterial pressures after haemorrhage and in models of nearly complete blood replacement. Microcirculatory effects of haemoglobin-based oxygen carriers are dependent on the respective organ and species in which they are applied and on their degree of purification and chemical modification. Because of different physico-chemical properties in comparison with red cells, haemoglobin solutions provide sufficient tissue oxygenation in areas with critically restricted perfusion even when applied in small doses. First studies in volunteers and patients showed efficacy and tolerability of different newly developed haemoglobin solutions during acute normovolaemic haemodilution and in perioperative blood replacement. However, only little information exists to date in terms of metabolism of haemoglobin preparations and their potential immunogenicity and immunosuppressive side effects. Technical problems with the clinical use of haemoglobin solutions arise because of interference of plasma haemoglobin with routine laboratory tests and oximetry. Future indications for haemoglobin solutions as an oxygen therapeutic allow for application of small doses of such preparations and may help to avoid major technical problems. More clinical studies have to be undertaken to confirm the effectivity and safety of the different haemoglobin solutions and to find out the optimal indications beyond acute preclinical and perioperative blood replacement.